The validation of tomotherapy dose calculations in low-density lung media

NASA Astrophysics Data System (ADS)

Chaudhari, Summer R.; Pechenaya, Olga L.; Goddu, S. Murty; Mutic, Sasa; Rangaraj, Dharanipathy; Bradley, Jeffrey D.; Low, Daniel

2009-04-01

The dose-calculation accuracy of the tomotherapy Hi-Art II® (Tomotherapy, Inc., Madison, WI) treatment planning system (TPS) in the presence of low-density lung media was investigated. In this evaluation, a custom-designed heterogeneous phantom mimicking the mediastinum geometry was used. Gammex LN300 and balsa wood were selected as two lung-equivalent materials with different densities. Film analysis and ionization chamber measurements were performed. Treatment plans for esophageal cancers were used in the evaluation. The agreement between the dose calculated by the TPS and the dose measured via ionization chambers was, in most cases, within 0.8%. Gamma analysis using 3% and 3 mm criteria for radiochromic film dosimetry showed that 98% and 95% of the measured dose distribution had passing gamma values <=1 for LN300 and balsa wood, respectively. For a homogeneous water-equivalent phantom, 95% of the points passed the gamma test. It was found that for the interface between the low-density medium and water-equivalent medium, the TPS calculated the dose distribution within acceptable limits. The phantom developed for this work enabled detailed quality-assurance testing under realistic conditions with heterogeneous media.

The validation of tomotherapy dose calculations in low-density lung media.

PubMed

Chaudhari, Summer R; Pechenaya, Olga L; Goddu, S Murty; Mutic, Sasa; Rangaraj, Dharanipathy; Bradley, Jeffrey D; Low, Daniel

2009-04-21

The dose-calculation accuracy of the tomotherapy Hi-Art II(R) (Tomotherapy, Inc., Madison, WI) treatment planning system (TPS) in the presence of low-density lung media was investigated. In this evaluation, a custom-designed heterogeneous phantom mimicking the mediastinum geometry was used. Gammex LN300 and balsa wood were selected as two lung-equivalent materials with different densities. Film analysis and ionization chamber measurements were performed. Treatment plans for esophageal cancers were used in the evaluation. The agreement between the dose calculated by the TPS and the dose measured via ionization chambers was, in most cases, within 0.8%. Gamma analysis using 3% and 3 mm criteria for radiochromic film dosimetry showed that 98% and 95% of the measured dose distribution had passing gamma values < or =1 for LN300 and balsa wood, respectively. For a homogeneous water-equivalent phantom, 95% of the points passed the gamma test. It was found that for the interface between the low-density medium and water-equivalent medium, the TPS calculated the dose distribution within acceptable limits. The phantom developed for this work enabled detailed quality-assurance testing under realistic conditions with heterogeneous media.

Muscle activity during leg strengthening exercise using free weights and elastic resistance: effects of ballistic vs controlled contractions.

PubMed

Jakobsen, Markus Due; Sundstrup, Emil; Andersen, Christoffer H; Aagaard, Per; Andersen, Lars L

2013-02-01

The present study's aim was to evaluate muscle activity during leg exercises using elastic vs. isoinertial resistance at different exertion and loading levels, respectively. Twenty-four women and eighteen men aged 26-67 years volunteered to participate in the experiment. Electromyographic (EMG) activity was recorded in nine muscles during a standardized forward lunge movement performed with dumbbells and elastic bands during (1) ballistic vs. controlled exertion, and (2) at low, medium and high loads (33%, 66% and 100% of 10 RM, respectively). The recorded EMG signals were normalized to MVC EMG. Knee joint angle was measured using electronic inclinometers. The following results were obtained. Loading intensity affected EMG amplitude in the order: low

Proteomics of Pseudomonas aeruginosa Australian epidemic strain 1 (AES-1) cultured under conditions mimicking the cystic fibrosis lung reveals increased iron acquisition via the siderophore pyochelin.

PubMed

Hare, Nathan J; Soe, Cho Zin; Rose, Barbara; Harbour, Colin; Codd, Rachel; Manos, Jim; Cordwell, Stuart J

2012-02-03

Pseudomonas aeruginosa is an opportunistic pathogen that is the major cause of morbidity and mortality in patients with cystic fibrosis (CF). While most CF patients are thought to acquire P. aeruginosa from the environment, person-to-person transmissible strains have been identified in CF clinics worldwide, and the molecular basis for transmissibility remains poorly understood. We undertook a complementary proteomics approach to characterize protein profiles from a transmissible, acute isolate of the Australian epidemic strain 1 (AES-1R), the virulent burns/wound isolate PA14, and the poorly virulent, laboratory-associated strain PAO1 when grown in an artificial medium that mimics the CF lung environment compared to growth in standard laboratory medium. Proteins elevated in abundance in AES-1R included those involved in methionine and S-adenosylmethionine biosynthesis and in the synthesis of phenazines. Proteomic data were validated by measuring culture supernatant levels of the virulence factor pyocyanin, which is the final product of the phenazine pathway. AES-1R and PAO1 released higher extracellular levels of pyocyanin compared to PA14 when grown in conditions that mimic the CF lung. Proteins associated with biosynthesis of the iron-scavenging siderophore pyochelin (PchDEFGH and FptA) were also present at elevated abundance in AES-1R and at much higher levels than in PAO1, whereas they were reduced in PA14. These protein changes resulted phenotypically in increased extracellular iron acquisition potential and, specifically, elevated pyochelin levels in AES-1R culture supernatants as detected by chrome azurol-S assay and fluorometry, respectively. Transcript analysis of pyochelin genes (pchDFG and fptA) showed they were highly expressed during the early stage of growth in artificial sputum medium (18 h) but returned to basal levels following the establishment of microcolony growth (72 h) consistent with that observed in the CF lung. This provides further evidence that iron acquisition by pyochelin may play a role in the early stages of transmissible CF infection associated with AES-1R.

SU-F-T-369: Validation of Monte-Carlo Beam Model for a Range of Small Fields in Heterogeneous Medium - A Measurement Based Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karthikeyan, N; Bharathiya University, Coimbatore, Tamilnadu; Ganesh, KM

Purpose: To validate the Monaco montecorlo beam model for a range of small field in the heterogeneous medium. Methods: A in-house phantom with three different medium of Foam, PMMA and derlin resembling the densities of lung, soft tissue, and bone was used for the study. The field sizes of 8, 16, 24, 32 and 48mm were studied for the validation of montecarlo algorithm using 0.01cc volume ionchamber and gafchromic films. The 6MV photon beam from Elekta Beam modulator was used with 100cm SAD setup. The outputs were measured at the depth of 5, 10 and 20mm in every second mediummore » with 3cm buildup of first medium for the interface of lung-bone, lung-soft tissue, soft tissue-bone, bone-lung and soft tissue-lung. Similarly, the 2D dose analysis with gamma criteria of 2%2mm were done at the same depths using gafchromic film. For all the measurements 10.4×10.4cm were taken as reference to which the other field sizes were compared. Monaco TPSv.3.20 was used to calculate the dose distribution for all the simulated measurement setups. Results: The average maximum difference among the field sizes of 8, 16, 24, 32 and 48mm at the depth of 5mm in second medium with the interface of lung-bone, lung-soft tissue, soft tissue-bone, bone-lung and soft tissue-lung were observed as 1.29±0.14%, 0.49±0.16%, 0.87±0.23%, 0.92±0.11%, 1.01±0.19% respectively. The minimum and maximum variation of dose among different materials for the smallest field size of 8mm were observed as 0.23% and 1.67% respectively. The 2D analysis showed the average gamma passing of 98.9±0.5%. The calculated two-tailed P-value were showed insignificance with values of 0.562 and 0.452 for both ionchamber and film measurements. Conclusion: The accuracy of dose calculation for the small fields in Monaco Montecarlo TPS algorithm was validated in different inhomogeneous medium and found the results were well correlated with measurement data.« less

Rhythmic expression of DEC2 protein in vitro and in vivo.

PubMed

Sato, Fuyuki; Muragaki, Yasuteru; Kawamoto, Takeshi; Fujimoto, Katsumi; Kato, Yukio; Zhang, Yanping

2016-06-01

Basic helix-loop-helix (bHLH) transcription factor DEC2 (bHLHE41/Sharp1) is one of the clock genes that show a circadian rhythm in various tissues. DEC2 regulates differentiation, sleep length, tumor cell invasion and apoptosis. Although studies have been conducted on the rhythmic expression of DEC2 mRNA in various tissues, the precise molecular mechanism of DEC2 expression is poorly understood. In the present study, we examined whether DEC2 protein had a rhythmic expression. Western blot analysis for DEC2 protein revealed a rhythmic expression in mouse liver, lung and muscle and in MCF-7 and U2OS cells. In addition, AMP-activated protein kinase (AMPK) activity (phosphorylation of AMPK) in mouse embryonic fibroblasts (MEFs) exhibited a rhythmic expression under the condition of medium change or glucose-depleted medium. However, the rhythmic expression of DEC2 in MEF gradually decreased in time under these conditions. The medium change affected the levels of DEC2 protein and phosphorylation of AMPK. In addition, the levels of DEC2 protein showed a rhythmic expression in vivo and in MCF-7 and U2OS cells. The results showed that the phosphorylation of AMPK immunoreactivity was strongly detected in the liver and lung of DEC2 knockout mice compared with that of wild-type mice. These results may provide new insights into rhythmic expression and the regulation between DEC2 protein and AMPK activity.

Concentration of (+/-)-propranolol in isolated, perfused lungs of rat.

PubMed Central

Dollery, C T; Junod, A F

1976-01-01

1 The metabolism and the accumulation of (+/-)-propranolol have been studied in isolated lungs of the rat, perfused with an artificial medium. 2 Little or no metabolism took place during the perfusion periods (up to 10 minutes). 3 Accumulation was observed with high tissue/medium ratios for substrate concentrations of 0.2 muM to 1 mM; there was evidence for saturability, but no real plateau could be seen. The presence of two binding sites with different affinities was established. 4 Cold greatly inhibited the accumulation process at low substrate concentrations, but had no effect at 1 mM propranolol. 5 Inhibition of accumulation was measured in the presence of imipramine, desmethylimipramine, nortryptiline, chlorpromazine and of Na+-free medium. Cocaine, 5-hydroxytryptamine and noradrenaline had no effect. Lidocaine enhanced the accumulation process. Release of previously bound propranolol was accelerated in the presence of propranolol and imipramine, unaffected by a Na+-free medium and decreased by cold and by lidocaine. 6 Experiments on lung tissue slices yielded qualitatively similar results to those obtained with perfused lungs. Ouabain and KCN had no or little effect on propranolol accumulation. PMID:1276542

Liquid culture enhances diagnosis of patients with milder forms of non-tuberculous mycobacterial lung disease.

PubMed

Lee, H; Han, J-H; Park, H Y; Jeon, K; Huh, H J; Ki, C-S; Lee, N Y; Koh, W-J

2017-03-01

To evaluate the proportion and clinical characteristics of patients with non-tuberculous mycobacteria (NTM) lung disease diagnosed based on positive culture results in liquid medium only. We reviewed the medical records of 978 patients diagnosed with NTM lung disease. All clinical samples were cultured in both solid and liquid media. Of the 978 patients, 111 (11.3%) were culture-positive in liquid medium only (liquid culture group), and 867 (88.7%) (solid culture group) on solid medium, regardless of the culture results in liquid medium. At the time of diagnosis, the liquid culture group was less likely than the solid culture group to have haemoptysis (11.7% vs. 20.0%, P = 0.04), positive sputum smear for acid-fast bacilli (14.4% vs. 50.2%, P < 0.001) or the fibrocavitary form of NTM lung disease (3.6% vs. 14.6%, P = 0.001). During the median follow-up period of 28.9 months (interquartile range 19.1-41.6), the proportion of patients requiring antibiotic treatment was lower in the liquid culture group than in the solid culture group (44.1% vs. 61.6%, P < 0.001). Liquid media culture is helpful in the diagnosis of patients with less severe forms of NTM lung disease.

Calcium ions rescue human lung epithelial cells from the toxicity of zinc oxide nanoparticles.

PubMed

Hanagata, Nobutaka; Morita, Hiromi

2015-01-01

Contradictory results have been reported for in vitro evaluations of whether zinc oxide nanoparticles (ZnO NPs) are cytotoxic. Though there have been reports of ZnO NPs cytotoxicity due to Zn ions released from the nanoparticles, there have also been reports concluding that Zn ions are not cytotoxic. This inconsistency is mostly attributed to the types of cells used. In this research, we investigated the difference in the level of ZnO NPs cytotoxicity due to culturing conditions. The sensitivity of human lung epithelial cells to ZnO NPs cytotoxicity differed depending on the dispersing medium, physiological state of the cells resulting from their growth stage, and composition of the medium. Further, with regard to the toxicity of ZnO NPs, NPs internalized into cells had a greater cytotoxic effect than Zn ions released from ZnO NPs. Instead of inducing cell death, ZnO NPs internalized into cells slowed the rate of cell proliferation. Furthermore, the cytotoxicity of ZnO NPs depended greatly on the concentration of calcium ions (Ca2+) in the medium. When the concentration of Ca2+ was low, the cytotoxicity of ZnO NPs increased markedly. However, the toxicity of ZnO NPs was mitigated by the addition of CaCl2 to the medium. Global gene expression analysis revealed that Ca2+ -induced upregulation of cell cycle functions could be attributable to the mitigation of ZnO NP toxicity by Ca2+.

Pivotal role of oxidative stress in tumor metastasis under diabetic conditions in mice.

PubMed

Ikemura, Mai; Nishikawa, Makiya; Kusamori, Kosuke; Fukuoka, Miho; Yamashita, Fumiyoshi; Hashida, Mitsuru

2013-09-10

Diabetic patients are reported to have a high incidence and mortality of cancer, but little is known about the linkage. In this study, we investigated whether high oxidative stress is involved in the acceleration of tumor metastasis in diabetic mice. Murine melanoma B16-BL6 cells stably labeled with firefly luciferase (B16-BL6/Luc) were inoculated into the tail vein of streptozotocin (STZ)-treated or untreated mice. A luciferase assay demonstrated that tumor cells were present largely in the lung of untreated mice, whereas large numbers of tumor cells were detected in both the lung and liver of STZ-treated mice. Repeated injections of polyethylene glycol-conjugated catalase (PEG-catalase), a long-circulating derivative, reduced the elevated fasting blood glucose levels and plasma lipoperoxide levels of STZ-treated mice, but had no significant effects on these parameters in untreated mice. In addition, the injections significantly reduced the number of tumor cells in the lung and liver in both untreated and STZ-treated mice. Culture of B16-BL6/Luc cells in medium containing over 45 mg/dl glucose hardly affected the proliferation of the cells, whereas the addition of plasma of STZ-treated mice to the medium significantly increased the number of cells. Plasma samples of STZ-treated mice receiving PEG-catalase exhibited no such effect on proliferation. These findings indicate that a hyperglycemia-induced increase in oxidative stress is involved in the acceleration of tumor metastasis, and the removal of systemic hydrogen peroxide by PEG-catalase can inhibit the progression of diabetic conditions and tumor metastasis in diabetes. Copyright © 2013 Elsevier B.V. All rights reserved.

Optimized enhancement in helical CT: experiences with a real-time bolus tracking system in 628 patients.

PubMed

Kirchner, J; Kickuth, R; Laufer, U; Noack, M; Liermann, D

2000-05-01

Ultrafast detector technology enables bolus-triggered application of contrast media. In a prospective study we investigated the benefit of this new method with the intention of optimizing enhancement during examination of the chest and abdomen. In total, we examined 548 patients under standardized conditions. All examinations were performed on a Somatom Plus 4 Power CT system (Siemens Corp., Forchheim, Germany) using the CARE-Bolus software. This produces repetitive low-dose test images (e.g. for the lung: 140 kV, 43 mA, TI 0.5 s) and measures the Hounsfield attenuation in a pre-selected region of interest. After exceeding a defined threshold, a diagnostic spiral CT examination was begun automatically. The data obtained from 321 abdominal CT and 179 lung CT examinations were correlated with different parameters such as age, weight and height of the patients and parameters of vascular access. In a group of 80 patients, the injection of contrast medium was stopped after reaching a pre-defined threshold of an increase of 100 HU over the baseline. Then, we assessed the maximal enhancement of liver, pulmonal artery trunk and aortic arch. There was no correlation between bolus geometry and age, body surface or weight. In helical CT of the abdomen the threshold was reached after a mean trigger time of 27 s (range 13-67 s) and only 65 ml (range 41-105 ml) of contrast medium were administered. In helical CT of the lung the threshold was reached after 21 s (range 12-48 s) and the mean amount of administered contrast medium was 48 ml (range 38-71 ml). Bolus triggering allows optimized enhancement of the organs and reduces the dose of contrast material required compared with standard administration. Copyright 2000 The Royal College of Radiologists.

[Effect of cisplatin on the expression of Pokemon gene: experiment with different human lung cancer cells].

PubMed

Zhao, Zhi-Hong; Wang, Sheng-Fa; Yu, Liang; Wang, Ju; Cong, De-Gang; Chang, Hao; Wang, Xue-Feng; Zhang, Tie-Wa; Zhang, Jian; Fu, Kai; Jiang, Jiu-Yang

2008-04-29

To investigate the correlation between Pokemon gene and cisplatin mechanism. Human lung adenocarcinoma cells of the lines A549 and AGZY83-a, human lung squamous carcinoma cells of the line HE-99, and human giant cell lung cancer cells of the line 95D were cultured and cisplatin was added into the medium. Other lung cancer cells of the above mentioned lines were cultured in the medium without cisplatin and were used as control groups. RT-PCR and Western blotting were used to detect the mRNA and protein expression of Pokemon. Pokemon mRNA and protein were expressed highly in all the 4 cell lines. The Pokemon gene expression did not changed significantly after cisplatin treatment groups. There were not significant differences in the mRNA and protein expression of Pokemon among the 4 experiment groups and the control groups (all P > 0.05). Cisplatin has no effect on the Pokemon gene expression of the human lung cancer cells.

Loss of the endothelial glycocalyx is associated with increased E-selectin mediated adhesion of lung tumour cells to the brain microvascular endothelium.

PubMed

Rai, Srijana; Nejadhamzeeigilani, Zaynab; Gutowski, Nicholas J; Whatmore, Jacqueline L

2015-09-25

Arrest of metastasising lung cancer cells to the brain microvasculature maybe mediated by interactions between ligands on circulating tumour cells and endothelial E-selectin adhesion molecules; a process likely to be regulated by the endothelial glycocalyx. Using human cerebral microvascular endothelial cells and non-small cell lung cancer (NSCLC) cell lines, we describe how factors secreted by NSCLC cells i.e. cystatin C, cathepsin L, insulin-like growth factor-binding protein 7 (IGFBP7), vascular endothelial growth factor (VEGF) and tumour necrosis factor-alpha (TNF-α), damage the glycocalyx and enhance initial contacts between lung tumour and cerebral endothelial cells. Endothelial cells were treated with tumour secreted-proteins or lung tumour conditioned medium (CM). Surface levels of E-selectin were quantified by ELISA. Adhesion of A549 and SK-MES-1 cells was examined under flow conditions (1 dyne/cm(2)). Alterations in the endothelial glycocalyx were quantified by binding of fluorescein isothiocyanate-linked wheat germ agglutinin (WGA-FITC). A549 and SK-MES-1 CM and secreted-proteins significantly enhanced endothelial surface E-selectin levels after 30 min and 4 h and tumour cell adhesion after 30 min, 4 and 24 h. Both coincided with significant glycocalyx degradation; A549 and SK-MES-1 CM removing 55 ± 12 % and 58 ± 18.7 % of WGA-FITC binding, respectively. Inhibition of E-selectin binding by monoclonal anti-E-selectin antibody completely attenuated tumour cell adhesion. These data suggest that metastasising lung cancer cells facilitate their own adhesion to the brain endothelium by secreting factors that damage the endothelial glycocalyx, resulting in exposure of the previously shielded adhesion molecules and engagement of the E-selectin-mediated adhesion axis.

Regulation of mouse lung development by the extracellular calcium-sensing receptor, CaR

PubMed Central

Finney, Brenda A; del Moral, Pierre M; Wilkinson, William J; Cayzac, Sebastien; Cole, Martin; Warburton, David; Kemp, Paul J; Riccardi, Daniela

2008-01-01

Postnatal lung function is critically dependent upon optimal embryonic lung development. As the free ionized plasma calcium concentration ([Ca2+]o) of the fetus is higher than that of the adult, the process of lung development occurs in a hypercalcaemic environment. In the adult, [Ca2+]o is monitored by the G-protein coupled, extracellular calcium-sensing receptor (CaR), but neither its ontogeny nor its potential role in lung development are known. Here, we demonstrate that CaR is expressed in the mouse lung epithelium, and that its expression is developmentally regulated, with a peak of expression at embryonic day 12.5 (E12.5) and a subsequent decrease by E18, after which the receptor is absent. Experiments carried out using the lung explant culture model in vitro show that lung branching morphogenesis is sensitive to [Ca2+]o, being maximal at physiological adult [Ca2+]o (i.e. 1.0–1.3 mm) and lowest at the higher, fetal (i.e. 1.7 mm) [Ca2+]o. Administration of the specific CaR positive allosteric modulator, the calcimimetic R-568, mimics the suppressive effects of high [Ca2+]o on branching morphogenesis while both phospholipase C and PI3 kinase inhibition reverse these effects. CaR activation suppresses cell proliferation while it enhances intracellular calcium signalling, lung distension and fluid secretion. Conditions which are restrictive either to branching or to secretion can be rescued by manipulating [Ca2+]o in the culture medium. In conclusion, fetal Cao2+, acting through a developmentally regulated CaR, is an important extrinsic factor that modulates the intrinsic lung developmental programme. Our observations support a novel role for the CaR in preventing hyperplastic lung disease in utero. PMID:18955379

CXCL16 and CXCR6 are coexpressed in human lung cancer in vivo and mediate the invasion of lung cancer cell lines in vitro.

PubMed

Hu, Weidong; Liu, Yue; Zhou, Wenhui; Si, Lianlian; Ren, Liang

2014-01-01

Despite advances in early diagnosis and multimodality therapy for cancers, most of lung cancer patients have been locally advanced or metastatic at the time of diagnosis, suggesting the highly progressive characteristic of lung cancer cells. The mechanisms underling invasiveness and metastasis of lung cancer are yet to be elucidated. In the present study, immunohistochemistry was performed to detect the expression of CXCL16-CXCR6 in human lung cancer tissues. It was demonstrated that similar to CXCL12 and CXCR4, CXCL16 and CXCR6 were also coexpressed in human primary lung cancer tissues. After confirming the functional existence of CXCL16 and CXCR6 protein in A549, 95D and H292 cells by ELSA and flow cytometry analysis, we further explored the significance of CXCL16-CXCR6 axis in the biological functions of lung cancer cell lines in vitro. It was found that CXCL16 had no effects on the PCNA (proliferating cell nuclear antigen) expression of A549, 95D and H292 cells. However, both exogenous CXCL16 and CM (conditioned medium from A549, 95D or H292) significantly improved the in vitro viability and invasion of three lung cancer cell lines. The neutralizing antibody to CXCL16 or down-regulation of CXCR6 was able to inhibit the increased viability and invasiveness of A549, 95D and H292 cells stimulated by CXCL16 or CM. Our results imply that CXCL16-CXCR6 axis is involved in the regulation of viability and invasion rather than PCNA expression of lung caner cells, which opens the door for better understanding the mechanisms of lung tumor progression and metastasis.

CXCL16 and CXCR6 Are Coexpressed in Human Lung Cancer In Vivo and Mediate the Invasion of Lung Cancer Cell Lines In Vitro

PubMed Central

Hu, Weidong; Liu, Yue; Zhou, Wenhui; Si, Lianlian; Ren, Liang

2014-01-01

Despite advances in early diagnosis and multimodality therapy for cancers, most of lung cancer patients have been locally advanced or metastatic at the time of diagnosis, suggesting the highly progressive characteristic of lung cancer cells. The mechanisms underling invasiveness and metastasis of lung cancer are yet to be elucidated. In the present study, immunohistochemistry was performed to detect the expression of CXCL16-CXCR6 in human lung cancer tissues. It was demonstrated that similar to CXCL12 and CXCR4, CXCL16 and CXCR6 were also coexpressed in human primary lung cancer tissues. After confirming the functional existence of CXCL16 and CXCR6 protein in A549, 95D and H292 cells by ELSA and flow cytometry analysis, we further explored the significance of CXCL16-CXCR6 axis in the biological functions of lung cancer cell lines in vitro. It was found that CXCL16 had no effects on the PCNA (proliferating cell nuclear antigen) expression of A549, 95D and H292 cells. However, both exogenous CXCL16 and CM (conditioned medium from A549, 95D or H292) significantly improved the in vitro viability and invasion of three lung cancer cell lines. The neutralizing antibody to CXCL16 or down-regulation of CXCR6 was able to inhibit the increased viability and invasiveness of A549, 95D and H292 cells stimulated by CXCL16 or CM. Our results imply that CXCL16-CXCR6 axis is involved in the regulation of viability and invasion rather than PCNA expression of lung caner cells, which opens the door for better understanding the mechanisms of lung tumor progression and metastasis. PMID:24897301

Intrapulmonary percussive ventilation improves lung function in cystic fibrosis patients chronically colonized with Pseudomonas aeruginosa: a pilot cross-over study.

PubMed

Dingemans, Jozef; Eyns, Hanneke; Willekens, Julie; Monsieurs, Pieter; Van Houdt, Rob; Cornelis, Pierre; Malfroot, Anne; Crabbé, Aurélie

2018-06-01

High levels of shear stress can prevent and disrupt Pseudomonas aeruginosa biofilm formation in vitro. Intrapulmonary percussive ventilation (IPV) could be used to introduce shear stress into the lungs of cystic fibrosis (CF) patients to disrupt biofilms in vivo. We performed a first-of-its-kind pilot clinical study to evaluate short-term IPV therapy at medium (200 bursts per minute, bpm) and high frequency (400 bpm) as compared to autogenic drainage (AD) on lung function and the behavior of P. aeruginosa in the CF lung in four patients who are chronically colonized by P. aeruginosa. A significant difference between the three treatment groups was observed for both the forced expiratory volume in 1 s (FEV1) and the forced vital capacity (FVC) (p < 0.05). More specifically, IPV at high frequency significantly increased FEV1 and FVC compared to AD (p < 0.05) and IPV at medium frequency (p < 0.001). IPV at high frequency enhanced the expression levels of P. aeruginosa planktonic marker genes, which was less pronounced with IPV at medium frequency or AD. In conclusion, IPV at high frequency could potentially alter the behavior of P. aeruginosa in the CF lung and improve lung function. The trail was retrospectively registered at the ISRCTN registry on 6 June 2013, under trial registration number ISRCTN75391385.

Mechanisms for Cellular NO Oxidation and Nitrite Formation in Lung Epithelial Cells

PubMed Central

Zhao, Xue-Jun; Wang, Ling; Shiva, Sruti; Tejero, Jesus; Wang, Jun; Frizzell, Sam; Gladwin, Mark T.

2013-01-01

Airway lining fluid contains relatively high concentrations of nitrite and arterial blood levels of nitrite are higher than venous levels, suggesting the lung epithelium may represent an important source of nitrite in vivo. To investigate whether lung epithelial cells possess the ability to convert NO to nitrite by oxidation, and the effect of oxygen reactions on nitrite formation, the NO donor DETA NONOate was incubated with or without A549 cells or primary human bronchial epithelial (HBE) cells for 24 hrs under normoxic (21% O2) and hypoxic (1% O2) conditions. Nitrite production was significantly increased under all conditions in the presence of A549 or HBE cells, suggesting that both A549 and HBE cells have the capacity to oxidize NO to nitrite even under low oxygen conditions. The addition of oxy-hemoglobin (oxy-Hb) to the A549 cell media decreased the production of nitrite, consistent with NO scavenging limiting nitrite formation. Heat-denatured A549 cells produced much lower nitrite and bitrate, suggesting an enzymatic activity is required. This NO oxidation activity was found to be highest in membrane bound proteins with molecular sizes < 100 kDa. In addition, 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one] (ODQ) and cyanide inhibited formation of nitrite in A549 cells. It has been shown that ceruloplasmin (Cp) possesses an NO oxidase and nitrite synthase activity in plasma based on NO oxidation to nitrosonium cation (NO+). We observed that Cp is expressed intracellularly in lung epithelial A549 cells and secreted into medium under basal conditions and during cytokine stimulation. However, an analysis of Cp expression level and activity measured via ρ-phenylenediamine oxidase activity assay revealed very low activity compared with plasma, suggesting that there is insufficient Cp to contribute to detectable NO oxidation to nitrite in A549 cells. Additionally, Cp levels were knocked down using siRNA by more than 75% in A549 cells, with no significant change in either nitrite or cellular S-nitrosothiol (SNO) formation compared to scrambled siRNA control under basal conditions or cytokine stimulation. These data suggest that lung epithelial cells possess NO oxidase activity, which is enhanced in cell membrane associated proteins and not regulated by intracellular or secreted Cp, indicating that alternative NO oxidases determine hypoxic and normoxic nitrite formation from NO in human lung epithelial cells. PMID:23639566

Dusp3 deletion in mice promotes experimental lung tumour metastasis in a macrophage dependent manner

PubMed Central

Vandereyken, Maud; Jacques, Sophie; Van Overmeire, Eva; Amand, Mathieu; Rocks, Natacha; Delierneux, Céline; Singh, Pratibha; Singh, Maneesh; Ghuysen, Camille; Wathieu, Caroline; Zurashvili, Tinatin; Sounni, Nor Eddine; Moutschen, Michel; Gilles, Christine; Oury, Cécile; Cataldo, Didier; Van Ginderachter, Jo A.

2017-01-01

Vaccinia-H1 Related (VHR) dual-specificity phosphatase, or DUSP3, plays an important role in cell cycle regulation and its expression is altered in several human cancers. In mouse model, DUSP3 deletion prevents neo-angiogenesis and b-FGF-induced microvessel outgrowth. Considering the importance of angiogenesis in metastasis formation, our study aimed to investigate the role of DUSP3 in tumour cell dissemination. Using a Lewis Lung carcinoma (LLC) experimental metastasis model, we observed that DUSP3-/- mice developed larger lung metastases than littermate controls. DUSP3-/- bone marrow transfer to lethally irradiated DUSP3+/+ mice was sufficient to transfer the phenotype to DUSP3+/+ mice, indicating that hematopoietic cells compartment was involved in the increased tumour cell dissemination to lung tissues. Interestingly, we found a higher percentage of tumour-promoting Ly6Cint macrophages in DUSP3-/- LLC-bearing lung homogenates that was at least partially due to a better recruitment of these cells. This was confirmed by 1) the presence of higher number of the Ly6Bhi macrophages in DUSP3-/- lung homogenates and by 2) the better migration of DUSP3-/- bone marrow sorted monocytes, peritoneal macrophages and bone marrow derived macrophages (BMDMs), compared to DUSP3+/+ monocytes, macrophages and BMDMs, in response to LLC-conditioned medium. Our study demonstrates that DUSP3 phosphatase plays a key role in metastatic growth through a mechanism involving the recruitment of macrophages towards LLC-bearing lungs. PMID:29020102

Functional and cytometric examination of different human lung epithelial cell types as drug transport barriers.

PubMed

Min, Kyoung Ah; Rosania, Gus R; Kim, Chong-Kook; Shin, Meong Cheol

2016-03-01

To develop inhaled medications, various cell culture models have been used to examine the transcellular transport or cellular uptake properties of small molecules. For the reproducible high throughput screening of the inhaled drug candidates, a further verification of cell architectures as drug transport barriers can contribute to establishing appropriate in vitro cell models. In the present study, side-by-side experiments were performed to compare the structure and transport function of three lung epithelial cells (Calu-3, normal human bronchial primary cells (NHBE), and NL-20). The cells were cultured on the nucleopore membranes in the air-liquid interface (ALI) culture conditions, with cell culture medium in the basolateral side only, starting from day 1. In transport assays, paracellular transport across all three types of cells appeared to be markedly different with the NHBE or Calu-3 cells, showing low paracellular permeability and high TEER values, while the NL-20 cells showed high paracellular permeability and low TEER. Quantitative image analysis of the confocal microscope sections further confirmed that the Calu-3 cells formed intact cell monolayers in contrast to the NHBE and NL-20 cells with multilayers. Among three lung epithelial cell types, the Calu-3 cell cultures under the ALI condition showed optimal cytometric features for mimicking the biophysical characteristics of in vivo airway epithelium. Therefore, the Calu-3 cell monolayers could be used as functional cell barriers for the lung-targeted drug transport studies.

Functional and cytometric examination of different human lung epithelial cell types as drug transport barriers

PubMed Central

Min, Kyoung Ah; Rosania, Gus R.; Kim, Chong-Kook; Shin, Meong Cheol

2016-01-01

To develop inhaled medications, various cell culture models have been used to examine the transcellular transport or cellular uptake properties of small molecules. For the reproducible high throughput screening of the inhaled drug candidates, a further verification of cell architectures as drug transport barriers can contribute to establishing appropriate in vitro cell models. In the present study, side-by-side experiments were performed to compare the structure and transport function of three lung epithelial cells (Calu-3, normal human bronchial primary cells (NHBE), and NL-20). The cells were cultured on the nucleopore membranes in the air-liquid interface (ALI) culture conditions, with cell culture medium in the basolateral side only, starting from day 1. In transport assays, paracellular transport across all three types of cells appeared to be markedly different with the NHBE or Calu-3 cells, showing low paracellular permeability and high TEER values, while the NL-20 cells showed high paracellular permeability and low TEER. Quantitative image analysis of the confocal microscope sections further confirmed that the Calu-3 cells formed intact cell monolayers in contrast to the NHBE and NL-20 cells with multilayers. Among three lung epithelial cell types, the Calu-3 cell cultures under the ALI condition showed optimal cytometric features for mimicking the biophysical characteristics of in vivo airway epithelium. Therefore, the Calu-3 cell monolayers could be used as functional cell barriers for the lung-targeted drug transport studies. PMID:26746641

Secretion of the endoplasmic reticulum stress protein, GRP78, into the BALF is increased in cigarette smokers.

PubMed

Aksoy, Mark O; Kim, Victor; Cornwell, William D; Rogers, Thomas J; Kosmider, Beata; Bahmed, Karim; Barrero, Carlos; Merali, Salim; Shetty, Neena; Kelsen, Steven G

2017-05-02

Identification of biomarkers of cigarette smoke -induced lung damage and early COPD is an area of intense interest. Glucose regulated protein of 78 kD (i.e., GRP78), a multi-functional protein which mediates cell responses to oxidant stress, is increased in the lungs of cigarette smokers and in the serum of subjects with COPD. We have suggested that secretion of GRP78 by lung cells may explain the increase in serum GRP78 in COPD. To assess GRP78 secretion by the lung, we assayed GRP78 in bronchoalveolar lavage fluid (BALF) in chronic smokers and non-smokers. We also directly assessed the acute effect of cigarette smoke material on GRP78 secretion in isolated human airway epithelial cells (HAEC). GRP78 was measured in BALF of smokers (S; n = 13) and non-smokers (NS; n = 11) by Western blotting. GRP78 secretion by HAEC was assessed by comparing its concentration in cell culture medium and cell lysates. Cells were treated for 24 h with either the volatile phase of cigarette smoke (cigarette smoke extract (CSE) or the particulate phase (cigarette smoke condensate (CSC)). GRP78 was present in the BALF of both NS and S but levels were significantly greater in S (p = 0.04). GRP78 was secreted constitutively in HAEC. CSE 15% X 24 h increased GRP78 in cell-conditioned medium without affecting its intracellular concentration. In contrast, CSC X 24 h increased intracellular GRP78 expression but did not affect GRP78 secretion. Brefeldin A, an inhibitor of classical Golgi secretion pathways, did not inhibit GRP78 secretion indicating that non-classical pathways were involved. The present study indicates that GRP78 is increased in BALF in cigarette smokers; that HAEC secrete GRP78; and that GRP78 secretion by HAEC is augmented by cigarette smoke particulates. Enhanced secretion of GRP78 by lung cells makes it a potential biomarker of cigarette smoke-induced lung injury.

Re-irradiation in lung disease by SBRT: a retrospective, single institutional study.

PubMed

Caivano, Donatella; Valeriani, Maurizio; De Matteis, Sara; Bonome, Paolo; Russo, Ivana; De Sanctis, Vitaliana; Minniti, Giuseppe; Osti, Mattia Falchetto

2018-05-08

The loco regional relapse is frequent in the lung disease. The aim of this study was to evaluate the outcomes of re-irradiation by SBRT in terms of Local Control (LC) and toxicities. From April 2011 to December 2016, twenty-two patients received a re-irradiation by SBRT. Twenty- seven lesions were treated. The medium BED(10) of re-irradiation was 100.6 Gy (range: 48-151.2 Gy) and the medium EQD2(10) was 93.8 Gy (range: 40-126 Gy). In the previous treatment the medium BED(10) was 97.2 Gy (range: 40-120 Gy), the medium EQD2(10) was 81 Gy (range: 32.5-100 Gy). The median time between the first and the second treatment was 18 months. Local Control was reached in 18 out of 27 (66%) re-irradiated lesions, with rates of 67 and 54% at 1- year and 2- years respectively. The treatment was well tolerated; the maximum recorded toxicity was Grade 3. Re- irradiation by SBRT may represent an option for the treatment of lung disease with good results in terms of LC and toxicity.

Metabolic studies of mammalian cells by 31P-NMR using a continuous perfusion technique.

PubMed

Knop, R H; Chen, C W; Mitchell, J B; Russo, A; McPherson, S; Cohen, J S

1984-07-20

Levels of ATP and Pi in metabolically active Chinese hamster lung fibroblasts were monitored noninvasively by 31P-NMR over many hours and under a variety of conditions. The cells were embedded in a matrix of agarose gel in the form of fine threads which were continuously perfused in a standard NMR tube. The small diameter of the thread allows rapid diffusion of metabolites and drugs into the cells. The changes in ATP and Pi levels were followed as a function of time in response to perfusion with a glucose-containing medium, with isotonic saline and with a medium containing 2,4-dinitrophenol, an uncoupler of oxidative phosphorylation. This gel-thread perfusion method should enable routine NMR studies of cellular metabolism, and may have other potential biological applications.

Effect of Fetal Mouse Lung Tissue Co-Culture on In Vitro Maturation of Mouse Immature Oocytes.

PubMed

Belbasi, Masomeh; Jorsaraei, Seyed Gholam Ali; Gholamitabar Tabari, Maryam; Khanbabaei, Ramzan

2017-10-01

The aim of this study was to evaluate the fetal mouse lung tissue co-culture on in vitro maturation (IVM) of mouse immature oocytes. In this experimental study, germinal vesicle (GV) oocytes from ovaries of a group of 25 female mice, 6-8 weeks of age, were dissected after being stimulated by 7.5 IU pregnant mare serum gonadotropin (PMSG) through an intraperitoneal (IP) injection. The fetal lung tissues were then prepared and cultured individually. A total number of 300 oocytes were cultured in the following three groups for 24 hours: control group (n=100) containing only base medium, group I (n=100) containing base medium co-cultured with 11.5- to 12.5-day old fetal mouse lung tissues, and group II (n=100) containing base medium co-cultured with 12.5- to 13.5-day old fetal mouse lung tissues. The proportion of GV and metaphase І (MI) oocytes matured into MІІ oocytes were compared among the three groups using analysis of variance (ANOVA). Correlation test were also used to evaluate the successful rate of IVM oocytes. The proportions of GV oocytes reaching MІІ stage were 46, 65, and 56%, in control, I and II groups, respectively (P<0.05). The percentage of the oocytes remaining at the GV stage were higher in control group as compared with two treatment groups (P<0.05). This study indicated that fetal mouse lung tissue co-culture method increased the percentage of GV oocytes reaching MII stage. Copyright© by Royan Institute. All rights reserved.

Factors secreted from dental pulp stem cells show multifaceted benefits for treating acute lung injury in mice.

PubMed

Wakayama, Hirotaka; Hashimoto, Naozumi; Matsushita, Yoshihiro; Matsubara, Kohki; Yamamoto, Noriyuki; Hasegawa, Yoshinori; Ueda, Minoru; Yamamoto, Akihito

2015-08-01

Acute respiratory distress syndrome (ARDS) is a severe inflammatory disorder characterized by acute respiratory failure, resulting from severe, destructive lung inflammation and irreversible lung fibrosis. We evaluated the use of stem cells derived from human exfoliated deciduous teeth (SHEDs) or SHED-derived serum-free conditioned medium (SHED-CM) as treatments for bleomycin (BLM)-induced mice acute lung injury (ALI), exhibiting several pathogenic features associated with the human disease ARDS. Mice with BLM-induced ALI with or without SHED or SHED-CM treatment were examined for weight loss and survival. The lung tissue was characterized by histological and real-time quantitative polymerase chain reaction analysis. The effects of SHED-CM on macrophage differentiation in vitro were also assessed. A single intravenous administration of either SHEDs or SHED-CM attenuated the lung injury and weight loss in BLM-treated mice and improved their survival rate. Similar recovery levels were seen in the SHEDs and SHED-CM treatment groups, suggesting that SHED improves ALI by paracrine mechanisms. SHED-CM contained multiple therapeutic factors involved in lung-regenerative mechanisms. Importantly, SHED-CM attenuated the BLM-induced pro-inflammatory response and generated an anti-inflammatory/tissue-regenerating environment, accompanied by the induction of anti-inflammatory M2-like lung macrophages. Furthermore, SHED-CM promoted the in vitro differentiation of bone marrow-derived macrophages into M2-like cells, which expressed high levels of Arginase1, CD206 and Ym-1. Our results suggest that SHED-secreted factors provide multifaceted therapeutic effects, including a strong M2-inducing activity, for treating BLM-induced ALI. This work may open new avenues for research on stem cell-based ARDS therapies. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Cotton dust, endotoxin and cancer mortality among the Shanghai textile workers cohort: a 30-year analysis

PubMed Central

Fang, S C; Mehta, A J; Hang, J Q; Eisen, E A; Dai, H L; Zhang, H X; Su, L; Christiani, D C

2013-01-01

Background Although occupational exposure to cotton dust and endotoxin is associated with adverse respiratory health, associations with cancer are unclear. We investigated cancer mortality in relation to cotton dust and endotoxin exposure in the Shanghai textile workers cohort. Methods We followed 444 cotton textile and a reference group of 467 unexposed silk workers for 30 years (26 777 person-years). HRs for all cancers combined (with and without lung cancer) and gastrointestinal cancer were estimated in Cox regression models as functions of cotton textile work and categories of cumulative exposure (low, medium, high), after adjustment for covariates including pack-years smoked. Different lag years accounted for disease latency. Results Risks of mortality from gastrointestinal cancers and all cancers combined, with the exclusion of lung cancer, were increased in cotton workers relative to silk workers. When stratified by category of cumulative cotton exposure, in general, risks were greatest for 20-year lagged medium exposure (all cancers HR=2.7 (95% CI 1.4 to 5.2); cancer excluding lung cancer HR=3.4 (1.7–7.0); gastrointestinal cancer HR=4.1 (1.8–9.7)). With the exclusion of lung cancer, risks of cancer were more pronounced. When stratified by category of cumulative endotoxin exposure, consistent associations were not observed for all cancers combined. However, excluding lung cancer, medium endotoxin exposure was associated with all cancers and gastrointestinal cancer in almost all lag models. Conclusions Cotton dust may be associated with cancer mortality, especially gastrointestinal cancer, and endotoxin may play a causative role. Findings also indirectly support a protective effect of endotoxin on lung cancer. PMID:23828454

Inhaled Corticosteroids in Lung Diseases

PubMed Central

Raissy, Hengameh H.; Kelly, H. William; Harkins, Michelle

2013-01-01

Inhaled corticosteroids (ICSs) are used extensively in the treatment of asthma and chronic obstructive pulmonary disease (COPD) due to their broad antiinflammatory effects. They improve lung function, symptoms, and quality of life and reduce exacerbations in both conditions but do not alter the progression of disease. They decrease mortality in asthma but not COPD. The available ICSs vary in their therapeutic index and potency. Although ICSs are used in all age groups, younger and smaller children may be at a greater risk for adverse systemic effects because they can receive higher mg/kg doses of ICSs compared with older children. Most of the benefit from ICSs occurs in the low to medium dose range. Minimal additional improvement is seen with higher doses, although some patients may benefit from higher doses. Although ICSs are the preferred agents for managing persistent asthma in all ages, their benefit in COPD is more controversial. When used appropriately, ICSs have few adverse events at low to medium doses, but risk increases with high-dose ICSs. Although several new drugs are being developed and evaluated, it is unlikely that any of these new medications will replace ICSs as the preferred initial long-term controller therapy for asthma, but more effective initial controller therapy could be developed for COPD. PMID:23370915

Synthetic cystic fibrosis sputum medium diminishes Burkholderia cenocepacia antifungal activity against Aspergillus fumigatus independently of phenylacetic acid production.

PubMed

Lightly, Tasia Joy; Phung, Ryan R; Sorensen, John L; Cardona, Silvia T

2017-05-01

Phenylacetic acid (PAA), an intermediate of phenylalanine degradation, is emerging as a signal molecule in microbial interactions with the host. In this work, we explore the presence of phenylalanine and PAA catabolism in 3 microbial pathogens of the cystic fibrosis (CF) lung microbiome: Pseudomonas aeruginosa, Burkholderia cenocepacia, and Aspergillus fumigatus. While in silico analysis of B. cenocepacia J2315 and A. fumigatus Af293 genome sequences showed complete pathways from phenylalanine to PAA, the P. aeruginosa PAO1 genome lacked several coding genes for phenylalanine and PAA catabolic enzymes. High-performance liquid chromatography analysis of supernatants from B. cenocepacia K56-2 detected PAA when grown in Luria-Bertani medium but not in synthetic cystic fibrosis sputum medium (SCFM). However, we were unable to identify PAA production by A. fumigatus or P. aeruginosa in any of the conditions tested. The inhibitory effect of B. cenocepacia on A. fumigatus growth was evaluated using agar plate interaction assays. Inhibition of fungal growth by B. cenocepacia was lessened in SCFM but this effect was not dependent on bacterial production of PAA. In summary, while we demonstrated PAA production by B. cenocepacia, we were not able to link this metabolite with the B. cenocepacia - A. fumigatus microbial interaction in CF nutritional conditions.

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

PubMed

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

2009-11-01

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

Efficient zinc uptake is critical for the ability of Pseudomonas aeruginosa to express virulence traits and colonize the human lung.

PubMed

Mastropasqua, Maria Chiara; Lamont, Iain; Martin, Lois W; Reid, David W; D'Orazio, Melania; Battistoni, Andrea

2018-07-01

We have recently shown that Pseudomonas aeruginosa, an opportunistic pathogen that chronically infects the lungs of patients with cystic fibrosis (CF) and other forms of lung disease, is extremely efficient in recruiting zinc from the environment and that this capability is required for its ability to cause acute lung infections in mice. To verify that P. aeruginosa faces zinc shortage when colonizing the lungs of human patients, we analyzed the expression of three genes that are highly induced under conditions of zinc deficiency (zrmA, dksA2 and rpmE2), in bacteria in the sputum of patients with inflammatory lung disease. All three genes were expressed in all the analyzed sputum samples to a level much higher than that of bacteria grown in zinc-containing laboratory medium, supporting the hypothesis that P. aeruginosa is under zinc starvation during lung infections. We also found that the expression of several virulence traits that play a central role in the ability of P. aeruginosa to colonize the lung is affected by disruption of the most important zinc importing systems. Virulence features dependent on zinc intake include swarming and swimming motility and the ability to form biofilms. Furthermore, alterations in zinc assimilation interfere with the synthesis of the siderophore pyoverdine, suggesting that zinc recruitment could modulate iron uptake and affect siderophore-mediated cell signaling. Our results reveal that zinc uptake is likely to play a key role in the ability of P. aeruginosa to cause chronic lung infections and strongly modulates critical virulence traits of the pathogen. Taking into account the recent discovery that zinc uptake in P. aeruginosa is promoted by the release of a small molecular weight molecule showing high affinity for zinc, our data suggest novel and effective possibilities to control lung infections by these bacteria. Copyright © 2018 Elsevier GmbH. All rights reserved.

Xenon Treatment Protects against Remote Lung Injury after Kidney Transplantation in Rats.

PubMed

Zhao, Hailin; Huang, Han; Ologunde, Rele; Lloyd, Dafydd G; Watts, Helena; Vizcaychipi, Marcela P; Lian, Qingquan; George, Andrew J T; Ma, Daqing

2015-06-01

Ischemia-reperfusion injury (IRI) of renal grafts may cause remote organ injury including lungs. The authors aimed to evaluate the protective effect of xenon exposure against remote lung injury due to renal graft IRI in a rat renal transplantation model. For in vitro studies, human lung epithelial cell A549 was challenged with H2O2, tumor necrosis factor-α, or conditioned medium from human kidney proximal tubular cells (HK-2) after hypothermia-hypoxia insults. For in vivo studies, the Lewis renal graft was stored in 4°C Soltran preserving solution for 24 h and transplanted into the Lewis recipient, and the lungs were harvested 24 h after grafting. Cultured lung cells or the recipient after engraftment was exposed to 70% Xe or N2. Phospho (p)-mammalian target of rapamycin (mTOR), hypoxia-inducible factor-1α (HIF-1α), Bcl-2, high-mobility group protein-1 (HMGB-1), TLR-4, and nuclear factor κB (NF-κB) expression, lung inflammation, and cell injuries were assessed. Recipients receiving ischemic renal grafts developed pulmonary injury. Xenon treatment enhanced HIF-1α, which attenuated HMGB-1 translocation and NF-κB activation in A549 cells with oxidative and inflammatory stress. Xenon treatment enhanced p-mTOR, HIF-1α, and Bcl-2 expression and, in turn, promoted cell proliferation in the lung. Upon grafting, HMGB-1 translocation from lung epithelial nuclei was reduced; the TLR-4/NF-κB pathway was suppressed by xenon treatment; and subsequent tissue injury score (nitrogen vs. xenon: 26 ± 1.8 vs. 10.7 ± 2.6; n = 6) was significantly reduced. Xenon treatment confers protection against distant lung injury triggered by renal graft IRI, which is likely through the activation of mTOR-HIF-1α pathway and suppression of the HMGB-1 translocation from nuclei to cytoplasm.

Early tumor growth in metastatic organs influenced by the microenvironment is an important factor which provides organ specificity of colon cancer metastasis.

PubMed

Hara, Y; Ogata, Y; Shirouzu, K

2000-12-01

We have previously demonstrated that liver metastases in nude mice and lung metastases in nude rats occurred specifically, when KM12SM human colon carcinoma cells were inoculated orthotopically into the cecal wall of nude mice and rats. To clarify the relationship between the tumor growth potential in the metastatic organs and the metastatic organ preference in these two metastatic models, we have evaluated the in vitro cell growth activities affected by the organ conditioned medium (CM) from the liver and lung, and the in vivo growth activities of the ectopic implanted tumors in the liver and lung. The tumorigenicity of the ectopic implanted tumors was 100% in mouse liver, 33% in rat liver, 50% in mouse lung, and 75% in rat lung. The crude liver CM of the animals showed inhibitory activities for KM12SM cell growth in a dosage-dependent manner, and the crude lung CM stimulated KM12SM cell growth. The liver CM of nude mice inhibited the KM12SM cell growth more strongly compared with the CM of nude rats, and the lung CM of nude rats was more strongly stimulated compared with the CM of nude mice. The liver CM of nude mice had non-heparin binding factors, which stimulated or inhibited KM12SM cell growth, in a molecular weight range of 50 to 100 kDa. By contrast, the liver CM of nude rats showed no growth stimulating activity for KM12SM cells. These results suggest that the metastatic organ specificity of KM12SM cells may depend on the early tumor growth influenced by the microenvironment in metastatic organs.

Metabolic profiling of human lung cancer blood plasma using 1H NMR spectroscopy

NASA Astrophysics Data System (ADS)

Kokova, Daria; Dementeva, Natalia; Kotelnikov, Oleg; Ponomaryova, Anastasia; Cherdyntseva, Nadezhda; Kzhyshkowska, Juliya

2017-11-01

Lung cancer (both small cell and non-small cell) is the second most common cancer in both men and women. The article represents results of evaluating of the plasma metabolic profiles of 100 lung cancer patients and 100 controls to investigate significant metabolites using 400 MHz 1H NMR spectrometer. The results of multivariate statistical analysis show that a medium-field NMR spectrometer can obtain the data which are already sufficient for clinical metabolomics.

Lysophosphatidic acid stimulates epidermal growth factor-family ectodomain shedding and paracrine signaling from human lung fibroblasts.

PubMed

Shiomi, Tetsuya; Boudreault, Francis; Padem, Nurcicek; Higashiyama, Shigeki; Drazen, Jeffrey M; Tschumperlin, Daniel J

2011-01-01

Lysophospatidic acid (LPA) is a bioactive lipid mediator implicated in tissue repair and wound healing. It mediates diverse functional effects in fibroblasts, including proliferation, migration and contraction, but less is known about its ability to evoke paracrine signaling to other cell types involved in wound healing. We hypothesized that human pulmonary fibroblasts stimulated by LPA would exhibit ectodomain shedding of epidermal growth factor receptor (EGFR) ligands that signal to lung epithelial cells. To test this hypothesis, we used alkaline phosphatase-tagged EGFR ligand plasmids transfected into lung fibroblasts, and enzyme-linked immunosorbent assays to detect shedding of native ligands. LPA induced shedding of alkaline phosphatase-tagged heparin-binding epidermal growth factor (HB-EGF), amphiregulin, and transforming growth factor-a; non-transfected fibroblasts shed amphiregulin and HBEGF under baseline conditions, and increased shedding of HB-EGF in response to LPA. Treatment of fibroblasts with LPA resulted in elevated phosphorylation of extracellular signal-regulated kinase 1/2, enhanced expression of mRNA for c-fos, HB-EGF and amphiregulin, and enhanced proliferation at 96 hours. However, none of these fibroblast responses to LPA required ectodomain shedding or EGFR activity. To test the ability of LPA to stimulate paracrine signaling from fibroblasts, we transferred conditioned medium from LPA-stimulated cells, and found enhanced EGFR and extracellular signal-regulated kinase 1/2 phosphorylation in reporter A549 cells in excess of what could be accounted for by transferred LPA alone. These data show that LPA mediates EGF-family ectodomain shedding, resulting in enhanced paracrine signaling from lung fibroblasts to epithelial cells. © 2011 by the Wound Healing Society.

SU-F-T-415: Differences in Lung Sparing in Deep Inspiration Breath-Hold and Free Breathing Breast Plans Calculated in Pinnacle and Monaco

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saenz, D; Stathakis, S

Purpose: Deep inspiration breath-hold (DIBH) is used for left-sided breast radiotherapy to spare the heart and lung. The magnitude of sparing has been shown to be significant. Monte Carlo, furthermore, has the potential to calculate most accurately the dose in the heterogeneous lung medium at the interface with the lung wall. The lung dose was investigated in Monaco to determine the level of sparing relative to that calculated in Pinnacle{sup 3}. Methods: Five patients undergoing DIBH radiotherapy on an Elekta Versa HD linear accelerator in conjunction with the Catalyst C-RAD surface imaging system were planned using Phillips Pinnacle{sup 3}. Freemore » breathing plans were also created to clinically assure a benefit. Both plans were re-calculated in Monaco to determine if there were any significant differences. The mean heart dose, mean left lung, and mean total lung dose were compared in addition to the V20 for left and both lungs. Dose was calculated as dose to medium as well as dose to water with a statistical precision of 0.7%. Results: Mean lung dose was significantly different (p < 0.003) between the two calculations for both DIBH (11.6% higher in Monaco) and free breathing (14.2% higher in Monaco). V20 was also higher in Monaco (p < 0.05) for DIBH (5.7% higher) and free breathing (4.9% higher). The mean heart dose was not significantly different between the dose calculations for either DIBH or free breathing. Results were no more than 0.1% different when calculated as dose to water. Conclusion: The use of Monte Carlo can provide insight on the lung dose for both free breathing and DIBH techniques for whole breast irradiation. While the sparing (dose reductions with DIBH as compared to free breathing) is equivalent for either planning system, the lung doses themselves are higher when calculated with Monaco.« less

A novel sorptive extraction method based on polydimethylsiloxane frit for determination of lung cancer biomarkers in human serum.

PubMed

Xu, Hui; Wang, Shuyu

2012-04-29

In this study, a porous polypropylene frit was coated with polydimethylsiloxane (PDMS) as extraction medium, based on the home-made PDMS-frit, a rapid, simple and sensitive sorptive extraction method was established for analysis of potential biomarkers of lung cancer (hexanal and heptanal) in human serum samples. In the method, derivatization and extraction occurred simultaneously on the PDMS-frit, then the loaded frit was ultrasonically desorbed in acetonitrile. Polymerization, derivatization-extraction and desorption conditions were optimized. Under the optimal conditions, satisfactory results were gained, a wide linear application range was obtained in the range of 0.002-5.0 μmol L(-1) (R>0.997) for two aldehydes, the detection limits (SN(-1)=3) were 0.5 nmol L(-1) for hexanal and 0.4 nmol L(-1) for heptanal. The relative standard deviations (RSDs, n=5) of the method were below 7.9% and the recoveries were above 72.7% for the spiked serum. All these results hint that the proposed method is potential for disease markers analysis in complex biological samples. Copyright © 2012 Elsevier B.V. All rights reserved.

SU-E-T-791: Validation of a Determinant Based Photon Transport Solver in Dose Perturbed By Diverse Media

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuo, H; Tome, W; Yaparpalvi, R

Purpose: To validate a determinant based photon transport solver in dose imparted within different transition zone between different medium. Methods: Thickness (.2cm,.5cm, 1cm, 3cm) from various materials (Air - density=0.0012g/cm3, Cork-0.19g/cm3, Lung-0.26g/cm3, Bone-1.85g/cm3, Aluminum (Al)-2.7g/cm3, Titanium (Ti)-4.42g/cm3, Iron (Fe)-8g/cm3) were sandwiched by 10cm solid water. 6MV were used to study the calculation difference between a superposition photon beam model (AAA) and the determinant based Boltzmann photon transport solver (XB) at the upstream (I) and downstream boarder (II) of the medium, within the medium (III), and at far distance downstream away from medium (IV). Calculation was validated with available thickness ofmore » Air, Cork, Lung, Al, Ti and Fe. Results are presented as the ratio of the dose at the point with medium perturbation to the same point dose without perturbation. Results: Zone I showed different backscatter enhancement from high-density materials within the 5mm of the upstream border. AAA showed no backscatter at all, XB showed good agreement beyond 1mm upstream (1.18 vs 1.14, 1.09 vs 1.10, and 1.04 vs 1.05 for Fe, Ti, and Fe, respectively). Zone II showed a re-buildup after exiting high-density medium and Air but no build up for density close to water in both of the measurement and XB. AAA yielded the opposite results in Zone II. XB and AAA showed in Zone III very different absorption in high density medium and the Air. XB and measurement had high concordance regarding photon attenuation in Zone IV. AAA showed less agreement especially when the medium was Air or Fe. Conclusion: XB compared well with measurement in regions 1mm away from the interface. Planning using XB should be beneficial for External Beam Planning in situations with large air cavity, very low lung density, compact bone, and any kind of metal implant.« less

CIGB-300, an anti-CK2 peptide, inhibits angiogenesis, tumor cell invasion and metastasis in lung cancer models.

PubMed

Benavent Acero, Fernando; Capobianco, Carla S; Garona, Juan; Cirigliano, Stéfano M; Perera, Yasser; Urtreger, Alejandro J; Perea, Silvio E; Alonso, Daniel F; Farina, Hernan G

2017-05-01

Casein kinase 2 (CK2) is overexpressed in several types of cancer. It has more than 300 substrates mainly involved in DNA reparation and replication, chromatin remodeling and cellular growth. In recent years CK2 became an interesting target for anticancer drug development. CIGB-300 is a peptidic inhibitor of CK2 activity, designed to bind to the phospho-acceptor domain of CK2 substrates, impairing the correct phosphorylation by the enzyme. The aim of this work was to explore the antitumor effects of this inhibitor in preclinical lung cancer models. Human H125 and murine 3LL Lewis lung carcinoma cell lines were used to evaluate the effect of CIGB-300 treatment in vitro. For this purpose, adhesion, migration and invasion capabilities of cancer cells were tested. Proteolytic activity of tumor cell-secreted uPA and MMP after CIGB-300 incubation was also analyzed. In vivo anticancer efficacy of the peptide was evaluated using experimental and spontaneous lung colonization assays in C57BL/6 mice. Finally, in order to test the effect of CIGB-300 on tumor cell-induced angiogenesis, a modified Matrigel plug assay was conducted. We demonstrate that treatment with low micromolar concentrations of CIGB-300 caused a drastic reduction of adhesion, migration and invasion of lung cancer cells. Reduced invasiveness after CIGB-300 incubation was associated with decreased proteolytic activity of tumor cell-conditioned medium. In vivo, intravenous administration of CIGB-300 (10mg/kg) markly decreased lung colonization and metastasis development of 3LL cells. Interestingly, after 5days of systemic treatment with CIGB-300, tumor cell-driven neovascularization was significantly reduced in comparison to control group. Altogether our data suggest an important role of CK2 in lung tumor development, suggesting a potential use of CIGB-300 as a novel therapeutic agent against lung cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Emodin suppresses pulmonary metastasis of breast cancer cells accompanied with decreased macrophage recruitment and M2 polarization in the lungs

PubMed Central

Jia, Xuemei; Yu, Fang; Wang, Junfeng; Iwanowycz, Stephen; Saaoud, Fatma; Wang, Yuzhen; Hu, Jun; Wang, Qian; Fan, Daping

2014-01-01

Purpose Breast cancer is the leading cause of death in female cancer patients due to the lack of effective treatment for metastasis. Macrophages are the most abundant immune cells in the primary and metastatic tumors, and contribute to tumor initiation, progression and metastasis. Emodin has been found to exert anti-tumor effects through promoting cell cycle arrest and apoptosis, and inhibiting angiogenesis, but its effects on tumor-associated macrophages during cancer metastasis have not been investigated. Methods Mice inoculated with 4T1 or EO771 breast cancer cells orthotopically were treated with Emodin after the primary tumors reached 200 mm3 in size. Primary tumor growth, lung metastasis, and macrophage infiltration in the lungs were analyzed. In vitro experiments were performed to examine the effects of Emodin on macrophage migration and M2 polarization, and the underlying mechanisms. Results Emodin significantly suppressed breast cancer lung metastasis in both orthotopic mouse models without apparent effects on primary tumors. Reduced infiltration of F4/80+ macrophages and Ym1+ M2 macrophages in lungs was observed in Emodin-treated mice. In vitro experiments demonstrated that Emodin decreased the migration of macrophages towards tumor cell conditioned medium (TCM) and inhibited macrophage M2 polarization induced by TCM. Mechanistically, Emodin suppressed STAT6 phosphorylation and C/EBPβ expression, two crucial signaling events in macrophage M2 polarization, in macrophages treated with IL-4 or TCM. Conclusion Taken together, our study, for the first time, demonstrated that Emodin suppressed pulmonary metastasis of breast cancer probably through inhibiting macrophage recruitment and M2 polarization in the lungs by reducing STAT6 phosphorylation and C/EBPβ expression. PMID:25311112

Release of an endogenous pyrogen in vitro from rabbit mononuclear cells.

PubMed

Atkins, E; Bodel, P; Francis, L

1967-08-01

The capacity of rabbit mononuclear cells to release an endogenous pyrogen (EP) in vitro has been studied. After incubation with tuberculin, preparations of predominantly monocytic cells, derived from the respiratory passages of the lungs of rabbits sensitized with BCG, were activated to release EP. Pyrogen production occurred more slowly with lung monocytes than with blood leukocytes of similarly sensitized rabbits and 9 to 10 hr incubation in a fully supportive medium was required to produce clear-cut results. As previously reported with blood leukocytes, mononuclear cells from the lungs of normal animals were also activated by tuberculin but to a lesser degree than were those from specifically sensitized rabbits. Under a variety of conditions, mononuclear cells from either spleen or lymph nodes of the same sensitized rabbits failed to release detectable amounts of pyrogen when incubated with tuberculin in vitro but were activated in a majority of instances when phagocytosis of heat-killed staphylococci was used as the stimulus. Release of pyrogen from lung monocytes appears to be an active process that is both temperature-dependent and requires protein synthesis. Neither serum antibody nor complement appears to play a role in this process. Evidence is presented that the granulocyte is the main source of pyrogen evolved by blood leukocytes incubated in vitro with OT or heat-killed staphylococci, whereas the lung macrophage and/or monocyte is responsible for most of the pyrogen released from the lung cell preparations. From these studies, it is concluded that mononuclear cells can be activated in vitro by several microbial stimuli and must be considered an additional cellular source of EP. The clinical implications of these findings for the pathogenesis of fever in granulomatous diseases where the monocyte is the predominant cell are discussed.

Which Is the Optimal Biologically Effective Dose of Stereotactic Body Radiotherapy for Stage I Non-Small-Cell Lung Cancer? A Meta-Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Jian; Yang Fujun; Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan

2011-11-15

Purpose: To assess the relationship between biologically effective dose (BED) and efficacy of stereotactic body radiation therapy (SBRT) and to explore the optimal BED range for Stage I non-small-cell lung cancer (NSCLC). Methods and Materials: Eligible studies were identified on Medline, Embase, the Cochrane Library, and the proceedings of annual meetings through June 2010. According to the quartile of included studies, BED was divided into four dose groups: low (<83.2 Gy), medium (83.2-106 Gy), medium to high (106-146 Gy), high (>146 Gy). To obtain pooled estimates of overall survival (OS), cancer-specific survival (CSS), and local control rate (LCR), data weremore » combined in a random effect model. Pooled estimates were corrected for the percentage of small tumors (<3 cm). Results: Thirty-four observational studies with a total of 2,587 patients were included in the meta-analysis. Corrected pooled estimates of 2- or 3-year OS in the medium BED (76.1%, 63.5%) or the medium to high BED (68.3%, 63.2%) groups were higher than in the low (62.3%, 51.9%) or high groups (55.9%, 49.5%), respectively (p {<=} 0.004). Corrected 3-year CSS in the medium (79.5%), medium to high (80.6%), and high groups (90.0%) were higher than in the low group (70.1%, p = 0.016, 0.018, 0.001, respectively). Conclusion: The OS for the medium or medium to high BED groups were higher than those for the low or high BED group for SBRT in Stage I NSCLC. The medium or medium to high BED (range, 83.2-146 Gy) for SBRT may currently be more beneficial and reasonable in Stage I NSCLC.« less

Isolation of a cDNA for a Growth Factor of Vascular Endothelial Cells from Human Lung Cancer Cells: Its Identity with Insulin‐like Growth Factor II

PubMed Central

Hagiwara, Koichi; Kobayashi, Tatsuo; Tobita, Masato; Kikyo, Nobuaki; Yazaki, Yoshio

1995-01-01

We have found growth‐promoting activity for vascular endothelial cells in the conditioned medium of a human lung cancer cell line, T3M‐11. Purification and characterization of the growth‐promoting activity have been carried out using ammonium sulfate precipitation and gel‐exclusion chromatography. The activity migrated as a single peak just after ribonuclease. It did not bind to a heparin affinity column. These results suggest that the activity is not a heparin‐binding growth factor (including fibroblast growth factors) or a vascular endothelial growth factor. To identify the molecule exhibiting the growth‐promoting activity, a cDNA encoding the growth factor was isolated through functional expression cloning in COS‐1 cells from a cDNA library prepared from T3M‐11 cells. The nucleotide sequence encoded by the cDNA proved to be identical with that of insulin‐like growth factor II. PMID:7730145

Development and Validation of a qRT-PCR Classifier for Lung Cancer Prognosis

PubMed Central

Chen, Guoan; Kim, Sinae; Taylor, Jeremy MG; Wang, Zhuwen; Lee, Oliver; Ramnath, Nithya; Reddy, Rishindra M; Lin, Jules; Chang, Andrew C; Orringer, Mark B; Beer, David G

2011-01-01

Purpose This prospective study aimed to develop a robust and clinically-applicable method to identify high-risk early stage lung cancer patients and then to validate this method for use in future translational studies. Patients and Methods Three published Affymetrix microarray data sets representing 680 primary tumors were used in the survival-related gene selection procedure using clustering, Cox model and random survival forest (RSF) analysis. A final set of 91 genes was selected and tested as a predictor of survival using a qRT-PCR-based assay utilizing an independent cohort of 101 lung adenocarcinomas. Results The RSF model built from 91 genes in the training set predicted patient survival in an independent cohort of 101 lung adenocarcinomas, with a prediction error rate of 26.6%. The mortality risk index (MRI) was significantly related to survival (Cox model p < 0.00001) and separated all patients into low, medium, and high-risk groups (HR = 1.00, 2.82, 4.42). The MRI was also related to survival in stage 1 patients (Cox model p = 0.001), separating patients into low, medium, and high-risk groups (HR = 1.00, 3.29, 3.77). Conclusions The development and validation of this robust qRT-PCR platform allows prediction of patient survival with early stage lung cancer. Utilization will now allow investigators to evaluate it prospectively by incorporation into new clinical trials with the goal of personalized treatment of lung cancer patients and improving patient survival. PMID:21792073

Wnt5a Increases Properties of Lung Cancer Stem Cells and Resistance to Cisplatin through Activation of Wnt5a/PKC Signaling Pathway

PubMed Central

Yang, Jiali; Zhang, Kangjian; Wu, Jing; Shi, Juan; Xue, Jing; Li, Jing; Zhu, Yongzhao; Wei, Jun

2016-01-01

The development of chemoresistance to cisplatin regimens causes a poor prognosis in patients with advanced NSCLC. The role of noncanonical Wnt signaling in the regulation of properties of lung cancer stem cells and chemoresistance was interrogated, by accessing capacities of cell proliferation, migration, invasion, and clonogenicity as well as the apoptosis in A549 cell lines and cisplatin-resistant A549 cells treated with Wnt5a conditional medium or protein kinase C (PKC) inhibitor GF109203X. Results showed that the noncanonical Wnt signaling ligand, Wnt5a, could promote the proliferation, migration, invasion, and colony formation in A549 lung adenocarcinoma cells and cisplatin-resistant A549/DDP cells and increase the fraction of ALDH-positive cell in A549/DDP cells. An exposure of cells to Wnt5a led to a significant reduction of A549/DDP cell apoptosis but not A549 cells. An addition of GF109203X could both strikingly increase the baseline apoptosis and resensitize the Wnt5a-inhibited cell apoptosis. Interestingly, an inhibition of Wnt/PKC signaling pathway could reduce properties of lung cancer stem cells, promote cell apoptosis, and resensitize cisplatin-resistant cells to cisplatin via a caspase/AIF-dependent pathway. These data thus suggested that the Wnt5a could promote lung cancer cell mobility and cisplatin-resistance through a Wnt/PKC signaling pathway and a blockage of this signaling may be an alternative therapeutic strategy for NSCLC patients with resistance to chemotherapies. PMID:27895670

Cystic echinococcosis in cattle slaughtered at Shashemanne Municipal Abattoir, south central Oromia, Ethiopia: prevalence, cyst distribution and fertility.

PubMed

Negash, Kedir; Beyene, Desta; Kumsa, Bersissa

2013-04-01

Cystic echinococcosis is one of the most widespread zoonoses, causing morbidity and mortality in humans and huge economic losses in livestock. It is caused by metacestodes of the tapeworm Echinococcus granulosus. The metacestodes cause hydatid cysts in the lungs, liver and other organs of intermediate hosts. A study was made from December 2010 through March 2011 to determine the prevalence, organ distribution and characteristics of hydatid cysts in cattle slaughtered at Shashemanne Municipal Abattoir in Oromia, Ethiopia. Antemortem examination of 384 cattle was followed by standard postmortem inspection of their internal organs including lungs, liver, kidneys, spleen and heart for the presence of hydatid cysts. The overall prevalence of hydatid cysts recorded in cattle slaughtered at Shashemanne Municipal Abattoir was 49.5% (190/384). Hydatid cyst prevalence was significantly higher in cattle more than 7 years old compared with those aged 7 years or less, in male cattle compared with female cattle (51.9% vs 31.9%), and in cattle with a body condition score of lean or medium rather than fat (54.05% and 83.2% vs 22.9%). The greatest proportions of cysts were recorded in the lungs (71.6%) and liver (24.1%). Lungs and liver were more commonly infected (95.5%) than other organs. Of the cysts recorded, 15.9% were fertile, 71.7% sterile and 12.2% calcified. The percentage of fertile cysts in the lungs was higher than that in any other organ. Our study showed widespread occurrence of cystic echinococcosis in cattle, which may have a role in the lifecycle of this serious zoonosis.

Whole-breast irradiation: a subgroup analysis of criteria to stratify for prone position treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ramella, Sara, E-mail: s.ramella@unicampus.it; Trodella, Lucio; Ippolito, Edy

2012-07-01

To select among breast cancer patients and according to breast volume size those who may benefit from 3D conformal radiotherapy after conservative surgery applied with prone-position technique. Thirty-eight patients with early-stage breast cancer were grouped according to the target volume (TV) measured in the supine position: small ({<=}400 mL), medium (400-700 mL), and large ({>=}700 ml). An ad-hoc designed and built device was used for prone set-up to displace the contralateral breast away from the tangential field borders. All patients underwent treatment planning computed tomography in both the supine and prone positions. Dosimetric data to explore dose distribution and volumemore » of normal tissue irradiated were calculated for each patient in both positions. Homogeneity index, hot spot areas, the maximum dose, and the lung constraints were significantly reduced in the prone position (p < 0.05). The maximum heart distance and the V{sub 5Gy} did not vary consistently in the 2 positions (p = 0.06 and p = 0.7, respectively). The number of necessary monitor units was significantly higher in the supine position (312 vs. 232, p < 0.0001). The subgroups analysis pointed out the advantage in lung sparing in all TV groups (small, medium and large) for all the evaluated dosimetric constraints (central lung distance, maximum lung distance, and V{sub 5Gy}, p < 0.0001). In the small TV group, a dose reduction in nontarget areas of 22% in the prone position was detected (p = 0.056); in the medium and high TV groups, the difference was of about -10% (p = NS). The decrease in hot spot areas in nontarget tissues was 73%, 47%, and 80% for small, medium, and large TVs in the prone position, respectively. Although prone breast radiotherapy is normally proposed in patients with breasts of large dimensions, this study gives evidence of dosimetric benefit in all patient subgroups irrespective of breast volume size.« less

In Vitro Analysis of Pseudomonas aeruginosa Virulence Using Conditions That Mimic the Environment at Specific Infection Sites.

PubMed

Colmer-Hamood, J A; Dzvova, N; Kruczek, C; Hamood, A N

2016-01-01

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that causes chronic lung infection in patients with cystic fibrosis (CF) and acute systemic infections in severely burned patients and immunocompromised patients including cancer patients undergoing chemotherapy and HIV infected individuals. In response to the environmental conditions at specific infection sites, P. aeruginosa expresses certain sets of cell-associated and extracellular virulence factors that produce tissue damage. Analyzing the mechanisms that govern the production of these virulence factors in vitro requires media that closely mimic the environmental conditions within the infection sites. In this chapter, we review studies based on media that closely resemble three in vivo conditions, the thick mucus accumulated within the lung alveoli of CF patients, the serum-rich wound bed and the bloodstream. Media resembling the CF alveolar mucus include standard laboratory media supplemented with sputum obtained from CF patients as well as prepared synthetic mucus media formulated to contain the individual components of CF sputum. Media supplemented with serum or individual serum components have served as surrogates for the soluble host components of wound infections, while whole blood has been used to investigate the adaptation of pathogens to the bloodstream. Studies using these media have provided valuable information regarding P. aeruginosa gene expression in different host environments as varying sets of genes were differentially regulated during growth in each medium. The unique effects observed indicate the essential role of these in vitro media that closely mimic the in vivo conditions in providing accurate information regarding the pathogenesis of P. aeruginosa infections. Copyright © 2016 Elsevier Inc. All rights reserved.

Ethylene-vinyl acetate foam as a new lung substitute in radiotherapy.

PubMed

Marqués, Enrique; Mancha, Pedro J

2018-04-01

The purpose of this study was to evaluate ethylene-vinyl acetate (EVA) foam as a new lung substitute in radiotherapy and to study its physical and dosimetric characteristics. We calculated the ideal vinyl acetate (VA) content of EVA foam sheets to mimic the physical and dosimetric characteristics of the ICRU lung tissue. We also computed the water-to-medium mass collision stopping power ratios, mass attenuation coefficients, CT numbers, effective atomic numbers and electron densities for: ICRU lung tissue, the RANDO commercial phantom, scaled WATER and EVA foam sheets with varying VA contents in a range between the minimum and maximum values supplied by the manufacturer. For all these substitutes, we simulated percent depth-dose curves with EGSnrc Monte Carlo (MC PDDs) in a water-lung substitute-water slab phantom expressed as dose-to-medium and dose-to-water for 3 × 3- and 10 × 10-cm 2 field sizes. PDD for the 10 × 10-cm 2 field size was also calculated with the MultiGrid Superposition algorithm (MGS PDD) for a relative electron density to water ratio of 0.26. The latter was compared with the MC PDDs in dose-to-water for scaled WATER and EVA foam sheets with the VA content that was most similar to the calculated ideal content that is physically achievable in practice. We calculated an ideal VA content of 55%; however, the maximum physically achievable content with current manufacturing techniques is 40%. The physical characteristics of the EVA foam sheets with a VA content of 40% (EVA40) are very close to those of the ICRU lung reference. The physical densities of the EVA40 foam sheets ranged from 0.030 to 0.965 g/cm 3 , almost covering the entire physical density range of the inflated/deflated lung (0.260-1.050 g/cm 3 ). Its mass attenuation coefficient at the effective energy of a 6-MV photon beam agrees within 0.8% of the ICRU reference value, and its CT number agrees within 6 HU. The effective atomic number for EVA40 varies by less than 0.42 of the ICRU value, and its effective electron density is within 0.9%. PDDs expressed in dose-to-medium and dose-to-water agree with the ICRU curve within 2% in all regions. PDDs calculated with both MC and MGS were within 1.5%. The EVA40 is an excellent cork-like lung substitute for radiotherapy applications. From a sole material used in footwear, it is possible to obtain a lung substitute that mimics the physical and dosimetric characteristics of ICRU lung tissue even better than the RANDO commercial phantom. © 2018 American Association of Physicists in Medicine.

FTIR characterization of animal lung cells: normal and precancerous modified e10 cell line

NASA Astrophysics Data System (ADS)

Zezell, D. M.; Pereira, T. M.; Mennecier, G.; Bachmann, L.; Govone, A. B.; Dagli, M. L. Z.

2012-06-01

The chemical carcinogens from tobacco are related to over 90% of lung cancers around the world. The risk of death of this kind of cancer is high because the diagnosis usually is made only in advanced stages. Therefore, it is necessary to develop new diagnostic methods for detecting the lung cancer in earlier stages. The Fourier Transform Infrared Spectroscopy (FTIR) can offer high sensibility and accuracy to detect the minimal chemical changes into the biological sample. The aim of this study is to evaluate the differences on infrared spectra between normal lung cells and precancerous lung cells transformed by NNK. Non-cancerous lung cell line e10 (ATCC) and NNK-transformed e10 cell lines were maintained in complete culture medium (1:1 mixture of Dulbecco's modified Eagle's medium and Ham's F12 [DMEM/Ham's F12], supplemented with 100 ng/ml cholera enterotoxin, 10 lg/ml insulin, 0.5 lg/ml. hydrocortisol, 20 ng/ml epidermal growth factor, and 5% horse serum. The cultures were maintained in alcohol 70%. The infrared spectra were acquired on ATR-FTIR Nicolet 6700 spectrophotometer at 4 cm-1 resolution, 30 scans, in the 1800-900 cm-1 spectral range. Each sample had 3 spectra recorded, 30 infrared spectra were obtained from each cell line. The second derivate of spectra indicates that there are displacement in 1646 cm-1 (amine I) and 1255 cm-1(DNA), allowing the possibility to differentiate the two king of cells, with accuracy of 89,9%. These preliminary results indicate that ATR-FTIR is useful to differentiate normal e10 lung cells from precancerous e10 transformed by NNK.

Direct Exposure of Monolayers of Mammalian Cells to Airborne Pollutants in a Unique Culture System.

DTIC Science & Technology

1981-02-01

of growth medium through the filter from the side opposite the cells so that they are nourished and kept moist. Growth medium perfusing through the...planting dispersed cells (Line V79, Chinese hamster lung fibroblasts) on the membrane filters and exposing to the test gas. The toxic effect was... Medium which perfuses through the filters is drawn off through the tubes at the rear wall of the chamber. The test gas enters at the left end of the

Accuracy of the raw-data-based effective atomic numbers and monochromatic CT numbers for contrast medium with a dual-energy CT technique.

PubMed

Kawahara, Daisuke; Ozawa, Shuichi; Yokomachi, Kazushi; Tanaka, Sodai; Higaki, Toru; Fujioka, Chikako; Suzuki, Tatsuhiko; Tsuneda, Masato; Nakashima, Takeo; Ohno, Yoshimi; Nagata, Yasushi

2018-02-01

To evaluate the accuracy of raw-data-based effective atomic number (Z eff ) values and monochromatic CT numbers for contrast material of varying iodine concentrations, obtained using dual-energy CT. We used a tissue characterization phantom and varying concentrations of iodinated contrast medium. A comparison between the theoretical values of Z eff and that provided by the manufacturer was performed. The measured and theoretical monochromatic CT numbers at 40-130 keV were compared. The average difference between the Z eff values of lung (inhale) inserts in the tissue characterization phantom was 81.3% and the average Z eff difference was within 8.4%. The average difference between the Z eff values of the varying concentrations of iodinated contrast medium was within 11.2%. For the varying concentrations of iodinated contrast medium, the differences between the measured and theoretical monochromatic CT values increased with decreasing monochromatic energy. The Z eff and monochromatic CT numbers in the tissue characterization phantom were reasonably accurate. The accuracy of the raw-data-based Z eff values was higher than that of image-based Z eff values in the tissue-equivalent phantom. The accuracy of Z eff values in the contrast medium was in good agreement within the maximum SD found in the iodine concentration range of clinical dynamic CT imaging. Moreover, the optimum monochromatic energy for human tissue and iodinated contrast medium was found to be 70 keV. Advances in knowledge: The accuracy of the Z eff values and monochromatic CT numbers of the contrast medium created by raw-data-based, dual-energy CT could be sufficient in clinical conditions.

Genetics Home Reference: brain-lung-thyroid syndrome

MedlinePlus

... Twitter Home Health Conditions Brain-lung-thyroid syndrome Brain-lung-thyroid syndrome Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description Brain-lung-thyroid syndrome is a group of conditions ...

Recent developments in human biomonitoring: non-invasive assessment of target tissue dose and effects of pneumotoxic metals.

PubMed

Mutti, A; Corradi, M

2006-01-01

Tobacco smoke and polluted environments substantially increase the lung burden of pneumotoxic chemicals, particularly pneumotoxic metallic elements. To achieve a better understanding of the early events between exposure to inhaled toxicants and the onset of adverse effects on the lung, the characterization of dose at the target organ would be extremely useful. Exhaled breath condensate (EBC), obtained by cooling exhaled air under conditions of spontaneous breathing, is a novel technique that could provide a non-invasive assessment of pulmonary pathobiology. Considering that EBC is water practically free of interfering solutes, it represents an ideal biological matrix for elemental characterization. Published data show that several toxic metals and trace elements are detectable in EBC, raising the possibility of using this medium to quantify the lung tissue dose of pneumotoxic substances. This novel approach may represent a significant advance over the analysis of alternative media (blood, serum, urine, hair), which are not as reliable (owing to interfering substances in the complex matrix) and reflect systemic rather than lung (target tissue) levels of both toxic metals and essential trace elements. Data obtained among workers occupationally exposed to either hard metals or chromium (VI) and in smokers with or without chronic obstructive pulmonary disease (COPD) are reviewed to show that--together with biomarkers of exposure--EBC also allows the simultaneous quantification of biomarkers of effect directly sampled from the epithelial lining fluid, thus providing novel insights on both kinetic and dynamic aspects of metal toxicology.

Mortality on the Waiting List for Lung Transplantation in Patients with Idiopathic Pulmonary Fibrosis: A Single-Centre Experience.

PubMed

Bennett, David; Fossi, Antonella; Bargagli, Elena; Refini, Rosa Metella; Pieroni, Maria; Luzzi, Luca; Ghiribelli, Claudia; Paladini, Piero; Voltolini, Luca; Rottoli, Paola

2015-10-01

Lung transplantation (LTX) is nowadays accepted as a treatment option for selected patients with end-stage pulmonary disease. Idiopathic pulmonary fibrosis (IPF) is characterized by the radiological and histologic appearance of usual interstitial pneumonia. It is associated with a poor prognosis, and LTX is considered an effective treatment to significantly modify the natural history of this disease. The aim of the present study was to analyse mortality during the waiting list in IPF patients at a single institution. A retrospective analysis on IPF patients (n = 90) referred to our Lung Transplant Program in the period 2001-2014 was performed focusing on patients' characteristics and associated risk factors. Diagnosis of IPF was associated with high mortality on the waiting list with respect to other diagnosis (p < 0.05). No differences in demographic, clinical, radiological data and time spent on the waiting list were observed between IPF patients who underwent to LTX or lost on the waiting list. Patients who died showed significant higher levels of pCO2 and needed higher flows of O2-therapy on effort (p < 0.05). Pulmonary function tests failed to predict mortality and no other medical conditions were associated with survival. Patients newly diagnosed with IPF, especially in small to medium lung transplant volume centres and in Countries where a long waiting list is expected, should be immediately referred to transplantation, delay results in increased mortality. Early identification of IPF patients with a rapid progressive phenotype is strongly needed.

Mesenchymal stem cells for acute lung injury: Preclinical evidence

PubMed Central

Matthay, Michael A.; Goolaerts, Arnaud; Howard, James P.; Lee, Jae Woo

2013-01-01

Several experimental studies have suggested that mesenchymal stem cells may have value for the treatment of clinical disorders, including myocardial infarction, diabetes, acute renal failure, sepsis, and acute lung injury. In preclinical studies, mesenchymal stem cells have been effective in reducing lung injury from endotoxin, live bacteria, bleomycin, and hyperoxia. In some studies, the cultured medium from mesenchymal stem cells has been as effective as the mesenchymal stem cells themselves. Several paracrine mediators that can mediate the effect of mesenchymal stem cells have been identified, including interleukin-10, interleukin-1ra, keratinocyte growth factor, and prostaglandin E2. Further preclinical studies are needed, as is planning for clinical trials for acute lung injury. PMID:21164399

Active Oxygen Metabolites and Thromboxane in Phorbol Myristate Acetate Toxicity to the Isolated, Perfused Rat Lung.

NASA Astrophysics Data System (ADS)

Carpenter, Laurie Jean

When administered intravenously or intratracheally to rats, rabbits and sheep, phorbol myristate acetate (PMA) produces changes in lung morphology and function are similar to those seen in humans with the adult respiratory distress syndrome (ARDS). Therefore, it is thought that information about the mechanism of ARDS development can be gained from experiments using PMA-treated animals. Currently, the mechanisms by which PMA causes pneumotoxicity are unknown. Results from other studies in rabbits and in isolated, perfused rabbit lungs suggest that PMA-induced lung injury is mediated by active oxygen species from neutrophils (PMN), whereas studies in sheep and rats suggest that PMN are not required for the toxic response. The role of PMN, active oxygen metabolites and thromboxane (TxA_2) in PMA-induced injury to isolated, perfused rat lungs (IPLs) was examined in this thesis. To determine whether PMN were required for PMA to produce toxicity to the IPL, lungs were perfused for 30 min with buffer containing various concentrations of PMA (in the presence or absence of PMN). When concentrations >=q57 ng/ml were added to medium devoid of added PMN, perfusion pressure and lung weight increased. When a concentration of PMA (14-28 ng/ml) that did not by itself cause lungs to accumulate fluid was added to the perfusion medium containing PMN (1 x 10 ^8), perfusion pressure increased, and lungs accumulated fluid. These results indicate that high concentrations of PMA produce lung injury which is independent of PMN, whereas injury induced by lower concentrations is PMN-dependent. To examine whether active oxygen species were involved in mediating lung injury induced by PMA and PMN, lungs were coperfused with the oxygen radical scavengers SOD and/or catalase. Coperfusion with either or both of these enzymes totally protected lungs against injury caused by PMN and PMA. These results suggest that active oxygen species (the hydroxyl radical in particular), mediate lung injury in this model. To determine whether TxA_2 was involved in toxicity induced by PMN and PMA, lungs were coperfused with the cyclooxygenase inhibitor, indomethacin or the thromboxane synthase inhibitor, Dazmegrel. Experiments were also performed using lungs and/or PMN that had been pretreated with aspirin. These drug treatments had little effect, if any, on the pressure increase; however, they protected lungs against edema development. These results suggest that TxA_2 may participate in the pathogenesis of edema by some other mechanism than by increasing vascular pressure. In conclusion, results from studies performed in this thesis suggest that both active oxygen species and thromboxane are involved in toxicity to the isolated rat lung induced by PMA and PMN. How both of these interact to produce lung injury is a question which remains to be answered.

Lysophosphatidic acid-induced ADAM12 expression mediates human adipose tissue-derived mesenchymal stem cell-stimulated tumor growth.

PubMed

Do, Eun Kyoung; Kim, Young Mi; Heo, Soon Chul; Kwon, Yang Woo; Shin, Sang Hun; Suh, Dong-Soo; Kim, Ki-Hyung; Yoon, Man-Soo; Kim, Jae Ho

2012-11-01

Lysophosphatidic acid (LPA) is involved in mesenchymal stem cell-stimulated tumor growth in vivo. However, the molecular mechanism by which mesenchymal stem cells promote tumorigenesis remains elusive. In the present study, we demonstrate that conditioned medium from A549 human lung adenocarcinoma cells (A549 CM) induced the expression of ADAM12, a disintegrin and metalloproteases family member, in human adipose tissue-derived mesenchymal stem cells (hASCs). A549 CM-stimulated ADAM12 expression was abrogated by pretreatment of hASCs with the LPA receptor 1 inhibitor Ki16425 or by small interfering RNA-mediated silencing of LPA receptor 1, suggesting a key role for the LPA-LPA receptor 1 signaling axis in A549 CM-stimulated ADAM12 expression. Silencing of ADAM12 expression using small interfering RNA or short hairpin RNA abrogated LPA-induced expression of both α-smooth muscle actin, a marker of carcinoma-associated fibroblasts, and ADAM12 in hASCs. Using a xenograft transplantation model of A549 cells, we demonstrated that silencing of ADAM12 inhibited the hASC-stimulated in vivo growth of A549 xenograft tumors and the differentiation of transplanted hASCs to α-smooth muscle actin-positive carcinoma-associated fibroblasts. LPA-conditioned medium from hASCs induced the adhesion of A549 cells and silencing of ADAM12 inhibited LPA-induced expression of extracellular matrix proteins, periostin and βig-h3, in hASCs and LPA-conditioned medium-stimulated adhesion of A549 cells. These results suggest a pivotal role for LPA-stimulated ADAM12 expression in tumor growth and the differentiation of hASCs to carcinoma-associated fibroblasts expressing α-smooth muscle actin, periostin, and βig-h3. Copyright © 2012 Elsevier Ltd. All rights reserved.

Valproic acid attenuates skeletal muscle wasting by inhibiting C/EBPβ-regulated atrogin1 expression in cancer cachexia.

PubMed

Sun, Rulin; Zhang, Santao; Hu, Wenjun; Lu, Xing; Lou, Ning; Yang, Zhende; Chen, Shaoyong; Zhang, Xiaoping; Yang, Hongmei

2016-07-01

Muscle wasting is the hallmark of cancer cachexia and is associated with poor quality of life and increased mortality. Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, has important biological effects in the treatment of muscular dystrophy. To verify whether VPA could ameliorate muscle wasting induced by cancer cachexia, we explored the role of VPA in two cancer cachectic mouse models [induced by colon-26 (C26) adenocarcinoma or Lewis lung carcinoma (LLC)] and atrophied C2C12 myotubes [induced by C26 cell conditioned medium (CCM) or LLC cell conditioned medium (LCM)]. Our data demonstrated that treatment with VPA increased the mass and cross-sectional area of skeletal muscles in tumor-bearing mice. Furthermore, treatment with VPA also increased the diameter of myotubes cultured in conditioned medium. The skeletal muscles in cachectic mice or atrophied myotubes treated with VPA exhibited reduced levels of CCAAT/enhancer binding protein beta (C/EBPβ), resulting in atrogin1 downregulation and the eventual alleviation of muscle wasting and myotube atrophy. Moreover, atrogin1 promoter activity in myotubes was stimulated by CCM via activating the C/EBPβ-responsive cis-element and subsequently inhibited by VPA. In contrast to the effect of VPA on the levels of C/EBPβ, the levels of inactivating forkhead box O3 (FoxO3a) were unaffected. In summary, VPA attenuated muscle wasting and myotube atrophy and reduced C/EBPβ binding to atrogin1 promoter locus in the myotubes. Our discoveries indicate that HDAC inhibition by VPA might be a promising new approach for the preservation of skeletal muscle in cancer cachexia. Copyright © 2016 the American Physiological Society.

Toxicological Profiling of Highly Purified Single-Walled Carbon Nanotubes with Different Lengths in the Rodent Lung and Escherichia Coli.

PubMed

Wang, Xiang; Lee, Jae-Hyeok; Li, Ruibin; Liao, Yu-Pei; Kang, Joohoon; Chang, Chong Hyun; Guiney, Linda M; Mirshafiee, Vahid; Li, Linjiang; Lu, Jianqin; Xia, Tian; Hersam, Mark C; Nel, André E

2018-06-01

Carbon nanotubes (CNTs) exhibit a number of physicochemical properties that contribute to adverse biological outcomes. However, it is difficult to define the independent contribution of individual properties without purified materials. A library of highly purified single-walled carbon nanotubes (SWCNTs) of different lengths is prepared from the same base material by density gradient ultracentrifugation, designated as short (318 nm), medium (789 nm), and long (1215 nm) SWCNTs. In vitro screening shows length-dependent interleukin-1β (IL-1β) production, in order of long > medium > short. However, there are no differences in transforming growth factor-β1 production in BEAS-2B cells. Oropharyngeal aspiration shows that all the SWCNTs induce profibrogenic effects in mouse lung at 21 d postexposure, but there are no differences between tube lengths. In contrast, these SWCNTs demonstrate length-dependent antibacterial effects on Escherichia coli, with the long SWCNT exerting stronger effects than the medium or short tubes. These effects are reduced by Pluronic F108 coating or supplementing with glucose. The data show length-dependent effects on proinflammatory response in macrophage cell line and antibacterial effects, but not on collagen deposition in the lung. These data demonstrate that over the length scale tested, the biological response to highly purified SWCNTs is dependent on the complexity of the nano/bio interface. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hyperoxia and hypergravity are independent risk factors of atelectasis in healthy sitting humans: a pulmonary ultrasound and SPECT/CT study.

PubMed

Dussault, C; Gontier, E; Verret, C; Soret, M; Boussuges, A; Hedenstierna, G; Montmerle-Borgdorff, S

2016-07-01

Aeroatelectasis has developed in aircrew flying routine peacetime flights on the latest generation high-performance aircraft, when undergoing excessive oxygen supply. To single out the effects of hyperoxia and hypergravity on lung tissue compression, and on ventilation and perfusion, eight subjects were studied before and after 1 h 15 min exposure to +1 to +3.5 Gz in a human centrifuge. They performed the protocol three times, breathing air, 44.5% O2, or 100% O2 and underwent functional and topographical imaging of the whole lung by ultrasound and single-photon emission computed tomography combined with computed tomography (SPECT/CT). Ultrasound lung comets (ULC) and atelectasis both increased after exposure. The number of ULC was <1 pre protocol (i.e., normal lung) and larger post 100% O2 (22 ± 3, mean ± SD) than in all other conditions (P < 0.001). Post 44.5% O2 differed from air (P < 0.05). Seven subjects showed low- to medium-grade atelectasis post 100% O2 There was an effect on grade of gas mixture and hypergravity, with interaction (P < 0.001, respectively); 100% O2, 44.5% O2, and air differed from each other (P < 0.05). SPECT ventilation and perfusion were always normal. Ultrasound concurred with CT in showing normal lung in the upper third and ULC/atelectasis in posterior and inferior areas, not for other localizations. In conclusion, hyperoxia and hypergravity are independent risk factors of reversible atelectasis formation. Ultrasound is a useful screening tool. Together with electrical impedance tomography measurements (reported separately), these findings show that zones with decreased ventilation prone to transient airway closure are present above atelectatic areas. Copyright © 2016 the American Physiological Society.

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.

PubMed

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.

Analytic Intermodel Consistent Modeling of Volumetric Human Lung Dynamics.

PubMed

Ilegbusi, Olusegun; Seyfi, Behnaz; Neylon, John; Santhanam, Anand P

2015-10-01

Human lung undergoes breathing-induced deformation in the form of inhalation and exhalation. Modeling the dynamics is numerically complicated by the lack of information on lung elastic behavior and fluid-structure interactions between air and the tissue. A mathematical method is developed to integrate deformation results from a deformable image registration (DIR) and physics-based modeling approaches in order to represent consistent volumetric lung dynamics. The computational fluid dynamics (CFD) simulation assumes the lung is a poro-elastic medium with spatially distributed elastic property. Simulation is performed on a 3D lung geometry reconstructed from four-dimensional computed tomography (4DCT) dataset of a human subject. The heterogeneous Young's modulus (YM) is estimated from a linear elastic deformation model with the same lung geometry and 4D lung DIR. The deformation obtained from the CFD is then coupled with the displacement obtained from the 4D lung DIR by means of the Tikhonov regularization (TR) algorithm. The numerical results include 4DCT registration, CFD, and optimal displacement data which collectively provide consistent estimate of the volumetric lung dynamics. The fusion method is validated by comparing the optimal displacement with the results obtained from the 4DCT registration.

Adoptive transfer of natural killer cells promotes the anti-tumor efficacy of T cells.

PubMed

Goding, Stephen R; Yu, Shaohong; Bailey, Lisa M; Lotze, Michael T; Basse, Per H

2017-04-01

The density of NK cells in tumors correlates positively with prognosis in many types of cancers. The average number of infiltrating NK cells is, however, quite modest (approximately 30 NK cells/sq.mm), even in tumors deemed to have a "high" density of infiltrating NK cells. It is unclear how such low numbers of tumor-infiltrating NK cells can influence outcome. Here, we used ovalbumin-expressing tumor cell lines and TCR transgenic, OVA-specific cytotoxic T lymphocytes (OT-I-CTLs) to determine whether the simultaneous attack by anti-tumor CTLs and IL-2-activated NK (A-NK) cells synergistically increases the overall tumor cell kill and whether upregulation of tumor MHC class-I by NK cell-derived interferon-gamma (IFNγ) improves tumor-recognition and kill by anti-tumor CTLs. At equal E:T ratios, A-NK cells killed OVA-expressing tumor cells better than OT-I-CTLs. The cytotoxicity against OVA-expressing tumor cells increased by combining OT-I-CTLs and A-NK cells, but the increase was additive rather than synergistic. A-NK cells adenovirally-transduced to produce IL-12 (A-NK IL-12 ) produced high amounts of IFNγ. The addition of a low number of A-NK IL-12 cells to OT-I-CTLs resulted in a synergistic, albeit modest, increase in overall cytotoxicity. Pre-treatment of tumor cells with NK cell-conditioned medium increased tumor MHC expression and sensitivity to CTL-mediated killing. Pre-treatment of CTLs with NK cell-conditioned medium had no effect on CTL cytotoxicity. In vivo, MHC class-I expression by OVA-expressing B16 melanoma lung metastases increased significantly within 24-48h after adoptive transfer of A-NK IL-12 cells. OT-I-CTLs and A-NK IL-12 cells localized selectively and equally well into OVA-expressing B16 lung metastases and treatment of mice bearing 7-days-old OVA-B16 lung metastases with both A-NK IL-12 cells and OT-I-CTLs lead to a significant prolongation of survival. Thus, an important function of tumor-infiltrating NK cells may be to increase tumor cell expression of MHC class-I through secretion of IFNγ, to prepare them for recognition by tumor-specific CTLs. Copyright © 2016 Elsevier Inc. All rights reserved.

NEIL2 Protects against Oxidative DNA Damage Induced by Sidestream Smoke in Human Cells

PubMed Central

Sarker, Altaf H.; Chatterjee, Arpita; Williams, Monique; Lin, Sabrina; Havel, Christopher; Jacob III, Peyton; Boldogh, Istvan; Hazra, Tapas K.; Talbot, Prudence; Hang, Bo

2014-01-01

Secondhand smoke (SHS) is a confirmed lung carcinogen that introduces thousands of toxic chemicals into the lungs. SHS contains chemicals that have been implicated in causing oxidative DNA damage in the airway epithelium. Although DNA repair is considered a key defensive mechanism against various environmental attacks, such as cigarette smoking, the associations of individual repair enzymes with susceptibility to lung cancer are largely unknown. This study investigated the role of NEIL2, a DNA glycosylase excising oxidative base lesions, in human lung cells treated with sidestream smoke (SSS), the main component of SHS. To do so, we generated NEIL2 knockdown cells using siRNA-technology and exposed them to SSS-laden medium. Representative SSS chemical compounds in the medium were analyzed by mass spectrometry. An increased production of reactive oxygen species (ROS) in SSS-exposed cells was detected through the fluorescent detection and the induction of HIF-1α. The long amplicon–quantitative PCR (LA-QPCR) assay detected significant dose-dependent increases of oxidative DNA damage in the HPRT gene of cultured human pulmonary fibroblasts (hPF) and BEAS-2B epithelial cells exposed to SSS for 24 h. These data suggest that SSS exposure increased oxidative stress, which could contribute to SSS-mediated toxicity. siRNA knockdown of NEIL2 in hPF and HEK 293 cells exposed to SSS for 24 h resulted in significantly more oxidative DNA damage in HPRT and POLB than in cells with control siRNA. Taken together, our data strongly suggest that decreased repair of oxidative DNA base lesions due to an impaired NEIL2 expression in non-smokers exposed to SSS would lead to accumulation of mutations in genomic DNA of lung cells over time, thus contributing to the onset of SSS-induced lung cancer. PMID:24595271

Lodixanol inhibits exogenous surfactant therapy in rats with acute respiratory distress syndrome.

PubMed

Kesecioglu, J; Schultz, M J; Haitsma, J J; den Heeten, G J; Lachmann, B

2002-05-01

Optimal alveolar distribution of exogenous surfactant is an important determinant of its beneficial effect. This distribution can be determined by suspending surfactant in a radiological contrast medium before intratracheal instillation, followed by radiological imaging. Iodixanol is reported to be a safe contrast medium that causes no lung injury when instilled intratracheally. In this study, the effects of surfactant suspended in saline were compared with surfactant suspended either in 4:1 saline-iodixanol (64 mg iodine x mL(-1)) or in 1:1 saline-iodixanol (160 mg iodine x mL(-1)), on oxygenation and lung mechanics in a rat model of adult respiratory distress syndrome (ARDS) induced by lung lavage. After the induction of ARDS, surfactant instillation improved oxygenation, total lung volume at inflation with a distending pressure of 35 cmH2O, lung volume at transpulmonary pressure of 5 cmH2O and Gruenwald index. The effects of surfactant suspended in 4:1 saline-iodixanol were similar to those of surfactant alone. However, instillation of surfactant suspended in 1:1 saline-iodixanol resulted in significantly lower values in all measured parameters. Surface tension was the lowest in surfactant suspended in saline alone and addition of iodixanol led to an increase in surface tension in a dose-dependent manner. In conclusion, iodixanol at the higher dose caused an inhibition of the exogenous surfactant effect, characterized as a lack of improvement in oxygen tension in arterial blood, low total lung compliance, volume at 5 cmH2O end-expiration and Gruenwald index. This effect of iodixanol was probably due to its high surface tension, especially if a high concentration was used. Surfactant suspended in a lower concentration of iodixanol seems a better alternative, allowing for radiological imaging of the distribution of surfactant when intratracheally instilled.

Amniotic fluid stem cells rescue both in vitro and in vivo growth, innervation, and motility in nitrofen-exposed hypoplastic rat lungs through paracrine effects.

PubMed

Pederiva, F; Ghionzoli, M; Pierro, A; De Coppi, P; Tovar, J A

2013-01-01

Lung hypoplasia can be prevented in vitro by retinoic acid (RA). Recent evidence suggests that amniotic fluid stem (AFS) cells may integrate injured lungs and influence their recovery. We tested the hypothesis that AFS cells might improve lung growth and motility by paracrine mechanisms. Pregnant rats received either nitrofen or vehicle on E9.5. In vitro E13 embryonic lungs were cultured in the presence of culture medium alone or with RA, basophils, or AFS cells. In vivo green fluorescent protein-expressing (GFP(+)) rat AFS cells were transplanted in nitrofen-exposed rats on E10.5. E13 lung explants were cultured before analysis. The surface, the number of terminal buds, and the frequency of bronchial contractions were assessed. Protein gene product 9.5 (PGP 9.5) and α-actin protein levels were measured. The lung explants transplanted with AFS cells were stained for α-actin, PGP 9.5, and TTF-1. The levels of FGF-10, VEGFα, and TGF-β1 secreted by the AFS cells in the culture medium were measured. Comparison between groups was made by ANOVA. In vitro, the surface, the number of terminal buds, and the bronchial peristalsis were increased in nitrofen+AFS cell explants in comparison with nitrofen-exposed lungs. While nitrofen+RA lungs were similar to nitrofen+AFS ones, basophils did not normalize these measurements. PGP 9.5 protein was decreased in nitrofen lungs, but after adding AFS cells, the value was similar to controls. No differences were found in the expression of α-actin. In vivo, the surface, number of terminal buds, and peristalsis were similar to control after injection of AFS cells in nitrofen-exposed rats. Colocalization with TTF-1-positive cells was found. The levels of FGF-10 and VEGFα were increased in nitrofen+AFS cell explants, while the levels of TGF-β1 were similar to controls. Lung growth, bronchial motility, and innervation were decreased in nitrofen explants and rescued by AFS cells both in vitro and in vivo, similarly to that observed before with RA. The AFS cell beneficial effect was probably related to paracrine action of growth factor secretion.

Aryl Hydrocarbon Receptor Protects Lungs from Cockroach Allergen-Induced Inflammation by Modulating Mesenchymal Stem Cells.

PubMed

Xu, Ting; Zhou, Yufeng; Qiu, Lipeng; Do, Danh C; Zhao, Yilin; Cui, Zhuang; Wang, Heng; Liu, Xiaopeng; Saradna, Arjun; Cao, Xu; Wan, Mei; Gao, Peisong

2015-12-15

Exposure to cockroach allergen leads to allergic sensitization and increased risk of developing asthma. Aryl hydrocarbon receptor (AhR), a receptor for many common environmental contaminants, can sense not only environmental pollutants but also microbial insults. Mesenchymal stem cells (MSCs) are multipotent progenitor cells with the capacity to modulate immune responses. In this study, we investigated whether AhR can sense cockroach allergens and modulate allergen-induced lung inflammation through MSCs. We found that cockroach allergen-treated AhR-deficient (AhR(-/-)) mice showed exacerbation of lung inflammation when compared with wild-type (WT) mice. In contrast, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an AhR agonist, significantly suppressed allergen-induced mouse lung inflammation. MSCs were significantly reduced in cockroach allergen-challenged AhR(-/-) mice as compared with WT mice, but increased in cockroach allergen-challenged WT mice when treated with TCDD. Moreover, MSCs express AhR, and AhR signaling can be activated by cockroach allergen with increased expression of its downstream genes cyp1a1 and cyp1b1. Furthermore, we tracked the migration of i.v.-injected GFP(+) MSCs and found that cockroach allergen-challenged AhR(-/-) mice displayed less migration of MSCs to the lungs compared with WT. The AhR-mediated MSC migration was further verified by an in vitro Transwell migration assay. Epithelial conditioned medium prepared from cockroach extract-challenged epithelial cells significantly induced MSC migration, which was further enhanced by TCDD. The administration of MSCs significantly attenuated cockroach allergen-induced inflammation, which was abolished by TGF-β1-neutralizing Ab. These results suggest that AhR plays an important role in protecting lungs from allergen-induced inflammation by modulating MSC recruitment and their immune-suppressive activity. Copyright © 2015 by The American Association of Immunologists, Inc.

Muscle and intensity based hamstring exercise classification in elite female track and field athletes: implications for exercise selection during rehabilitation.

PubMed

Tsaklis, Panagiotis; Malliaropoulos, Nikos; Mendiguchia, Jurdan; Korakakis, Vasileios; Tsapralis, Kyriakos; Pyne, Debasish; Malliaras, Peter

2015-01-01

Hamstring injuries are common in many sports, including track and field. Strains occur in different parts of the hamstring muscle but very little is known about whether common hamstring loading exercises specifically load different hamstring components. The purpose of this study was to investigate muscle activation of different components of the hamstring muscle during common hamstring loading exercises. Twenty elite female track and field athletes were recruited into this study, which had a single-sample, repeated-measures design. Each athlete performed ten hamstring loading exercises, and an electromyogram (EMG) was recorded from the biceps femoris and semitendinosus components of the hamstring. Hamstring EMG during maximal voluntary isometric contraction (MVIC) was used to normalize the mean data across ten repetitions of each exercise. An electrogoniometer synchronized to the EMG was used to determine whether peak EMG activity occurred during muscle-tendon unit lengthening, shortening, or no change in length. Mean EMG values were compared between the two recording sites for each exercise using the Student's t-test. The lunge, dead lift, and kettle swings were low intensity (<50% MVIC) and all showed higher EMG activity for semitendinosus than for biceps femoris. Bridge was low but approaching medium intensity, and the TRX, hamstring bridge, and hamstring curl were all medium intensity exercises (≥50% or <80% MVIC). The Nordic, fitball, and slide leg exercises were all high intensity exercises. Only the fitball exercise showed higher EMG activity in the biceps femoris compared with the semitendinosus. Only lunge and kettle swings showed peak EMG in the muscle-tendon unit lengthening phase and both these exercises involved faster speed. Some exercises selectively activated the lateral and medial distal hamstrings. Low, medium, and high intensity exercises were demonstrated. This information enables the clinician, strength and conditioning coach and physiotherapist to better understand intensity- and muscle-specific activation during hamstring muscle rehabilitation. Therefore, these results may help in designing progressive strengthening and rehabilitation and prevention programs.

Effects of Nrf2 knockdown on the properties of irradiated cell conditioned medium from A549 human lung cancer cells.

PubMed

Yoshino, Hironori; Murakami, Kanna; Nawamaki, Mikoto; Kashiwakura, Ikuo

2018-05-01

The nuclear factor erythroid 2-related factor 2 (Nrf2) plays an important role in cellular defense against oxidative stress. Recent studies have demonstrated that Nrf2 is a useful target for cancer treatment, including radiation therapy. Ionizing radiation affects, not only the irradiated cells, but also the non-irradiated neighboring cells, and this effect is known as radiation-induced bystander effect. Upon exposure to radiation, the irradiated cells transmit signals to the non-irradiated cells via gap junctions or soluble factors. These signals in turn cause biological effects, such as a decrease in the clonogenic potential and cell death, in the non-irradiated neighboring cells. Nrf2 inhibition enhances cellular radiosensitivity. However, whether this modification of radiosensitivity by Nrf2 inhibition affects the radiation-induced bystander effects is unknown. In this study, we prepared an Nrf2 knockdown human lung cancer cell A549 and investigated whether the effects of irradiated cell conditioned medium (ICCM) on cell growth and cell death induction of non-irradiated cells vary depending on the Nrf2 knockdown. We found that Nrf2 knockdown resulted in a decrease in the cell growth and an increase in the radiosensitivity of A549 cells. When non-irradiated A549 cells were transfected with control siRNA and treated with ICCM, no significant difference was observed in the cell growth and proportion of Annexin V + dead cells between ICCM from non-irradiated cells and that from 2 or 8 Gy-irradiated cells. Similarly, no significant difference was observed in the cell growth and cell death induction upon treatment with ICCM in the Nrf2 knockdown A549 cells. Taken together, these results suggest that Nrf2 knockdown decreases cell growth and enhances the radiosensitivity of A549 cells; however, it does not alter the effect of ICCM on cell growth.

A strategy to analyse activity-based profiling of tyrosine kinase substrates in OCT-embedded lung cancer tissue.

PubMed

Arni, Stephan; de Wijn, Rik; Garcia-Villegas, Refugio; Bitanihirwe, Byron K Y; Caviezel, Claudio; Weder, Walter; Hillinger, Sven

2018-04-15

The use of optimal cutting temperature (OCT) medium has served to improve the long-term preservation of surgical tissue specimens. Unfortunately, the presence of polymers in OCT has been found to generate signal interference in proteomic-based techniques. Indeed the presence of OCT medium in tissue lysates precludes the analysis of activity based proteomic profiles obtained from lung adenocarcinoma (LuAdCa) resection specimens. In order to probe this question further tissue lysates were prepared from 47 lung non-neoplastic and tumour, node, metastasis (TNM) stage 1 LuAdCa resection specimens embedded with or without OCT, and data of activity based multiplex profiles of protein tyrosine kinase peptide substrates were obtained. We found that changes in overall phosphorylation level coincided with the use of OCT and subsequently developed an OCT per peptide median correcting strategy by performing median centering on the values of each peptide. Application of this post-analytical strategy not only can identify changes in kinase activity but can also assist in identifying novel targets for therapeutic intervention against LuAdCa. Copyright © 2018 Elsevier Inc. All rights reserved.

Trunk position influences the kinematics, kinetics, and muscle activity of the lead lower extremity during the forward lunge exercise.

PubMed

Farrokhi, Shawn; Pollard, Christine D; Souza, Richard B; Chen, Yu-Jen; Reischl, Stephen; Powers, Christopher M

2008-07-01

Experimental laboratory study. To examine how a change in trunk position influences the kinematics, kinetics, and muscle activity of the lead lower extremity during the forward lunge exercise. Altering the position of the trunk during the forward lunge exercise is thought to affect the muscular actions of the lead lower extremity. However, no studies have compared the biomechanical differences between the traditional forward lunge and its variations. Ten healthy adults (5 males, 5 females; mean age +/- SD, 26.7 +/- 3.2 years) participated. Lower extremity kinematics, kinetics, and surface electromyographic (EMG) data were obtained while subjects performed 3 lunge exercises: normal lunge with the trunk erect (NL), lunge with the trunk forward (LTF), and lunge with trunk extension (LTE). A 1-way analysis of variance with repeated measures was used to compare lower extremity kinematics, joint impulse (area under the moment-time curve), and normalized EMG (highest 1-second window of activity for selected lower extremity muscles) among the 3 lunge conditions. During the LTF condition, significant increases were noted in peak hip flexion angle, hip extensor and ankle plantar flexor impulse, as well as gluteus maximus and biceps femoris EMG (P<.015) when compared to the NL condition. During the LTE condition, a significant increase was noted in peak ankle dorsiflexion and a significant decrease was noted in peak hip flexion angle (P<.015) compared to the NL condition. Performing a lunge with the trunk forward increased the hip extensor impulse and the recruitment of the hip extensors. In contrast, performing a forward lunge with the trunk extended did not alter joint impulse or activation of the lower extremity musculature. Therapy, level 5.

Lung pair phantom

DOEpatents

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.

Lung pair phantom

DOEpatents

Olsen, P.C.; Gordon, N.R.; Simmons, K.L.

1993-11-30

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.

Silica nanoparticles are less toxic to human lung cells when deposited at the air–liquid interface compared to conventional submerged exposure

PubMed Central

Saathoff, Harald; Leisner, Thomas; Al-Rawi, Marco; Simon, Michael; Seemann, Gunnar; Dössel, Olaf; Mülhopt, Sonja; Paur, Hanns-Rudolf; Fritsch-Decker, Susanne

2014-01-01

Summary Background: Investigations on adverse biological effects of nanoparticles (NPs) in the lung by in vitro studies are usually performed under submerged conditions where NPs are suspended in cell culture media. However, the behaviour of nanoparticles such as agglomeration and sedimentation in such complex suspensions is difficult to control and hence the deposited cellular dose often remains unknown. Moreover, the cellular responses to NPs under submerged culture conditions might differ from those observed at physiological settings at the air–liquid interface. Results: In order to avoid problems because of an altered behaviour of the nanoparticles in cell culture medium and to mimic a more realistic situation relevant for inhalation, human A549 lung epithelial cells were exposed to aerosols at the air–liquid interphase (ALI) by using the ALI deposition apparatus (ALIDA). The application of an electrostatic field allowed for particle deposition efficiencies that were higher by a factor of more than 20 compared to the unmodified VITROCELL deposition system. We studied two different amorphous silica nanoparticles (particles produced by flame synthesis and particles produced in suspension by the Stöber method). Aerosols with well-defined particle sizes and concentrations were generated by using a commercial electrospray generator or an atomizer. Only the electrospray method allowed for the generation of an aerosol containing monodisperse NPs. However, the deposited mass and surface dose of the particles was too low to induce cellular responses. Therefore, we generated the aerosol with an atomizer which supplied agglomerates and thus allowed a particle deposition with a three orders of magnitude higher mass and of surface doses on lung cells that induced significant biological effects. The deposited dose was estimated and independently validated by measurements using either transmission electron microscopy or, in case of labelled NPs, by fluorescence analyses. Surprisingly, cells exposed at the ALI were less sensitive to silica NPs as evidenced by reduced cytotoxicity and inflammatory responses. Conclusion: Amorphous silica NPs induced qualitatively similar cellular responses under submerged conditions and at the ALI. However, submerged exposure to NPs triggers stronger effects at much lower cellular doses. Hence, more studies are warranted to decipher whether cells at the ALI are in general less vulnerable to NPs or specific NPs show different activities dependent on the exposure method. PMID:25247141

Use of the short-term inflammatory response in the mouse peritoneal cavity to assess the biological activity of leached vitreous fibers.

PubMed Central

Donaldson, K; Addison, J; Miller, B G; Cullen, R T; Davis, J M

1994-01-01

We used a special-purpose glass microfiber sample, Johns-Manville Code 100/475, to study the effects of various acid and alkali treatments on biological activity as assessed by inflammation in the mouse peritoneal cavity, the leaching of Si, and the phase contrast optical microscopy (PCOM) fiber number. We used mild and medium treatments with oxalic acid and Tris buffer and harsh treatment with concentrated HCl and NaOH. Mild oxalic acid and Tris treatment for 2 weeks had no effect on any of the end-points, but prolonging the mild oxalic acid treatment time to 2 months reduced the biological activity and the fiber number. Medium oxalic acid treatment reduced the biological activity and the fiber number and caused a loss of Si. Medium Tris alkali treatment reduced the PCOM-countable fibers and the biological activity but did not cause a substantial loss of Si. Harsh treatment with strong HCl did not affect the fiber number or cause leaching but the biological activity was reduced; strong NaOH reduced the fiber number and biological activity, and caused marked leaching of Si. The medium oxalic acid conditions (pH 1.4) were more acid than those found in lung cells but produced the same effects (reduction in fiber number and biological activity) as the more physiological mild treatment (pH 4.0), when prolonged. This study suggests that medium oxalic acid treatment can be used as a short-term assay to compare loss of Si, reduction in fiber number, and change in biological activity of vitreous fibers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7882922

Effect of an exercise training intervention with resistance bands on blood cell counts during chemotherapy for lung cancer: a pilot randomized controlled trial.

PubMed

Karvinen, Kristina H; Esposito, David; Raedeke, Thomas D; Vick, Joshua; Walker, Paul R

2014-01-01

Chemotherapy for lung cancer can have a detrimental effect on white blood cell (WBC) and red blood cell (RBC) counts. Physical exercise may have a role in improving WBCs and RBCs, although few studies have examined cancer patients receiving adjuvant therapies. The purpose of this pilot trial was to examine the effects of an exercise intervention utilizing resistance bands on WBCs and RBCs in lung cancer patients receiving curative intent chemotherapy. A sample of lung cancer patients scheduled for curative intent chemotherapy was randomly assigned to the exercise intervention (EX) condition or usual care (UC) condition. The EX condition participated in a three times weekly exercise program using resistance bands for the duration of chemotherapy. A total of 14 lung cancer patients completed the trial. EX condition participants completed 79% of planned exercise sessions. The EX condition was able to maintain WBCs over the course of the intervention compared to declines in the UC condition (p = .008; d = 1.68). There were no significant differences in change scores in RBCs. Exercise with resistance bands may help attenuate declines in WBCs in lung cancer patients receiving curative intent chemotherapy. Larger trials are warranted to validate these findings. Ultimately these findings could be informative for the development of supportive care strategies for lung cancer patients receiving chemotherapy. Clinical Trials Registration #: NCT01130714.

Hypoxia-induced mitogenic factor (FIZZ1/RELMα) induces endothelial cell apoptosis and subsequent interleukin-4-dependent pulmonary hypertension

PubMed Central

Takimoto, Eiki; Zhang, Ailan; Weiner, Noah C.; Meuchel, Lucas W.; Berger, Alan E.; Cheadle, Chris; Johns, Roger A.

2014-01-01

Pulmonary hypertension (PH) is characterized by elevated pulmonary artery pressure that leads to progressive right heart failure and ultimately death. Injury to endothelium and consequent wound repair cascades have been suggested to trigger pulmonary vascular remodeling, such as that observed during PH. The relationship between injury to endothelium and disease pathogenesis in this disorder remains poorly understood. We and others have shown that, in mice, hypoxia-induced mitogenic factor (HIMF, also known as FIZZ1 or RELMα) plays a critical role in the pathogenesis of lung inflammation and the development of PH. In this study, we dissected the mechanism by which HIMF and its human homolog resistin (hRETN) induce pulmonary endothelial cell (EC) apoptosis and subsequent lung inflammation-mediated PH, which exhibits many of the hallmarks of the human disease. Systemic administration of HIMF caused increases in EC apoptosis and interleukin (IL)-4-dependent vascular inflammatory marker expression in mouse lung during the early inflammation phase. In vitro, HIMF, hRETN, and IL-4 activated pulmonary microvascular ECs (PMVECs) by increasing angiopoietin-2 expression and induced PMVEC apoptosis. In addition, the conditioned medium from hRETN-treated ECs had elevated levels of endothelin-1 and caused significant increases in pulmonary vascular smooth muscle cell proliferation. Last, HIMF treatment caused development of PH that was characterized by pulmonary vascular remodeling and right heart failure in wild-type mice but not in IL-4 knockout mice. These data suggest that HIMF contributes to activation of vascular inflammation at least in part by inducing EC apoptosis in the lung. These events lead to subsequent PH. PMID:24793164

Wharton's jelly mesenchymal stromal cells have contrasting effects on proliferation and phenotype of cancer stem cells from different subtypes of lung cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vulcano, Francesca, E-mail: francesca.vulcano@iss.it; Milazzo, Luisa, E-mail: luisa.milazzo@iss.it; Ciccarelli, Carmela, E-mail: carmela.ciccarelli@univaq.it

Studies on the role of multipotent mesenchymal stromal cells (MSC) on tumor growth have reported both a tumor promoting and a suppressive effect. The aim of the present study was to determine the effect of MSC isolated from Wharton's jelly of umbilical cord (WJMSC) on lung cancer stem cells (LCSC) derived from human lung tumors: two adenocarcinomas (AC) and two squamous cell carcinomas (SCC). LCSC derived from SCC and AC expressed, to varying extents, the more relevant stem cell markers. The effect of WJMSC on LCSC was investigated in vitro using conditioned medium (WJ-CM): a proliferation increase in AC-LCSC wasmore » observed, with an increase in the ALDH+ and in the CD133+ cell population. By contrast, WJ-CM hampered the growth of SCC-LCSC, with an increase in the pre-G1 phase indicating the induction of apoptosis. Furthermore, the ALDH+ and CD133+ population was also reduced. In vivo, subcutaneous co-transplantation of AC-LCSC/WJMSC generated larger tumors than AC-LCSC alone, characterized by an increased percentage of CD133+ and CD166+ cells. By contrast, co-transplantation of WJMSC and SCC-LCSC did not affect the tumor size. Our results strongly suggest that WJMSC exert, both in vitro and in vivo, contrasting effects on LCSC derived from different lung tumor subtypes. - Highlights: • CM from WJMSC induces apoptosis of SCC-LCSC and reduction of ALDH+ and CD133+ cells. • Specificity of SCC-LCSC inhibition by WJ-CM is proved by the use of a CM from NHDF. • WJ-CM enhance AC-LCSC proliferation and increase CD133+ and ALDH+ cell fractions. • Coinjection of WJMSC with AC-LCSC increase tumor growth with SCC-LCSC has no effect.« less

Influence of socioeconomic and demographic status on spirometry testing in patients initiating medication targeting obstructive lung disease: a population-based cohort study.

PubMed

Koefoed, Mette M; Søndergaard, Jens; Christensen, René dePont; Jarbøl, Dorte E

2013-06-14

Socioeconomic status is known to influence the prevalence, severity and mortality of obstructive lung diseases, but it is uncertain whether it affects the use of diagnostic spirometry in patients initiating treatment for these conditions. The objective of this paper was to examine a possible association between education, income, labour market affiliation, cohabitation status and having spirometry performed when initiating medication targeting obstructive pulmonary disease. We conducted a population-based cohort study. Danish national registers were linked, retrieving data on prescriptions, spirometry testing, socioeconomic and demographic variables in all first time users of medication targeting obstructive lung disease in 2008. A total of 37,734 persons were included and approximately half of the cohort had spirometry performed. Among medication users under 65 years of age, being unemployed was significantly associated with reduced odds of having spirometry performed, the strongest association was seen in men (OR = 0.82, CI = 0.73-0.91). Medium income was associated with increased odds of having spirometry performed in men (OR =1.18, CI = 1.06-1.30) and high educational level (>12 years) was associated with reduced odds of having spirometry performed in women (OR = 0.86, CI = 0.78-0.94). Cohabitation status was not associated with having spirometry performed. Among medication users over 65 years of age, living alone was associated with reduced odds of having spirometry performed among men (OR = 0.78, CI = 0.69-0.88). Social inequity in spirometry testing among patients initiating medication targeting obstructive lung disease was confirmed in this study. Increased focus on spirometry testing among elderly men living alone, among the unemployed and among women with higher education is required when initiating medication.

TREM-2 serves as a negative immune regulator through Syk pathway in an IL-10 dependent manner in lung cancer

PubMed Central

Chen, Junjun; Xu, Weiyi; Yang, Guangdie; Bao, Zhang; Xia, Dajing; Lu, Guohua; Hu, Shuwen; Zhou, Jianying

2016-01-01

During infection, triggering receptor expressed on myeloid cells-2 (TREM-2) restrains dendritic cells (DCs) and macrophages (MΦs) phagocytosis, as well as reduces pro-inflammatory cytokines release through DNAX-activation protein 12 (DAP12) signaling. However, the role of TREM-2 signaling in cancer has never been elucidated. In the current study, we found that TREM-2 was up-regulated on peripheral blood monocytes in tumor-bearing host. More TREM-2+DCs were detected in the lung of 3LL tumor-bearing mice. On the other hand, the level of TREM-2 on pulmonary MΦs positively correlated with the pathological staging of lung cancer. However, surgical or chemotherapeutic reduction of tumor burden led to the obvious decline of TREM-2. In vitro, TREM-2 expression of bone marrow (BM)-derived DCs and MΦs was induced by conditional medium (CM) containing the supernatant of 3LL cells. TREM-2+DCs from CM and/or tumor-bearing mice held altered phenotypes (CD80LowCD86LowMHCIILow) and impaired functions, such as, reduced interleukin (IL)-12 secretion, increased IL-10 production, and weakened ovalbumin (OVA)-endocytic capacity; also developed potent inhibitory effect on T cell proliferation that could be partially reversed by TREM-2 blockage. Moreover, spleen tyrosine kinase (Syk) inhibitor restrained IL-10 production of TREM-2+DC. Remarkably, IL-10 neutralizing antibody and Syk inhibitor both lowered the suppressive potential of TREM-2+DCs in T cell proliferation. Also, adoptive transfer of this TREM-2+DCs accelerated the tumor growth rather than jeopardized survival in lung cancer-bearing mice. In conclusion, these results indicate that TREM-2 might act as a negative immuno-regulatory molecule through Syk pathway in an IL-10 dependent manner and partially predicts prognosis in lung cancer patients. PMID:27102437

A one-dimensional model for the propagation of transient pressure waves through the lung.

PubMed

Grimal, Quentin; Watzky, Alexandre; Naili, Salah

2002-08-01

The propagation of pressure waves in the lung has been investigated by many authors concerned with respiratory physiology, ultrasound medical techniques or thoracic impact injuries. In most of the theoretical studies, the lung has been modeled as an isotropic and homogeneous medium, and by using Hooke's constitutive law (see e.g. Ganesan et al. Respir. Physiol. 110 (1997) 19; Jahed et al. J. Appl. Physiol. 66 (1989) 2675; Grimal et al. C.R. Acad. Sci., Paris 329 (IIb) (2001) 655-662), or more elaborated material laws (see, e.g. Bush and Challener (Proceedings of the International Research Council on Biokinetics Impacts (IRCOBI), Bergish-gladbach, 1988); Stuhmiller et al. J. Trauma 28 (1988) S132; Yang and Wang, Finite element modeling of the human thorax. Web page: http://wwwils.nlm.nih.gov/research/visible/vhpconf98/AUTHORS/YANG/YANG.HTM.). The hypothesis of homogeneous medium may be inappropriate for certain problems. Because of its foam-like structure, the behavior of the lung-even if the air and the soft tissue are assumed to behave like linearly elastic materials-is susceptible to be frequency dependent. In the present study, the lung is viewed as a one-dimensional stack of air and soft tissue layers; wave propagation in such a stack can be investigated in an equivalent mass-spring chain (El-Raheb (J. Acoust. Soc. Am. 94 (1993) 172; Int. J. Solids Struct. 34 (1997) 2969), where the masses and springs, respectively, represent the alveolar walls and alveolar gas. Results are presented in the time and frequency domains. The frequency dependence (cutoff frequency, variations in phase velocity) of the lung model is found to be highly dependent on the mean alveolar size. We found that short pulses induced by high velocity impacts (bullet stopped by a bulletproof jacket) can be highly distorted during the propagation. The pressure differential between two alveoli is discussed as a possible injury criterion.

A Model of Cancer Stem Cells Derived from Mouse Induced Pluripotent Stem Cells

PubMed Central

Chen, Ling; Kasai, Tomonari; Li, Yueguang; Sugii, Yuh; Jin, Guoliang; Okada, Masashi; Vaidyanath, Arun; Mizutani, Akifumi; Satoh, Ayano; Kudoh, Takayuki; Hendrix, Mary J. C.; Salomon, David S.; Fu, Li; Seno, Masaharu

2012-01-01

Cancer stem cells (CSCs) are capable of continuous proliferation and self-renewal and are proposed to play significant roles in oncogenesis, tumor growth, metastasis and cancer recurrence. CSCs are considered derived from normal stem cells affected by the tumor microenvironment although the mechanism of development is not clear yet. In 2007, Yamanaka's group succeeded in generating Nanog mouse induced pluripotent stem (miPS) cells, in which green fluorescent protein (GFP) has been inserted into the 5′-untranslated region of the Nanog gene. Usually, iPS cells, just like embryonic stem cells, are considered to be induced into progenitor cells, which differentiate into various normal phenotypes depending on the normal niche. We hypothesized that CSCs could be derived from Nanog miPS cells in the conditioned culture medium of cancer cell lines, which is a mimic of carcinoma microenvironment. As a result, the Nanog miPS cells treated with the conditioned medium of mouse Lewis lung carcinoma acquired characteristics of CSCs, in that they formed spheroids expressing GFP in suspension culture, and had a high tumorigenicity in Balb/c nude mice exhibiting angiogenesis in vivo. In addition, these iPS-derived CSCs had a capacity of self-renewal and expressed the marker genes, Nanog, Rex1, Eras, Esg1 and Cripto, associated with stem cell properties and an undifferentiated state. Thus we concluded that a model of CSCs was originally developed from miPS cells and proposed the conditioned culture medium of cancer cell lines might perform as niche for producing CSCs. The model of CSCs and the procedure of their establishment will help study the genetic alterations and the secreted factors in the tumor microenvironment which convert miPS cells to CSCs. Furthermore, the identification of potentially bona fide markers of CSCs, which will help the development of novel anti-cancer therapies, might be possible though the CSC model. PMID:22511923

Pyogranulomatous Pneumonia in Goats Caused by an Undescribed Porphyromonas Species, “Porphyromonas katsikii”

PubMed Central

Filioussis, George; Petridou, Evanthia; Karavanis, Emmanouel

2014-01-01

A yet-undescribed bacterial species, tentatively named “Porphyromonas katsikii,” was isolated from individuals of a small goat herd with pyogranulomatous pneumonia during an outbreak of acute respiratory disease. The isolated bacteria grew in the form of black-pigmented colonies after 14 days of incubation under anaerobic conditions at 37°C on a tryptic soy blood agar medium. The bacteria were identified as a yet-undescribed Porphyromonas species by determination of the nucleotide sequence of the rrs 16S rRNA gene, and this species was tentatively named Porphyromonas katsikii. PCR amplification with specific primers for this yet-undescribed species revealed the presence of P. katsikii in the lung tissue of all affected animals, while no PCR signals were evidenced from the lungs of healthy goats or from goats with pasteurellosis caused by Mannheimia haemolytica. These data indicate P. katsikii as the causative agent of acute respiratory distress. P. katsikii is phylogenetically related to Porphyromonas somerae and Porphyromonas levii, which cause pathologies in humans and animals, respectively. P. katsikii was not detected by PCR from samples of the gingival pockets or of the faces of healthy goats. PMID:25540395

Antibacterial Effect of Human Mesenchymal Stem Cells Is Mediated in Part from Secretion of the Antimicrobial Peptide LL-37

PubMed Central

Krasnodembskaya, Anna; Song, Yuanlin; Fang, Xiaohui; Gupta, Naveen; Serikov, Vladimir; Lee, Jae-Woo; Matthay, Michael A.

2012-01-01

Recent in vivo studies indicate that mesenchymal stem cells (MSCs) may have beneficial effects in the treatment of sepsis induced by bacterial infection. Administration of MSCs in these studies improved survival and enhanced bacterial clearance. The primary objective of this study was to test the hypothesis that human MSCs possessed intrinsic antimicrobial properties. We studied the effect of human MSCs derived from bone marrow on the bacterial growth of Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria. MSCs as well as their conditioned medium (CM) demonstrated marked inhibition of bacterial growth in comparison with control medium or normal human lung fibroblasts (NHLF). Analysis of expression of major antimicrobial peptides indicated that one of the factors responsible for the antimicrobial activity of MSC CM against Gram-negative bacteria was the human cathelicidin antimicrobial peptide, hCAP-18/LL-37. Both m-RNA and protein expression data showed that the expression of LL-37 in MSCs increased after bacterial challenge. Using an in vivo mouse model of E. coli pneumonia, intratracheal administration of MSCs reduced bacterial growth (in colony-forming unit) in the lung homogenates and in the bronchoalveolar lavage (BAL) fluid, and administration of MSCs simultaneously with a neutralizing antibody to LL-37 resulted in a decrease in bacterial clearance. In addition, the BAL itself from MSC-treated mice had a greater antimicrobial activity in comparison with the BAL of phosphate buffered saline (PBS)-treated mice. Human bone marrow-derived MSCs possess direct antimicrobial activity, which is mediated in part by the secretion of human cathelicidin hCAP-18/LL-37. PMID:20945332

Modulation of Gene Expression in Actinobacillus pleuropneumoniae Exposed to Bronchoalveolar Fluid

PubMed Central

Lone, Abdul G.; Deslandes, Vincent; Nash, John H. E.; Jacques, Mario; MacInnes, Janet I.

2009-01-01

Background Actinobacillus pleuropneumoniae, the causative agent of porcine contagious pleuropneumonia, is an important pathogen of swine throughout the world. It must rapidly overcome the innate pulmonary immune defenses of the pig to cause disease. To better understand this process, the objective of this study was to identify genes that are differentially expressed in a medium that mimics the lung environment early in the infection process. Methods and Principal Findings Since bronchoalveolar lavage fluid (BALF) contains innate immune and other components found in the lungs, we examined gene expression of a virulent serovar 1 strain of A. pleuropneumoniae after a 30 min exposure to BALF, using DNA microarrays and real-time PCR. The functional classes of genes found to be up-regulated most often in BALF were those encoding proteins involved in energy metabolism, especially anaerobic metabolism, and in cell envelope, DNA, and protein biosynthesis. Transcription of a number of known virulence genes including apxIVA and the gene for SapF, a protein which is involved in resistance to antimicrobial peptides, was also up-regulated in BALF. Seventy-nine percent of the genes that were up-regulated in BALF encoded a known protein product, and of these, 44% had been reported to be either expressed in vivo and/or involved in virulence. Conclusions The results of this study suggest that in early stages of infection, A. pleuropneumoniae may modulate expression of genes involved in anaerobic energy generation and in the synthesis of proteins involved in cell wall biogenesis, as well as established virulence factors. Given that many of these genes are thought to be expressed in vivo or involved in virulence, incubation in BALF appears, at least partially, to simulate in vivo conditions and may provide a useful medium for the discovery of novel vaccine or therapeutic targets. PMID:19578537

Limitations of current dosimetry for intracavitary accelerated partial breast irradiation with high dose rate iridium-192 and electronic brachytherapy sources

NASA Astrophysics Data System (ADS)

Raffi, Julie A.

Intracavitary accelerated partial breast irradiation (APBI) is a method of treating early stage breast cancer using a high dose rate (HDR) brachytherapy source positioned within the lumpectomy cavity. An expandable applicator stretches the surrounding tissue into a roughly spherical or elliptical shape and the dose is prescribed to 1 cm beyond the edge of the cavity. Currently, dosimetry for these treatments is most often performed using the American Association of Physicists in Medicine Task Group No. 43 (TG-43) formalism. The TG-43 dose-rate equation determines the dose delivered to a homogeneous water medium by scaling the measured source strength with standardized parameters that describe the radial and angular features of the dose distribution. Since TG-43 parameters for each source model are measured or calculated in a homogeneous water medium, the dosimetric effects of the patient's dimensions and composition are not accounted for. Therefore, the accuracy of TG-43 calculations for intracavitary APBI is limited by the presence of inhomogeneities in and around the target volume. Specifically, the breast is smaller than the phantoms used to determine TG-43 parameters and is surrounded by air, ribs, and lung tissue. Also, the composition of the breast tissue itself can affect the dose distribution. This dissertation is focused on investigating the limitations of TG-43 dosimetry for intracavitary APBI for two HDR brachytherapy sources: the VariSource TM VS2000 192Ir source and the AxxentRTM miniature x-ray source. The dose for various conditions was determined using thermoluminescent dosimeters (TLDs) and Monte Carlo (MC) calculations. Accurate measurements and calculations were achieved through the implementation of new measurement and simulation techniques and a novel breast phantom was developed to enable anthropomorphic phantom measurements. Measured and calculated doses for phantom and patient geometries were compared with TG-43 calculated doses to illustrate the limitations of TG-43 dosimetry for intracavitary APBI. TG-43 dose calculations overestimate the dose for regions approaching the lung and breast surface and underestimate the dose for regions in and beyond less-attenuating media such as lung tissue, and for lower energies, breast tissue as well.

Effect of Folic Acid and Vitamin B12 on Pemetrexed Antifolate Chemotherapy in Nutrient Lung Cancer Cells

PubMed Central

Yang, Tsung-Ying; Chang, Gee-Chen; Hsu, Shih-Lan; Huang, Yi-Rou; Chiu, Ling-Yen

2013-01-01

Pemetrexed (MTA) is a multitargeted antifolate drug approved for lung cancer therapy. Clinically, supplementation with high doses of folic acid (FA) and vitamin B12 (VB12) lowers MTA cytotoxicities. An antagonistic effect of FA/VB12 on MTA efficacy has been proposed. However, patients who receive FA/VB12 show better tolerance to MTA with improved survival. The aims of this study are to investigate the modulation of FA and VB12 on MTA drug efficacy in human nonsmall cell lung cancer (NSCLC) cell lines. The sensitivities of cells, apoptosis, and MTA-regulated proteins were characterized to determine the possible effects of high doses of FA and VB12 on MTA efficacy. MTA has the lowest efficacy under 10% serum conditions. However, supplementation with FA and VB12 individually and additively reversed the insensitivity of NSCLC cells to MTA treatment with 10% serum. The enhanced sensitivities of cells following FA/VB12 treatment were correlated with increasing apoptosis and were specific to MTA but not to 5-fluorouracil (5-FU). Enhanced sensitivity was also associated with p21WAF1/Cip1 expression level. Our results revealed no antagonistic effect of high doses of FA/VB12 on MTA efficacy in cancer cells grown in nutrient medium. Furthermore, these data may partially explain why supplementation of FA and VB12 resulted in better survival in MTA-treated patients. PMID:23984356

[Occurrence and survival condition of lung cancer with different histologies among residents in Pudong new area].

PubMed

Chen, Hanyi; Yang, Chen; Yan, Bei; Sun, Lianghong; Wu, Zheng; Li, Xiaopan; Zhang, Meiyu; Li, Xiaoli; Yang, Liming

2014-03-01

Different histologies of lung cancer vary in occurrence and prognosis. This study aims to analyze the incidence and occurrence trend of lung cancer and investigate the survival rate and its influential factors among lung cancer patients with different histologies. Permanent residents were recruited between 2002 and 2009 in Pudong New Area (former Nanhui Area and former Pudong Area), Shanghai, China. Annual percent changes were estimated by a linear regression of the logarithm on the incidence rates for eight years. Survival rates were calculated and compared by using life-table analysis and Log-rank test, respectively. The standardized incidence rates of lung cancer were 52.28 and 18.86 per 100,000 in males and females, respectively. The median survival time was 410.72 days for specific classified lung cancer. The incidence rates of adenocarcinoma ranked the highest and showed an upward tendency (P<0.05). Patients with small cell lung cancer showed the worst survival condition. The survival condition in males with squamous cell lung cancer living in former Nanhui Area was better compared with those living in former Pudong Area. Lung cancers with different histologies demonstrated different occurrence trends and survival rates. Gender, age, and living area influence the survival rates of lung cancer with different histologies.

The Audible Human Project: Modeling Sound Transmission in the Lungs and Torso

NASA Astrophysics Data System (ADS)

Dai, Zoujun

Auscultation has been used qualitatively by physicians for hundreds of years to aid in the monitoring and diagnosis of pulmonary diseases. Alterations in the structure and function of the pulmonary system that occur in disease or injury often give rise to measurable changes in lung sound production and transmission. Numerous acoustic measurements have revealed the differences of breath sounds and transmitted sounds in the lung under normal and pathological conditions. Compared to the extensive cataloging of lung sound measurements, the mechanism of sound transmission in the pulmonary system and how it changes with alterations of lung structural and material properties has received less attention. A better understanding of sound transmission and how it is altered by injury and disease might improve interpretation of lung sound measurements, including new lung imaging modalities that are based on an array measurement of the acoustic field on the torso surface via contact sensors or are based on a 3-dimensional measurement of the acoustic field throughout the lungs and torso using magnetic resonance elastography. A long-term goal of the Audible Human Project (AHP ) is to develop a computational acoustic model that would accurately simulate generation, transmission and noninvasive measurement of sound and vibration within the pulmonary system and torso caused by both internal (e.g. respiratory function) and external (e.g. palpation) sources. The goals of this dissertation research, fitting within the scope of the AHP, are to develop specific improved theoretical understandings, computational algorithms and experimental methods aimed at transmission and measurement. The research objectives undertaken in this dissertation are as follows. (1) Improve theoretical modeling and experimental identification of viscoelasticity in soft biological tissues. (2) Develop a poroviscoelastic model for lung tissue vibroacoustics. (3) Improve lung airway acoustics modeling and its coupling to the lung parenchyma; and (4) Develop improved techniques in array acoustic measurement on the torso surface of sound transmitted through the pulmonary system and torso. Tissue Viscoelasticity. Two experimental identification approaches of shear viscoelasticity were used. The first approach is to directly estimate the frequency-dependent surface wave speed and then to optimize the coefficients in an assumed viscoelastic model type. The second approach is to measure the complex-valued frequency response function (FRF) between the excitation location and points at known radial distances. The FRF has embedded in it frequency-dependent information about both surface wave phase speed and attenuation that can be used to directly estimate the complex shear modulus. The coefficients in an assumed viscoelastic tissue model type can then be optimized. Poroviscoelasticity Model for Lung Vibro-acoustics. A poroviscoelastic model based on Biot theory of wave propagation in porous media was used for compression waves in the lungs. This model predicts a fast compression wave speed close to the one predicted by the effective medium theory at low frequencies and an additional slow compression wave due to the out of phase motion of the air and the lung parenchyma. Both compression wave speeds vary with frequency. The fast compression wave speed and attenuation were measured on an excised pig lung under two different transpulmonary pressures. Good agreement was achieved between the experimental observation and theoretical predictions. Sound Transmission in Airways and Coupling to Lung Parenchyma. A computer generated airway tree was simplified to 255 segments and integrated into the lung geometry from the Visible Human Male for numerical simulations. Acoustic impedance boundary conditions were applied at the ends of the terminal segments to represent the unmodeled downstream airway segments. Experiments were also carried out on a preserved pig lung and similar trends of lung surface velocity distribution were observed between the experiments and simulations. This approach provides a feasible way of simplifying the airway tree and greatly reduces the computation time. Acoustic Measurements of Sound Transmission in Human Subjects. Scanning laser Doppler vibrometry (SLDV) was used as a gold standard for transmitted sound measurements on a human subject. A low cost piezodisk sensor array was also constructed as an alternative to SLDV. The advantages and disadvantages of each technique are discussed.

Increase in interleukin-8 production from circulating neutrophils upon antibiotic therapy in cystic fibrosis patients.

PubMed

Montemurro, Pasqualina; Mariggiò, Maria A; Barbuti, Giovanna; Cassano, Amalia; Vincenti, Alessandra; Serio, Gabriella; Guerra, Lorenzo; Diana, Anna; Santostasi, Teresa; Polizzi, Angela; Fumarulo, Ruggiero; Casavola, Valeria; Manca, Antonio; Conese, Massimo

2012-12-01

It is not known whether antibiotic therapy for lung disease in cystic fibrosis (CF) has an influence on circulating polymorphonuclear neutrophil (PMN) function and apoptosis. Blood PMNs were obtained from 14 CF patients before and after antibiotic treatment for an acute exacerbation, and from 10 healthy controls. PMNs were evaluated for production of reactive oxygen species (ROS) by spectrophotometry, of cytokines in the conditioned medium by ELISA, and apoptotic response by cytofluorimetry. ROS and interleukin (IL)-8 were produced at higher levels by CF PMNs pre-therapy than control PMNs under basal conditions. IL-8 levels further increased after therapy. Early apoptotic response was higher in CF PMNs pre-therapy than in control PMNs, and this pattern did not change after antibiotic treatment. Circulating PMNs are primed in CF acute patients. Further studies are needed to consider PMN-produced IL-8 as a biomarker to evaluate response to antibiotic therapy in CF patients. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Impact of pulmonary arterial endothelial cells on duroquinone redox status.

PubMed

Merker, Marilyn P; Bongard, Robert D; Krenz, Gary S; Zhao, Hongtao; Fernandes, Viola S; Kalyanaraman, Balaraman; Hogg, Neil; Audi, Said H

2004-07-01

The study objective was to use pulmonary arterial endothelial cells to examine kinetics and mechanisms contributing to the disposition of the quinone 2,3,5,6-tetramethyl-1,4-benzoquinone (duroquinone, DQ) observed during passage through the pulmonary circulation. The approach was to add DQ, durohydroquinone (DQH2), or DQ with the cell membrane-impermeant oxidizing agent, ferricyanide (Fe(CN)6(3)-), to the cell medium, and to measure the medium concentrations of substrates and products over time. Studies were carried out under control conditions and with dicumarol, to inhibit NAD(P)H:quinone oxidoreductase 1 (NQO1), or cyanide, to inhibit mitochondrial electron transport. In control cells, DQH2 appears in the extracellular medium of cells incubated with DQ, and DQ appears when the cells are incubated with DQH2. Dicumarol blocked the appearance of DQH2 when DQ was added to the cell medium, and cyanide blocked the appearance of DQ when DQH2 was added to the cell medium, suggesting that the two electron reductase NQO1 dominates DQ reduction and mitochondrial electron transport complex III is the predominant route of DQH2 oxidation. In the presence of cyanide, the addition of DQ also resulted in an increased rate of appearance of DQH2 and stimulation of cyanide-insensitive oxygen consumption. As DQH2 does not autoxidize-comproportionate over the study time course, these observations suggest a cyanide-stimulated one-electron DQ reduction and durosemiquinone (DQ*-) autoxidation. The latter processes are apparently confined to the cell interior, as the cell membrane impermeant oxidant, ferricyanide, did not inhibit the DQ-stimulated cyanide-insensitive oxygen consumption. Thus, regardless of whether DQ is reduced via a one- or two-electron reduction pathway, the net effect in the extracellular medium is the appearance of DQH2. These endothelial redox functions and their apposition to the vessel lumen are consistent with the pulmonary endothelium being an important site of DQ reduction to DQH2 observed in the lungs. Copyright 2004 Elsevier Inc.

In Vitro Impact of Conditioned Medium From Demineralized Freeze-Dried Bone on Human Umbilical Endothelial Cells.

PubMed

Harnik, Branko; Miron, Richard J; Buser, Daniel; Gruber, Reinhard

2017-03-01

Angiogenesis is essential for the consolidation of bone allografts. The underlying molecular mechanism, however, remains unclear. Soluble factors released from demineralized freeze-dried bone target mesenchymal cells; however, their effect on endothelial cells has not been investigated so far. The aim of the present study was therefore to examine the effect of conditioned medium from demineralized freeze-dried bone on human umbilical endothelial cells in vitro. Conditioned medium was first prepared from demineralized freeze-dried bone following 24 hours incubation at room temperature to produce demineralized bone conditioned media. Thereafter, conditioned medium was used to stimulate human umbilical vein endothelial cells in vitro by determining the cell response based on viability, proliferation, expression of apoptotic genes, a Boyden chamber to determine cell migration, and the formation of branches. The authors report here that conditioned medium decreased viability and proliferation of endothelial cells. Neither of the apoptotic marker genes was significantly altered when endothelial cells were exposed to conditioned medium. The Boyden chamber revealed that endothelial cells migrate toward conditioned medium. Moreover, conditioned medium moderately stimulated the formation of branches. These findings support the concept that conditioned medium from demineralized freeze-dried bone targets endothelial cells by decreasing their proliferation and enhancing their motility under these in vitro conditions.

Opposite Effects of Soluble Factors Secreted by Adipose Tissue on Proliferating and Quiescent Osteosarcoma Cells.

PubMed

Avril, Pierre; Duteille, Franck; Ridel, Perrine; Heymann, Marie-Françoise; De Pinieux, Gonzague; Rédini, Françoise; Blanchard, Frédéric; Heymann, Dominique; Trichet, Valérie; Perrot, Pierre

2016-03-01

Autologous adipose tissue transfer may be performed for aesthetic needs following resection of osteosarcoma, the most frequent primary malignant tumor of bone, excluding myeloma. The safety of autologous adipose tissue transfer regarding the potential risk of cancer recurrence must be addressed. Adipose tissue injection was tested in a human osteosarcoma preclinical model induced by MNNG-HOS cells. Culture media without growth factors from fetal bovine serum were conditioned with adipose tissue samples and added to two osteosarcoma cell lines (MNNG-HOS and MG-63) that were cultured in monolayer or maintained in nonadherent spheres, favoring a proliferation or quiescent stage, respectively. Proliferation and cell cycle were analyzed. Adipose tissue injection increased local growth of osteosarcoma in mice but was not associated with aggravation of lung metastasis or osteolysis. Adipose tissue-derived soluble factors increased the in vitro proliferation of osteosarcoma cells up to 180 percent. Interleukin-6 and leptin were measured in higher concentrations in adipose tissue-conditioned medium than in osteosarcoma cell-conditioned medium, but the authors' results indicated that they were not implicated alone. Furthermore, adipose tissue-derived soluble factors did not favor a G0-to-G1 phase transition of MNNG-HOS cells in nonadherent oncospheres. This study indicates that adipose tissue-soluble factors activate osteosarcoma cell cycle from G1 to mitosis phases, but do not promote the transition from quiescent G0 to G1 phases. Autologous adipose tissue transfer may not be involved in the activation of dormant tumor cells or cancer stem cells.

Physico-chemical properties and cytotoxic potential of Cordyceps sinensis metabolites.

PubMed

Lee, Eun-Jeong; Jang, Ka-Hee; Im, Seon-Young; Lee, Yoon-Kyung; Farooq, Muhammad; Farhoudi, Rozbeh; Lee, Dong-Jin

2015-01-01

This study was conducted to estimate the antioxidant activities, biochemical properties and biological activities of one of the entomopathogenic fungi, Cordyceps sinensis. Analysis of fungal metabolites indicated that the most abundant free sugar was glucose; the highest component of organic acids was citric acid from 10-day culture medium and the glutamate was the predominant amino acid observed from 3-day culture medium. Maximum total polyphenols and flavonoids were detected in the 15-day culture medium. For cytotoxicity test, three cancer cell lines, HepG2 (liver), MCF-7 (breast) and A549 (lung) were used. The IC50 values of the highest toxicity of HepG2 cell lines were observed from 10-day cultured medium, whereas the highest toxicity of MCF-7 and A549 was observed on 5-day cultured medium. This is the first study reporting on the strong antioxidant and cytotoxic potential of C. sinensis. Culture medium of C. sinensis may thus be used as an effective antioxidant and anticancer treatment of natural origin.

Lung transplantation for non-cystic fibrosis bronchiectasis: analysis of a 13-year experience.

PubMed

Beirne, Paul Adrian; Banner, Nicholas R; Khaghani, Asghar; Hodson, Margaret E; Yacoub, Magdi H

2005-10-01

Lung transplantation is a well-established treatment for end-stage cystic fibrosis, and there are considerable data on medium- and long-term results. However, less information exists about transplantation for non-cystic fibrosis bronchiectasis. Between December 1988 and June 2001, 22 patients (12 men, 10 women) underwent transplantation for bronchiectasis not due to cystic fibrosis. Procedures were bilateral sequential single-lung transplants (BSSLTX) in 4 patients, en bloc double lung transplants (DLTX) in 5, heart-lung transplants (HLTX) in 6, and single-lung transplants (SLTX) in 7. Lifelong outpatient follow-up was continued at a minimum of every 6 months. One-year Kaplan-Meier survival for all patients was 68% (95% confidence interval [CI], 54%-91%), and 5-year survival was 62% (95% CI, 41-83%). One-year survival after SLTX was 57% (95% CI, 20%-94%) vs 73% (95% CI, 51-96%) for those receiving 2 lungs. At 6 months, mean forced expiratory volume in 1 second was 73% predicted (range, 58%-97%), and mean forced vital capacity was 68% predicted (range, 53%-94%) after receiving 2 lungs (n = 10); in the SLTX group at 6 months, mean forced expiratory volume in 1 second was 50% predicted (range, 34%-61%), and mean forced vital capacity was 53% predicted (range 46-63%) (n = 4). Survival and lung function after transplantation for non-cystic fibrosis bronchiectasis was similar to that after transplantation for cystic fibrosis. A good outcome is possible after single lung transplantation in selected patients.

Muscle and intensity based hamstring exercise classification in elite female track and field athletes: implications for exercise selection during rehabilitation

PubMed Central

Tsaklis, Panagiotis; Malliaropoulos, Nikos; Mendiguchia, Jurdan; Korakakis, Vasileios; Tsapralis, Kyriakos; Pyne, Debasish; Malliaras, Peter

2015-01-01

Background Hamstring injuries are common in many sports, including track and field. Strains occur in different parts of the hamstring muscle but very little is known about whether common hamstring loading exercises specifically load different hamstring components. The purpose of this study was to investigate muscle activation of different components of the hamstring muscle during common hamstring loading exercises. Methods Twenty elite female track and field athletes were recruited into this study, which had a single-sample, repeated-measures design. Each athlete performed ten hamstring loading exercises, and an electromyogram (EMG) was recorded from the biceps femoris and semitendinosus components of the hamstring. Hamstring EMG during maximal voluntary isometric contraction (MVIC) was used to normalize the mean data across ten repetitions of each exercise. An electrogoniometer synchronized to the EMG was used to determine whether peak EMG activity occurred during muscle-tendon unit lengthening, shortening, or no change in length. Mean EMG values were compared between the two recording sites for each exercise using the Student’s t-test. Results The lunge, dead lift, and kettle swings were low intensity (<50% MVIC) and all showed higher EMG activity for semitendinosus than for biceps femoris. Bridge was low but approaching medium intensity, and the TRX, hamstring bridge, and hamstring curl were all medium intensity exercises (≥50% or <80% MVIC). The Nordic, fitball, and slide leg exercises were all high intensity exercises. Only the fitball exercise showed higher EMG activity in the biceps femoris compared with the semitendinosus. Only lunge and kettle swings showed peak EMG in the muscle-tendon unit lengthening phase and both these exercises involved faster speed. Conclusion Some exercises selectively activated the lateral and medial distal hamstrings. Low, medium, and high intensity exercises were demonstrated. This information enables the clinician, strength and conditioning coach and physiotherapist to better understand intensity- and muscle-specific activation during hamstring muscle rehabilitation. Therefore, these results may help in designing progressive strengthening and rehabilitation and prevention programs. PMID:26170726

Interactions between DPPC as a component of lung surfactant and amorphous silica nanoparticles investigated by HILIC-ESI-MS.

PubMed

Silina, Yuliya E; Welck, Jennifer; Kraegeloh, Annette; Koch, Marcus; Fink-Straube, Claudia

2016-09-01

This paper reports a rapid HILIC-ESI-MS assay to quantify dipalmitoylphosphatidylcholine (DPPC) as component of lung surfactant for nanosafety studies. The technique was used to investigate the concentration-dependent sorption of DPPC to two-sizes of amorphous SiO2 nanoparticles (SiO2-NPs) in a MeOH:H2O (50/50v/v) mixture and in cell culture medium. In MeOH:H2O (50/50v/v), the sorption of DPPC was positively correlated with the nanoparticles concentration. A substantial affinity of small amorphous SiO2-NPs (25nm) to DPPC standard solution compared to bigger SiO2-NPs (75nm) was not confirmed for biological specimens. After dispersion of SiO2-NPs in DPPC containing cell culture medium, the capacity of the SiO2-NPs to bind DPPC was reduced in comparison to a mixture of MeOH:H2O (50/50v/v) regardless from the nanoparticles size. Furthermore, HILIC-ESI-MS revealed that A549 cells internalized DPPC during growth in serum containing medium complemented with DPPC. This finding was in a good agreement with the potential of alveolar type II cells to recycle surfactant components. Binding of lipids present in the cell culture medium to amorphous SiO2-NPs was supported by means of HILIC-ESI-MS, TEM and ICP-MS independently. Copyright © 2016 Elsevier B.V. All rights reserved.

Lung transplant in end-staged chronic obstructive pulmonary disease (COPD) patients: a concise review.

PubMed

Aziz, Fahad; Penupolu, Sudheer; Xu, Xin; He, Jianxing

2010-06-01

Lung transplantation is commonly used for patients with end-stage lung disease. However, there is continuing debate on the optimal operation for patients with chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis. Single-lung transplantation (SLT) provides equivalent short- and medium-term results compared with bilateral lung transplantation (BLT), but long-term survival appears slightly better in BLT recipients (especially in patients with COPD). The number of available organs for lung transplantation also influences the choice of operation. Recent developments suggest that the organ donor shortage is not as severe as previously thought, making BLT a possible alternative for more patients. Among the different complications, re-implantation edema, infection, rejection, and bronchial complications predominate. Chronic rejection, also called obliterative bronchiolitis syndrome, is a later complication which can be observed in about half of the patients. Improvement in graft survival depends greatly in improvement in prevention and management of complications. Despite such complications, graft survival in fibrosis patients is greater than spontaneous survival on the waiting list; idiopathic fibrosis is associated with the highest mortality on the waiting list. Patients should be referred early for the pre-transplantation work-up because individual prognosis is very difficult to predict.

Lung transplant in end-staged chronic obstructive pulmonary disease (COPD) patients: a concise review

PubMed Central

Aziz, Fahad; Penupolu, Sudheer; Xu, Xin; He, Jianxing

2010-01-01

Lung transplantation is commonly used for patients with end-stage lung disease. However, there is continuing debate on the optimal operation for patients with chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis. Single-lung transplantation (SLT) provides equivalent short- and medium-term results compared with bilateral lung transplantation (BLT), but long-term survival appears slightly better in BLT recipients (especially in patients with COPD). The number of available organs for lung transplantation also influences the choice of operation. Recent developments suggest that the organ donor shortage is not as severe as previously thought, making BLT a possible alternative for more patients. Among the different complications, re-implantation edema, infection, rejection, and bronchial complications predominate. Chronic rejection, also called obliterative bronchiolitis syndrome, is a later complication which can be observed in about half of the patients. Improvement in graft survival depends greatly in improvement in prevention and management of complications. Despite such complications, graft survival in fibrosis patients is greater than spontaneous survival on the waiting list; idiopathic fibrosis is associated with the highest mortality on the waiting list. Patients should be referred early for the pre-transplantation work-up because individual prognosis is very difficult to predict. PMID:22263028

Efficiency of low dosage apatinib in post-first-line treatment of advanced lung adenocarcinoma.

PubMed

Zeng, Da-Xiong; Wang, Chang-Guo; Lei, Wei; Huang, Jian-An; Jiang, Jun-Hong

2017-09-12

Chemotherapy is the standard treatment of in advanced lung adenocarcinoma patients without driver mutation. However, few drugs could be selected when diseases progressed after second-line treatment. As a small molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), apatinib was suggested mainly using in advanced gastric cancer. In this study, we showed the results of apatinib as second-line to fourth-line treatment in EGFR wild-type advanced lung adenocarcinoma patients. 16 EGFR wild-type advanced lung adenocarcinoma patients were administrated apatinib (250-500 mg/d) orally. 3 patients showed partial response and 8 patients showed stable diseases response to apatinib, with a medium progression-free survival (PFS) of 4.4 month (2-10 months). The objective remission rate (ORR) was 18.75%(3/16). The total disease control rate (DCR) was 68.75% (11/16). The main toxicities were hypertension, hand-foot syndrome, proteinuria and thrombocytopenia which were tolerable and manageable. So, apatinib might be an optional choice for post-first-line treatment of EGFR wild-type advanced lung adenocarcinoma patients.

Investigation of Aspergillus fumigatus biofilm formation by various “omics” approaches

PubMed Central

Muszkieta, Laetitia; Beauvais, Anne; Pähtz, Vera; Gibbons, John G.; Anton Leberre, Véronique; Beau, Rémi; Shibuya, Kazutoshi; Rokas, Antonis; Francois, Jean M.; Kniemeyer, Olaf; Brakhage, Axel A.; Latgé, Jean P.

2013-01-01

In the lung, Aspergillus fumigatus usually forms a dense colony of filaments embedded in a polymeric extracellular matrix called biofilm (BF). This extracellular matrix embeds and glues hyphae together and protects the fungus from an outside hostile environment. This extracellular matrix is absent in fungal colonies grown under classical liquid shake conditions (PL), which were historically used to understand A. fumigatus pathobiology. Recent works have shown that the fungus in this aerial grown BF-like state exhibits reduced susceptibility to antifungal drugs and undergoes major metabolic changes that are thought to be associated to virulence. These differences in pathological and physiological characteristics between BF and liquid shake conditions suggest that the PL condition is a poor in vitro disease model. In the laboratory, A. fumigatus mycelium embedded by the extracellular matrix can be produced in vitro in aerial condition using an agar-based medium. To provide a global and accurate understanding of A. fumigatus in vitro BF growth, we utilized microarray, RNA-sequencing, and proteomic analysis to compare the global gene and protein expression profiles of A. fumigatus grown under BF and PL conditions. In this review, we will present the different signatures obtained with these three “omics” methods. We will discuss the advantages and limitations of each method and their complementarity. PMID:23407341

Intercostal muscle flap to protect the bronchial stump in pediatric lobectomy for lung abscess.

PubMed

Lisi, Gabriele; Lauriti, Giuseppe; Cascini, Valentina; Lococo, Achille; Chiesa, Pierluigi Lelli

2013-01-01

Lung suppurative diseases in children are usually responsive to medical treatment or percutaneous drainage. Rarely, pulmonary resection is required for lung abscess in childhood, particularly in presence of co-morbidities. In these cases, a lobectomy is usually performed through an open thoracotomy, with a reported incidence of bronco-pleural fistula up to 9.1% of pediatric series. This consequence is mainly due to the inflammatory condition; however the lack of knowledge of pediatric and thoracic surgeons with this rare condition in childhood can also play a role. In adults with lung cancer, the buttressing of bronchial stump with the additional support of an intercostal muscle (ICM) flap has proved to prevent this complication, as well as to reduce post-operative pain. We report the first pediatric experience of ICM flap used in 2 immunocompetent children requiring lobectomy for suppurative lung conditions. Our preliminary experience confirms the feasibility of protecting the bronchial stump after lobectomy in children, especially in conditions at risk for bronco-pleural fistula development.

Lungs from donation after circulatory death donors: an alternative source to brain-dead donors? Midterm results at a single institution.

PubMed

Zych, Bartlomiej; Popov, Aron-Frederik; Amrani, Mohamed; Bahrami, Toufan; Redmond, Karen Christina; Krueger, Heike; Carby, Martin; Simon, André Ruediger

2012-09-01

Donor organ shortage remains to be the major limitation in lung transplantation, and donation after circulatory death (DCD) might represent one way to alleviate this problem. DCD was introduced to our institution in 2007 and has been a part of our clinical routine since then. Here, we present the mid-term results of lung transplantation from DCD in a single institution and compare the outcomes with the lung recipient cohort receiving lungs from donation after brain death (DBD). Since initiation of the DCD programme in March 2007, of the 157 lung transplantations performed, 26 (16.5%) were retrieved from DCD donors, with 25 double- and 1 single-lung transplants being performed. Results were compared with standard DBD transplantations. Analyses included, amongst others, donor characteristics, survival, prevalence of primary graft dysfunction, acute rejection, lung function tests during follow-up, onset of bronchiolitis obliterans syndrome (BOS) as well as duration of mechanical ventilation, hospital and intensive care unit length of stay. While there was no significant difference between lung function, BOS and survival between the two groups, lungs from DCD donors had a higher PaO(2) (median; interquartile range) 498.3 (451.5; 525) vs. DBD 442.5 (371.25; 502) kPa before retrieval (P = 0.009). There was also a longer total ischaemic time in the DCD vs. DBD group: 320 min (298.75; 393.25) vs. 285.5 min (240; 373) (P = 0.025). All other parameters were comparable. Medium-term results after lung transplantation with organs procured after circulatory death are comparable with those obtained after standard lung transplantation. Therefore, DCD could be used to significantly increase the donor pool.

[Total flavonoids from Astragalus complanatus attenuates lung injury following paraquat poisoning in rats through inhibiting excessive endoplasmic reticulum stress and c-Jun N-terminal kinase pathway].

PubMed

Zhang, Zhijian; Dong, Yaoyao; Li, Xiaoping; Peng, Libo

2014-06-01

To investigate the effect of total flavonoids from astragalus complanatus (FAC) on attenuating lung injury resulted from paraquat (PQ) poisoning by inhibiting excessive endoplasmic reticulum stress (ERS) and c-Jun N-terminal kinase (JNK) pathway in rat. Forty-eight Sprague-Dawley (SD) rats were randomly divided into six groups (n=8 in each group), including control group, model group, dimethyl sulfoxide (DMSO) vehicle control group, and FAC in low, medium, and high dosage groups. The model was reproduced by giving PQ 80 mg/kg orally to induce lung injury. The rats in control group were treated with saline by gavage. The rats in DMSO group were given 10% DMSO 20 mL/kg by gavage 2 hours before intraperitoneal injection of PQ, and those in FAC low, medium and high dosage groups received 40, 80, 160 mg×kg(-1)×d(-1) of FAC solution intraperitoneally after the PQ administration. The rats were sacrificed 72 hours after giving PQ, and the left lung tissue was harvested 72 hours after the reproduction of experimental model. The ratio of wet/dry weight (W/D) and total lung water content (TLW) were determined. The pathohistological changes of the left lung was observed under light microscope, and scored with alveolar damage index of quantitative assessment (IQA). The mRNA expressions of JNK and glucose regulated protein 78 (GRP78) were determined by reverse transcription-polymerase chain reaction (RT-PCR), and the protein expression of JNK, phosphorylation-JNK (p-JNK), and GRP78 were determined by Western Blot. Compared with control group, the W/D ratio, TLW and IQA were increased significantly in model group and DMSO group, and the mRNA expressions of JNK and GRP78 and the protein expressions of JNK, p-JNK and GRP78 were markedly increased. Compared with the model group, the W/D ratio, TLW and IQA, and the expressions of JNK mRNA and p-JNK protein were significantly decreased in the FAC groups, especially in FAC high dosage group [W/D ratio: 3.0±0.3 vs. 5.5±0.5, TLW: 2.2±0.3 vs. 4.7±0.4, IQA: (15.4±3.0)% vs. (40.0±5.7)%, JNK mRNA: 0.21±0.08 vs. 0.82±0.27, p-JNK protein: 0.31±0.09 vs. 0.78±0.25, all P<0.01]. The mRNA expression of GRP78 and the protein expressions of JNK and GRP78 were highly expressed in FAC low, medium and high dosage groups, and there was no significant difference compared with those in model group (GRP78 mRNA: 0.54±0.18 vs. 0.74±0.20, JNK protein: 0.76±0.27 vs. 0.80±0.28, GRP78 protein: 0.51±0.18 vs. 0.69±0.21, all P>0.05). PQ induces excessive ERS in the lung tissue resulting in lung injury. FAC has a protective effect on lung against PQ injury, and it may be related with inhibition JNK pathway in ERS.

Stochastic rat lung dosimetry for inhaled radon progeny: a surrogate for the human lung for lung cancer risk assessment.

PubMed

Winkler-Heil, R; Hussain, M; Hofmann, W

2015-05-01

Laboratory rats are frequently used in inhalation studies as a surrogate for human exposures. The objective of the present study was therefore to develop a stochastic dosimetry model for inhaled radon progeny in the rat lung, to predict bronchial dose distributions and to compare them with corresponding dose distributions in the human lung. The most significant difference between human and rat lungs is the branching structure of the bronchial tree, which is relatively symmetric in the human lung, but monopodial in the rat lung. Radon progeny aerosol characteristics used in the present study encompass conditions typical for PNNL and COGEMA rat inhalation studies, as well as uranium miners and human indoor exposure conditions. It is shown here that depending on exposure conditions and modeling assumptions, average bronchial doses in the rat lung ranged from 5.4 to 7.3 mGy WLM(-1). If plotted as a function of airway generation, bronchial dose distributions exhibit a significant maximum in large bronchial airways. If, however, plotted as a function of airway diameter, then bronchial doses are much more uniformly distributed throughout the bronchial tree. Comparisons between human and rat exposures indicate that rat bronchial doses are slightly higher than human bronchial doses by about a factor of 1.3, while lung doses, averaged over the bronchial (BB), bronchiolar (bb) and alveolar-interstitial (AI) regions, are higher by about a factor of about 1.6. This supports the current view that the rat lung is indeed an appropriate surrogate for the human lung in case of radon-induced lung cancers. Furthermore, airway diameter seems to be a more appropriate morphometric parameter than airway generations to relate bronchial doses to bronchial carcinomas.

Lung Transplantation for Hypersensitivity Pneumonitis

PubMed Central

Singer, Jonathan P.; Koth, Laura; Mooney, Joshua; Golden, Jeff; Hays, Steven; Greenland, John; Wolters, Paul; Ghio, Emily; Jones, Kirk D.; Leard, Lorriana; Kukreja, Jasleen; Blanc, Paul D.

2015-01-01

BACKGROUND: Hypersensitivity pneumonitis (HP) is an inhaled antigen-mediated interstitial lung disease (ILD). Advanced disease may necessitate the need for lung transplantation. There are no published studies addressing lung transplant outcomes in HP. We characterized HP outcomes compared with referents undergoing lung transplantation for idiopathic pulmonary fibrosis (IPF). METHODS: To identify HP cases, we reviewed records for all ILD lung transplantation cases at our institution from 2000 to 2013. We compared clinical characteristics, survival, and acute and chronic rejection for lung transplant recipients with HP to referents with IPF. We also reviewed diagnoses of HP discovered only by explant pathology and looked for evidence of recurrent HP after transplant. Survival was compared using Kaplan-Meier methods and Cox proportional hazard modeling. RESULTS: We analyzed 31 subjects with HP and 91 with IPF among 183 cases undergoing lung transplantation for ILD. Survival at 1, 3, and 5 years after lung transplant in HP compared with IPF was 96%, 89%, and 89% vs 86%, 67%, and 49%, respectively. Subjects with HP manifested a reduced adjusted risk for death compared with subjects with IPF (hazard ratio, 0.25; 95% CI, 0.08-0.74; P = .013). Of the 31 cases, the diagnosis of HP was unexpectedly made at explant in five (16%). Two subjects developed recurrent HP in their allografts. CONCLUSIONS: Overall, subjects with HP have excellent medium-term survival after lung transplantation and, relative to IPF, a reduced risk for death. HP may be initially discovered only by review of the explant pathology. Notably, HP may recur in the allograft. PMID:25412059

The effects of storage and sterilization on de-cellularized and re-cellularized whole lung.

PubMed

Bonenfant, Nicholas R; Sokocevic, Dino; Wagner, Darcy E; Borg, Zachary D; Lathrop, Melissa J; Lam, Ying Wai; Deng, Bin; Desarno, Michael J; Ashikaga, Taka; Loi, Roberto; Weiss, Daniel J

2013-04-01

Despite growing interest on the potential use of de-cellularized whole lungs as 3-dimensional scaffolds for ex vivo lung tissue generation, optimal processing including sterilization and storage conditions, are not well defined. Further, it is unclear whether lungs need to be obtained immediately or may be usable even if harvested several days post-mortem, a situation mimicking potential procurement of human lungs from autopsy. We therefore assessed effects of delayed necropsy, prolonged storage (3 and 6 months), and of two commonly utilized sterilization approaches: irradiation or final rinse with peracetic acid, on architecture and extracellular matrix (ECM) protein characteristics of de-cellularized mouse lungs. These different approaches resulted in significant differences in both histologic appearance and in retention of ECM and intracellular proteins as assessed by immunohistochemistry and mass spectrometry. Despite these differences, binding and proliferation of bone marrow-derived mesenchymal stromal cells (MSCs) over a one month period following intratracheal inoculation was similar between experimental conditions. In contrast, significant differences occurred with C10 mouse lung epithelial cells between the different conditions. Therefore, delayed necropsy, duration of scaffold storage, sterilization approach, and cell type used for re-cellularization may significantly impact the usefulness of this biological scaffold-based model of ex vivo lung tissue regeneration. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of Didecyldimethylammonium Chloride on Sprague-Dawley Rats after Two Weeks of Inhalation Exposure

PubMed Central

Chung, Yong-Hyun

2014-01-01

Didecyldimethylammonium chloride (DDAC) is used for various purposes, such as a fungicide for coolants, an antiseptic for wood, and disinfectant for cleaning. Despite the increasing likelihood of DDAC inhalation, available data on its toxicity from inhalation are scarce. Therefore, this study was aimed at confirming the toxicity of DDAC after inhalation exposure for 2 wk. Male Sprague-Dawley rats were exposed to approximately 0.15 mg/m3, 0.6 mg/m3, and 3.6 mg/m3 DDAC aerosols in whole-body exposure chambers. After DDAC exposure for 2 wk, effects of DDAC on body weight, blood, bronchoalveolar lavage (BAL), and the lungs were verified. The mass median aerodynamic diameter of DDAC aerosols was 1.86 μm and the geometric standard deviation was 2.75. The concentrations of DDAC aerosols for the low, medium, and high groups were 0.15 ± 0.15 mg/m3, 0.58 ± 0.40 mg/m3, and 3.63 ± 1.56 mg/m3, respectively. Body weight gain was significantly influenced by DDAC exposure. In the high group, a body weight decrease of 2.6 g was observed, whereas a 25.8 g increase was observed in the normal control group after the first 3 days. The low and medium groups showed 23.3 g and 20.4 g increases, respectively, after the first 3 days. Decreases in body weight were recovered during the next 4 days. In contrast, no changes were noted in hematological and blood biochemistry parameters after DDAC exposure. Furthermore, only mild effects were observed on bronchoalveolar cell differentiation counts and cell damage parameters in the BAL fluids of the medium and high groups. Although inflammatory cell infiltration and interstitial pneumonia were partially observed, fibrosis was not found in the lungs of the medium and high groups. In conclusion, body weight gain and the lungs were mainly affected by DDAC exposure. The noobserved-adverse-effect level (NOAEL) for DDAC was determined as 0.15 mg/m3. PMID:25343015

GROα regulates human embryonic stem cell self-renewal or adoption of a neuronal fate

PubMed Central

Krtolica, Ana; Larocque, Nick; Genbacev, Olga; Ilic, Dusko; Coppe, Jean-Philippe; Patil, Christopher K.; Zdravkovic, Tamara; McMaster, Michael; Campisi, Judith; Fisher, Susan J.

2012-01-01

Previously we reported that feeders formed from human placental fibroblasts (hPFs) support derivation and long-term self-renewal of human embryonic stem cells (hESCs) under serum-free conditions. Here, we show, using antibody array and ELISA platforms, that hPFs secrete ~6-fold higher amounts of the CXC-type chemokine, GROα, than IMR 90, a human lung fibroblast line, which does not support hESC growth. Furthermore, immunocytochemistry and immunoblot approaches revealed that hESCs express CXCR, a GROα receptor. We used this information to develop defined culture medium for feeder-free propagation of hESCs in an undifferentiated state. Cells passaged as small aggregates and maintained in the GROα-containing medium had a normal karyotype, expressed pluripotency markers, and exhibited apical–basal polarity, i.e., had the defining features of pluripotent hESCs. They also differentiated into the three primary (embryonic) germ layers and formed teratomas in immunocompromised mice. hESCs cultured as single cells in the GROα-containing medium also had a normal karyotype, but they downregulated markers of pluripotency, lost apical–basal polarity, and expressed markers that are indicative of the early stages of neuronal differentiation—βIII tubulin, vimentin, radial glial protein, and nestin. These data support our hypothesis that establishing and maintaining cell polarity is essential for the long-term propagation of hESCs in an undifferentiated state and that disruption of cell–cell contacts can trigger adoption of a neuronal fate. PMID:21396766

SU-E-T-551: Monitor Unit Optimization in Stereotactic Body Radiation Therapy for Stage I Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, B-T; Lu, J-Y

2015-06-15

Purpose: The study aims to reduce the monitor units (MUs) in the stereotactic body radiation therapy (SBRT) treatment for lung cancer by adjusting the optimizing parameters. Methods: Fourteen patients suffered from stage I Non-Small Cell Lung Cancer (NSCLC) were enrolled. Three groups of parameters were adjusted to investigate their effects on MU numbers and organs at risk (OARs) sparing: (1) the upper objective of planning target volume (UOPTV); (2) strength setting in the MU constraining objective; (3) max MU setting in the MU constraining objective. Results: We found that the parameters in the optimizer influenced the MU numbers in amore » priority, strength and max MU dependent manner. MU numbers showed a decreasing trend with the UOPTV increasing. MU numbers with low, medium and high priority for the UOPTV were 428±54, 312±48 and 258±31 MU/Gy, respectively. High priority for UOPTV also spared the heart, cord and lung while maintaining comparable PTV coverage than the low and medium priority group. It was observed that MU numbers tended to decrease with the strength increasing and max MU setting decreasing. With maximum strength, the MU numbers reached its minimum while maintaining comparable or improved dose to the normal tissues. It was also found that the MU numbers continued to decline at 85% and 75% max MU setting but no longer to decrease at 50% and 25%. Combined with high priority for UOPTV and MU constraining objectives, the MU numbers can be decreased as low as 223±26 MU/Gy. Conclusion:: The priority of UOPTV, MU constraining objective in the optimizer impact on the MU numbers in SBRT treatment for lung cancer. Giving high priority to the UOPTV, setting the strength to maximum value and the max MU to 50% in the MU objective achieves the lowest MU numbers while maintaining comparable or improved OAR sparing.« less

Induction of MHC-mismatched Mouse Lung Allograft Acceptance with Combined Donor Bone Marrow: Lung Transplant using a 12-Hour Nonmyeloablative Conditioning Regimen

PubMed Central

Vulic, Ante; Panoskaltsis-Mortari, Angela; McDyer, John F.; Luznik, Leo

2016-01-01

Background Despite broad and intense conventional immunosuppression, long-term survival after lung transplantation lags behind that for other solid organ transplants, primarily because of allograft rejection. Therefore, new strategies to promote lung allograft acceptance are urgently needed. The purpose of the present study was to induce allograft tolerance with a protocol compatible with deceased donor organ utilization. Methods Using the MHC-mismatched mouse orthotopic lung transplant model, we investigated a conditioning regimen consisting of pretransplant T cell depletion, low dose total body irradiation and posttransplant (donor) bone marrow and splenocyte infusion followed by posttransplantation cyclophosphamide (PTTT-PTB/PTCy). Results Our results show that C57BL/6 recipients of BALB/c lung allografts undergoing this complete short-duration nonmyeloablative conditioning regimen had durable lung allograft acceptance. Mice that lacked 1 or more components of this regimen exhibited significant graft loss. Mechanistically, animals with lung allograft acceptance had established higher levels of donor chimerism, lymphocyte responses which were attenuated to donor antigens but maintained to third-party antigens, and clonal deletion of donor-reactive host Vβ T cells. Frequencies of Foxp3+ T regulatory cells were comparable in both surviving and rejected allografts implying that their perturbation was not a dominant cell-regulatory mechanism. Donor chimerism was indispensable for sustained tolerance, as evidenced by acute rejection of allografts in established chimeric recipients of PTTT-PTB/PTCy following a chimerism-ablating secondary recipient lymphocyte infusion. Conclusion Together, these data provide proof-of-concept for establishing lung allograft tolerance with tandem donor bone marrow transplantation (BMT) using a short-duration nonmyeloablative conditioning regimen and PTCy. PMID:27861294

Sub-inhibitory concentrations of some antibiotics can drive diversification of Pseudomonas aeruginosa populations in artificial sputum medium

PubMed Central

2013-01-01

Background Pseudomonas aeruginosa populations within the cystic fibrosis lung exhibit extensive phenotypic and genetic diversification. The resultant population diversity is thought to be crucial to the persistence of infection and may underpin the progression of disease. However, because cystic fibrosis lungs represent ecologically complex and hostile environments, the selective forces driving this diversification in vivo remain unclear. We took an experimental evolution approach to test the hypothesis that sub-inhibitory antibiotics can drive diversification of P. aeruginosa populations. Replicate populations of P. aeruginosa LESB58 were cultured for seven days in artificial sputum medium with and without sub-inhibitory concentrations of various clinically relevant antibiotics. We then characterised diversification with respect to 13 phenotypic and genotypic characteristics. Results We observed that higher population diversity evolved in the presence of azithromycin, ceftazidime or colistin relative to antibiotic-free controls. Divergence occurred due to alterations in antimicrobial susceptibility profiles following exposure to azithromycin, ceftazidime and colistin. Alterations in colony morphology and pyocyanin production were observed following exposure to ceftazidime and colistin only. Diversification was not observed in the presence of meropenem. Conclusions Our study indicates that certain antibiotics can promote population diversification when present in sub-inhibitory concentrations. Hence, the choice of antibiotic may have previously unforeseen implications for the development of P. aeruginosa infections in the lungs of cystic fibrosis patients. PMID:23879797

Quantitative CT characterization of pediatric lung development using routine clinical imaging

PubMed Central

Stein, Jill M.; Walkup, Laura L.; Brody, Alan S.; Fleck, Robert J.

2016-01-01

Background 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. Objective 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. Materials and methods 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. Results 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. Conclusion 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. PMID:27576458

Possibilities of vaccine manufacture in human diploid cell strains with a serum replacement factor.

PubMed

Candal, F J; George, V G; Ades, E W

1991-07-01

Cell lines MDCK (canine kidney), BGM (Buffalo green monkey kidney) and human embryonic lung fibroblast will support viral growth efficiently in medium without serum. Both MRC-5 and WI-38 cell strains have been approved by the Food and Drug Administration for manufacturing viral vaccines against cytomegalovirus and varicella-zoster virus. In this study we examine these two cell lines and viruses for their ability to grow in medium containing a serum replacement. The serum substitute used is LPSR-1 (low protein serum replacement). Using LPSR-1 in defined medium, we demonstrate multipassage cell growth and viral cultivation and replication equivalent to those obtained in medium containing fetal bovine serum (FBS). Viral growth after complete elimination of FBS varies and depends on cell line and virus. Serum substitutes can eliminate FBS in the viral growth phase of vaccine production and reduce costs.

Role of pulmonary diseases and physical condition in the regulation of vasoactive hormones.

PubMed

Hietanen, E; Marniemi, J; Liippo, K; Seppänen, A; Hartiala, J; Viinamäki, O

1988-12-01

Lungs have many non-respiratory metabolic functions, of which some take place in the capillary endothelium, while others are in parenchymal lung tissue. We have studied the role of the lungs in the metabolism of vasoactive and some other hormones by comparing patients who have undergone lung resection to those having various obstructive or fibrotic lung diseases. We have also compared these groups with persons in good physical health. The data suggested that lung resection patients had low angiotensin II levels in plasma but the response of angiotensin II to exercise was normal. Also adrenalin concentration was low in the lung resection group while dopamine did not show any significant difference between the groups. When hormone levels were correlated to the exercise data, renin levels were especially related to physical condition. Serum post-exercise renin values were inversely related to the uneven distribution of lung perfusion, possibly thus reflecting the diminished pulmonary vascularization. A negative association was found between angiotensin II and diffusion capacity. Thus, the angiotensin II levels may preferably be controlled by the non-circulatory functions of the lungs.

A study on volatile organic compounds emitted by in-vitro lung cancer cultured cells using gas sensor array and SPME-GCMS.

PubMed

Thriumani, Reena; Zakaria, Ammar; Hashim, Yumi Zuhanis Has-Yun; Jeffree, Amanina Iymia; Helmy, Khaled Mohamed; Kamarudin, Latifah Munirah; Omar, Mohammad Iqbal; Shakaff, Ali Yeon Md; Adom, Abdul Hamid; Persaud, Krishna C

2018-04-02

Volatile organic compounds (VOCs) emitted from exhaled breath from human bodies have been proven to be a useful source of information for early lung cancer diagnosis. To date, there are still arguable information on the production and origin of significant VOCs of cancer cells. Thus, this study aims to conduct in-vitro experiments involving related cell lines to verify the capability of VOCs in providing information of the cells. The performances of e-nose technology with different statistical methods to determine the best classifier were conducted and discussed. The gas sensor study has been complemented using solid phase micro-extraction-gas chromatography mass spectrometry. For this purpose, the lung cancer cells (A549 and Calu-3) and control cell lines, breast cancer cell (MCF7) and non-cancerous lung cell (WI38VA13) were cultured in growth medium. This study successfully provided a list of possible volatile organic compounds that can be specific biomarkers for lung cancer, even at the 24th hour of cell growth. Also, the Linear Discriminant Analysis-based One versus All-Support Vector Machine classifier, is able to produce high performance in distinguishing lung cancer from breast cancer cells and normal lung cells. The findings in this work conclude that the specific VOC released from the cancer cells can act as the odour signature and potentially to be used as non-invasive screening of lung cancer using gas array sensor devices.

Long-term Pulmonary Responses to Quadweekly Intermittent Intratracheal Spray Instillations of Magnetite (Fe3O4) Nanoparticles for 52 Weeks in Fischer 344 Rats.

PubMed

Tada, Yukie; Yano, Norio; Takahashi, Hiroshi; Yuzawa, Katsuhiro; Ando, Hiroshi; Kubo, Yoshikazu; Nagasawa, Akemichi; Inomata, Akiko; Ogata, Akio; Nakae, Dai

2013-12-01

Information about potential risks of iron nanomaterials is still limited, while a wide variety of applications are expected. We recently reported acute phase responses of male and female Fischer 344 rats after a single intratracheal spray instillation of Fe3O4 nanoparticles (magnetite), clearly showing dose-dependent pulmonary inflammatory changes (Tada et al., J Toxicol Pathol 25, 233-239, 2012). The present study assessed long-term responses of male and female Fischer 344 rats to multiple administrations of magnetite. Ten-week-old male and female Fischer 344 rats (n=20/group) were exposed to a total of 13 quadweekly intermittent intratracheal spray instillations of magnetite during the experimental period of 52 weeks, at doses of 0, 0.2 (low), 1.0 (medium) and 5.0 (high-dose) mg/kg body weight per administration. Absolute and relative lung weights of the high-dose group were significantly higher than those of the control group. Macroscopically, slight enlargement and scattered black patches were recognized in the lungs and the lung-associated lymph nodes of the high-dose group. Histopathologically, infiltration of macrophages phagocytosing magnetite (all dose groups) and of chronic inflammatory cells (medium- and high-dose males and high-dose females), alveolar bronchiolization and granuloma (high-dose group) were observed. In addition, alveolar hyperplasias were observed in some rats of the high-dose group, and cytoplasmic overexpression of β-catenin protein was immunohistochemically found in such lesions. The present results clearly show that instilled magnetite causes chronic inflammatory responses in the lung. These responses occur in a dose-dependent manner without apparent differences among sexes.

Utilization of the organ care system as ex-vivo lung perfusion after cold storage transportation.

PubMed

Mohite, P N; Maunz, O; Popov, A-F; Zych, B; Patil, N P; Simon, A R

2015-11-01

The Organ Care System (OCS) allows perfusion and ventilation of the donor lungs under physiological conditions. Ongoing trials to compare preservation with OCS Lung with standard cold storage do not include donor lungs with suboptimal gas exchange and donor lungs treated with OCS following cold storage transportation. We present a case of a 48-yr-old man who received such lungs after cold storage transportation treated with ex-vivo lung perfusion utilizing OCS. © The Author(s) 2015.

Modeling pressure relationships of inspired air into the human lung bifurcations through simulations

NASA Astrophysics Data System (ADS)

Aghasafari, Parya; Ibrahim, Israr B. M.; Pidaparti, Ramana

2018-03-01

Applied pressure on human lung wall has great importance on setting up protective ventilatory strategies, therefore, estimating pressure relationships in terms of specific parameters would provide invaluable information specifically during mechanical ventilation (MV). A three-dimensional model from a healthy human lung MRI is analyzed by computational fluid dynamic (CFD), and results for pressure are curve fitted to estimate relationships that associate pressure to breathing time, cross section and generation numbers of intended locations. Among all possible functions, it is observed that exponential and polynomial pressure functions present most accurate results for normal breathing (NB) and MV, respectively. For validation, pressure-location curves from CFD and results from this study are compared and good correlations are found. Also, estimated pressure values are used to calculate pressure drop and airway resistance to the induced air into the lung bifurcations. It is concluded that maximum pressure drop appeared in generation number 2 and medium sized airways show higher resistance to air flow and that resistance decreased as cross sectional area increased through the model. Results from this study are in good agreement with previous studies and provide potentials for further studies on influence of air pressure on human lung tissue and reducing lung injuries during MV.

Measurement of vibration-induced volumetric strain in the human lung.

PubMed

Hirsch, Sebastian; Posnansky, Oleg; Papazoglou, Sebastian; Elgeti, Thomas; Braun, Jürgen; Sack, Ingolf

2013-03-01

Noninvasive image-based measurement of intrinsic tissue pressure is of great interest in the diagnosis and characterization of diseases. Therefore, we propose to exploit the capability of phase-contrast MRI to measure three-dimensional vector fields of tissue motion for deriving volumetric strain induced by external vibration. Volumetric strain as given by the divergence of mechanical displacement fields is related to tissue compressibility and is thus sensitive to the state of tissue pressure. This principle is demonstrated by the measurement of three-dimensional vector fields of 50-Hz oscillations in a compressible agarose phantom and in the lungs of nine healthy volunteers. In the phantom, the magnitude of the oscillating divergence increased by about 400% with 4.8 bar excess air pressure, corresponding to an effective-medium compression modulus of 230 MPa. In lungs, the averaged divergence magnitude increased in all volunteers (N = 9) between 7 and 78% from expiration to inspiration. Measuring volumetric strain by MRI provides a compression-sensitive parameter of tissue mechanics, which varies with the respiratory state in the lungs. In future clinical applications for diagnosis and characterization of lung emphysema, fibrosis, or cancer, divergence-sensitive MRI may serve as a noninvasive marker sensitive to disease-related alterations of regional elastic recoil pressure in the lungs. Copyright © 2012 Wiley Periodicals, Inc.

Target of obstructive sleep apnea syndrome merge lung cancer: based on big data platform.

PubMed

Li, Lifeng; Lu, Jingli; Xue, Wenhua; Wang, Liping; Zhai, Yunkai; Fan, Zhirui; Wu, Ge; Fan, Feifei; Li, Jieyao; Zhang, Chaoqi; Zhang, Yi; Zhao, Jie

2017-03-28

Based on our hospital database, the incidence of lung cancer diagnoses was similar in obstructive sleep apnea Syndrome (OSAS) and hospital general population; among individual with a diagnosis of lung cancer, the presence of OSAS was associated with an increased risk for mortality. In the gene expression and network-level information, we revealed significant alterations of molecules related to HIF1 and metabolic pathways in the hypoxic-conditioned lung cancer cells. We also observed that GBE1 and HK2 are downstream of HIF1 pathway important in hypoxia-conditioned lung cancer cell. Furthermore, we used publicly available datasets to validate that the late-stage lung adenocarcinoma patients showed higher expression HK2 and GBE1 than early-stage ones. In terms of prognostic features, a survival analysis revealed that the high GBE1 and HK2 expression group exhibited poorer survival in lung adenocarcinoma patients. By analyzing and integrating multiple datasets, we identify molecular convergence between hypoxia and lung cancer that reflects their clinical profiles and reveals molecular pathways involved in hypoxic-induced lung cancer progression. In conclusion, we show that OSAS severity appears to increase the risk of lung cancer mortality.

Evaluation of amniotic mesenchymal cell derivatives on cytokine production in equine alveolar macrophages: an in vitro approach to lung inflammation.

PubMed

Zucca, Enrica; Corsini, Emanuela; Galbiati, Valentina; Lange-Consiglio, Anna; Ferrucci, Francesco

2016-09-20

Data obtained in both animal models and clinical trials suggest that cell-based therapies represent a potential therapeutic strategy for lung repair and remodeling. Recently, new therapeutic approaches based on the use of stem cell derivatives (e.g., conditioned medium (CM) and microvesicles (MVs)) to regenerate tissues and improve their functions were proposed. The aim of this study was to investigate the immunomodulatory effects of equine amniotic mesenchymal cell derivatives on lipopolysaccharide (LPS)-induced cytokine production in equine alveolar macrophages, which may be beneficial in lung inflammatory disorders such as recurrent airway obstruction (RAO) in horses. RAO shares many features with human asthma, including an increased number of cells expressing mRNA for interleukin (IL)-4 and IL-5 and a decreased expression of IFN-γ in bronchoalveolar lavage fluid (BALF) of affected horses. The release of TNF-α, IL-6, and TGF-β1 at different time points (1, 24, 48, and 72 h) was measured in equine alveolar macrophages stimulated or not with LPS (10 and 100 ng/mL) in the presence or absence of 10 % CM or 50 × 10(6) MVs/mL. Cytokines were measured using commercially available ELISA kits. For multiple comparisons, analysis of variance was used with Tukey post-hoc test. Differences were considered significant at p ≤ 0.05. Significant modulatory effects of CM on LPS-induced TNF-α release at 24 h, and of both CM and MVs on TNF-α release at 48 h were observed. A trend toward a modulatory effect of both CM and MVs on the release of TGF-β and possibly IL-6 was visible over time. Results support the potential use of CM and MVs in lung regenerative medicine, especially in situations in which TGF-β may be detrimental, such as respiratory allergy. Further studies should evaluate the potential clinical applications of CM and MVs in equine lung diseases, such as RAO and other inflammatory disorders.

Conditionally reprogrammed cells (CRC) methodology does not allow the in vitro expansion of patient-derived primary and metastatic lung cancer cells.

PubMed

Sette, Giovanni; Salvati, Valentina; Giordani, Ilenia; Pilozzi, Emanuela; Quacquarini, Denise; Duranti, Enrico; De Nicola, Francesca; Pallocca, Matteo; Fanciulli, Maurizio; Falchi, Mario; Pallini, Roberto; De Maria, Ruggero; Eramo, Adriana

2018-07-01

Availability of tumor and non-tumor patient-derived models would promote the development of more effective therapeutics for non-small cell lung cancer (NSCLC). Recently, conditionally reprogrammed cells (CRC) methodology demonstrated exceptional potential for the expansion of epithelial cells from patient tissues. However, the possibility to expand patient-derived lung cancer cells using CRC protocols is controversial. Here, we used CRC approach to expand cells from non-tumoral and tumor biopsies of patients with primary or metastatic NSCLC as well as pulmonary metastases of colorectal or breast cancers. CRC cultures were obtained from both tumor and non-malignant tissues with extraordinary high efficiency. Tumor cells were tracked in vitro through tumorigenicity assay, monitoring of tumor-specific genetic alterations and marker expression. Cultures were composed of EpCAM+ lung epithelial cells lacking tumorigenic potential. NSCLC biopsies-derived cultures rapidly lost patient-specific genetic mutations or tumor antigens. Similarly, pulmonary metastases of colon or breast cancer generated CRC cultures of lung epithelial cells. All CRC cultures examined displayed epithelial lung stem cell phenotype and function. In contrast, brain metastatic lung cancer biopsies failed to generate CRC cultures. In conclusion, patient-derived primary and metastatic lung cancer cells were negatively selected under CRC conditions, limiting the expansion to non-malignant lung epithelial stem cells from either tumor or non-tumor tissue sources. Thus, CRC approach cannot be applied for direct therapeutic testing of patient lung tumor cells, as the tumor-derived CRC cultures are composed of (non-tumoral) airway basal cells. © 2018 UICC.

Is Previous Respiratory Disease a Risk Factor for Lung Cancer?

PubMed Central

Denholm, Rachel; Schüz, Joachim; Straif, Kurt; Stücker, Isabelle; Jöckel, Karl-Heinz; Brenner, Darren R.; De Matteis, Sara; Boffetta, Paolo; Guida, Florence; Brüske, Irene; Wichmann, Heinz-Erich; Landi, Maria Teresa; Caporaso, Neil; Siemiatycki, Jack; Ahrens, Wolfgang; Pohlabeln, Hermann; Zaridze, David; Field, John K.; McLaughlin, John; Demers, Paul; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Dumitru, Rodica Stanescu; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Kendzia, Benjamin; Peters, Susan; Behrens, Thomas; Vermeulen, Roel; Brüning, Thomas; Kromhout, Hans

2014-01-01

Rationale: Previous respiratory diseases have been associated with increased risk of lung cancer. Respiratory conditions often co-occur and few studies have investigated multiple conditions simultaneously. Objectives: Investigate lung cancer risk associated with chronic bronchitis, emphysema, tuberculosis, pneumonia, and asthma. Methods: The SYNERGY project pooled information on previous respiratory diseases from 12,739 case subjects and 14,945 control subjects from 7 case–control studies conducted in Europe and Canada. Multivariate logistic regression models were used to investigate the relationship between individual diseases adjusting for co-occurring conditions, and patterns of respiratory disease diagnoses and lung cancer. Analyses were stratified by sex, and adjusted for age, center, ever-employed in a high-risk occupation, education, smoking status, cigarette pack-years, and time since quitting smoking. Measurements and Main Results: Chronic bronchitis and emphysema were positively associated with lung cancer, after accounting for other respiratory diseases and smoking (e.g., in men: odds ratio [OR], 1.33; 95% confidence interval [CI], 1.20–1.48 and OR, 1.50; 95% CI, 1.21–1.87, respectively). A positive relationship was observed between lung cancer and pneumonia diagnosed 2 years or less before lung cancer (OR, 3.31; 95% CI, 2.33–4.70 for men), but not longer. Co-occurrence of chronic bronchitis and emphysema and/or pneumonia had a stronger positive association with lung cancer than chronic bronchitis “only.” Asthma had an inverse association with lung cancer, the association being stronger with an asthma diagnosis 5 years or more before lung cancer compared with shorter. Conclusions: Findings from this large international case–control consortium indicate that after accounting for co-occurring respiratory diseases, chronic bronchitis and emphysema continue to have a positive association with lung cancer. PMID:25054566

Characterization of the Lung Parenchyma Using Ultrasound Multiple Scattering.

PubMed

Mohanty, Kaustav; Blackwell, John; Egan, Thomas; Muller, Marie

2017-05-01

The purpose of the study described here was to showcase the application of ultrasound to quantitative characterization of the micro-architecture of the lung parenchyma to predict the extent of pulmonary edema. The lung parenchyma is a highly complex and diffusive medium for which ultrasound techniques have remained qualitative. The approach presented here is based on ultrasound multiple scattering and exploits the complexity of ultrasound propagation in the lung structure. The experimental setup consisted of a linear transducer array with an 8-MHz central frequency placed in contact with the lung surface. The diffusion constant D and transport mean free path L* of the lung parenchyma were estimated by separating the incoherent and coherent intensities in the near field and measuring the growth of the incoherent diffusive halo over time. Significant differences were observed between the L* values obtained in healthy and edematous rat lungs in vivo. In the control rat lung, L* was found to be 332 μm (±48.8 μm), whereas in the edematous lung, it was 1040 μm (±90 μm). The reproducibility of the measurements of L* and D was tested in vivo and in phantoms made of melamine sponge with varying air volume fractions. Two-dimensional finite difference time domain numerical simulations were carried out on rabbit lung histology images with varying degrees of lung collapse. Significant correlations were observed between air volume fraction and L* in simulation (r = -0.9542, p < 0.0117) and sponge phantom (r = -0.9932, p < 0.0068) experiments. Ex vivo measurements of a rat lung in which edema was simulated by adding phosphate-buffered saline revealed a linear relationship between the fluid volume fraction and L*. These results illustrate the potential of methods based on ultrasound multiple scattering for the quantitative characterization of the lung parenchyma. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Congenital Lung Agenesis: Incidence and Outcome in the North of England.

PubMed

Thomas, Matthew; Robertson, Nic; Miller, Nicola; Rankin, Judith; McKean, Michael; Brodlie, Malcom

2017-07-03

Unilateral lung agenesis is an uncommon congenital abnormality, with a lack of reported accurate incidence estimates. Prognosis is also uncertain, with older literature reporting poor outcomes. The North of England register of congenital anomalies (Northern Congenital Abnormality Survey) records cases of congenital anomalies to mothers' resident in the region. We used the register to identify all patients with congenital lung agenesis born between 2004 and 2013 to calculate an accurate incidence estimate and report clinical outcomes with contemporary management. Four patients with congenital lung agenesis were born during the study period, giving an estimated incidence in the North of England of 1.22 per 100,000 live births (95% confidence interval, 0.33-3.11). Two patients had associated congenital heart disease requiring corrective surgery, and one had musculoskeletal anomalies. All four patients are alive and well without a regular oxygen requirement. Contrary to previous reports, the medium term outcomes in our patients have been good, even when lung agenesis is associated with other congenital anomalies. Long-term prognosis with modern management remains unknown, and the potential for the development of pulmonary hypertension remains a concern. Birth Defects Research 109:857-859, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Obesity: “Priming” the Lung for Injury

PubMed Central

Konter, Jason; Baez, Elizabeth; Summer, Ross S

2012-01-01

Acute lung injury (ALI) is a severe inflammatory condition that develops in response to local and systemic lung challenges. To date, specific risk factors for development of ALI remain poorly defined. Recent epidemiological studies have reported obesity as an important predisposing factor in the development of this condition. Although the pathogenic mechanisms linking obesity and ALI have not been well-elucidated, emerging scientific evidence has described factors secreted by adipose tissue that have important biological activities in lung and has suggested that altered secretion of these factors during obesity contributes to increased ALI susceptibility. The objective of this manuscript is to highlight recent clinical evidence supporting the association between obesity and ALI and to discuss the posited role for adipose tissue-derived factors in the pathogenesis of this condition. PMID:22449512

Modeling Approach for Oxygen Exchange in the Human Lung under Hypobaric Conditions

DTIC Science & Technology

2001-06-01

Operational Medical Issues in Hypo-and Hyperbaric Conditions [les Questions medicales a caractere oprationel liees aux conditions hypobares ou hyperbares ] To...under Hypobaric Conditions DISTRIBUTION: Approved for public release, distribution unlimited This paper is part of the following report: TITLE...Approach for Oxygen Exchange in the Human Lung under Hypobaric Conditions Ing J.P.F. Lindhout*, Drs M. van de Graaff*, Ir Drs R.C. van de Graaff*, Dr

Investigation of mitomycin-C-treated fibroblasts in 3-D collagen gel and conditioned medium for keratinocyte proliferation.

PubMed

Huang, Yi-Chau; Wang, Tzu-Wei; Sun, Jui-Sheng; Lin, Feng-Huei

2006-03-01

Fibroblasts produce a spectrum of necessary growth factors essential for growth and proliferation of a variety of cell types. In this study, the paracrine effect of mitomycin-C-treated fibroblasts with various densities in collagen gel for keratinocyte proliferation was investigated from which an optimum cell density and optimum conditioned medium would be determined to expand keratinocyte without further differentiation for skin equivalent tissue engineering. The optimum cell density in collagen feeder gel for optimum collected medium preparation will be determined by checking the level of keratinocyte growth factor and granulocyte macrophage colony-stimulating factor in conventional medium. The results showed that the cell density of 1 x 10(5) cells/gel in the feeder gel is better to produce optimum collected medium. The conditioned medium is prepared by mixing together the optimum collected medium and molecular cellular and developmental biology (MCDB) 153 medium in different ratios for keratinocyte growth. The keratinocyte viability will be measured by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to determine the optimum conditioned medium. From the study, 67% conditioned medium was supposed as the better medium for keratinocyte proliferation. In this experiment, the optimum cell density in feeder gel to coculture with keratinocytes is also determined as 1 x 10(5) cells/gel. Keratin 10 (K10) and Terminal Deoxynucleotidyl Transferase Mediated dUTP Nick End Labeling stain will be used to check the cell differentiation and apoptosis, respectively. The results suggest that keratinocytes should not be cultured in postconfluent conditions due to undesired apoptosis and differentiation. The result of cell viability from passages to passages shows that the optimum feeder gel plays a more important role to the keratinocyte proliferation than that of optimum conditioned medium. Keratinocytes cultured with optimum feeder gel in 67% conditioned medium could effectively promote proliferation, inhibit apoptosis, and prevent differentiation. The combination of conditioned media and feeder gel to culture keratinocytes without external supplements can provide an inexpensive way for keratinocyte proliferation and construct an environment for real-time communication between the two cells. The results conclude that keratinocyte cultivation in feeder gel with modified medium should be feasible in the production of high quality keratinocytes for skin equivalents preparation.

Squamous cell lung cancer in a male with pulmonary tuberculosis.

PubMed

Skowroński, Marcin; Iwanik, Katarzyna; Halicka, Anna; Barinow-Wojewódzki, Aleksander

2015-01-01

Lung cancer and pulmonary tuberculosis (TB) are highly prevalent and representing major public health issues. They share common risk factors and clinical manifestations. It is also suggested that TB predicts raised lung cancer risk likely related to chronic inflammation in the lungs. However, it does not seem to influence the clinical course of lung cancer provided that it is properly treated. We present a case report of a 57-year old male with concurrent TB and lung cancer. He was diagnosed with positive sputum smear for acid fast bacilli (AFB) and subsequent culture of Mycobacterium tuberculosis. Besides, his comorbid conditions were chronic hepatitis C virus (HCV) infection and peripheral artery disease (PAD). Later while on anti-tuberculous treatment (ATT) squamous cell lung cancer (SCC) was confirmed with computed tomography (CT) guided biopsy. Due to poor general condition the patient was not fit for either surgery or radical chemo- and radiotherapy. He was transferred to hospice for palliative therapy. We want to emphasize that both TB and lung cancer should be actively sought for in patients with either disorder. In addition, there is no doubt that these patients with lung cancer and with good response to TB treatment should be promptly considered for appropriate anticancer therapy.

What is the role of amnioinfusion in modern day obstetrics?

PubMed

Dad, Nimra; Abushama, Mandy; Konje, Justin C; Ahmed, Badreldeen

2016-09-01

Amniotic fluid (AF) is a dynamic medium that plays a significant role in fetal well-being. It is production and amount varies with gestational age. It plays a vital role in fetal life as it contains antimicrobial factors, growth factors and it help the fetal lung to grow and expand. Amnioinfusion can be performed either transabdominally or transvaginal. Amnioinfuion can be done antenatally and during labor. Aminoinfusion can be used for diagnostic purposes to enable better visualization of the fetus as liquor is very important acoustic widow for better fetal examination. Amnioinfusion have some therapeutic benefits in conditions like early premature rupture of membrane and may help cases of external cephalic version for breech presentation at term. Amnioinfusion has been shown to reduce the incidence of variable deceleration due to cord compression, reduces the risk of meconium aspiration and it will help reduce cesarean delivery.

Bilateral cervical lung hernia with T1 nerve compression.

PubMed

Rahman, Mesbah; Buchan, Keith G; Mandana, Kyapanda M; Butchart, Eric G

2006-02-01

Lung hernia is a rare condition. Approximately one third of cases occur in the cervical position. We report a case of bilateral cervical lung hernia associated with neuralgic pain that was repaired using bovine pericardium and biological glue.

Video-assisted repair of cervical lung hernia.

PubMed

Zhang, P; Jiang, G; Xie, B; Ding, J

2010-04-01

Lung hernia is an extremely rare condition and the treatments vary. We report a case of cervical lung hernia without any trauma. The patient underwent video-assisted repair with a satisfactory result. Georg Thieme Verlag KG Stuttgart New York.

Prospect of stem cell conditioned medium in regenerative medicine.

PubMed

Pawitan, Jeanne Adiwinata

2014-01-01

Stem cell-derived conditioned medium has a promising prospect to be produced as pharmaceuticals for regenerative medicine. To investigate various methods to obtain stem cell-derived conditioned medium (CM) to get an insight into their prospect of application in various diseases. Systematic review using keywords "stem cell" and "conditioned medium" or "secretome" and "therapy." Data concerning treated conditions/diseases, type of cell that was cultured, medium and supplements to culture the cells, culture condition, CM processing, growth factors and other secretions that were analyzed, method of application, and outcome were noted, grouped, tabulated, and analyzed. Most of CM using studies showed good results. However, the various CM, even when they were derived from the same kind of cells, were produced by different condition, that is, from different passage, culture medium, and culture condition. The growth factor yields of the various types of cells were available in some studies, and the cell number that was needed to produce CM for one application could be computed. Various stem cell-derived conditioned media were tested on various diseases and mostly showed good results. However, standardized methods of production and validations of their use need to be conducted.

Trauma of lung due to impact load.

PubMed

Yen, R T; Fung, Y C; Liu, S Q

1988-01-01

A quantitative evaluation of lung injury due to impact loading is of general interest. Hemorrhage and edema are the usual sequelae to traumatic pulmonary impact. To gain some quantitative understanding of the phenomena, we perfused excised rabbit lung with Macrodex at isogravimetric condition and monitored lung weight continuously after impact. It is shown that a factor of importance is the rigidity of the surface on which the lung rests. The rate of lung weight increase is smaller if the lung was 'freely' supported on a soft cloth, more if it was supported on a rigid plate. This suggests the influence of stress wave reflection. The critical condition correlates with the initial velocity of impact at the surface of the lung, or with the maximum deflection. For a freely supported lung, the rate of lung weight increase was 22% of the initial total lung weight per h after impact when the impact velocity was 11.5 ms-1, 30% when the velocity was 13.2 ms-1, several 100% at 13.5 ms-1, signaling massive lung injury. Since the velocity of sound in rabbit lung is 33.3 ms-1 when the inflation (transpulmonary) pressure is 10 cm H2O, the critical velocity of 13.5 ms-1 corresponds to a Mach number of 0.4. The maximum surface displacement of the lung is almost linearly proportional to the initial velocity of impact. The exact cause of edema and hemorrhage is unknown; we hypothesize that it is due to tensile stress in the alveolar wall caused by the impact.

Dosimetric feasibility of 4DCT-ventilation imaging guided proton therapy for locally advanced non-small-cell lung cancer.

PubMed

Huang, Qijie; Jabbour, Salma K; Xiao, Zhiyan; Yue, Ning; Wang, Xiao; Cao, Hongbin; Kuang, Yu; Zhang, Yin; Nie, Ke

2018-04-25

The principle aim of this study is to incorporate 4DCT ventilation imaging into functional treatment planning that preserves high-functioning lung with both double scattering and scanning beam techniques in proton therapy. Eight patients with locally advanced non-small-cell lung cancer were included in this study. Deformable image registration was performed for each patient on their planning 4DCTs and the resultant displacement vector field with Jacobian analysis was used to identify the high-, medium- and low-functional lung regions. Five plans were designed for each patient: a regular photon IMRT vs. anatomic proton plans without consideration of functional ventilation information using double scattering proton therapy (DSPT) and intensity modulated proton therapy (IMPT) vs. functional proton plans with avoidance of high-functional lung using both DSPT and IMPT. Dosimetric parameters were compared in terms of tumor coverage, plan heterogeneity, and avoidance of normal tissues. Our results showed that both DSPT and IMPT plans gave superior dose advantage to photon IMRTs in sparing low dose regions of the total lung in terms of V5 (volume receiving 5Gy). The functional DSPT only showed marginal benefit in sparing high-functioning lung in terms of V5 or V20 (volume receiving 20Gy) compared to anatomical plans. Yet, the functional planning in IMPT delivery, can further reduce the low dose in high-functioning lung without degrading the PTV dosimetric coverages, compared to anatomical proton planning. Although the doses to some critical organs might increase during functional planning, the necessary constraints were all met. Incorporating 4DCT ventilation imaging into functional proton therapy is feasible. The functional proton plans, in intensity modulated proton delivery, are effective to further preserve high-functioning lung regions without degrading the PTV coverage.

Scenarios of future lung cancer incidence by educational level: Modelling study in Denmark.

PubMed

Menvielle, Gwenn; Soerjomataram, Isabelle; de Vries, Esther; Engholm, Gerda; Barendregt, Jan J; Coebergh, Jan Willem; Kunst, Anton E

2010-09-01

To model future trends in lung cancer incidence in Denmark by education under different scenarios for cigarette smoking. Lung cancer incidence until 2050 was modelled using Prevent software. We estimated lung cancer incidence under a baseline scenario and under four alternative scenarios for smoking reduction: decreasing initiation rates among the young, increasing cessation rates among smokers, a scenario combining both changes and a levelling-up scenario in which people with low and medium levels of education acquired the smoking prevalence of the highly educated. Danish National Health Interview Surveys (1987-2005) and cancer registry data combined with individual education status from Statistics Denmark were used for empirical input. Under the baseline scenario, lung cancer rates are expected to decrease for most educational groups during the next few decades, but educational inequalities will increase further. Under the alternative scenarios, an additional decrease in lung cancer rates will be observed from 2030 onwards, but only from 2050 onwards it will be observed under the initiation scenario. The cessation and the combined scenarios show the largest decrease in lung cancer rates for all educational groups. However, in none of these scenarios would the relative differences between educational groups be reduced. A modest decrease in these inequalities will be observed under the levelling-up scenario. Our analyses show that relative inequalities in lung cancer incidence rates will tend to increase. They may be reduced to a small extent if the smoking prevalence of people with a low level of education was to converge towards those more highly educated people. An important decrease in lung cancer rates will be observed in all educational groups, however, especially when focusing on both initiation and cessation strategies. Copyright © 2010 Elsevier Ltd. All rights reserved.

Regulation of Proinflammatory Cytokines in Human Lung Epithelial Cells Infected with Mycoplasma pneumoniae

PubMed Central

Yang, Jun; Hooper, W. Craig; Phillips, Donald J.; Talkington, Deborah F.

2002-01-01

Mycoplasma pneumoniae is a small bacterium without a cell wall that causes tracheobronchitis and atypical pneumonia in humans. It has also been associated with chronic conditions, such as arthritis, and extrapulmonary complications, such as encephalitis. Although the interaction of mycoplasmas with respiratory epithelial cells is a critical early phase of pathogenesis, little is known about the cascade of events initiated by infection of respiratory epithelial cells by mycoplasmas. Previous studies have shown that M. pneumoniae can induce proinflammatory cytokines in several different study systems including cultured murine and human monocytes. In this study, we demonstrate that M. pneumoniae infection also induces proinflammatory cytokine expression in A549 human lung carcinoma cells. Infection of A549 cells resulted in increased levels of interleukin-8 (IL-8) and tumor necrosis factor alpha mRNA, and both proteins were secreted into culture medium. IL-1β mRNA also increased after infection and IL-1β protein was synthesized, but it remained intracellular. In contrast, levels of IL-6 and gamma interferon mRNA and protein remained unchanged or undetectable. Using protease digestion and antibody blocking methods, we found that M. pneumoniae cytadherence is important for the induction of cytokines. On the other hand, while M. pneumoniae protein synthesis and DNA synthesis do not appear to be prerequisites for the induction of cytokine gene expression, A549 cellular de novo protein synthesis is responsible for the increased cytokine protein levels. These results suggest a novel role for lung epithelial cells in the pathogenesis of M. pneumoniae infection and provide a better understanding of M. pneumoniae pathology at the cellular level. PMID:12065506

Airway Delivery of Soluble Factors from Plastic-Adherent Bone Marrow Cells Prevents Murine Asthma

PubMed Central

Ionescu, Lavinia I.; Alphonse, Rajesh S.; Arizmendi, Narcy; Morgan, Beverly; Abel, Melanie; Eaton, Farah; Duszyk, Marek; Vliagoftis, Harissios; Aprahamian, Tamar R.; Walsh, Kenneth

2012-01-01

Asthma affects an estimated 300 million people worldwide and accounts for 1 of 250 deaths and 15 million disability-adjusted life years lost annually. Plastic-adherent bone marrow–derived cell (BMC) administration holds therapeutic promise in regenerative medicine. However, given the low cell engraftment in target organs, including the lung, cell replacement cannot solely account for the reported therapeutic benefits. This suggests that BMCs may act by secreting soluble factors. BMCs also possess antiinflammatory and immunomodulatory properties and may therefore be beneficial for asthma. Our objective was to investigate the therapeutic potential of BMC-secreted factors in murine asthma. In a model of acute and chronic asthma, intranasal instillation of BMC conditioned medium (CdM) prevented airway hyperresponsiveness (AHR) and inflammation. In the chronic asthma model, CdM prevented airway smooth muscle thickening and peribronchial inflammation while restoring blunted salbutamol-induced bronchodilation. CdM reduced lung levels of the TH2 inflammatory cytokines IL-4 and IL-13 and increased levels of IL-10. CdM up-regulated an IL-10–induced and IL-10–secreting subset of T regulatory lymphocytes and promoted IL-10 expression by lung macrophages. Adiponectin (APN), an antiinflammatory adipokine found in CdM, prevented AHR, airway smooth muscle thickening, and peribronchial inflammation, whereas the effect of CdM in which APN was neutralized or from APN knock-out mice was attenuated compared with wild-type CdM. Our study provides evidence that BMC-derived soluble factors prevent murine asthma and suggests APN as one of the protective factors. Further identification of BMC-derived factors may hold promise for novel approaches in the treatment of asthma. PMID:21903873

Airway delivery of soluble factors from plastic-adherent bone marrow cells prevents murine asthma.

PubMed

Ionescu, Lavinia I; Alphonse, Rajesh S; Arizmendi, Narcy; Morgan, Beverly; Abel, Melanie; Eaton, Farah; Duszyk, Marek; Vliagoftis, Harissios; Aprahamian, Tamar R; Walsh, Kenneth; Thébaud, Bernard

2012-02-01

Asthma affects an estimated 300 million people worldwide and accounts for 1 of 250 deaths and 15 million disability-adjusted life years lost annually. Plastic-adherent bone marrow-derived cell (BMC) administration holds therapeutic promise in regenerative medicine. However, given the low cell engraftment in target organs, including the lung, cell replacement cannot solely account for the reported therapeutic benefits. This suggests that BMCs may act by secreting soluble factors. BMCs also possess antiinflammatory and immunomodulatory properties and may therefore be beneficial for asthma. Our objective was to investigate the therapeutic potential of BMC-secreted factors in murine asthma. In a model of acute and chronic asthma, intranasal instillation of BMC conditioned medium (CdM) prevented airway hyperresponsiveness (AHR) and inflammation. In the chronic asthma model, CdM prevented airway smooth muscle thickening and peribronchial inflammation while restoring blunted salbutamol-induced bronchodilation. CdM reduced lung levels of the T(H)2 inflammatory cytokines IL-4 and IL-13 and increased levels of IL-10. CdM up-regulated an IL-10-induced and IL-10-secreting subset of T regulatory lymphocytes and promoted IL-10 expression by lung macrophages. Adiponectin (APN), an antiinflammatory adipokine found in CdM, prevented AHR, airway smooth muscle thickening, and peribronchial inflammation, whereas the effect of CdM in which APN was neutralized or from APN knock-out mice was attenuated compared with wild-type CdM. Our study provides evidence that BMC-derived soluble factors prevent murine asthma and suggests APN as one of the protective factors. Further identification of BMC-derived factors may hold promise for novel approaches in the treatment of asthma.

Controlled lung reperfusion to reduce pulmonary ischaemia/reperfusion injury after cardiopulmonary bypass in a porcine model.

PubMed

Slottosch, Ingo; Liakopoulos, Oliver; Kuhn, Elmar; Deppe, Antje; Lopez-Pastorini, Alberto; Schwarz, David; Neef, Klaus; Choi, Yeong-Hoon; Sterner-Kock, Anja; Jung, Kristina; Mühlfeld, Christian; Wahlers, Thorsten

2014-12-01

Ischaemia/reperfusion (I/R) injury of the lungs contributes to pulmonary dysfunction after cardiac surgery with cardiopulmonary bypass (CPB), leading to increased morbidity and mortality of patients. This study investigated the value of controlled lung reperfusion strategies on lung ischaemia-reperfusion injury in a porcine CPB model. Pigs were subjected to routine CPB for 120 min with 60 min of blood cardioplegic cardiac arrest (CCA). Following CCA, the uncontrolled reperfusion (UR, n = 6) group was conventionally weaned from CPB. Two groups underwent controlled lung reperfusion strategies (CR group: controlled reperfusion conditions, n = 6; MR group: controlled reperfusion conditions and modified reperfusate, n = 6) via the pulmonary artery before CPB weaning. Sham-operated pigs (n = 7) served as controls. Animals were followed up until 4 h after CPB. Pulmonary function, haemodynamics, markers of inflammation, endothelial injury and oxidative stress as well as morphological lung alterations were analysed. CPB (UR group) induced deterioration of pulmonary function (lung mechanics, oxygenation index and lung oedema). Also, controlled lung reperfusion groups (CR and MR) presented with pulmonary dysfunction after CPB. However, compared with UR, controlled lung reperfusion strategies (CR and MR) improved lung mechanics and reduced markers of oxidative stress, but without alteration of haemodynamics, oxygenation, inflammation, endothelial injury and lung morphology. Both controlled reperfusion groups were similar without relevant differences. Controlled lung reperfusion strategies attenuated a decrease in lung mechanics and an increase in oxidative stress, indicating an influence on CPB-related pulmonary injury. However, they failed to avoid completely CPB-related lung injury, implying the need for additional strategies given the multifactorial pathophysiology of postoperative pulmonary dysfunction. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Predicting Long-Term Outcomes in Pleural Infections. RAPID Score for Risk Stratification.

PubMed

White, Heath D; Henry, Christopher; Stock, Eileen M; Arroliga, Alejandro C; Ghamande, Shekhar

2015-09-01

Pleural infections are associated with significant morbidity and mortality. The recently developed RAPID (renal, age, purulence, infection source, and dietary factors) score consists of five clinical factors that can identify patients at risk for increased mortality. The objective of this study was to further validate the RAPID score in a diverse cohort, identify factors associated with mortality, and provide long-term outcomes. We evaluated a single-center retrospective cohort of 187 patients with culture-positive pleural infections. Patients were classified by RAPID scores into low-risk (0-2), medium-risk (3-4), and high-risk (5-7) groups. The Social Security Death Index was used to determine date of death. All-cause mortality was assessed at 3 months, 1 year, 3 years, and 5 years. Clinical factors and comorbid conditions were evaluated for association. Three-month mortality for low-, medium-, and high-risk groups was 1.5, 17.8, and 47.8%, respectively. Increased odds were observed among medium-risk (odds ratio, 14.3; 95% confidence interval, 1.8-112.6; P = 0.01) and high-risk groups (odds ratio, 53.3; 95% confidence interval, 6.8-416.8; P < 0.01). This trend continued at 1, 3, and 5 years. Factors associated with high-risk scores include gram-negative rod infections, heart disease, diabetes, cancer, lung disease, and increased length of stay. When applied to a diverse patient cohort, the RAPID score predicts outcomes in patients up to 5 years and may aid in long-term risk stratification on presentation.

Pseudo tumors of the lung after lung volume reduction surgery.

PubMed

Oey, Inger F; Jeyapalan, Kanagaratnam; Entwisle, James J; Waller, David A

2004-03-01

We describe 2 patients who underwent lung volume reduction surgery, who postoperatively had computed tomographic scans that showed symptomatic mass lesions suggestive of malignancy and an inhaled foreign body. Investigations excluded these conditions with the remaining likely diagnosis of pseudotumor secondary to buttressing material. These potential sequelae of lung volume reduction surgery should be recognized in follow-up investigations.

Severe acute interstitial lung disease in a patient with anaplastic lymphoma kinase rearrangement-positive non-small cell lung cancer treated with alectinib.

PubMed

Yamamoto, Yuzo; Okamoto, Isamu; Otsubo, Kohei; Iwama, Eiji; Hamada, Naoki; Harada, Taishi; Takayama, Koichi; Nakanishi, Yoichi

2015-10-01

Alectinib, the second generation anaplastic lymphoma kinase (ALK) inhibitor, has significant potency in patients with ALK rearrangement positive non-small cell lung cancer (NSCLC), and its toxicity is generally well tolerable. We report a patient who developed severe acute interstitial lung disease after alectinib treatment. An 86-year-old woman with stage IV lung adenocarcinoma positive for rearrangement of ALK gene was treated with alectinib. On the 215th day after initiation of alectinib administration, she was admitted to our hospital with the symptom of progressive dyspnea. Computed tomography (CT) revealed diffuse ground glass opacities and consolidations in both lungs, and analysis of bronchoalveolar lavage fluid revealed pronounced lymphocytosis. There was no evidence of infection or other specific causes of her condition, and she was therefore diagnosed with interstitial lung disease induced by alectinib. Her CT findings and respiratory condition improved after steroid pulse therapy. As far as we are aware, this is the first reported case of alectinib-induced severe interstitial lung disease (ILD). We should be aware of the possibility of such a severe adverse event and should therefore carefully monitor patients treated with this drug.

Comparison of exact, efron and breslow parameter approach method on hazard ratio and stratified cox regression model

NASA Astrophysics Data System (ADS)

Fatekurohman, Mohamat; Nurmala, Nita; Anggraeni, Dian

2018-04-01

Lungs are the most important organ, in the case of respiratory system. Problems related to disorder of the lungs are various, i.e. pneumonia, emphysema, tuberculosis and lung cancer. Comparing all those problems, lung cancer is the most harmful. Considering about that, the aim of this research applies survival analysis and factors affecting the endurance of the lung cancer patient using comparison of exact, Efron and Breslow parameter approach method on hazard ratio and stratified cox regression model. The data applied are based on the medical records of lung cancer patients in Jember Paru-paru hospital on 2016, east java, Indonesia. The factors affecting the endurance of the lung cancer patients can be classified into several criteria, i.e. sex, age, hemoglobin, leukocytes, erythrocytes, sedimentation rate of blood, therapy status, general condition, body weight. The result shows that exact method of stratified cox regression model is better than other. On the other hand, the endurance of the patients is affected by their age and the general conditions.

Developmental expression of the receptor for advanced glycation end-products (RAGE) and its response to hyperoxia in the neonatal rat lung

PubMed Central

Lizotte, Pierre-Paul; Hanford, Lana E; Enghild, Jan J; Nozik-Grayck, Eva; Giles, Brenda-Louise; Oury, Tim D

2007-01-01

Background The receptor for advanced glycation end products (mRAGE) is associated with pathology in most tissues, while its soluble form (sRAGE) acts as a decoy receptor. The adult lung is unique in that it expresses high amounts of RAGE under normal conditions while other tissues express low amounts normally and up-regulate RAGE during pathologic processes. We sought to determine the regulation of the soluble and membrane isoforms of RAGE in the developing lung, and its expression under hyperoxic conditions in the neonatal lung. Results Fetal (E19), term, 4 day, 8 day and adult rat lung protein and mRNA were analyzed, as well as lungs from neonatal (0–24 hrs) 2 day and 8 day hyperoxic (95% O2) exposed animals. mRAGE transcripts in the adult rat lung were 23% greater than in neonatal (0–24 hrs) lungs. On the protein level, rat adult mRAGE expression was 2.2-fold higher relative to neonatal mRAGE expression, and adult sRAGE protein expression was 2-fold higher compared to neonatal sRAGE. Fetal, term, 4 day and 8 day old rats had a steady increase in both membrane and sRAGE protein expression evaluated by Western Blot and immunohistochemistry. Newborn rats exposed to chronic hyperoxia showed significantly decreased total RAGE expression compared to room air controls. Conclusion Taken together, these data show that rat pulmonary RAGE expression increases with age beginning from birth, and interestingly, this increase is counteracted under hyperoxic conditions. These results support the emerging concept that RAGE plays a novel and homeostatic role in lung physiology. PMID:17343756

78 FR 77137 - Agency Information Collection Activities: Proposed Collection: Public Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-20

.... Other measures will account for secondary conditions common to miners (e.g., cardiovascular disease) and... associated with occupationally-related coal mine dust lung disease. Primary services provided for active... reducing the morbidity of coal mine dust lung disease (CMDLD) and secondary conditions; enhancing access to...

Computational Fluid Dynamics and Experimental Characterization of the Pediatric Pump-Lung.

PubMed

Wu, Zhongjun J; Gellman, Barry; Zhang, Tao; Taskin, M Ertan; Dasse, Kurt A; Griffith, Bartley P

2011-12-01

The pediatric pump-lung (PediPL) is a miniaturized integrated pediatric pump-oxygenator specifically designed for cardiac or cardiopulmonary support for patients weighing 5-20 kg to allow mobility and extended use for 30 days. The PediPL incorporates a magnetically levitated impeller with uniquely configured hollow fiber membranes into a single unit capable of performing both pumping and gas exchange. A combined computational and experimental study was conducted to characterize the functional and hemocompatibility performances of this newly developed device. The three-dimensional flow features of the PediPL and its hemolytic characteristics were analyzed using computational fluid dynamics based modeling. The oxygen exchange was modeled based on a convection-diffusion-reaction process. The hollow fiber membranes were modeled as a porous medium which incorporates the flow resistance in the bundle by an added momentum sink term. The pumping function was evaluated for the required range of operating conditions (0.5-2.5 L/min and 1000-3000 rpm). The blood damage potentials were further analyzed in terms of flow and shear stress fields, and the calculations of hemolysis index. In parallel, the hydraulic pump performance, oxygen transfer and hemolysis level were quantified experimentally. Based on the computational and experimental results, the PediPL device is found to be functional to provide necessary oxygen transfer and blood pumping requirements for the pediatric patients. Smooth blood flow characteristics and low blood damage potential were observed in the entire device. The in-vitro tests further confirmed that the PediPL can provide adequate blood pumping and oxygen transfer over the range of intended operating conditions with acceptable hemolytic performance. The rated flow rate for oxygenation is 2.5 L/min. The normalized index of hemolysis is 0.065 g/100L at 1.0 L/min and 3000 rpm.

Live Imaging of the Lung

PubMed Central

Looney, Mark R.; Bhattacharya, Jahar

2015-01-01

Live lung imaging has spanned the discovery of capillaries in the frog lung by Malpighi to the current use of single and multiphoton imaging of intravital and isolated perfused lung preparations incorporating fluorescent molecular probes and transgenic reporter mice. Along the way, much has been learned about the unique microcirculation of the lung, including immune cell migration and the mechanisms by which cells at the alveolar-capillary interface communicate with each other. In this review, we highlight live lung imaging techniques as applied to the role of mitochondria in lung immunity, mechanisms of signal transduction in lung compartments, studies on the composition of alveolar wall liquid, and neutrophil and platelet trafficking in the lung under homeostatic and inflammatory conditions. New applications of live lung imaging and the limitations of current techniques are discussed. PMID:24245941

Mesenchymal Stem Cells From Bone Marrow, Adipose Tissue, and Lung Tissue Differentially Mitigate Lung and Distal Organ Damage in Experimental Acute Respiratory Distress Syndrome.

PubMed

Silva, Johnatas D; Lopes-Pacheco, Miquéias; Paz, Ana H R; Cruz, Fernanda F; Melo, Elga B; de Oliveira, Milena V; Xisto, Débora G; Capelozzi, Vera L; Morales, Marcelo M; Pelosi, Paolo; Cirne-Lima, Elizabeth; Rocco, Patricia R M

2018-02-01

Mesenchymal stem cells-based therapies have shown promising effects in experimental acute respiratory distress syndrome. Different mesenchymal stem cells sources may result in diverse effects in respiratory diseases; however, there is no information regarding the best source of mesenchymal stem cells to treat pulmonary acute respiratory distress syndrome. We tested the hypothesis that mesenchymal stem cells derived from bone marrow, adipose tissue, and lung tissue would lead to different beneficial effects on lung and distal organ damage in experimental pulmonary acute respiratory distress syndrome. Animal study and primary cell culture. Laboratory investigation. Seventy-five Wistar rats. Wistar rats received saline (control) or Escherichia coli lipopolysaccharide (acute respiratory distress syndrome) intratracheally. On day 2, acute respiratory distress syndrome animals were further randomized to receive saline or bone marrow, adipose tissue, or lung tissue mesenchymal stem cells (1 × 10 cells) IV. Lung mechanics, histology, and protein levels of inflammatory mediators and growth factors were analyzed 5 days after mesenchymal stem cells administration. RAW 264.7 cells (a macrophage cell line) were incubated with lipopolysaccharide followed by coculture or not with bone marrow, adipose tissue, and lung tissue mesenchymal stem cells (10 cells/mL medium). Regardless of mesenchymal stem cells source, cells administration improved lung function and reduced alveolar collapse, tissue cellularity, collagen, and elastic fiber content in lung tissue, as well as decreased apoptotic cell counts in liver. Bone marrow and adipose tissue mesenchymal stem cells administration also reduced levels of tumor necrosis factor-α, interleukin-1β, keratinocyte-derived chemokine, transforming growth factor-β, and vascular endothelial growth factor, as well as apoptotic cell counts in lung and kidney, while increasing expression of keratinocyte growth factor in lung tissue. Additionally, mesenchymal stem cells differently modulated the secretion of biomarkers by macrophages depending on their source. Mesenchymal stem cells from different sources led to variable responses in lungs and distal organs. Bone marrow and adipose tissue mesenchymal stem cells yielded greater beneficial effects than lung tissue mesenchymal stem cells. These findings may be regarded as promising in clinical trials.

Lung cancer and air pollution.

PubMed

Aoki, K; Shimizu, H

1977-12-01

The relationship between incidence of lung cancer and the volume of traffic as indicated by auto exhaust concentration was examined; the results, though suggestive, did not yield consistent evidence of the association between them. Traffic jams in Nagoya began 15 years ago, a period that may not be long enough to provide definitive data on the incidence of lung cancer. The high standardized mortality ratio (SMR) of lung cancer was observed in cities with a population of less than 1 million and guns (rural areas) along the coast, although those in the metropolitan areas with populations of more than 1 million were average. The SMR did not correlate with various socioeconomic conditions and industrial air pollution. Meteorologic or geologic conditions and ocean currents were not associated with SMR of lung cancer by city and gun. The population of a gun or of some cities was not large enough to be statistically significant, and the mortality rate of lung cancer was not always stable.

Non-Small Cell Carcinoma of the Lung With Osteoclast-Like Giant Cells.

PubMed

Dahm, Hans Helmut

2017-05-01

Carcinomas of the lung with benign osteoclast-like giant cells are rare. A literature search showed only 8 previously reported examples. These tumors resemble a giant cell tumor of bone. Many of these tumors, which occur in most epithelium-containing organs, are composed of an undifferentiated, sarcomatoid component that contains benign osteoclast-like giant cells and a conventional carcinoma. In some tumors the epithelial origin may be revealed by immunohistochemistry only; others lack any evidence of an epithelial component. A 59-year-old man had an inoperable tumor in the upper lobe of the left lung. The tumor did not respond to radiation therapy, and chemotherapy resulted in minimal relief of symptoms. Light microscopy of biopsy samples showed benign osteoclast-like giant cells distributed irregularly between proliferations of undifferentiated medium-sized tumor cells. Approximately one third of the undifferentiated tumor cells were cytokeratin AE1/AE3-positive, and a minor alveolar clear cell component of the tumor was cytokeratin 7-positive. The osteoclast-like giant cells were strongly CD68-positive. The clinical and histologic findings supported the diagnosis of a non-small cell carcinoma of the lung with benign osteoclast-like giant cells. The differential diagnosis is composed of giant cell carcinoma, carcinosarcoma, and mesenchymal tumors of the lung.

Uptake of all-trans retinoic acid–containing aerosol by inhalation to lungs in a guinea pig model system—A pilot study

PubMed Central

Schäffer, Michael W.; Roy, Somdutta Sinha; Mukherjee, Shyamali; Ong, David E.; Das, Salil K.

2010-01-01

Systemic therapies with retinoic acid (RA) can result in toxic side effects without yielding biologically effective levels in target tissues such as lung. The authors adapted a PARI LC Star nebulizer to create a tubular system for short-term inhalation treatment of guinea pigs using a water-miscible formulation of all-trans RA (ATRA) or vehicle. Based on the initial average weight, animals received an estimated average ATRA doses of either 0.32 mg·kg−1 (low dose, 1.4 mM), or 0.62 mg·kg−1 (medium dose, 2.8 mM), or 1.26 mg·kg−1 (high dose, 5.6 mM) 20 minutes per day for 6 consecutive days. This system led to a rise of ATRA levels in lung, but not liver or plasma. Cellular lung levels of retinol, retinyl palmitate, and retinyl stearate also appeared to be unaffected (245.6 ± 10.7, 47.4 ± 3.4, and 132.8 ± 7.7 ng·g−1 wet weight, respectively). The application of this aerosolized ATRA also induced a dose-dependent protein expression of the cellular retinol-binding protein 1 (CRBP-1) in lung, without apparent harmful side effects. PMID:21043991

Editorial: The role of medical physics in lung SBRT.

PubMed

Mancosu, Pietro; Nisbet, Andrew; Jornet, Núria

2018-01-01

Stereotactic body radiation therapy (SBRT) has become a standard treatment for non-operable patients with early stage non-small cell lung cancer (NSCLC). In this context, medical physics community has largely helped in the starting and the growth of this technique. In fact, SBRT requires the convergence of many different features for delivering large doses in few fractions to small moving target in an heterogeneous medium. The special issue of last month, was focused on the different physics challenges in lung SBRT. Eleven reviews were presented, covering: imaging for treatment planning and for treatment assessment; dosimetry and planning optimization; treatment delivery possibilities; image guidance during delivery; radiobiology. The current cutting edge role of medical physics was reported. We aimed to give a complete overview of different aspects of lung SBRT that would be of interest to both physicists implementing this technique in their institutions and more experienced physicists that would be inspired to start research projects in areas that still need further developments. We also feel that the role that medical physicists have played in the development and safe implementation of SBRT, particularly in lung region, can be taken as an excellent example to be translated to other areas, not only in Radiation Oncology but also in other health sectors. Copyright © 2018 Associazione Italiana di Fisica Medica. All rights reserved.

STUDIES ON THE NASOPHARYNGEAL SECRETIONS FROM PATIENTS WITH COMMON COLDS.

PubMed

Olitsky, P K; McCartney, J E

1923-09-30

From the foregoing experiments it appears that with the filtered nasopharyngeal secretions from early cases of typical infections common colds in the first 3 to 18 hours of the disease, a similar condition can be transmitted to man. With the unheated but not with the heated secretions from four of six such patients we have succeeded in transmitting an affection indistinguishable from common cold to four men and in two instances the condition was conveyed from the person with the experimental disease to a second individual -in all, therefore, to six supposedly normal subjects. The periods of incubation in the experimental disease varied from 8 to 48 hours. We failed to obtain these results with the filtered secretions from cases of common colds 18 and 20 hours after the onset of symptoms and from a patient with the experimental disease 20 hours after the first symptoms. It would appear that the secretions are more active in the early hours of the affection. We also failed in the two instances in which colds were caused by exposure to the elements, or chilling of the body, and not by definite contact with other cases of common colds. Intratracheal inoculations in rabbits with unfiltered and filtered nasopharyngeal washings obtained from patients with common colds induce no characteristic or distinctive effects on the tissues, from which no constant, pathogenic agent has, as yet, been recovered. In comparison, similar material from cases of epidemic influenza do, however, cause particular changes in the blood and lungs of these animals, cultures of the lungs often yielding Bacterium pneumosintes. In view of these facts and since the clinical pictures exhibited by these diseases differ, the conclusion may be drawn that infectious common colds and epidemic influenza are separate and distinct diseases. On the other hand, the negative results obtained with materials derived from common colds and from parallel series of experiments with secretions from supposedly healthy persons, serve as a control to the effects produced with the nasopharyngeal washings obtained from influenza patients. Aerobic and anaerobic cultures of the filtered nasopharyngeal washings from 40 early cases of infectious common colds have thus far yielded no constant, pathogenic agent which can be regarded as the incitant of the disease. The filtered washings of nineteen cases were studied by the combined method of Smith-Noguchi fluid medium and anaerobic blood agar plates. In these instances representatives of the three groups of anaerobic filter-passing, Gram-negative bacteria, described by Olitsky and Gates were cultured from twelve patients. The irregularity of their occurrence not only in common colds but in influenza and supposedly normal persons and their lack of pathogenicity for rabbits and man indicate that these bacteria are not peculiar to common colds. This method has opened to view a number of hitherto undescribed microorganisms which can be found in different respiratory affections and in health. Furthermore, by morphological, cultural, and serological means, the separation into distinct species of each of these groups of bacteria has again been demonstrated. It is noteworthy that Bacterium pneumosintes was not found in any of the cultures from the 40 patients. Special attention was given to the detection of elements similar to Foster's globoid bodies in the cultures derived from common colds and from the experimental disease in man, and from the lungs of inoculated rabbits. We have not been able to determine the presence of these bodies, although the precipitate which forms in fresh rabbit kidney tissue-ascitic fluid medium was illusory in such relation since it was a common experience to find this precipitate simulating the globoid bodies of poliomyelitis. Still more disturbing is the fact, that these particles could be carried over from subplant to subplant and even showed pseudo colony formation in the Noguchi semisolid medium in tubes. But when the particles were put to rigorous test for a living and multiplying organism, the tests failed to reveal multiplication. The increasing importance of the tissue-ascitic fluid medium in bacteriological technique warrants a detailed description of the requirements necessary for the determination of the living nature of formed elements in cultures in this medium, (a) No one method of staining can be relied upon, for stain precipitate in itself adds to the confusion. A specimen for examination should be stained separately by Gram's and Giemsa's methods and with another nudear dye, such as polychrome methylene blue. As a rule, microorganisms will reveal their morphological characters in more than one stain, whereas precipitate may be found in only one and not in the others. The experienced eye will discern the precipitated particles in selected parts of the stained preparation where they often occur in enormous numbers, clumped into irregular masses of varying forms from the periphery of which there is a gradual fading out to finer, more uniform structures. (b) In addition, suspected growths should be tested in the dialysate medium of Gates since by this method the precipitated material of the medium is kept from admixing with the growth, and a clear view of any microorganisms, if present, is obtained, (c) Another requirement is colony formation of the suspected culture. This is an absolute essential and can be effected by planting the material to be tested on solid plate media, incubated aerobically, and anaerobically in Brown's jar. Semisolid medium in long tubes should also be employed but care is needed to avoid mistaking small particles of precipitate for actual colonies of bacteria. To make certain of growth of microorganisms in semisolid medium, however, subplanting to a precipitate-free, dialysate medium is required. By following this method minute microorganisms which are obscured, or simulated, by precipitate in the Smith-Noguchi medium, can be identified.

Comparison of the efficiency of transplantation of bone marrow multipotent mesenchymal stromal cells cultured under normoxic and hypoxic conditions and their conditioned media on the model of acute lung injury.

PubMed

Chailakhyan, R K; Aver'yanov, A V; Zabozlaev, F G; Sobolev, P A; Sorokina, A V; Akul'shin, D A; Gerasimov, Yu V

2014-05-01

The therapeutic efficiency of intravenous injection of rat bone marrow multipotent mesenchymal stromal cells grown under conditions of normoxia and hypoxia (3% O2) and conditioned media from these cultures were compared on the rat model of acute lung injury induced by intraperitoneal injection of lipopolysaccharide. The best therapeutic efficiency was demonstrated by cells grown under hypoxic conditions. The effect of conditioned media was less pronounced and did not depend on the culturing conditions.

Comparison of flow and gas washout characteristics between pressure control and high-frequency percussive ventilation using a test lung

PubMed Central

Dutta, Rabijit; Xing, Tao; Swanson, Craig; Heltborg, Jeff; Murdoch, Gordon K

2018-01-01

Objective A comparison between flow and gas washout data for high-frequency percussive ventilation (HFPV) and pressure control ventilation (PCV) under similar conditions is currently not available. This bench study aims to compare and describe the flow and gas washout behavior of HFPV and PCV in a newly designed experimental setup and establish a framework for future clinical and animal studies. Approach We studied gas washout behavior using a newly designed experimental setup that is motivated by the multi-breath nitrogen washout measurements. In this procedure, a test lung was filled with nitrogen gas before it was connected to a ventilator. Pressure, volume, and oxygen concentrations were recorded under different compliance and resistance conditions. PCV was compared with two settings of HFPV, namely, HFPV-High and HFPV-Low, to simulate the different variations in its clinical application. In the HFPV-Low mode, the peak pressures and drive pressures of HFPV and PCV are matched, whereas in the HFPV-High mode, the mean airway pressures (MAP) are matched. Main results HFPV-Low mode delivers smaller tidal volume (VT) as compared to PCV under all lung conditions, whereas HFPV-High delivers a larger VT. HFPV-High provides rapid washout as compared to PCV under all lung conditions. HFPV-Low takes a longer time to wash out nitrogen except at a low compliance, where it expedites washout at a smaller VT and MAP compared to PCV washout. Significance Various flow parameters for HFPV and PCV are mathematically defined. A shorter washout time at a small VT in low compliant test lungs for HFPV could be regarded as a hypothesis for lung protective ventilation for animal or human lungs. PMID:29369819

Comparison of flow and gas washout characteristics between pressure control and high-frequency percussive ventilation using a test lung.

PubMed

Dutta, Rabijit; Xing, Tao; Swanson, Craig; Heltborg, Jeff; Murdoch, Gordon K

2018-03-15

A comparison between flow and gas washout data for high-frequency percussive ventilation (HFPV) and pressure control ventilation (PCV) under similar conditions is currently not available. This bench study aims to compare and describe the flow and gas washout behavior of HFPV and PCV in a newly designed experimental setup and establish a framework for future clinical and animal studies. We studied gas washout behavior using a newly designed experimental setup that is motivated by the multi-breath nitrogen washout measurements. In this procedure, a test lung was filled with nitrogen gas before it was connected to a ventilator. Pressure, volume, and oxygen concentrations were recorded under different compliance and resistance conditions. PCV was compared with two settings of HFPV, namely, HFPV-High and HFPV-Low, to simulate the different variations in its clinical application. In the HFPV-Low mode, the peak pressures and drive pressures of HFPV and PCV are matched, whereas in the HFPV-High mode, the mean airway pressures (MAP) are matched. HFPV-Low mode delivers smaller tidal volume (V T ) as compared to PCV under all lung conditions, whereas HFPV-High delivers a larger V T . HFPV-High provides rapid washout as compared to PCV under all lung conditions. HFPV-Low takes a longer time to wash out nitrogen except at a low compliance, where it expedites washout at a smaller V T and MAP compared to PCV washout. Various flow parameters for HFPV and PCV are mathematically defined. A shorter washout time at a small V T in low compliant test lungs for HFPV could be regarded as a hypothesis for lung protective ventilation for animal or human lungs.

Development of three-dimensional lung multicellular spheroids in air- and liquid-interface culture for the evaluation of anticancer therapeutics.

PubMed

Meenach, Samantha A; Tsoras, Alexandra N; McGarry, Ronald C; Mansour, Heidi M; Hilt, J Zach; Anderson, Kimberly W

2016-04-01

Three-dimensional (3D) lung multicellular spheroids (MCS) in liquid-covered culture (LCC) and air-interface culture (AIC) conditions have both been developed for the evaluation of aerosol anticancer therapeutics in solution and aerosols, respectively. The MCS were formed by seeding lung cancer cells on top of collagen where they formed spheroids due to the prevalence of cell-to-cell interactions. LCC MCS were exposed to paclitaxel (PTX) in media whereas AIC MCS were exposed to dry powder PEGylated phospholipid aerosol microparticles containing paclitaxel. The difference in viability for 2D versus 3D culture for both LCC and AIC was evaluated along with the effects of the particles on lung epithelium via transepithelial electrical resistance (TEER) measurements. For LCC and AIC conditions, the 3D spheroids were more resistant to treatment with higher IC50 values for A549 and H358 cell lines. TEER results initially indicated a decrease in resistance upon drug or particle exposure, however, these values increased over the course of several days indicating the ability of the cells to recover. Overall, these studies offer a comprehensive in vitro evaluation of aerosol particles used in the treatment of lung cancer while introducing a new method for culturing lung cancer MCS in both LCC and AIC conditions.

Socioeconomic disparities in lung cancer mortality in Belgian men and women (2001-2011): does it matter who you live with?

PubMed

Vanthomme, Katrien; Vandenheede, Hadewijch; Hagedoorn, Paulien; Gadeyne, Sylvie

2016-06-10

Ample studies have observed an adverse association between individual socioeconomic position (SEP) and lung cancer mortality. Moreover, the presence of a partner has shown to be a crucial determinant of health. Yet, few studies have assessed whether partner's SEP affects health in addition to individual SEP. This paper will study whether own SEP (education), partner's SEP (partner's education) and own and partner's SEP combined (housing conditions), are associated with lung cancer mortality in Belgium. Data consist of the Belgian 2001 census linked to register data on cause-specific mortality for 2001-2011. The study population includes all married or cohabiting Belgian inhabitants aged 40-84 years. Age-standardized lung cancer mortality rates (direct standardization) and mortality rate ratios (Poisson regression) were computed for the different SEP groups. In men, we observed a clear inverse association between all SEP indicators (own and partner's education, and housing conditions) and lung cancer mortality. Men benefit from having a higher educated partner in terms of lower lung cancer mortality rates. These observations hold for both middle-aged and older men. For women, the picture is less uniform. In middle-aged and older women, housing conditions is inversely associated with lung cancer mortality. As for partner's education, for middle-aged women, the association is rather weak whereas for older women, there is no such association. Whereas the educational level of middle-aged women is inversely associated with lung cancer mortality, in older women this association disappears in the fully adjusted model. Both men and women benefit from being in a relationship with a high-educated partner. It seems that for men, the educational level of their partner is of great importance while for women the housing conditions is more substantial. Both research and policy interventions should allow for the family level as well.

The role of interleukin-1β as a predictive biomarker and potential therapeutic target during clinical ex vivo lung perfusion.

PubMed

Andreasson, Anders S I; Borthwick, Lee A; Gillespie, Colin; Jiwa, Kasim; Scott, Jonathan; Henderson, Paul; Mayes, Jonny; Romano, Rosalba; Roman, Marius; Ali, Simi; Fildes, James E; Marczin, Nandor; Dark, John H; Fisher, Andrew J

2017-09-01

Extended criteria donor lungs deemed unsuitable for immediate transplantation can be reconditioned using ex vivo lung perfusion (EVLP). Objective identification of which donor lungs can be successfully reconditioned and will function well post-operatively has not been established. This study assessed the predictive value of markers of inflammation and tissue injury in donor lungs undergoing EVLP as part of the DEVELOP-UK study. Longitudinal samples of perfusate, bronchoalveolar lavage, and tissue from 42 human donor lungs undergoing clinical EVLP assessments were analyzed for markers of inflammation and tissue injury. Levels were compared according to EVLP success and post-transplant outcomes. Neutrophil adhesion to human pulmonary microvascular endothelial cells (HPMECs) conditioned with perfusates from EVLP assessments was investigated on a microfluidic platform. The most effective markers to differentiate between in-hospital survival and non-survival post-transplant were perfusate interleukin (IL)-1β (area under the curve = 1.00, p = 0.002) and tumor necrosis factor-α (area under the curve = 0.95, p = 0.006) after 30 minutes of EVLP. IL-1β levels in perfusate correlated with upregulation of intracellular adhesion molecule-1 in donor lung vasculature (R 2 = 0.68, p < 0.001) and to a lesser degree upregulation of intracellular adhesion molecule-1 (R 2 = 0.30, p = 0.001) and E-selectin (R 2 = 0.29, p = 0.001) in conditioned HPMECs and neutrophil adhesion to conditioned HPMECs (R 2 = 0.33, p < 0.001). Neutralization of IL-1β in perfusate effectively inhibited neutrophil adhesion to conditioned HPMECs (91% reduction, p = 0.002). Donor lungs develop a detectable and discriminatory pro-inflammatory signature in perfusate during EVLP. Blocking the IL-1β pathway during EVLP may reduce endothelial activation and subsequent neutrophil adhesion on reperfusion; this requires further investigation in vivo. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Generation of dendritic cell-based vaccine using high hydrostatic pressure for non-small cell lung cancer immunotherapy

PubMed Central

Hradilova, Nada; Sadilkova, Lenka; Palata, Ondrej; Mysikova, Dagmar; Mrazkova, Hana; Lischke, Robert; Spisek, Radek; Adkins, Irena

2017-01-01

High hydrostatic pressure (HHP) induces immunogenic death of tumor cells which confer protective anti-tumor immunity in vivo. Moreover, DC pulsed with HHP-treated tumor cells induced therapeutic effect in mouse cancer model. In this study, we tested the immunogenicity, stability and T cell stimulatory activity of human monocyte-derived dendritic cell (DC)-based HHP lung cancer vaccine generated in GMP compliant serum free medium using HHP 250 MPa. DC pulsed with HHP-killed lung cancer cells and poly(I:C) enhanced DC maturation, chemotactic migration and production of pro-inflammatory cytokines after 24h. Moreover, DC-based HHP lung cancer vaccine showed functional plasticity after transfer into serum-containing media and stimulation with LPS or CD40L after additional 24h. LPS and CD40L stimulation further differentially enhanced the expression of costimulatory molecules and production of IL-12p70. DC-based HHP lung cancer vaccine decreased the number of CD4+CD25+Foxp3+ T regulatory cells and stimulated IFN-γ-producing tumor antigen-specific CD4+ and CD8+ T cells from non-small cell lung cancer (NSCLC) patients. Tumor antigen specific CD8+ and CD4+ T cell responses were detected in NSCLC patient’s against a selected tumor antigens expressed by lung cancer cell lines used for the vaccine generation. We also showed for the first time that protein antigen from HHP-killed lung cancer cells is processed and presented by DC to CD8+ T cells. Our results represent important preclinical data for ongoing NSCLC Phase I/II clinical trial using DC-based active cellular immunotherapy (DCVAC/LuCa) in combination with chemotherapy and immune enhancers. PMID:28187172

Electrical impedance tomography compared to positron emission tomography for the measurement of regional lung ventilation: an experimental study

PubMed Central

Richard, JC; Pouzot, C; Gros, A; Tourevieille, C; Lebars, D; Lavenne, F; Frerichs, I; Guérin, C

2009-01-01

Introduction Electrical impedance tomography (EIT), which can assess regional lung ventilation at the bedside, has never been compared with positron-emission tomography (PET), a gold-standard to quantify regional ventilation. This experiment systematically compared both techniques in injured and non-injured lungs. Methods The study was performed in six mechanically ventilated female piglets. In normal lungs, tidal volume (VT) was randomly changed to 6, 8, 10 and 15 ml/kg on zero end-expiratory pressure (ZEEP), then, at VT 10 ml/kg, positive end-expiratory pressure (PEEP) was randomly changed to 5, 10 and 15 cmH2O. Afterwards, acute lung injury (ALI) was subsequently created in three animals by injecting 3 ml/kg hydrochloric acid into the trachea. Then at PEEP 5 cmH2O, VT was randomly changed to 8 and 12 ml/kg and PEEP of 10 and 15 cmH2O applied at VT 10 ml/kg. EIT and PET examinations were performed simultaneously. EIT ventilation (VTEIT) and lung volume (VL) were measured in the anterior and posterior area of each lung. On the same regions of interest, ventilation (VPET) and aerated lung volume (VAatten) were determined with PET. Results On ZEEP, VTEIT and VPET significantly correlated for global (VTEIT = VPET - 2E-13, R2 = 0.95, P < 0.001) and regional (VTEIT = 0.81VPET+7.65, R2 = 0.63, P < 0.001) ventilation over both conditions. For ALI condition, corresponding R2 were 0.91 and 0.73 (P < 0.01). Bias was = 0 and limits of agreement were -37.42 and +37.42 ml/min for global ventilation over both conditions. These values were 0.04 and -29.01 and +29.08 ml/min, respectively, for regional ventilation. Significant correlations were also found between VL and VAatten for global (VL = VAatten+1E-12, R2 = 0.93, P < 0.0001) and regional (VL = 0.99VAatten+0.92, R2 = 0.65, P < 0.001) volume. For ALI condition, corresponding R2 were 0.94 (P < 0.001) and 0.54 (P < 0.05). Bias was = 0 and limits of agreement ranged -38.16 and +38.16 ml for global ventilation over both conditions. These values were -0.24 and -31.96 to +31.48 ml, respectively, for regional ventilation. Conclusions Regional lung ventilation and volume were accurately measured with EIT in healthy and injured lungs and validated by simultaneous PET imaging. PMID:19480694

Thermal processing of bone: in vitro response of mesenchymal cells to bone-conditioned medium.

PubMed

Sawada, K; Caballé-Serrano, J; Schuldt Filho, G; Bosshardt, D D; Schaller, B; Buser, D; Gruber, R

2015-08-01

The autoclaving, pasteurization, and freezing of bone grafts to remove bacteria and viruses, and for preservation, respectively, is considered to alter biological properties during graft consolidation. Fresh bone grafts release paracrine-like signals that are considered to support tissue regeneration. However, the impact of the autoclaving, pasteurization, and freezing of bone grafts on paracrine signals remains unknown. Therefore, conditioned medium was prepared from porcine cortical bone chips that had undergone thermal processing. The biological properties of the bone-conditioned medium were assessed by examining the changes in expression of target genes in oral fibroblasts. The data showed that conditioned medium obtained from bone chips that had undergone pasteurization and freezing changed the expression of adrenomedullin, pentraxin 3, BTB/POZ domain-containing protein 11, interleukin 11, NADPH oxidase 4, and proteoglycan 4 by at least five-fold in oral fibroblasts. Bone-conditioned medium obtained from autoclaved bone chips, however, failed to change the expression of the respective genes. Also, when bone-conditioned medium was prepared from fresh bone chips, autoclaving blocked the capacity of bone-conditioned medium to modulate gene expression. These in vitro results suggest that pasteurization and freezing of bone grafts preserve the release of biologically active paracrine signals, but autoclaving does not. Copyright © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Oxymorphone

MedlinePlus

... ever had lung disease such as chronic obstructive pulmonary disease (COPD; a group of lung diseases that includes chronic bronchitis and emphysema), a head injury, brain tumor, any condition that ...

Epidemiology, incidence and mortality of lung cancer and their relationship with the development index in the world

PubMed Central

Rafiemanesh, Hosein; Mehtarpour, Mojtaba; Khani, Farah; Hesami, Sayed Mohammadali; Shamlou, Reza; Towhidi, Farhad; Makhsosi, Behnam Reza; Moini, Ali

2016-01-01

Background The highest incidence of lung cancer is seen in North America and the lowest incidence in central Africa. Socioeconomic factors of inequality reflect regional disparities in human development. Due to the importance of awareness about incidence and mortality of lung cancer in health programming and the possible role of the human development index (HDI), this study was done with the aim to investigate the epidemiology of lung cancer in the world and its relationship with HDI. Methods The study was conducted based on data from the world data of cancer and the World Bank (including the HDI and its components). Data about the age-specific incidence and mortality rate (ASR) for every country in 2012 were getting from the global cancer project. To analyze data, correlation tests between incidence and death rates, and HDI and its components were employed with a significance level of 0.05 using SPSS software. Results Lung cancer with standardized incidence rate (ASIR) and standardized mortality rate (ASMR), equal to 23.1 and 19.7 (in 100,000 people), respectively. The highest and lowest values of mortality incidence ratio (MIR) for lung cancer due to continents division were 0.93 and 0.71 for Eastern Africa and Australia/New Zealand, respectively. Univariate analysis showed significant relationship (P<0.0001) between ASIR and ASMR with life expectancy at birth and mean years of schooling. Conclusions The highest MIR for lung cancer was for medium human development countries. Linear regression analysis showed a reverse significant relationship between MIR and HDI. PMID:27293825

Epidemiology, incidence and mortality of lung cancer and their relationship with the development index in the world.

PubMed

Rafiemanesh, Hosein; Mehtarpour, Mojtaba; Khani, Farah; Hesami, Sayed Mohammadali; Shamlou, Reza; Towhidi, Farhad; Salehiniya, Hamid; Makhsosi, Behnam Reza; Moini, Ali

2016-06-01

The highest incidence of lung cancer is seen in North America and the lowest incidence in central Africa. Socioeconomic factors of inequality reflect regional disparities in human development. Due to the importance of awareness about incidence and mortality of lung cancer in health programming and the possible role of the human development index (HDI), this study was done with the aim to investigate the epidemiology of lung cancer in the world and its relationship with HDI. The study was conducted based on data from the world data of cancer and the World Bank (including the HDI and its components). Data about the age-specific incidence and mortality rate (ASR) for every country in 2012 were getting from the global cancer project. To analyze data, correlation tests between incidence and death rates, and HDI and its components were employed with a significance level of 0.05 using SPSS software. Lung cancer with standardized incidence rate (ASIR) and standardized mortality rate (ASMR), equal to 23.1 and 19.7 (in 100,000 people), respectively. The highest and lowest values of mortality incidence ratio (MIR) for lung cancer due to continents division were 0.93 and 0.71 for Eastern Africa and Australia/New Zealand, respectively. Univariate analysis showed significant relationship (P<0.0001) between ASIR and ASMR with life expectancy at birth and mean years of schooling. The highest MIR for lung cancer was for medium human development countries. Linear regression analysis showed a reverse significant relationship between MIR and HDI.

Design of a numerical model of lung by means of a special boundary condition in the truncated branches.

PubMed

Tena, Ana F; Fernández, Joaquín; Álvarez, Eduardo; Casan, Pere; Walters, D Keith

2017-06-01

The need for a better understanding of pulmonary diseases has led to increased interest in the development of realistic computational models of the human lung. To minimize computational cost, a reduced geometry model is used for a model lung airway geometry up to generation 16. Truncated airway branches require physiologically realistic boundary conditions to accurately represent the effect of the removed airway sections. A user-defined function has been developed, which applies velocities mapped from similar locations in fully resolved airway sections. The methodology can be applied in any general purpose computational fluid dynamics code, with the only limitation that the lung model must be symmetrical in each truncated branch. Unsteady simulations have been performed to verify the operation of the model. The test case simulates a spirometry because the lung is obliged to rapidly perform both inspiration and expiration. Once the simulation was completed, the obtained pressure in the lower level of the lung was used as a boundary condition. The output velocity, which is a numerical spirometry, was compared with the experimental spirometry for validation purposes. This model can be applied for a wide range of patient-specific resolution levels. If the upper airway generations have been constructed from a computed tomography scan, it would be possible to quickly obtain a complete reconstruction of the lung specific to a specific person, which would allow individualized therapies. Copyright © 2016 John Wiley & Sons, Ltd.

Human Bioresponse to Low-Frequency Underwater Sound

DTIC Science & Technology

2009-02-02

polyhedrons. Figure 4.2 shows a vertical array of two alveolar duct units. Fung focused only on the morphometric accuracy of this geometrical ...created that includes idealized geometrical representations of the lungs, ribs, trachea, bronchiole tubes, spine, sternum, and a generalized...clusters subjected to different excitations and geometric constraints will be shown. With the objective of developing an effective medium model that

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

EPA Science Inventory

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...

[Rare earth elements contents and distribution characteristics in nasopharyngeal carcinoma tissue].

PubMed

Zhang, Xiangmin; Lan, Xiaolin; Zhang, Lingzhen; Xiao, Fufu; Zhong, Zhaoming; Ye, Guilin; Li, Zong; Li, Shaojin

2016-03-01

To investigate the rare earth elements(REEs) contents and distribution characteristics in nasopharyngeal carcinoma( NPC) tissue in Gannan region. Thirty patients of NPC in Gannan region were included in this study. The REEs contents were measured by tandem mass spectrometer inductively coupled plasma(ICP-MS/MS) in 30 patients, and the REEs contents and distribution were analyzed. The average standard deviation value of REEs in lung cancer and normal lung tissues was the minimum mostly. Light REEs content was higher than the medium REEs, and medium REEs content was higher than the heavy REEs content. REEs contents changes in nasopharyngeal carcinoma were variable obviously, the absolute value of Nd, Ce, Pr, Gd and other light rare earth elements were variable widely. The degree of changes on Yb, Tb, Ho and other heavy rare earth elements were variable widely, and there was presence of Eu, Ce negative anomaly(δEu=0. 385 5, δCe= 0. 523 4). The distribution characteristic of REEs contents in NPC patients is consistent with the parity distribution. With increasing atomic sequence, the content is decline wavy. Their distribution patterns were a lack of heavy REEs and enrichment of light REEs, and there was Eu , Ce negative anomaly.

[Diagnostics and surgical treatment of lung cancer in conditions of special thoracal department for patients with purulent lung diseases].

PubMed

Deĭnega, I V; Egorov, V I; Ionov, P M; Akopov, A L

2014-01-01

The authors investigated features of diagnostics and surgical treatment of lung cancer which was complicated by purulent destructive process. The possibilities of radical operative intervention were considered after preliminary adequate treatment of purulent complications in 226 patients. It was noted, that the diagnostic thoracotomy should be used in doubtful cases in order to estimate the resectability of lung cancer.

Cystic Fibrosis Transmembrane Conductance Regulator Controls Lung Proteasomal Degradation and Nuclear Factor-κB Activity in Conditions of Oxidative Stress

PubMed Central

Boncoeur, Emilie; Roque, Telma; Bonvin, Elise; Saint-Criq, Vinciane; Bonora, Monique; Clement, Annick; Tabary, Olivier; Henrion-Caude, Alexandra; Jacquot, Jacky

2008-01-01

Cystic fibrosis is a lethal inherited disorder caused by mutations in a single gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein, resulting in progressive oxidative lung damage. In this study, we evaluated the role of CFTR in the control of ubiquitin-proteasome activity and nuclear factor (NF)-κB/IκB-α signaling after lung oxidative stress. After a 64-hour exposure to hyperoxia-mediated oxidative stress, CFTR-deficient (cftr−/−) mice exhibited significantly elevated lung proteasomal activity compared with wild-type (cftr+/+) animals. This was accompanied by reduced lung caspase-3 activity and defective degradation of NF-κB inhibitor IκB-α. In vitro, human CFTR-deficient lung cells exposed to oxidative stress exhibited increased proteasomal activity and decreased NF-κB-dependent transcriptional activity compared with CFTR-sufficient lung cells. Inhibition of the CFTR Cl− channel by CFTRinh-172 in the normal bronchial immortalized cell line 16HBE14o− increased proteasomal degradation after exposure to oxidative stress. Caspase-3 inhibition by Z-DQMD in CFTR-sufficient lung cells mimicked the response profile of increased proteasomal degradation and reduced NF-κB activity observed in CFTR-deficient lung cells exposed to oxidative stress. Taken together, these results suggest that functional CFTR Cl− channel activity is crucial for regulation of lung proteasomal degradation and NF-κB activity in conditions of oxidative stress. PMID:18372427

Gene Expression Analysis to Assess the Relevance of Rodent Models to Human Lung Injury.

PubMed

Sweeney, Timothy E; Lofgren, Shane; Khatri, Purvesh; Rogers, Angela J

2017-08-01

The relevance of animal models to human diseases is an area of intense scientific debate. The degree to which mouse models of lung injury recapitulate human lung injury has never been assessed. Integrating data from both human and animal expression studies allows for increased statistical power and identification of conserved differential gene expression across organisms and conditions. We sought comprehensive integration of gene expression data in experimental acute lung injury (ALI) in rodents compared with humans. We performed two separate gene expression multicohort analyses to determine differential gene expression in experimental animal and human lung injury. We used correlational and pathway analyses combined with external in vitro gene expression data to identify both potential drivers of underlying inflammation and therapeutic drug candidates. We identified 21 animal lung tissue datasets and three human lung injury bronchoalveolar lavage datasets. We show that the metasignatures of animal and human experimental ALI are significantly correlated despite these widely varying experimental conditions. The gene expression changes among mice and rats across diverse injury models (ozone, ventilator-induced lung injury, LPS) are significantly correlated with human models of lung injury (Pearson r = 0.33-0.45, P < 1E -16 ). Neutrophil signatures are enriched in both animal and human lung injury. Predicted therapeutic targets, peptide ligand signatures, and pathway analyses are also all highly overlapping. Gene expression changes are similar in animal and human experimental ALI, and provide several physiologic and therapeutic insights to the disease.

Resident alveolar macrophages are master regulators of arrested alveolarization in experimental bronchopulmonary dysplasia.

PubMed

Kalymbetova, Tatiana V; Selvakumar, Balachandar; Rodríguez-Castillo, José Alberto; Gunjak, Miša; Malainou, Christina; Heindl, Miriam Ruth; Moiseenko, Alena; Chao, Cho-Ming; Vadász, István; Mayer, Konstantin; Lohmeyer, Jürgen; Bellusci, Saverio; Böttcher-Friebertshäuser, Eva; Seeger, Werner; Herold, Susanne; Morty, Rory E

2018-06-01

Trophic functions for macrophages are emerging as key mediators of developmental processes, including bone, vessel, and mammary gland development. Yolk sac-derived macrophages mature in the distal lung shortly after birth. Myeloid-lineage macrophages are recruited to the lung and are activated under pathological conditions. These pathological conditions include bronchopulmonary dysplasia (BPD), a common complication of preterm birth characterized by stunted lung development, where the formation of alveoli is blocked. No study has addressed causal roles for immune cells in lung alveolarization. We employed antibody-based and transgenic death receptor-based depletion approaches to deplete or prevent lung recruitment of immune cell populations in a hyperoxia-based mouse model of BPD. Neither neutrophils nor exudate macrophages (which might include lung interstitial macrophages) contributed to structural perturbations to the lung that were provoked by hyperoxia; however, cells of the Csf1r-expressing monocyte/macrophage lineage were implicated as causal mediators of stunted lung development. We propose that resident alveolar macrophages differentiate into a population of CD45 + CD11c + SiglecF + CD11b + CD68 + MHCII + cells, which are activated by hyperoxia, and contribute to disturbances to the structural development of the immature lung. This is the first report that causally implicates immune cells in pathological disturbances to postnatal lung organogenesis. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Smoking-related interstitial lung diseases.

PubMed

Caminati, A; Graziano, P; Sverzellati, N; Harari, S

2010-12-01

In pulmonary pathology, a wide spectrum of morphological changes is related to the consequences of smoking, and recognizing them on surgical specimens and on small transbronchial biopsies represents a challenge for the pathologist. Respiratory bronchiolitis, also referred to as smoker's bronchiolitis, is a common histologic feature found in the lung tissue of cigarette smokers. When identified as the sole histopathologic finding in the clinical setting of symptomatic interstitial lung disease, a diagnosis of respiratory bronchiolitis-interstitial lung disease is made. Since smoking is recognized to cause a variety of histologic patterns encompassing respiratory bronchiolitis, respiratory bronchiolitis-interstitial lung disease, desquamative interstitial pneumonia and pulmonary Langerhans cell hystiocytosis, smoking-related interstitial lung disease may be a useful concept to keep in mind for the pathologists. The relationship of smoking with each of these entities has been largely established on the basis of epidemiologic evidence. Although they have been retained as distinct and separate conditions in various classifications of interstitial lung diseases, these entities share a number of clinical, radiologic, and pathologic features suggesting that they represent a spectrum of patterns of interstitial lung disease occurring in predisposed individuals who smoke. Evaluation of histologic features, particularly in surgical lung biopsy samples, is important in making the distinction between these disorders. However, even after tissue biopsy, it may sometimes be difficult to clearly separate these entities. Recently, respiratory bronchiolitis-interstitial lung disease with fibrosis has been described and postulated that this is a smoking-related condition distinct from fibrotic non-specific interstitial pneumonia.

A 4DCT imaging-based breathing lung model with relative hysteresis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miyawaki, Shinjiro; Choi, Sanghun; Hoffman, Eric A.

To reproduce realistic airway motion and airflow, the authors developed a deforming lung computational fluid dynamics (CFD) model based on four-dimensional (4D, space and time) dynamic computed tomography (CT) images. A total of 13 time points within controlled tidal volume respiration were used to account for realistic and irregular lung motion in human volunteers. Because of the irregular motion of 4DCT-based airways, we identified an optimal interpolation method for airway surface deformation during respiration, and implemented a computational solid mechanics-based moving mesh algorithm to produce smooth deforming airway mesh. In addition, we developed physiologically realistic airflow boundary conditions for bothmore » models based on multiple images and a single image. Furthermore, we examined simplified models based on one or two dynamic or static images. By comparing these simplified models with the model based on 13 dynamic images, we investigated the effects of relative hysteresis of lung structure with respect to lung volume, lung deformation, and imaging methods, i.e., dynamic vs. static scans, on CFD-predicted pressure drop. The effect of imaging method on pressure drop was 24 percentage points due to the differences in airflow distribution and airway geometry. - Highlights: • We developed a breathing human lung CFD model based on 4D-dynamic CT images. • The 4DCT-based breathing lung model is able to capture lung relative hysteresis. • A new boundary condition for lung model based on one static CT image was proposed. • The difference between lung models based on 4D and static CT images was quantified.« less

Mechanical stretch-induced serotonin release from pulmonary neuroendocrine cells: implications for lung development.

PubMed

Pan, Jie; Copland, Ian; Post, Martin; Yeger, Herman; Cutz, Ernest

2006-01-01

Pulmonary neuroendocrine cells (PNEC) produce amine (serotonin, 5-HT) and peptides (e.g., bombesin, calcitonin) with growth factor-like properties and are thought to play an important role in lung development. Because physical forces are essential for lung growth and development, we investigated the effects of mechanical strain on 5-HT release in PNEC freshly isolated from rabbit fetal lung and in the PNEC-related tumor H727 cell line. Cultures exposed to sinusoidal cyclic stretch showed a significant 5-HT release inhibitable with gadolinium chloride (10 nM), a blocker of mechanosensitive channels. In contrast to hypoxia (Po2 approximately 20 mmHg), stretch-induced 5-HT release was not affected by Ca2+-free medium or nifedipine (50 microM), excluding the exocytic pathway. In H727 cells, stretch failed to release calcitonin, a peptide stored within dense core vesicles (DCV), whereas hypoxia caused massive calcitonin release. 5-HT released by mechanical stretch is derived predominantly from the cytoplasmic pool, because it is rapid ( approximately 5 min) and is releasable from early (20 days of gestation) fetal PNEC containing few DCV. Both mechanical stretch and hypoxia upregulated expression of tryptophan hydroxylase, the rate-limiting enzyme of 5-HT synthesis. We conclude that mechanical strain is an important physiological stimulus for the release of 5-HT from PNEC via mechanosensitive channels with potential effects on lung development and resorption of lung fluid at the time of birth.

A deep-learning based automatic pulmonary nodule detection system

NASA Astrophysics Data System (ADS)

Zhao, Yiyuan; Zhao, Liang; Yan, Zhennan; Wolf, Matthias; Zhan, Yiqiang

2018-02-01

Lung cancer is the deadliest cancer worldwide. Early detection of lung cancer is a promising way to lower the risk of dying. Accurate pulmonary nodule detection in computed tomography (CT) images is crucial for early diagnosis of lung cancer. The development of computer-aided detection (CAD) system of pulmonary nodules contributes to making the CT analysis more accurate and with more efficiency. Recent studies from other groups have been focusing on lung cancer diagnosis CAD system by detecting medium to large nodules. However, to fully investigate the relevance between nodule features and cancer diagnosis, a CAD that is capable of detecting nodules with all sizes is needed. In this paper, we present a deep-learning based automatic all size pulmonary nodule detection system by cascading two artificial neural networks. We firstly use a U-net like 3D network to generate nodule candidates from CT images. Then, we use another 3D neural network to refine the locations of the nodule candidates generated from the previous subsystem. With the second sub-system, we bring the nodule candidates closer to the center of the ground truth nodule locations. We evaluate our system on a public CT dataset provided by the Lung Nodule Analysis (LUNA) 2016 grand challenge. The performance on the testing dataset shows that our system achieves 90% sensitivity with an average of 4 false positives per scan. This indicates that our system can be an aid for automatic nodule detection, which is beneficial for lung cancer diagnosis.

Effects of •OH and •NO radicals in the aqueous phase on H2O2 and \\text{NO}_{2}^{-} generated in plasma-activated medium

NASA Astrophysics Data System (ADS)

Kurake, Naoyuki; Tanaka, Hiromasa; Ishikawa, Kenji; Takeda, Keigo; Hashizume, Hiroshi; Nakamura, Kae; Kajiyama, Hiroaki; Kondo, Takashi; Kikkawa, Fumitaka; Mizuno, Masaaki; Hori, Masaru

2017-04-01

A plasma-activated medium (PAM), which means a cell-culture medium irradiated with cold atmospheric plasmas or non-equilibrium atmospheric pressure plasma (NEAPP), has shown strong antitumor effects on various kinds of cells such as gastric cancer cells, human lung adenocarcinoma cells, human breast cancer cells and so on. In order to clarify the mechanism, it is extremely important to investigate the behaviors of stable and unstable reactive oxygen nitrogen species in culture medium irradiated by NEAPP. The roles of hydroxyl radicals (•OH) and nitric oxide (•NO) were studied to understand the dominant synthetic pathways of H2O2 and \\text{NO}2- in culture medium irradiated with NEAPP. In the PAM, •OH in the aqueous phase was generated predominantly by photo-dissociation. However, most of the H2O2 nor \\text{NO}2- generated in the PAM did not originate from aqueous •OH and •NO. Pathways for the generation of H2O2 and \\text{NO}2- are suggested based on the high concentrations of intermediates generated at the gas/aqueous-phase interface following NEAPP irradiation. On the basis of these results, the reaction model of chemical species in the culture medium is proposed.

Regional Distribution of Pulmonary Blood Volume with Dual-Energy Computed Tomography: Results in 42 Subjects.

PubMed

Felloni, Paul; Duhamel, Alain; Faivre, Jean-Baptiste; Giordano, Jessica; Khung, Suonita; Deken, Valérie; Remy, Jacques; Remy-Jardin, Martine

2017-11-01

The noninvasive approach of lung perfusion generated from dual-energy computed tomography acquisitions has entered clinical practice. The purpose of this study was to analyze the regional distribution of iodine within distal portions of the pulmonary arterial bed on dual-source, dual-energy computed tomography examinations in a cohort of subjects without cardiopulmonary pathologies. The study population included 42 patients without cardiorespiratory disease, enabling quantitative and qualitative analysis of pulmonary blood volume after administration of a 40% contrast agent. Qualitative analysis was based on visual assessment. Quantitative analysis was obtained after semiautomatic division of each lung into 18 areas. The iodine concentration did not significantly differ between the right (R) and left (L) lungs (P = .49), with a mean attenuation of 41.35 Hounsfield units (HU) and 41.14 HU, respectively. Three regional gradients of attenuation were observed between: (a) lung bases and apices (P < .001), linked to the conditions of examination (mean Δ: 6.23 in the R lung; 5.96 in the L lung); (b) posterior and anterior parts of the lung (P < .001) due to gravity (mean Δ: 11.92 in the R lung ; 15.93 in the L lung); and (c) medullary and cortical lung zones (P < .001) (mean Δ: 9.35 in the R lung ; 8.37 in the L lung). The intensity of dependent-nondependent (r = 0.42; P < .001) and corticomedullary (r = 0.58; P < .0001) gradients was correlated to the overall iodine concentration. Distribution of pulmonary blood volume is influenced by physiological gradients and scanning conditions. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Expression and Secretion of Endostar Protein by Escherichia Coli: Optimization of Culture Conditions Using the Response Surface Methodology.

PubMed

Mohajeri, Abbas; Abdolalizadeh, Jalal; Pilehvar-Soltanahmadi, Younes; Kiafar, Farhad; Zarghami, Nosratollah

2016-10-01

Endostar as a specific drug in treatment of the nonsmall cell lung cancer is produced using Escherichia coli expression system. Plackett-Burman design (PBD) and response surface methodology (RSM) are statistical tools for experimental design and optimization of biotechnological processes. This investigation aimed to predict and develop the optimal culture condition and its components for expression and secretion of endostar into the culture medium of E. coli. The synthetic endostar coding sequence was fused with PhoA signal peptide. The nine factors involved in the production of recombinant protein-postinduction temperature, cell density, rotation speed, postinduction time, concentration of glycerol, IPTG, peptone, glycine, and triton X-100-were evaluated using PBD. Four significant factors were selected based on PBD results for optimizing culture condition using RSM. Endostar was purified using cation exchange chromatography and size exclusion chromatography. The maximum level of endostar was obtained under the following condition: 13.57-h postinduction time, 0.76 % glycine, 0.7 % triton X-100, and 4.87 % glycerol. The predicted levels of endostar was significantly correlated with experimental levels (R 2 = 0.982, P = 0.00). The obtained results indicated that PBD and RSM are effective tools for optimization of culture condition and its components for endostar production in E. coli. The most important factors in the enhancement of the protein production are glycerol, glycine, and postinduction time.

Hypoxic-Preconditioned Bone Marrow Stem Cell Medium Significantly Improves Outcome After Retinal Ischemia in Rats

PubMed Central

Roth, Steven; Dreixler, John C.; Mathew, Biji; Balyasnikova, Irina; Mann, Jacob R.; Boddapati, Venkat; Xue, Lai; Lesniak, Maciej S.

2016-01-01

Purpose We have previously demonstrated the protective effect of bone marrow stem cell (BMSC)-conditioned medium in retinal ischemic injury. We hypothesized here that hypoxic preconditioning of stem cells significantly enhances the neuroprotective effect of the conditioned medium and thereby augments the protective effect in ischemic retina. Methods Rats were subjected to retinal ischemia by increasing intraocular pressure to 130 to 135 mm Hg for 55 minutes. Hypoxic-preconditioned, hypoxic unconditioned, or normoxic medium was injected into the vitreous 24 hours after ischemia ended. Recovery was assessed 7 days after injections by comparing electroretinography measurements, histologic examination, and apoptosis (TUNEL, terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling assay). To compare proteins secreted into the medium in the groups and the effect of hypoxic exposure, we used rat cytokine arrays. Results Eyes injected with hypoxic BMSC–conditioned medium 24 hours after ischemia demonstrated significantly enhanced return of retinal function, decreased retinal ganglion cell layer loss, and attenuated apoptosis compared to those administered normoxic or hypoxic unconditioned medium. Hypoxic-preconditioned medium had 21 significantly increased protein levels compared to normoxic medium. Conclusions The medium from hypoxic-preconditioned BMSCs robustly restored retinal function and prevented cell loss after ischemia when injected 24 hours after ischemia. The protective effect was even more pronounced than in our previous studies of normoxic conditioned medium. Prosurvival signals triggered by the secretome may play a role in this neuroprotective effect. PMID:27367588

Variability in CT lung-nodule quantification: Effects of dose reduction and reconstruction methods on density and texture based features.

PubMed

Lo, P; Young, S; Kim, H J; Brown, M S; McNitt-Gray, M F

2016-08-01

To investigate the effects of dose level and reconstruction method on density and texture based features computed from CT lung nodules. This study had two major components. In the first component, a uniform water phantom was scanned at three dose levels and images were reconstructed using four conventional filtered backprojection (FBP) and four iterative reconstruction (IR) methods for a total of 24 different combinations of acquisition and reconstruction conditions. In the second component, raw projection (sinogram) data were obtained for 33 lung nodules from patients scanned as a part of their clinical practice, where low dose acquisitions were simulated by adding noise to sinograms acquired at clinical dose levels (a total of four dose levels) and reconstructed using one FBP kernel and two IR kernels for a total of 12 conditions. For the water phantom, spherical regions of interest (ROIs) were created at multiple locations within the water phantom on one reference image obtained at a reference condition. For the lung nodule cases, the ROI of each nodule was contoured semiautomatically (with manual editing) from images obtained at a reference condition. All ROIs were applied to their corresponding images reconstructed at different conditions. For 17 of the nodule cases, repeat contours were performed to assess repeatability. Histogram (eight features) and gray level co-occurrence matrix (GLCM) based texture features (34 features) were computed for all ROIs. For the lung nodule cases, the reference condition was selected to be 100% of clinical dose with FBP reconstruction using the B45f kernel; feature values calculated from other conditions were compared to this reference condition. A measure was introduced, which the authors refer to as Q, to assess the stability of features across different conditions, which is defined as the ratio of reproducibility (across conditions) to repeatability (across repeat contours) of each feature. The water phantom results demonstrated substantial variability among feature values calculated across conditions, with the exception of histogram mean. Features calculated from lung nodules demonstrated similar results with histogram mean as the most robust feature (Q ≤ 1), having a mean and standard deviation Q of 0.37 and 0.22, respectively. Surprisingly, histogram standard deviation and variance features were also quite robust. Some GLCM features were also quite robust across conditions, namely, diff. variance, sum variance, sum average, variance, and mean. Except for histogram mean, all features have a Q of larger than one in at least one of the 3% dose level conditions. As expected, the histogram mean is the most robust feature in their study. The effects of acquisition and reconstruction conditions on GLCM features vary widely, though trending toward features involving summation of product between intensities and probabilities being more robust, barring a few exceptions. Overall, care should be taken into account for variation in density and texture features if a variety of dose and reconstruction conditions are used for the quantification of lung nodules in CT, otherwise changes in quantification results may be more reflective of changes due to acquisition and reconstruction conditions than in the nodule itself.

Microfocal angiography of the pulmonary vasculature

NASA Astrophysics Data System (ADS)

Clough, Anne V.; Haworth, Steven T.; Roerig, David T.; Linehan, John H.; Dawson, Christopher A.

1998-07-01

X-ray microfocal angiography provides a means of assessing regional microvascular perfusion parameters using residue detection of vascular indicators. As an application of this methodology, we studied the effects of alveolar hypoxia, a pulmonary vasoconstrictor, on the pulmonary microcirculation to determine changes in regional blood mean transit time, volume and flow between control and hypoxic conditions. Video x-ray images of a dog lung were acquired as a bolus of radiopaque contrast medium passed through the lobar vasculature. X-ray time-absorbance curves were acquired from arterial and microvascular regions-of-interest during both control and hypoxic alveolar gas conditions. A mathematical model based on indicator-dilution theory applied to image residue curves was applied to the data to determine changes in microvascular perfusion parameters. Sensitivity of the model parameters to the model assumptions was analyzed. Generally, the model parameter describing regional microvascular volume, corresponding to area under the microvascular absorbance curve, was the most robust. The results of the model analysis applied to the experimental data suggest a significant decrease in microvascular volume with hypoxia. However, additional model assumptions concerning the flow kinematics within the capillary bed may be required for assessing changes in regional microvascular flow and mean transit time from image residue data.

Thoracic Insufficiency Syndrome

MedlinePlus

... Patients with this condition can't maintain normal respiration or lung growth. The thorax (spine, rib cage, and sternum) is the engine of respiration. It must have adequate space for the lungs ...

The a“MAZE”ing World of Lung-Specific Transgenic Mice

PubMed Central

Rawlins, Emma L.

2012-01-01

The purpose of this review is to give a comprehensive overview of transgenic mouse lines suitable for studying gene function and cellular lineage relationships in lung development, homeostasis, injury, and repair. Many of the mouse strains reviewed in this Perspective have been widely shared within the lung research community, and new strains are continuously being developed. There are many transgenic lines that target subsets of lung cells, but it remains a challenge for investigators to select the correct transgenic modules for their experiment. This review covers the tetracycline- and tamoxifen-inducible systems and focuses on conditional lines that target the epithelial cells. We point out the limitations of each strain so investigators can choose the system that will work best for their scientific question. Current mesenchymal and endothelial lines are limited by the fact that they are not lung specific. These lines are summarized in a brief overview. In addition, useful transgenic reporter mice for studying lineage relationships, promoter activity, and signaling pathways will complete our lung-specific conditional transgenic mouse shopping list. PMID:22180870

Overexpression of Adenylyl Cyclase Encoded by the Mycobacterium tuberculosis Rv2212 Gene Confers Improved Fitness, Accelerated Recovery from Dormancy and Enhanced Virulence in Mice.

PubMed

Shleeva, Margarita O; Kondratieva, Tatyana K; Demina, Galina R; Rubakova, Elvira I; Goncharenko, Anna V; Apt, Alexander S; Kaprelyants, Arseny S

2017-01-01

Earlier we demonstrated that the adenylyl cyclase (AC) encoded by the MSMEG_4279 gene plays a key role in the resuscitation and growth of dormant Mycobacterium smegmatis and that overexpression of this gene leads to an increase in intracellular cAMP concentration and prevents the transition of M. smegmatis from active growth to dormancy in an extended stationary phase accompanied by medium acidification. We surmised that the homologous Rv2212 gene of M. tuberculosis ( Mtb ), the main cAMP producer, plays similar physiological roles by supporting, under these conditions, the active state and reactivation of dormant bacteria. To test this hypothesis, we established Mtb strain overexpressing Rv2212 and compared its in vitro and in vivo growth characteristics with a control strain. In vitro , the AC-overexpressing pMind Rv2212 strain demonstrated faster growth in a liquid medium, prolonged capacity to form CFUs and a significant delay or even prevention of transition toward dormancy. AC-overexpressing cells exhibited easier recovery from dormancy. In vivo , AC-overexpressing bacteria demonstrated significantly higher growth rates (virulence) in the lungs and spleens of infected mice compared to the control strain, and, unlike the latter, killed mice in the TB-resistant strain before month 8 of infection. Even in the absence of selecting hygromycin B, all pMind Rv2212 CFUs retained the Rv2212 insert during in vivo growth, strongly suggesting that AC overexpression is beneficial for bacteria. Taken together, our results indicate that cAMP supports the maintenance of Mtb cells vitality under unfavorable conditions in vitro and their virulence in vivo .

Ex vivo expansion of alveolar macrophages with Mycobacterium tuberculosis from the resected lungs of patients with pulmonary tuberculosis

PubMed Central

Petrunina, Ekaterina; Umpeleva, Tatiana; Karskanova, Svetlana; Bayborodin, Sergey; Vakhrusheva, Diana; Kravchenko, Marionella; Skornyakov, Sergey

2018-01-01

Tuberculosis (TB), with the Mycobacterium tuberculosis (Mtb) as the causative agent, remains to be a serious world health problem. Traditional methods used for the study of Mtb in the lungs of TB patients do not provide information about the number and functional status of Mtb, especially if Mtb are located in alveolar macrophages. We have developed a technique to produce ex vivo cultures of cells from different parts of lung tissues surgically removed from patients with pulmonary TB and compared data on the number of cells with Mtb inferred by the proposed technique to the results of bacteriological and histological analyses used for examination of the resected lungs. The ex vivo cultures of cells obtained from the resected lungs of all patients were largely composed of CD14-positive alveolar macrophages, foamy or not, with or without Mtb. Lymphocytes, fibroblasts, neutrophils, and multinucleate Langhans giant cells were also observed. We found alveolar macrophages with Mtb in the ex vivo cultures of cells from the resected lungs of even those TB patients, whose sputum smears and lung tissues did not contain acid-fast Mtb or reveal growing Mtb colonies on dense medium. The detection of alveolar macrophages with Mtb in ex vivo culture as soon as 16–18 h after isolation of cells from the resected lungs of all TB patients suggests that the technique proposed for assessing the level of infection in alveolar macrophages of TB patients has higher sensitivity than do prolonged bacteriological or pathomorphological methods. The proposed technique allowed us to rapidly (in two days after surgery) determine the level of infection with Mtb in the cells of the resected lungs of TB patients and, by the presence or absence of Mtb colonies, including those with cording morphology, the functional status of the TB agent at the time of surgery. PMID:29401466

Development of single nanometer-sized ultrafine oxygen bubbles to overcome the hypoxia-induced resistance to radiation therapy via the suppression of hypoxia-inducible factor-1α

PubMed Central

Honma, Kyoko; Nakano, Takashi; Asao, Takayuki; Kuwahara, Ryusuke; Aoyama, Kazuhiro; Yasuda, Hidehiro; Kelly, Matthew; Kuwano, Hiroyuki

2018-01-01

Radiation therapy can result in severe side-effects, including the development of radiation resistance. The aim of this study was to validate the use of oxygen nanobubble water to overcome resistance to radiation in cancer cell lines via the suppression of the hypoxia-inducible factor 1-α (HIF-1α) subunit. Oxygen nanobubble water was created using a newly developed method to produce nanobubbles in the single-nanometer range with the ΣPM-5 device. The size and concentration of the oxygen nanobubbles in the water was examined using a cryo-transmission electron microscope. The nanobubble size was ranged from 2 to 3 nm, and the concentration of the nanobubbles was calculated at 2×1018 particles/ml. Cell viability and HIF-1α levels were evaluated in EBC-1 lung cancer and MDA-MB-231 breast cancer cells treated with or without the nanobubble water and radiation under normoxic and hypoxic conditions in vitro. The cancer cells grown in oxygen nanobubble-containing media exhibited a clear suppression of hypoxia-induced HIF-1α expression compared to the cells grown in media made with distilled water. Under hypoxic conditions, the EBC-1 and MDA-MB231 cells displayed resistance to radiation compared to the cells cultured under normoxic cells. The use of oxygen nanobubble medium significantly suppressed the hypoxia-induced resistance to radiation compared to the use of normal medium at 2, 6, 10 and 14 Gy doses. Importantly, the use of nanobubble media did not affect the viability and radiation sensitivity of the cancer cell lines, or the non-cancerous cell line, BEAS-2B, under normoxic conditions. This newly created single-nanometer range oxygen nanobubble water, without any additives, may thus prove to be a promising agent which may be used to overcome the hypoxia-induced resistance of cancer cells to radiation via the suppression of HIF-1α. PMID:29393397

[Motivations and obstacles to occupational disease claims in lung cancer patients: an exploratory psychosocial study].

PubMed

Britel, Manon; Pérol, Olivia; Blois Da Conceiçao, Stéphanie; Ficty, Manon; Brunet, Houria; Avrillon, Virginie; Charbotel, Barbara; Fervers, Béatrice

2017-10-02

The proportion of lung cancers with an occupational origin has been estimated to be between 10 and 20%. They are largely under-reported, as 60% are not compensated as occupational disease. Although most patients are not familiar with the process of compensation, other factors could explain this under-reporting. The aim of this study was to identify psychosocial factors that could impact patients with occupational lung cancer to claim for compensation. We conducted a case study involving semi-structured interviews with eight lung cancer patients enrolled in a cohort designed to systematically screen occupational exposures and propose claims for compensation to work-related cancer patients. Seven interviewed patients were familiar with occupational cancers, but most of them did not believe that past exposure could be related to their current disease. Patients associated compensation claims with a long and complex procedure for an abstract purpose. Several patients expressed a certain attachment to their employers. Interviewed patients often considered compensation claims to be a grievance procedure against the employers whom they did not consider to be responsible for their disease. Lung cancer is itself an obstacle to compensation considering the aggressive treatments and related adverse events, the poor medium-term prognosis and the predominant role of smoking in the etiology of the disease. Patients mentioned the financial compensation and the role of healthcare professionals as key elements to motivate them to claim for compensation.

Peribronchial innervation of the rat lung.

PubMed

Artico, Marco; Bosco, Sandro; Bronzetti, Elena; Felici, Laura M; Pelusi, Giuseppe; Lo Vasco, Vincenza Rita; Vitale, Marco

2004-10-01

Mammalian peribronchial tissue is supplied by several peptide-containing nerve fibers. Although it is well established that different neuropeptides exert significant effects on bronchial and vascular tone in the lungs, the role played by some neuromediators on the general regulation, differentiation and release of locally active substances is still controversial. We studied the innervation of rat peribronchial tissue by immunohistochemical techniques. The immunoperoxidase method with nickel amplification was applied to detect the distribution of nerve fibers using antibodies against the general neuronal marker PGP 9.5 (neuron-specific cytoplasmic protein), while the cholinacetyltransferase immunoreactivity was studied by immunohistochemistry. A slight immunoreactivity for NT receptors is observed in lung bronchial epithelium. There is increasing evidence that NTs may act with a paracrine mechanism regulating functional activity of neuronal and non-neuronal structures. A specific immunoreactivity for NTs and NT receptors was also demonstrated within different layers of large, medium and small sized intrapulmonary arteries and veins, according to a recent study of our group. Moreover our data describe the expression of NTs and NT receptors in lymphoid aggregates of the lung (BALT) in which both lymphocytes and macrophages express TrkA receptor and synthesize NTs. Our results show the presence of an extensive network of innervation in the rat peribronchial tissue, confirming a morphological basis for a possible neural modulation of the respiratory mucosa and the physiological/pathophysiological mechanisms of the lung.

Markers of mechanical asphyxia: immunohistochemical study on autoptic lung tissues.

PubMed

Cecchi, R; Sestili, C; Prosperini, G; Cecchetto, G; Vicini, E; Viel, G; Muciaccia, B

2014-01-01

Forensic pathologists are often asked to provide evidence of asphyxia death in the trial and a histological marker of asphyxiation would be of great help. Data from the literature indicate that the reaction of lung tissue cells to asphyxia may be of more interest for forensic purposes than migrating cells. The lungs of 62 medico-legal autopsy cases, 34 acute mechanical asphyxia (AMA), and 28 control cases (CC), were immunostained with anti-P-selectin, anti-E-selectin, anti-SP-A, and anti-HIF1-α antibodies, in order to verify if some of them may be used as markers of asphyxia death. Results show that P- and E-selectins expression in lung vessels, being activated by several types of trigger stimuli not specific to hypoxia, cannot be used as indicator of asphyxia. Intra-alveolar granular deposits of SP-A seem to be related to an intense hypoxic stimulus, and when massively present, they can suggest, together with other elements, a severe hypoxia as the mechanism of death. HIF1-α was expressed in small-, medium-, and large-caliber lung vessels of the vast majority of mechanical asphyxia deaths and CO intoxications, with the number and intensity of positive-stained vessels increasing with the duration of the hypoxia. Although further confirmation studies are required, these preliminary data indicate an interesting potential utility of HIF1-α as a screening test for asphyxia deaths.

Imaging Lung Clearance of Radiolabeled Tumor Cells to Study Mice with Normal, Activated or Depleted Natural Killer (NK) Cells

NASA Astrophysics Data System (ADS)

Kulkarni, P. V.; Bennett, M.; Constantinescu, A.; Arora, V.; Viguet, M.; Antich, P.; Parkey, R. W.; Mathews, D.; Mason, R. P.; Oz, O. K.

2003-08-01

Lung clearance of 51CR and 125I iododeoxyuridine (IUDR) labeled cancer cells assess NK cell activity. It is desirable to develop noninvasive imaging technique to assess NK activity in mice. We labeled target YAC-1 tumor cells with 125I, 111In, 99mTc, or 67Ga and injected I.V. into three groups of BALB/c mice. Animals were treated with medium (group I), 300mg/kg cyclophosmamide (CY) to kill NK cell (group II), or anti-LY49C/1) (ab')2 mAb to augment NK function (group III). Lungs were removed 15 min or 2 h later for tissue counting. Control and treated mice were imaged every 5 min with a scintillating camera for 1 h after 15 min of infusion of the 111In labeled cells. Lung clearance increased after 15 min (lodging: 60-80%) and (2 h retention: 3-7%). Similar results were obtained with all the isotopes studied. Images distinguished the control and treated mice for lung activity. Cells labeled with 111In, 99mTc or 67Ga are cleared similar to those labeled with 51Cr or 125I. NK cell destruction of tumor cells may be assessed by noninvasive imaging method either by SPECT (99mTc, 111In, 67Ga) or by PET (68Ga).

Causes of death and competing risk analysis of the associated factors for non-small cell lung cancer using the Surveillance, Epidemiology, and End Results database.

PubMed

Wei, Shenhai; Tian, Jintao; Song, Xiaoping; Wu, Bingqun; Liu, Limin

2018-01-01

To investigate the probability of death (POD) from any causes by time after diagnosis of non-small cell lung cancer (NSCLC) and the factors associated with survival for NSCLC patients. A total of 202,914 patients with NSCLC from 2004 to 2013 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The overall survival (OS) and lung cancer-specific survival (LCSS) were calculated and POD from any causes at different time periods after diagnosis was explored. The predictive factors for OS, LCSS and survival from non-lung cancer deaths were investigated using multivariate analysis with Cox proportional hazards regression and competing risk regression analysis. The 5- and 10-year OS were 20.4% and 11.5%, accordingly that for LCSS were 25.5% and 18.4%, respectively. Lung cancer contributed 88.3% (n = 128,402) of the deaths. The POD from lung cancer decreased with time after diagnosis. In multivariate analysis, advanced age and advanced stage of NSCLC were associated with decreased OS and LCSS. Comparing to no surgery, any kind of resection conferred lower risk of death from lung cancer and higher risk of dying from non-lung cancer conditions except lobectomy or bilobectomy, which was associated with lower risk of death from both lung cancer and non-lung cancer conditions. Most of the patients with NSCLC died from lung cancer. Rational surveillance and treatment policies should be made for them. Early stage and lobectomy or bilobectomy were associated with improved OS and LCSS. It is reasonable to focus on early detection and optimal surgical treatment for NSCLC.

Automated diagnosis of interstitial lung diseases and emphysema in MDCT imaging

NASA Astrophysics Data System (ADS)

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

2007-09-01

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

Effects of vasoactive intestinal polypeptide on antigen-induced bronchoconstriction and thromboxane release in guinea-pig lung.

PubMed Central

Ciabattoni, G.; Montuschi, P.; Currò, D.; Togna, G.; Preziosi, P.

1993-01-01

1. Exogenous vasoactive intestinal polypeptide (VIP) infused into the pulmonary artery of isolated and ventilated lungs of guinea-pigs decreased, in a dose-dependent fashion (1.0-10.0 nmol), airway resistance and thromboxane B2 (TXB2, the stable hydrolysis product of TXA2) release in the perfusion medium. Prostacyclin (PGI2) synthesis, as reflected by the release of its stable hydrolysis product 6-oxo-PGF1 alpha, was unaffected. Pretreatment with the 5-lipoxygenase inhibitor BWA4c (3.5 x 10(-5) M) did not modify the bronchodilatory effect of VIP or its inhibitory action on TXB2 release. 2. Basal release of immunoreactive VIP from perfused lungs decreased from an initial value of 0.96 +/- 0.10 ng min-1 (mean +/- s.e.mean) in the first 2 min to an average of 0.58 +/- 0.10 ng min-1 in the following 15-20 min. 3. Antigen challenge with ovalbumin (0.1%) in sensitized lungs caused an anaphylactic reaction in 45% of tested lungs, concomitant with a 5 fold increase in both VIP and TXB2 release. Tetrodotoxin pretreatment (10(-6) M) reduced basal VIP release by > 80% and abolished the VIP increase observed during anaphylaxis, without modifying TXB2 release or the bronchoconstrictor response. 4. Indomethacin (10(-6) M) inhibited TXB2 synthesis and release by > 90%, delayed the bronchoconstrictor response and blunted the increased VIP release during lung anaphylaxis, without influencing basal VIP release. 5. The 5-lipoxygenase inhibitor BWA4c (3.5 x 10(-5) M) blunted the increase of TXB2 and VIP release from guinea-pig lung and attenuated the bronchoconstrictor response following ovalbumin challenge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8495242

Respiratory physiotherapy in the pre and postoperative myocardial revascularization surgery.

PubMed

Cavenaghi, Simone; Ferreira, Lucas Lima; Marino, Lais Helena Carvalho; Lamari, Neuseli Marino

2011-01-01

The cardiovascular diseases are among the main death causes in the developed world. They have been increasing epidemically in the developing countries. In spite of several alternatives for the treatment of the coronary artery disease; the surgery of the myocardial revascularization is an option with proper indications of medium and long-term with good results. It provides the remission of the angina symptoms contributing to the increase of the expectation and improvement of the life quality. Most of patients undergoing myocardial revascularization surgery develop postoperative lung dysfunction with important reduction of the lung volumes, damages in the respiratory mechanism, decrease in the lung indulgence and increase of the respiratory work. The reduction of volumes and lung capacities can contribute to alterations in the gas exchanges, resulting in hypoxemia and decrease in the diffusion capacity. Taking this into account, the Physiotherapy has been requested more and more to perform in the pre as well as in the postoperative period of this surgery. This study aimed at updating the knowledge regarding the respiratory physiotherapy performance in the pre and postoperative period of the myocardial revascularization surgery enhancing the prevention of lung complications. The Physiotherapy uses several techniques in the preoperative period; such as: the incentive spirometry, exercises of deep breathing, cough, inspiratory muscle training, earlier ambulation and physiotherapeutic orientations. While in the postoperative period, the objective is the treatment after lung complications took place, performed by means of physiotherapeutic maneuvers and noninvasive respiratory devices, aiming at improving the respiratory mechanism, the lung reexpansion and the bronchial hygiene. Respiratory physiotherapy is an integral part in the care management of the patient with cardiopathy, either in the pre or in the postoperative period, since it contributes significantly to a better prognosis of these patients with the use of specific techniques.

B cell lymphoma with lung involvement: what is it about?

PubMed

Mian, Michael; Wasle, Ines; Gritsch, Stefan; Willenbacher, Wolfgang; Fiegl, Michael

2015-01-01

Primary lymphoma of the lung or pleural is a very rare condition. Due to the outdated literature data, the approximate occurrence of primary and secondary lung and/or pleural involvement according to the most common B cell lymphoma entities is unknown. To answer this open question in Austria, we screened the Tyrolean registry for B cell non-Hodgkin's lymphomas regarding primary and secondary lung involvement. Of 854 patients affected by B cell lymphoma, 7.5% had lung/pleural disease. This organ was the primary site in only 0.7%, while a secondary involvement was registered in 6.8%. Most of them were affected by diffuse large B cell lymphoma (DLBCL; 29/368, 8%) followed by follicular lymphoma (7/188, 4%), mantle cell lymphoma (7/57, 12%), mucosa-associated tissue lymphoma (10/37, 27%), posttransplant lymphoproliferative disease (6/24, 25%), Burkitt lymphoma (3/19, 16%), other lymphomas (1/32, 3%) and Richter transformation (1/11, 9%). Moreover, primary lung/pleural lymphoma is one of the rarest neoplasias affecting the lung, accounting for only 0.4% of cases. Lung/pleural involvement is a very rare condition among B cell lymphomas since it mainly occurs in the setting of a generalized disease. A large majority of patients with secondary organ involvement are affected by DLBCL and have similar clinical features at diagnosis to others with advanced-stage disease. © 2014 S. Karger AG, Basel.

Biomechanical deformable image registration of longitudinal lung CT images using vessel information

NASA Astrophysics Data System (ADS)

Cazoulat, Guillaume; Owen, Dawn; Matuszak, Martha M.; Balter, James M.; Brock, Kristy K.

2016-07-01

Spatial correlation of lung tissue across longitudinal images, as the patient responds to treatment, is a critical step in adaptive radiotherapy. The goal of this work is to expand a biomechanical model-based deformable registration algorithm (Morfeus) to achieve accurate registration in the presence of significant anatomical changes. Six lung cancer patients previously treated with conventionally fractionated radiotherapy were retrospectively evaluated. Exhale CT scans were obtained at treatment planning and following three weeks of treatment. For each patient, the planning CT was registered to the follow-up CT using Morfeus, a biomechanical model-based deformable registration algorithm. To model the complex response of the lung, an extension to Morfeus has been developed: an initial deformation was estimated with Morfeus consisting of boundary conditions on the chest wall and incorporating a sliding interface with the lungs. It was hypothesized that the addition of boundary conditions based on vessel tree matching would provide a robust reduction of the residual registration error. To achieve this, the vessel trees were segmented on the two images by thresholding a vesselness image based on the Hessian matrix’s eigenvalues. For each point on the reference vessel tree centerline, the displacement vector was estimated by applying a variant of the Demons registration algorithm between the planning CT and the deformed follow-up CT. An expert independently identified corresponding landmarks well distributed in the lung to compute target registration errors (TRE). The TRE was: 5.8+/- 2.9 , 3.4+/- 2.3 and 1.6+/- 1.3 mm after rigid registration, Morfeus and Morfeus with boundary conditions on the vessel tree, respectively. In conclusion, the addition of boundary conditions on the vessels significantly improved the accuracy in modeling the response of the lung and tumor over the course of radiotherapy. Minimizing and modeling these geometrical uncertainties will enable future plan adaptation strategies.

Evidence of reversible bradycardia and arrhythmias caused by immunogenic proteins secreted by T. cruzi in isolated rat hearts.

PubMed

Rodríguez-Angulo, Héctor O; Toro-Mendoza, Jhoan; Marques, Juan A; Concepción, Juan L; Bonfante-Cabarcas, Rafael; Higuerey, Yoliver; Thomas, Luz E; Balzano-Nogueira, Leandro; López, José R; Mijares, Alfredo

2015-02-01

Chagas cardiomyopathy, caused by the protozoan Trypanosoma cruzi, is characterized by alterations in intracellular ion, heart failure and arrhythmias. Arrhythmias have been related to sudden death, even in asymptomatic patients, and their molecular mechanisms have not been fully elucidated. The aim of this study is to demonstrate the effect of proteins secreted by T. cruzi on healthy, isolated beating rat heart model under a non-damage-inducing protocol. We established a non-damage-inducing recirculation-reoxygenation model where ultrafiltrate fractions of conditioned medium control or conditioned infected medium were perfused at a standard flow rate and under partial oxygenation. Western blotting with chagasic patient serum was performed to determine the antigenicity of the conditioned infected medium fractions. We observed bradycardia, ventricular fibrillation and complete atrioventricular block in hearts during perfusion with >50 kDa conditioned infected culture medium. The preincubation of conditioned infected medium with chagasic serum abolished the bradycardia and arrhythmias. The proteins present in the conditioned infected culture medium of >50 kDa fractions were recognized by the chagasic patient sera associated with arrhythmias. These results suggest that proteins secreted by T. cruzi are involved in Chagas disease arrhythmias and may be a potential biomarker in chagasic patients.

Evidence of Reversible Bradycardia and Arrhythmias Caused by Immunogenic Proteins Secreted by T. cruzi in Isolated Rat Hearts

PubMed Central

Rodríguez-Angulo, Héctor O.; Toro-Mendoza, Jhoan; Marques, Juan A.; Concepción, Juan L.; Bonfante-Cabarcas, Rafael; Higuerey, Yoliver; Thomas, Luz E.; Balzano-Nogueira, Leandro; López, José R.; Mijares, Alfredo

2015-01-01

Rationale Chagas cardiomyopathy, caused by the protozoan Trypanosoma cruzi, is characterized by alterations in intracellular ion, heart failure and arrhythmias. Arrhythmias have been related to sudden death, even in asymptomatic patients, and their molecular mechanisms have not been fully elucidated. Objective The aim of this study is to demonstrate the effect of proteins secreted by T. cruzi on healthy, isolated beating rat heart model under a non-damage-inducing protocol. Methods and Results We established a non-damage-inducing recirculation-reoxygenation model where ultrafiltrate fractions of conditioned medium control or conditioned infected medium were perfused at a standard flow rate and under partial oxygenation. Western blotting with chagasic patient serum was performed to determine the antigenicity of the conditioned infected medium fractions. We observed bradycardia, ventricular fibrillation and complete atrioventricular block in hearts during perfusion with >50 kDa conditioned infected culture medium. The preincubation of conditioned infected medium with chagasic serum abolished the bradycardia and arrhythmias. The proteins present in the conditioned infected culture medium of >50 kDa fractions were recognized by the chagasic patient sera associated with arrhythmias. Conclusions These results suggest that proteins secreted by T. cruzi are involved in Chagas disease arrhythmias and may be a potential biomarker in chagasic patients. PMID:25647069

Neonatal lungs--can absolute lung resistivity be determined non-invasively?

PubMed

Brown, B H; Primhak, R A; Smallwood, R H; Milnes, P; Narracott, A J; Jackson, M J

2002-07-01

The electrical resistivity of lung tissue can be related to the structure and composition of the tissue and also to the air content. Conditions such as pulmonary oedema and emphysema have been shown to change lung resistivity. However, direct access to the lungs to enable resistivity to be measured is very difficult. We have developed a new method of using electrical impedance tomographic (EIT) measurements on a group of 142 normal neonates to determine the absolute resistivity of lung tissue. The methodology involves comparing the measured EIT data with that from a finite difference model of the thorax in which lung tissue resistivity can be changed. A mean value of 5.7 +/- 1.7 omega(m) was found over the frequency range 4 kHz to 813 kHz. This value is lower than that usually given for adult lung tissue but consistent with the literature on the composition of the neonatal lung and with structural modelling.

Impact of Nutrient Restriction on the Structure of Listeria monocytogenes Biofilm Grown in a Microfluidic System.

PubMed

Cherifi, Tamazight; Jacques, Mario; Quessy, Sylvain; Fravalo, Philippe

2017-01-01

Biofilm formation by the pathogen Listeria monocytogenes is a major concern in food industries. The aim of this work was to elucidate the effect of nutrient limitation on both biofilm architecture and on the viability of the bacteria in microfluidic growth conditions. Biofilm formation by two L. monocytogenes strains was performed in a rich medium (BHI) and in a 10-fold diluted BHI (BHI/10) at 30°C for 24 h by using both static conditions and the microfluidic system Bioflux. In dynamic conditions, biofilms grown in rich and poor medium showed significant differences as well in structure and in the resulting biovolume. In BHI/10, biofilm was organized in a knitted network where cells formed long chains, whereas in the rich medium, the observed structure was homogeneous cellular multilayers. Biofilm biovolume production in BHI/10 was significantly higher than in BHI in these dynamic conditions. Interestingly, biovolume of dead cells in biofilms formed under limited nutrient conditions (BHI/10) was significantly higher than in biofilms formed in the BHI medium. In the other hand, in static conditions, biofilm is organized in a multilayer cells and dispersed cells in a rich medium BHI and poor medium BHI/10 respectively. There was significantly more biomass in the rich medium compared to BHI/10 but no difference was noted in the dead/damaged subpopulation showing how L. monocytogenes biofilm could be affected by the growth conditions. This work demonstrated that nutrient concentration affects biofilm structure and the proportion of dead cells in biofilms under microfluidic condition. Our study also showed that limited nutrients play an important role in the structural stability of L. monocytogenes biofilm by enhancing cell death and liberating extracellular DNA.

Impact of Nutrient Restriction on the Structure of Listeria monocytogenes Biofilm Grown in a Microfluidic System

PubMed Central

Cherifi, Tamazight; Jacques, Mario; Quessy, Sylvain; Fravalo, Philippe

2017-01-01

Biofilm formation by the pathogen Listeria monocytogenes is a major concern in food industries. The aim of this work was to elucidate the effect of nutrient limitation on both biofilm architecture and on the viability of the bacteria in microfluidic growth conditions. Biofilm formation by two L. monocytogenes strains was performed in a rich medium (BHI) and in a 10-fold diluted BHI (BHI/10) at 30°C for 24 h by using both static conditions and the microfluidic system Bioflux. In dynamic conditions, biofilms grown in rich and poor medium showed significant differences as well in structure and in the resulting biovolume. In BHI/10, biofilm was organized in a knitted network where cells formed long chains, whereas in the rich medium, the observed structure was homogeneous cellular multilayers. Biofilm biovolume production in BHI/10 was significantly higher than in BHI in these dynamic conditions. Interestingly, biovolume of dead cells in biofilms formed under limited nutrient conditions (BHI/10) was significantly higher than in biofilms formed in the BHI medium. In the other hand, in static conditions, biofilm is organized in a multilayer cells and dispersed cells in a rich medium BHI and poor medium BHI/10 respectively. There was significantly more biomass in the rich medium compared to BHI/10 but no difference was noted in the dead/damaged subpopulation showing how L. monocytogenes biofilm could be affected by the growth conditions. This work demonstrated that nutrient concentration affects biofilm structure and the proportion of dead cells in biofilms under microfluidic condition. Our study also showed that limited nutrients play an important role in the structural stability of L. monocytogenes biofilm by enhancing cell death and liberating extracellular DNA. PMID:28567031

Genetically and Phenotypically Distinct Pseudomonas aeruginosa Cystic Fibrosis Isolates Share a Core Proteomic Signature

PubMed Central

Penesyan, Anahit; Kumar, Sheemal S.; Kamath, Karthik; Shathili, Abdulrahman M.; Venkatakrishnan, Vignesh; Krisp, Christoph; Packer, Nicolle H.; Molloy, Mark P.; Paulsen, Ian T.

2015-01-01

The opportunistic pathogen Pseudomonas aeruginosa is among the main colonizers of the lungs of cystic fibrosis (CF) patients. We have isolated and sequenced several P. aeruginosa isolates from the sputum of CF patients and compared them with each other and with the model strain PAO1. Phenotypic analysis of CF isolates showed significant variability in colonization and virulence-related traits suggesting different strategies for adaptation to the CF lung. Genomic analysis indicated these strains shared a large set of core genes with the standard laboratory strain PAO1, and identified the genetic basis for some of the observed phenotypic differences. Proteomics revealed that in a conventional laboratory medium PAO1 expressed 827 proteins that were absent in the CF isolates while the CF isolates shared a distinctive signature set of 703 proteins not detected in PAO1. PAO1 expressed many transporters for the uptake of organic nutrients and relatively few biosynthetic pathways. Conversely, the CF isolates expressed a narrower range of transporters and a broader set of metabolic pathways for the biosynthesis of amino acids, carbohydrates, nucleotides and polyamines. The proteomic data suggests that in a common laboratory medium PAO1 may transport a diverse set of “ready-made” nutrients from the rich medium, whereas the CF isolates may only utilize a limited number of nutrients from the medium relying mainly on their own metabolism for synthesis of essential nutrients. These variations indicate significant differences between the metabolism and physiology of P. aeruginosa CF isolates and PAO1 that cannot be detected at the genome level alone. The widening gap between the increasing genomic data and the lack of phenotypic data means that researchers are increasingly reliant on extrapolating from genomic comparisons using experimentally characterized model organisms such as PAO1. While comparative genomics can provide valuable information, our data suggests that such extrapolations may be fraught with peril. PMID:26431321

Linear dimensions and volumes of human lungs

DOE PAGES

Hickman, David P.

2012-03-30

TOTAL LUNG Capacity is defined as “the inspiratory capacity plus the functional residual capacity; the volume of air contained in the lungs at the end of a maximal inspiration; also equals vital capacity plus residual volume” (from MediLexicon.com). Within the Results and Discussion section of their April 2012 Health Physics paper, Kramer et al. briefly noted that the lungs of their experimental subjects were “not fully inflated.” By definition and failure to obtain maximal inspiration, Kramer et. al. did not measure Total Lung Capacity (TLC). The TLC equation generated from this work will tend to underestimate TLC and does notmore » improve or update total lung capacity data provided by ICRP and others. Likewise, the five linear measurements performed by Kramer et. al. are only representative of the conditions of the measurement (i.e., not at-rest volume, but not fully inflated either). While there was significant work performed and the data are interesting, the data does not represent a maximal situation, a minimal situation, or an at-rest situation. Moreover, while interesting, the linear data generated by this study is limited by the conditions of the experiment and may not be fully comparative with other lung or inspiratory parameters, measures, or physical dimensions.« less

Optimal flow conditions of a tracheobronchial model to reengineer lung structures

NASA Astrophysics Data System (ADS)

Casarin, Stefano; Aletti, Federico; Baselli, Giuseppe; Garbey, Marc

2017-04-01

The high demand for lung transplants cannot be matched by an adequate number of lungs from donors. Since fully ex-novo lungs are far from being feasible, tissue engineering is actively considering implantation of engineered lungs where the devitalized structure of a donor is used as scaffold to be repopulated by stem cells of the receiving patient. A decellularized donated lung is treated inside a bioreactor where transport through the tracheobronchial tree (TBT) will allow for both deposition of stem cells and nourishment for their subsequent growth, thus developing new lung tissue. The key concern is to set optimally the boundary conditions to utilize in the bioreactor. We propose a predictive model of slow liquid ventilation, which combines a one-dimensional (1-D) mathematical model of the TBT and a solute deposition model strongly dependent on fluid velocity across the tree. With it, we were able to track and drive the concentration of a generic solute across the airways, looking for its optimal distribution. This was given by properly adjusting the pumps' regime serving the bioreactor. A feedback system, created by coupling the two models, allowed us to derive the optimal pattern. The TBT model can be easily invertible, thus yielding a straightforward flow/pressure law at the inlet to optimize the efficiency of the bioreactor.

Mesenchymal stem cell-conditioned medium triggers neuroinflammation and reactive species generation in organotypic cultures of rat hippocampus.

PubMed

Horn, Ana Paula; Bernardi, Andressa; Luiz Frozza, Rudimar; Grudzinski, Patrícia Bencke; Hoppe, Juliana Bender; de Souza, Luiz Fernando; Chagastelles, Pedro; de Souza Wyse, Angela Terezinha; Bernard, Elena Aida; Battastini, Ana Maria Oliveira; Campos, Maria Martha; Lenz, Guido; Nardi, Nance Beyer; Salbego, Christianne

2011-07-01

Cell therapy using bone marrow-derived mesenchymal stem cells (MSCs) seems to be a new alternative for the treatment of neurodegenerative diseases. Despite several promising results with their use, possible side effects are still unknown. In a previous work, we have shown that MSC-conditioned medium is toxic to hippocampal slice cultures and aggravates cell death induced by oxygen and glucose deprivation. In this work, we investigated whether the inflammatory response and/or reactive species formation could be involved in that toxicity. Rat organotypic hippocampal cultures were exposed for 24 h to conditioned medium from MSCs isolated from rat bone marrow. A marked glial activation was observed after exposure of cultures to MSC-conditioned medium, as evidenced by glial fibrillary acid protein (GFAP) and isolectin B(4) increase. Tumor necrosis factor-α and interleukin-6 levels were increased in the culture medium, and 2,7-dihydrodichlorofluorescein diacetate oxidation (indicating reactive species generation) and inducible nitric oxide synthase (iNOS) immunocontent were also higher after exposure of cultures to MSC-conditioned medium. Antioxidants (ascorbic acid and TROLOX(®)), N(ω)-nitro-l-arginine methyl ester hydrochloride, and anti-inflammatory drugs (indomethacin and dexamethasone) reduced cell death in hippocampal organotypic cultures after their exposure to MSC-conditioned medium. The results obtained here suggest that MSC-secreted factors trigger reactive species generation and neuroinflammation in organotypic cultures of hippocampus, introducing a note of caution in the use of these cells for neurological application.

The increase of microRNA-21 during lung fibrosis and its contribution to epithelial-mesenchymal transition in pulmonary epithelial cells.

PubMed

Yamada, Mitsuhiro; Kubo, Hiroshi; Ota, Chiharu; Takahashi, Toru; Tando, Yukiko; Suzuki, Takaya; Fujino, Naoya; Makiguchi, Tomonori; Takagi, Kiyoshi; Suzuki, Takashi; Ichinose, Masakazu

2013-09-24

The excess and persistent accumulation of fibroblasts due to aberrant tissue repair results in fibrotic diseases such as idiopathic pulmonary fibrosis. Recent reports have revealed significant changes in microRNAs during idiopathic pulmonary fibrosis and evidence in support of a role for microRNAs in myofibroblast differentiation and the epithelial-mesenchymal transition in the context of fibrosis. It has been reported that microRNA-21 is up-regulated in myofibroblasts during fibrosis and promotes transforming growth factor-beta signaling by inhibiting Smad7. However, expression changes in microRNA-21 and the role of microRNA-21 in epithelial-mesenchymal transition during lung fibrosis have not yet been defined. Lungs from saline- or bleomycin-treated C57BL/6 J mice and lung specimens from patients with idiopathic pulmonary fibrosis were analyzed. Enzymatic digestions were performed to isolate single lung cells. Lung epithelial cells were isolated by flow cytometric cell sorting. The expression of microRNA-21 was analyzed using both quantitative PCR and in situ hybridization. To induce epithelial-mesenchymal transition in culture, isolated mouse lung alveolar type II cells were cultured on fibronectin-coated chamber slides in the presence of transforming growth factor-β, thus generating conditions that enhance epithelial-mesenchymal transition. To investigate the role of microRNA-21 in epithelial-mesenchymal transition, we transfected cells with a microRNA-21 inhibitor. Total RNA was isolated from the freshly isolated and cultured cells. MicroRNA-21, as well as mRNAs of genes that are markers of alveolar epithelial or mesenchymal cell differentiation, were quantified using quantitative PCR. The lung epithelial cells isolated from the bleomycin-induced lung fibrosis model system had decreased expression of epithelial marker genes, whereas the expression of mesenchymal marker genes was increased. MicroRNA-21 was significantly upregulated in isolated lung epithelial cells during bleomycin-induced lung fibrosis and human idiopathic pulmonary fibrosis. MicroRNA-21 was also upregulated in the cultured alveolar epithelial cells under the conditions that enhance epithelial-mesenchymal transition. Exogenous administration of a microRNA-21 inhibitor prevented the increased expression of vimentin and alpha-smooth muscle actin in cultured primary mouse alveolar type II cells under culture conditions that induce epithelial-mesenchymal transition. Our experiments demonstrate that microRNA-21 is increased in lung epithelial cells during lung fibrosis and that it promotes epithelial-mesenchymal transition.

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

NASA Astrophysics Data System (ADS)

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 echo characteristics on each patient group and their pulmonary pathology is made. It is concluded that the technique may provide a potential tool in detecting pulmonary abnormalities. More controlled patient studies, however, are indicated as necessary to determine the sensitivity of the ultrasound technique.

Prevention of abnormal pulmonary mechanics in the postmortem guinea pig lung.

PubMed

Reynolds, A M; McEvoy, R D

1988-04-01

Severe postmortem bronchoconstriction has been shown previously in guinea pig lungs and linked to pulmonary blood loss during exsanguination (Lai et al., J. Appl. Physiol. 56: 308-314, 1984). To reexamine this phenomenon we measured postmortem airway function in anesthetized open-chest guinea pigs after sudden circulatory arrest. Animals were divided into 4 groups of 10 and ventilated for 15 min postmortem with different gases: 1) room air, 2) conditioned air, 3) dry 5% CO2-21% O2-74% N2, and 4) conditioned 5% CO2-21% O2-74% N2. In room air-ventilated lungs there was a 50% decrease in dynamic compliance (Cdyn) by 15 min and marked gas trapping compared with control lungs. Conditioning the room air did not attenuate these changes, but when 5% CO2 was added to the conditioned postmortem inspirate, gas trapping was eliminated and the fall in Cdyn was almost abolished. Ventilation with a dry 5% CO2 gas mixture at room temperature resulted in a 31% fall in Cdyn at 15 min but no gas trapping. We conclude that marked abnormalities of airway function occur postmortem in room air-ventilated guinea pig lungs in the absence of pulmonary blood loss. The changes are mainly due to airway hypocarbia, a known cause of bronchoconstriction, but a reduction in Cdyn can also occur if there is marked airway cooling and drying. Acute postmortem airway dysfunction can be prevented in the guinea pig by maintaining normal airway gas composition.

Pneumomediastinum

MedlinePlus

Pneumomediastinum is uncommon. The condition can be caused by injury or disease. Most often, it occurs when air leaks from any part of the lung or airways into the mediastinum. Increased pressure in the lungs or airways may be caused ...

[The Evaluation of Medical Demographic and Economic Losses of the Region Conditioned by Mortality of Lung Cancer].

PubMed

Zukov, R A; Modestov, A A; Safontsev, I P; Slepov, E V; Narkevich, A N

2017-11-01

The article presents evaluation of medical demographic and economic losses of population of the Krasnoyarskii kraii conditioned by mortality of lung cancer in 2010-2014 using DALY technology. In the Krasnoyarskii kraii, during 2010-2014 64,712 individuals died because of lung cancer. The mortality of male population surpasses corresponding indices of mortality of females up to 3.9 times. In the region, the standardized indicator mortality of lung cancer among males annually surpasses the same indicator among females at maximum up to 8.1 times. The DALY maximal absolute losses of among males were registered in 2010 and 2013 and fell on age group of 55-59 years and among females on the age group of 60-64 years in 2014. The maximal (up to 5.2 times) difference in values of DALY indicator was established in 2010 between male and female population. the maximal gap in in DALY indices between male and female population was established in the age of 55-59 years. Almost half of DALY losses among males was established in 2013 and among females in 2014. The total losses of gross regional product in the region because of mortality conditioned by lung cancer made up to 29.8 billions of rubles in 2010-2014.

Lung cancer, pulmonary emphysema and pleural effusion: An autopsy study.

PubMed

Marel, Miloslav; Koubkova, Leona; Kovarikova, Zuzana; Grandcourtova, Alzbeta; Petrik, Frantisek; Hroudova, Hana; Capkova, Linda; Kodet, Roman; Fila, Libor

2015-12-01

To determine the exact incidence of lung cancer, pulmonary emphysema and pleural effusion we decided to carry out an autopsy study. In this autopsy study carried out over two years, we compared the results of autopsy findings with the clinical data in accompanying records of the deceased. Among the 708 deceased subjects, there were 398 males and 310 females with a median age of 71 years. At autopsy, 55 cases of lung carcinoma (BCA) were found, of which 24 have not been identified during life (44%). Among the deceased with BCA, emphysema was also observed at autopsy in 40% of the cases. Pulmonary emphysema was described macroscopically in 28% of the full set of 708 deceased, whereas the accompanying records of the deceased described this condition in only 12% of the cases. Microscopic changes compatible with emphysema were identified in 54% of the examined lungs. Pleural effusions were described in the accompanying records of 13% of the deceased, while the autopsies showed this condition in 33% of the deceased. BCA was accompanied by effusion in 25% of the cases. The obtained results show that the studied conditions are present in more cases than are reported by clinicians. The study confirms the commonly accepted association between lung cancer and emphysema.

Lung parenchymal analysis on dynamic MRI in thoracic insufficiency syndrome to assess changes following surgical intervention

NASA Astrophysics Data System (ADS)

Jagadale, Basavaraj N.; Udupa, Jayaram K.; Tong, Yubing; Wu, Caiyun; McDonough, Joseph; Torigian, Drew A.; Campbell, Robert M.

2018-02-01

General surgeons, orthopedists, and pulmonologists individually treat patients with thoracic insufficiency syndrome (TIS). The benefits of growth-sparing procedures such as Vertical Expandable Prosthetic Titanium Rib (VEPTR)insertionfor treating patients with TIS have been demonstrated. However, at present there is no objective assessment metricto examine different thoracic structural components individually as to their roles in the syndrome, in contributing to dynamics and function, and in influencing treatment outcome. Using thoracic dynamic MRI (dMRI), we have been developing a methodology to overcome this problem. In this paper, we extend this methodology from our previous structural analysis approaches to examining lung tissue properties. We process the T2-weighted dMRI images through a series of steps involving 4D image construction of the acquired dMRI images, intensity non-uniformity correction and standardization of the 4D image, lung segmentation, and estimation of the parameters describing lung tissue intensity distributions in the 4D image. Based on pre- and post-operative dMRI data sets from 25 TIS patients (predominantly neuromuscular and congenital conditions), we demonstrate how lung tissue can be characterized by the estimated distribution parameters. Our results show that standardized T2-weighted image intensity values decrease from the pre- to post-operative condition, likely reflecting improved lung aeration post-operatively. In both pre- and post-operative conditions, the intensity values decrease also from end-expiration to end-inspiration, supporting the basic premise of our results.

Pentagalloyl glucose increases elastin deposition, decreases reactive oxygen species and matrix metalloproteinase activity in pulmonary fibroblasts under inflammatory conditions.

PubMed

Parasaram, Vaideesh; Nosoudi, Nasim; Chowdhury, Aniqa; Vyavahare, Naren

2018-04-30

Emphysema is characterized by degradation of lung alveoli that leads to poor airflow in lungs. Irreversible elastic fiber degradation by matrix metalloproteinases (MMPs) and reactive oxygen species (ROS) activity leads to loss of elasticity and drives the progression of this disease. We investigated if a polyphenol, pentagalloyl glucose (PGG) can increase elastin production in pulmonary fibroblasts. We also studied the effect of PGG treatment in reducing MMP activity and ROS levels in cells. We exposed rat pulmonary fibroblasts to two different types of inflammatory environments i.e., tumor necrosis factor-α (TNF-α) and cigarette smoke extract (CSE) to mimic the disease. Parameters like lysyl oxidase (LOX) and elastin gene expression, MMP-9 activity in the medium, lysyl oxidase (LOX) activity and ROS levels were studied to assess the effect of PGG on pulmonary fibroblasts. CSE inhibited lysyl oxidase (LOX) enzyme activity that resulted in a decreased elastin formation. Similarly, TNF-α treated cells showed less elastin in the cell layers. Both these agents caused increase in MMP activity and ROS levels in cells. However, when supplemented with PGG treatment along with these two inflammatory agents, we saw a significant increase in elastin deposition, reduction in both MMP activity and ROS levels. Thus PGG, which has anti-inflammatory, anti-oxidant properties coupled with its ability to aid in elastic fiber formation, can be a multifunctional drug to potentially arrest the progression of emphysema. Copyright © 2018 Elsevier Inc. All rights reserved.

When the Battle is Lost and Won: Delayed Chest Closure After Bilateral Lung Transplantation.

PubMed

Soresi, Simona; Sabashnikov, Anton; Weymann, Alexander; Zeriouh, Mohamed; Simon, André R; Popov, Aron-Frederik

2015-10-12

In this article we summarize benefits of delayed chest closure strategy in lung transplantation, addressing indications, different surgical techniques, and additional perioperative treatment. Delayed chest closure seems to be a valuable and safe strategy in managing patients with various conditions after lung transplantation, such as instable hemodynamics, need for high respiratory pressures, coagulopathy, and size mismatch. Therefore, this approach should be considered in lung transplant centers to give patients time to recover before the chest is closed.

Lung lobar collapse as the first manifestation of pulmonary epithelioid haemangioendothelioma diagnosed with fibreoptic bronchoscopy.

PubMed

Abdalla, Ahmed; Seedahmed, Elfateh; Bachuwa, Ghassan; Congdon, Douglas

2016-10-24

Pulmonary epithelioid haemangioendothelioma (PEH) is a rare tumour of endothelial origin that usually occurs in the lung and liver. It usually presents as bilateral multiple nodular lesions. We report a middle-aged woman with a unique presentation of PEH with lung lobar collapse. The diagnosis was made with fibreoptic bronchoscopy rather than video-assisted thoracoscopy. Clinicians and pathologists should be aware of rare conditions that can present as lung lobar collapse. 2016 BMJ Publishing Group Ltd.

Concomitant pulmonary infection with Nocardia transvalensis and Aspergillus ustus in lung transplantation.

PubMed

Cabada, Miguel M; Nishi, Shawn P; Lea, Alfred S; Schnadig, Vicki; Lombard, Gisele A; Lick, Scott D; Valentine, Vincent G

2010-08-01

Lung infections with Nocardia and Aspergillus spp in lung transplant recipients (LTRs) create diagnostic and therapeutic challenges. The present case illustrates the difficulties in identifying these pathogens in LTRs. A high degree of clinical suspicion and aggressive early management are required to ensure good outcomes. Although prospective data on treating these conditions are scarce, the empiric use of combination broad-spectrum anti-microbials initially seems prudent. Copyright (c) 2010 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Pulmonary manifestation of immunoglobulin G4-related disease in a 7-year-old immunodeficient boy with Epstein-Barr virus infection: a case report.

PubMed

Szczawinska-Poplonyk, Aleksandra; Wojsyk-Banaszak, Irena; Jonczyk-Potoczna, Katarzyna; Breborowicz, Anna

2016-06-08

Immunoglobulin G4-related disease (IgG4-RD) is a multiorgan fibroinflammatory condition with lymphoplasmacytic infiltrates containing abundant IgG4-positive plasma cells. The immunopathogenesis of the disease and the potential role of triggering autoantigens or infectious factors have not been clearly defined. Immunoglobulin G4-related lung disease is a new and emerging condition in pediatric patients and to date, there have been only two reports regarding pulmonary manifestation of IgG4-RD in children recently published. This is the first report of IgG4-related lung disease in an immunodeficient child with Epstein-Barr virus infection. We report on the case of a 7-year old atopic boy who was hospitalized with an initial clinical and radiological diagnosis of pneumonia, positive Epstein-Barr virus (EBV)-DNA in the blood and defective adaptive immunity. The lung CT showed a consolidated mass lesion adjacent to the posterior wall of the chest and the diaphragm. The child underwent surgical resection of the tumor, and the histologic examination of the lung specimens revealed lymphoplasmacytic infiltrates with fibrosis and vasculitis correlating with IgG4-related lung disease. Subsequent monitoring of the patient with lung CT, pulmonary function tests and IgG4 levels did not show signs of active disease. The diagnosis of IgG4-related lung disease in children is challenging because of its rarity, nonspecific symptomatology and heterogeneous morphological manifestations. Further studies are required in children with pulmonary presentation of IgG4-RD to better understand pathogenesis of this condition, possible immunological or infectious triggering factors, and finally, to determine pediatric patient-targeted therapeutic interventions.

Home kitchen ventilation, cooking fuels, and lung cancer risk in a prospective cohort of never smoking women in Shanghai, China

PubMed Central

Kim, Christopher; Gao, Yu-Tang; Xiang, Yong-Bing; Barone-Adesi, Francesco; Zhang, Yawei; Hosgood, H. Dean; Ma, Shuangge; Shu, Xiao-ou; Ji, Bu-Tian; Chow, Wong-Ho; Seow, Wei Jie; Bassig, Bryan; Cai, Qiuyin; Zheng, Wei; Rothman, Nathaniel; Lan, Qing

2014-01-01

Indoor air pollution (IAP) caused by cooking has been associated with lung cancer risk in retrospective case-control studies in developing and rural countries. We report the association of cooking conditions, fuel use, oil use and risk of lung cancer in a developed urban population in a prospective cohort of women in Shanghai. A total of 71,320 never smoking women were followed from 1996 through 2009 and 429 incident lung cancer cases were identified. Questionnaires collected information on household living and cooking practices for the women’s three most recent residences and utilization of cooking fuel and oil, and ventilation conditions. Cox proportional hazards regression estimated the association for kitchen ventilation conditions, cooking fuels, and use of cooking oils for the risk of lung cancer by hazard ratios (HR) with 95% confidence intervals (95% CI). Ever poor kitchen ventilation was associated with a 49% increase in lung cancer risk (HR: 1.49; 95% CI: 1.15–1.95) compared to never poor ventilation. Ever use of coal was not significantly associated. However, ever coal use with poor ventilation (HR: 1.69; 95% CI: 1.22–2.35) and twenty or more years of using coal (HR: 2.03; 95% CI: 1.35–3.05) was significantly associated compared to no exposure to coal or poor ventilation. Cooking oil use was not significantly associated. These results demonstrate that IAP from poor ventilation of coal combustion increases the risk of lung cancer and is an important public health issue in cities across China where people may have lived in homes with inadequate kitchen ventilation. PMID:24917360

Home kitchen ventilation, cooking fuels, and lung cancer risk in a prospective cohort of never smoking women in Shanghai, China.

PubMed

Kim, Christopher; Gao, Yu-Tang; Xiang, Yong-Bing; Barone-Adesi, Francesco; Zhang, Yawei; Hosgood, H Dean; Ma, Shuangge; Shu, Xiao-ou; Ji, Bu-Tian; Chow, Wong-Ho; Seow, Wei Jie; Bassig, Bryan; Cai, Qiuyin; Zheng, Wei; Rothman, Nathaniel; Lan, Qing

2015-02-01

Indoor air pollution (IAP) caused by cooking has been associated with lung cancer risk in retrospective case-control studies in developing and rural countries. We report the association of cooking conditions, fuel use, oil use, and risk of lung cancer in a developed urban population in a prospective cohort of women in Shanghai. A total of 71,320 never smoking women were followed from 1996 through 2009 and 429 incident lung cancer cases were identified. Questionnaires collected information on household living and cooking practices for the three most recent residences and utilization of cooking fuel and oil, and ventilation conditions. Cox proportional hazards regression estimated the association for kitchen ventilation conditions, cooking fuels, and use of cooking oils for the risk of lung cancer by hazard ratios (HR) with 95% confidence intervals (95% CI). Ever poor kitchen ventilation was associated with a 49% increase in lung cancer risk (HR: 1.49; 95% CI: 1.15-1.95) compared to never poor ventilation. Ever use of coal was not significantly associated. However, ever coal use with poor ventilation (HR: 1.69; 95% CI: 1.22-2.35) and 20 or more years of using coal with poor ventilation (HR: 2.03; 95% CI: 1.35-3.05) was significantly associated compared to no exposure to coal or poor ventilation. Cooking oil use was not significantly associated. These results demonstrate that IAP from poor ventilation of coal combustion increases the risk of lung cancer and is an important public health issue in cities across China where people may have lived in homes with inadequate kitchen ventilation. © 2014 UICC.

An improved medium for the anaerobic growth of Paracoccus denitrificans Pd1222

PubMed Central

Hahnke, Stefanie M.; Moosmann, Philipp; Erb, Tobias J.; Strous, Marc

2014-01-01

Paracoccus denitrificans is a well studied model organism with respect to its aerobic and anaerobic respiratory enzymes. However, until now, the growth medium for this organism has not been optimized for anaerobic growth. In particular, the requirements of P. denitrificans for trace elements (TEs) are not well known. In the present study we aimed to improve growth rates of P. denitrificans Pd1222 on a defined medium under anoxic conditions. We designed media containing different combinations of TEs at various concentrations, and tested their performance against previously reported media. Our results suggest that growth rate and yield depend on the availability and concentration of TEs in the medium. A chelated TE solution was more suitable than an acidified TE solution. Highest growth rates were achieved with medium comprising the TEs iron, manganese, molybdenum, copper and zinc ranging from 0.1 to 9 μM. On this medium, P. denitrificans Pd1222 grew with a generation time of 4.4 h under anoxic conditions and 2.8 h under oxic conditions. Diauxic growth was clearly shown with respect to nitrate and nitrite reduction under anoxic conditions. PMID:24550891

An improved medium for the anaerobic growth of Paracoccus denitrificans Pd1222.

PubMed

Hahnke, Stefanie M; Moosmann, Philipp; Erb, Tobias J; Strous, Marc

2014-01-01

Paracoccus denitrificans is a well studied model organism with respect to its aerobic and anaerobic respiratory enzymes. However, until now, the growth medium for this organism has not been optimized for anaerobic growth. In particular, the requirements of P. denitrificans for trace elements (TEs) are not well known. In the present study we aimed to improve growth rates of P. denitrificans Pd1222 on a defined medium under anoxic conditions. We designed media containing different combinations of TEs at various concentrations, and tested their performance against previously reported media. Our results suggest that growth rate and yield depend on the availability and concentration of TEs in the medium. A chelated TE solution was more suitable than an acidified TE solution. Highest growth rates were achieved with medium comprising the TEs iron, manganese, molybdenum, copper and zinc ranging from 0.1 to 9 μM. On this medium, P. denitrificans Pd1222 grew with a generation time of 4.4 h under anoxic conditions and 2.8 h under oxic conditions. Diauxic growth was clearly shown with respect to nitrate and nitrite reduction under anoxic conditions.

The Role of Paracrine and Autocrine Signaling in the Early Phase of Adipogenic Differentiation of Adipose-derived Stem Cells

PubMed Central

Hemmingsen, Mette; Vedel, Søren; Skafte-Pedersen, Peder; Sabourin, David; Collas, Philippe; Bruus, Henrik; Dufva, Martin

2013-01-01

Introduction High cell density is known to enhance adipogenic differentiation of mesenchymal stem cells, suggesting secretion of signaling factors or cell-contact-mediated signaling. By employing microfluidic biochip technology, we have been able to separate these two processes and study the secretion pathways. Methods and results Adipogenic differentiation of human adipose-derived stem cells (ASCs) cultured in a microfluidic system was investigated under perfusion conditions with an adipogenic medium or an adipogenic medium supplemented with supernatant from differentiating ASCs (conditioned medium). Conditioned medium increased adipogenic differentiation compared to adipogenic medium with respect to accumulation of lipid-filled vacuoles and gene expression of key adipogenic markers (C/EBPα, C/EBPβ, C/EBPδ, PPARγ, LPL and adiponectin). The positive effects of conditioned medium were observed early in the differentiation process. Conclusions Using different cell densities and microfluidic perfusion cell cultures to suppress the effects of cell-released factors, we have demonstrated the significant role played by auto- or paracrine signaling in adipocyte differentiation. The cell-released factor(s) were shown to act in the recruitment phase of the differentiation process. PMID:23723991

Adjusting tidal volume to stress index in an open lung condition optimizes ventilation and prevents overdistension in an experimental model of lung injury and reduced chest wall compliance.

PubMed

Ferrando, Carlos; Suárez-Sipmann, Fernando; Gutierrez, Andrea; Tusman, Gerardo; Carbonell, Jose; García, Marisa; Piqueras, Laura; Compañ, Desamparados; Flores, Susanie; Soro, Marina; Llombart, Alicia; Belda, Francisco Javier

2015-01-13

The stress index (SI), a parameter derived from the shape of the pressure-time curve, can identify injurious mechanical ventilation. We tested the hypothesis that adjusting tidal volume (VT) to a non-injurious SI in an open lung condition avoids hypoventilation while preventing overdistension in an experimental model of combined lung injury and low chest-wall compliance (Ccw). Lung injury was induced by repeated lung lavages using warm saline solution, and Ccw was reduced by controlled intra-abdominal air-insufflation in 22 anesthetized, paralyzed and mechanically ventilated pigs. After injury animals were recruited and submitted to a positive end-expiratory pressure (PEEP) titration trial to find the PEEP level resulting in maximum compliance. During a subsequent four hours of mechanical ventilation, VT was adjusted to keep a plateau pressure (Pplat) of 30 cmH2O (Pplat-group, n = 11) or to a SI between 0.95 and 1.05 (SI-group, n = 11). Respiratory rate was adjusted to maintain a 'normal' PaCO2 (35 to 65 mmHg). SI, lung mechanics, arterial-blood gases haemodynamics pro-inflammatory cytokines and histopathology were analyzed. In addition Computed Tomography (CT) data were acquired at end expiration and end inspiration in six animals. PaCO2 was significantly higher in the Pplat-group (82 versus 53 mmHg, P = 0.01), with a resulting lower pH (7.19 versus 7.34, P = 0.01). We observed significant differences in VT (7.3 versus 5.4 mlKg(-1), P = 0.002) and Pplat values (30 versus 35 cmH2O, P = 0.001) between the Pplat-group and SI-group respectively. SI (1.03 versus 0.99, P = 0.42) and end-inspiratory transpulmonary pressure (PTP) (17 versus 18 cmH2O, P = 0.42) were similar in the Pplat- and SI-groups respectively, without differences in overinflated lung areas at end- inspiration in both groups. Cytokines and histopathology showed no differences. Setting tidal volume to a non-injurious stress index in an open lung condition improves alveolar ventilation and prevents overdistension without increasing lung injury. This is in comparison with limited Pplat protective ventilation in a model of lung injury with low chest-wall compliance.

Scleroderma Related Lung Disease: Is There a Pathogenic Role for Adipokines?

PubMed Central

Haley, Shannon; Shah, Dilip; Romero, Freddy; Summer, Ross

2013-01-01

Scleroderma is a systemic autoimmune disease of unknown etiology whose hallmark features include endothelial cell dysfunction, fibroblast proliferation and immune dysregulation. Although virtually any organ can be pathologically involved in scleroderma, lung complications including interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are the leading cause of death in patients with this condition. Currently, the molecular mechanisms leading to development of scleroderma-related lung disease are poorly understood; however, the systemic nature of this condition has led many to implicate circulating factors in the pathogenesis of some of its organ impairment. In this article, we focus on a new class of circulating factors derived from adipose-tissue called adipokines, which are known to be altered in scleroderma. Recently, the adipokines adiponectin and leptin have been found to regulate biological activities in endothelial, fibroblast and immune cell types in lung and in many other tissues. The pleiotropic nature of these circulating factors and their functional activity on many cell types implicated in the pathogenesis of ILD and PAH suggest these hormones may play a mechanistic role in the onset and/or progression of scleroderma-related lung diseases. PMID:24173692

Glutamine drives glutathione synthesis and contributes to radiation sensitivity of A549 and H460 lung cancer cell lines

PubMed Central

Sappington, Daniel R.; Siegel, Eric R.; Hiatt, Gloria; Desai, Abhishek; Penney, Rosalind B.; Jamshidi-Parsian, Azemat; Griffin, Robert J.; Boysen, Gunnar

2016-01-01

Background Increased glutamine uptake is known to drive cancer cell proliferation, making tumor cells glutamine-dependent. Glutamine provides additional carbon and nitrogen sources for cell growth. The first step in glutamine utilization is its conversion to glutamate by glutaminase (GLS). Glutamate is a precursor for glutathione synthesis, and we investigated the hypothesis that glutamine drives glutathione synthesis and thereby contributes to cellular defense systems. Methods The importance of glutamine for glutathione synthesis was studied in H460 and A549 lung cancer cell lines using glutamine-free medium and Bis-2-(5-phenyl-acetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) a GLS inhibitor. Metabolic activities were determined by targeted mass spectrometry. Results A significant correlation between glutamine consumption and glutathione excretion was demonstrated in H460 and A549 tumor cells. Culturing in the presence of [13C5]glutamine demonstrated that by 12 hrs >50% of excreted glutathione is derived from glutamine. Culturing in glutamine-free medium or treatment with BPTES, a glutaminase (GLS)-specific inhibitor, reduced cell proliferation and viability, and abolished glutathione excretion. Treatment with glutathione-ester prevented BPTES induced cytotoxicity. Inhibition of GLS markedly radiosensitized the lung tumor cell lines, suggesting an important role of glutamine-derived glutathione in determining radiation sensitivity. Conclusions We demonstrate here for the first time that a significant amount of extracellular glutathione is directly derived from glutamine. This finding adds yet another important function to the already known glutamine dependence of tumor cells and probably tumors as well. General significance Glutamine is essential for synthesis and excretion of glutathione to promote cell growth and viability. PMID:26825773

Existence, functional impairment, and lung repair potential of endothelial colony-forming cells in oxygen-induced arrested alveolar growth.

PubMed

Alphonse, Rajesh S; Vadivel, Arul; Fung, Moses; Shelley, William Chris; Critser, Paul John; Ionescu, Lavinia; O'Reilly, Megan; Ohls, Robin K; McConaghy, Suzanne; Eaton, Farah; Zhong, Shumei; Yoder, Merv; Thébaud, Bernard

2014-05-27

Bronchopulmonary dysplasia and emphysema are life-threatening diseases resulting from impaired alveolar development or alveolar destruction. Both conditions lack effective therapies. Angiogenic growth factors promote alveolar growth and contribute to alveolar maintenance. Endothelial colony-forming cells (ECFCs) represent a subset of circulating and resident endothelial cells capable of self-renewal and de novo vessel formation. We hypothesized that resident ECFCs exist in the developing lung, that they are impaired during arrested alveolar growth in experimental bronchopulmonary dysplasia, and that exogenous ECFCs restore disrupted alveolar growth. Human fetal and neonatal rat lungs contain ECFCs with robust proliferative potential, secondary colony formation on replating, and de novo blood vessel formation in vivo when transplanted into immunodeficient mice. In contrast, human fetal lung ECFCs exposed to hyperoxia in vitro and neonatal rat ECFCs isolated from hyperoxic alveolar growth-arrested rat lungs mimicking bronchopulmonary dysplasia proliferated less, showed decreased clonogenic capacity, and formed fewer capillary-like networks. Intrajugular administration of human cord blood-derived ECFCs after established arrested alveolar growth restored lung function, alveolar and lung vascular growth, and attenuated pulmonary hypertension. Lung ECFC colony- and capillary-like network-forming capabilities were also restored. Low ECFC engraftment and the protective effect of cell-free ECFC-derived conditioned media suggest a paracrine effect. Long-term (10 months) assessment of ECFC therapy showed no adverse effects with persistent improvement in lung structure, exercise capacity, and pulmonary hypertension. Impaired ECFC function may contribute to arrested alveolar growth. Cord blood-derived ECFC therapy may offer new therapeutic options for lung diseases characterized by alveolar damage. © 2014 American Heart Association, Inc.

Intrinsic catch-up growth of hypoplastic fetal lungs is mediated by interleukin-6.

PubMed

Nogueira-Silva, Cristina; Moura, Rute S; Esteves, Nuno; Gonzaga, Sílvia; Correia-Pinto, Jorge

2008-07-01

Fetal lung hypoplasia is a common finding in several fetal conditions such as congenital diaphragmatic hernia (CDH). Interestingly, previous studies have demonstrated that hypoplastic lungs have the ability to recover to normal size, when relieved from mechanical factors. However, the underlying mechanisms remain largely unknown. Recently, interleukin-6 (IL-6) has been involved in catch-up growth phenomenon in children. Thus, we hypothesized that IL-6 could mediate fetal growth recover from hypoplastic lungs. Control and nitrofen-induced hypoplastic lung explants were cultured either in normal conditions or with IL-6 neutralizing antibodies. The total number of peripheral airway buds, epithelial perimeter, and total explant area were analyzed and daily branching rates were calculated. Additionally, IL-6 mRNA and protein expression was assessed both in qualitative (by in situ hybridization and immunohistochemistry) and in quantitative (by real-time PCR and Western blot) approaches, in control and hypoplastic lungs (nitrofen and CDH groups). Nitrofen-induced hypoplastic lungs showed in vitro, out of systemic environment, the ability to recover from hypoplasia and presented daily branching rates significantly higher than controls. Blocking IL-6 activity significantly diminished the intrinsic capacity of hypoplastic fetal lungs to recover from hypoplasia and attenuated their daily branching rates. Although more exacerbated in CDH, both nitrofen-exposed lungs presented significant IL-6 mRNA and protein over-expression throughout all studied gestational ages. The present study suggests, for the first time, that fetal lung is able to recover from growth retardation through a way that resembles the catch-up growth phenomenon, and it seems to be, at least partially, orchestrated by intrinsic mechanisms implicating IL-6.

Medium factors on anaerobic production of rhamnolipids by Pseudomonas aeruginosa SG and a simplifying medium for in situ microbial enhanced oil recovery applications.

PubMed

Zhao, Feng; Zhou, Jidong; Han, Siqin; Ma, Fang; Zhang, Ying; Zhang, Jie

2016-04-01

Aerobic production of rhamnolipid by Pseudomonas aeruginosa was extensively studied. But effect of medium composition on anaerobic production of rhamnolipid by P. aeruginosa was unknown. A simplifying medium facilitating anaerobic production of rhamnolipid is urgently needed for in situ microbial enhanced oil recovery (MEOR). Medium factors affecting anaerobic production of rhamnolipid were investigated using P. aeruginosa SG (Genbank accession number KJ995745). Medium composition for anaerobic production of rhamnolipid by P. aeruginosa is different from that for aerobic production of rhamnolipid. Both hydrophobic substrate and organic nitrogen inhibited rhamnolipid production under anaerobic conditions. Glycerol and nitrate were the best carbon and nitrogen source. The commonly used N limitation under aerobic conditions was not conducive to rhamnolipid production under anaerobic conditions because the initial cell growth demanded enough nitrate for anaerobic respiration. But rhamnolipid was also fast accumulated under nitrogen starvation conditions. Sufficient phosphate was needed for anaerobic production of rhamnolipid. SO4(2-) and Mg(2+) are required for anaerobic production of rhamnolipid. Results will contribute to isolation bacteria strains which can anaerobically produce rhamnolipid and medium optimization for anaerobic production of rhamnolipid. Based on medium optimization by response surface methodology and ions composition of reservoir formation water, a simplifying medium containing 70.3 g/l glycerol, 5.25 g/l NaNO3, 5.49 g/l KH2PO4, 6.9 g/l K2HPO4·3H2O and 0.40 g/l MgSO4 was designed. Using the simplifying medium, 630 mg/l of rhamnolipid was produced by SG, and the anaerobic culture emulsified crude oil to EI24 = 82.5 %. The simplifying medium was promising for in situ MEOR applications.

Stochastic dosimetry model for radon progeny in the rat lung.

PubMed

Winkler-HeiI, R; Hofmann, W; Hussain, M

2014-07-01

The stochastic dosimetry model presented here considers the distinctly asymmetric, stochastic branching pattern reported in morphometric measurements. This monopodial structure suggests that an airway diameter is a more appropriate morphometric parameter to classify bronchial dose distributions for inhaled radon progeny than the commonly assigned airway generation numbers. Bronchial doses were calculated for the typical exposure conditions reported for the Pacific Northwest National Laboratory rat inhalation studies, yielding an average bronchial dose of 7.75 mGy WLM(-1). If plotted as functions of airway generations, the resulting dose distributions are highest in the central bronchial airways, while significantly decreasing towards peripheral generations. However, if plotted as functions of airway diameters, doses are much more uniformly distributed among bronchial airways. The comparison between rat and human lungs indicates that dose conversion coefficients for the rat lung are higher than the corresponding values for the human lung by a factor of 1.34 for the experimental PNNL exposure conditions, and of 1.25 for typical human indoor conditions. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Asymptomatic Pulmonary Allograft Kaposi Sarcoma: A Case Report.

PubMed

Nannini, Nazarena; Rebusso, Alessandro; Lunardi, Francesca; Loy, Monica; Calabrese, Francesca; Battistella, Lucia; Schiavon, Marco; Rea, Federico; Calabrese, Fiorella

2017-08-01

Solid-organ transplant recipients are at high risk of developing malignancies. A greater risk of Kaposi sarcoma has been reported in lung recipients in our country, particularly in those from Southern Italy, probably due to the high prevalence of Human herpes virus 8 infection. Kaposi sarcoma affecting only the lung allograft is extremely rare. We describe a case of a lung recipient who developed Kaposi sarcoma only in the graft, 22 months after transplant. The patient, a 65-year-old man from Southern Italy, underwent bilateral lung transplant for idiopathic pulmonary fibrosis in January 2009. He developed mild/moderate acute cellular rejection (≥A2) in 4 of 6 scheduled transbronchial biopsies thus was treated with increased immunosuppressive therapy, shifting from cyclosporine to tacrolimus and mycophenolate mofetil. In July 2010, a high-resolution computed tomography scan showed small bilateral lung nodules, despite a generally good condition. After 2 months, his condition worsened with a severe weight loss. A positron emission tomography scan showed mild metabolic activity in the lesions with no other localizations. In October 2010, a lung biopsy was performed, with results showing typical histologic and immunohistochemical features of Kaposi sarcoma. Molecular tissue evaluations and serologic analyses were positive for Human herpes virus 8. The patient's immunosuppressive therapy was suspended, and he started liposomal doxorubicin treatment; however, after the first cycle, he developed severe respiratory dysfunction. The patient died 27 months after lung transplant for neoplasm. Our report highlights the importance of considering Kaposi sarcoma in the differential diagnosis for lung nodules in lung transplant recipients, even in the absence of any initial specific symptom or cutaneous lesion.

Annexin II-Dependent Mechanism of Breast Cancer Progression

DTIC Science & Technology

2010-11-01

of the effects of tranexamic acid and urokinase on metastasis of Lewis lung carcinoma. Br. J. Cancer 46, 428–435. Tarui, T., et al., 2002. Plasmin...Lysine–Sepharose and ε- aminocaproic acid (ε-ACA)were procured from Sigma (St. Louis, MO). Chromatography and electrophoretic reagents were procured from...μl) with medium containing 10% fetal bovine serum (FBS). Test reagents (plasminogen, plasmin, angiostatin, ε-aminocaproic acid , or antibo- dies) were

Estimating oxygen diffusive conductances of gas-exchange systems: A stereological approach illustrated with the human placenta.

PubMed

Mayhew, Terry M

2014-01-01

For many organisms, respiratory gas exchange is a vital activity and different types of gas-exchange apparatus have evolved to meet individual needs. They include not only skin, gills, tracheal systems and lungs but also transient structures such as the chorioallantois of avian eggs and the placenta of eutherian mammals. The ability of these structures to allow passage of oxygen by passive diffusion can be expressed as a diffusive conductance (units: cm(3) O2 min(-1) kPa(-1)). Occasionally, the ability to estimate diffusive conductance by physiological techniques is compromised by the difficulty of obtaining O2 partial pressures on opposite sides of the tissue interface between the delivery medium (air, water, blood) and uptake medium (usually blood). An alternative strategy is to estimate a morphometric diffusive conductance by combining stereological estimates of key structural quantities (volumes, surface areas, membrane thicknesses) with complementary physicochemical data (O2-haemoglobin chemical reaction rates and Krogh's permeability coefficients). This approach has proved valuable in a variety of comparative studies on respiratory organs from diverse species. The underlying principles were formulated in pioneering studies on the pulmonary lung but are illustrated here by taking the human placenta as the gas exchanger. Copyright © 2012 Elsevier GmbH. All rights reserved.

Mycobacteriosis due to Mycobacterium genavense in six pet birds.

PubMed Central

Hoop, R K; Böttger, E C; Ossent, P; Salfinger, M

1993-01-01

Six cases of mycobacteriosis due to Mycobacterium genavense in three budgerigars (Melopsittacus undulatus), one orange-winged amazon (Amazona amazonica), one flycatcher (Cyanoptila cyanomelana), and one zebra finch (Taeniopygia guttata) are discussed. Gross lesions associated with the infection included a high degree of muscular wasting (five cases), hepatomegaly (four cases), and thickening of the wall of the small intestine (four cases). Granulomas were found in the lung (one case) and the subcutis (one case). Acid-fast bacilli were detected in the liver of all six birds. Only the use of acidic BACTEC mediums consistently led to growth, whereas the egg-based medium failed. These findings point to a possible role of the environment as a reservoir for M. genavense. Images PMID:8463407

Induction of endothelial cell proliferation by angiogenic factors released by activated monocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pakala, Rajbabu; Watanabe, Takuya; Benedict, Claude R

2002-06-01

Introduction: Cell-cell interaction is an essential component of atherosclerotic plaque development. Activated monocytes appear to play a central role in the development of atherosclerosis, not only through foam cell formation but also via the production of various growth factors that induce proliferation of different cell types that are involved in the plaque development. Using serum free co-culture method, we determined the effect of monocytes on endothelial cell proliferation. Methods: Endothelial cell proliferation is determined by the amount of [{sup 3}H]thymidine incorporated in to the DNA. Basic fibroblast growth factor (b-FGF), vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) levels inmore » the conditioned medium were determined by ELISA. Results: Conditioned medium from unactivated monocytes partially inhibited endothelial cell proliferation, whereas conditioned medium from activated monocytes promoted endothelial cell proliferation. The mitogenic effect of conditioned medium derived from activated monocytes is due to the presence of b-FGF, VEGF and IL-8. Neutralizing antibodies against b-FGF, VEGF and IL-8 partially reversed the mitogenic effect of conditioned medium derived from activated monocytes. When b-FGF, VEGF and IL-8 were immunoprecipitated from conditioned medium derived from activated monocytes, it is less mitogenic to endothelial cells. Conclusion: Activated monocytes may play an important role in the development of atherosclerotic plaque by producing endothelial cell growth factors.« less

Recurrent Soft Tissue Abscesses Caused by Legionella cincinnatiensis

PubMed Central

Gubler, Jacques G. H.; Schorr, Mirjam; Gaia, V.; Zbinden, R.; Altwegg, M.

2001-01-01

Recurrent soft tissue abscesses of the jaw, wrist, and arm developed in a 73-year-old housewife with nephrotic syndrome and immunoglobulin A(κ) gammopathy of unknown etiology. Conventional cultures remained negative, despite visible gram-negative rods on microscopy. Broad-spectrum PCR revealed Legionella cincinnatiensis, which was confirmed by isolation of the organism on special Legionella medium. Infections due to Legionella species outside the lungs are rare. L. cincinnatiensis has been implicated in only four cases of clinical infection; these involved the lungs in three patients and the central nervous system in one patient. We conclude that broad-spectrum PCR can be a valuable tool for the evaluation of culture-negative infections with a high probability of bacterial origin and that Legionella might be an underdiagnosed cause of pyogenic soft tissue infection. PMID:11724886

wnt3a but not wnt11 supports self-renewal of embryonic stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singla, Dinender K.; Schneider, David J.; LeWinter, Martin M.

2006-06-30

wnt proteins (wnts) promote both differentiation of midbrain dopaminergic cells and self-renewal of haematopoietic stem cells. Mouse embryonic stem (ES) cells can be maintained and self-renew on mouse feeder cell layers or in media containing leukemia inhibitory factor (LIF). However, the effects of wnts on ES cells self-renewal and differentiation are not clearly understood. In the present study, we found that conditioned medium prepared from L cells expressing wnt3a can replace feeder cell layers and medium containing LIF in maintaining ES cells in the proliferation without differentiation (self-renewal) state. By contrast, conditioned medium from NIH3T3 cells expressing wnt11 did not.more » Alkaline phosphatase staining and compact colony formation were used as criteria of cells being in the undifferentiated state. ES cells maintained in medium conditioned by Wnt3a expressing cells underwent freezing and thawing while maintaining properties seen with LIF maintained ES cells. Purified wnt3a did not maintain self-renewal of ES cells for prolonged intervals. Thus, other factors in the medium conditioned by wnt3a expressing cells may have contributed to maintenance of ES cells in a self-renewal state. Pluripotency of ES cells was determined with the use of embryoid bodies in vitro. PD98059, a MEK specific inhibitor, promoted the growth of undifferentiated ES cells maintained in conditioned medium from wnt3a expressing cells. By contrast, the P38 MAPK inhibitor SB230580 did not, suggesting a role for the MEK pathway in self-renewal and differentiation of ES cells maintained in the wnt3a cell conditioned medium. Thus, our results show that conditioned medium from wnt3a but not wnt11 expressing cells can maintain ES cells in self-renewal and in a pluripotent state.« less

Epidemiology of lung cancer prognosis: quantity and quality of life.

PubMed

Yang, Ping

2009-01-01

Primary lung cancer is very heterogeneous in its clinical presentation, histopathology, and treatment response; and like other diseases, the prognosis consists of two essential facets: survival and quality of life (QOL). Lung cancer survival is mostly determined by disease stage and treatment modality, and the 5-Year survival rate has been in a plateau of 15% for three decades. QOL is focused on life aspects that are affected by health conditions and medical interventions; the balance of physical functioning and suffering from treatment side effects has long been a concern of care providers as well as patients. Obviously needed are easily measurable biologic markers to stratify patients before treatment for optimal results in survival and QOL and to monitor treatment responses and toxicities. Targeted therapies toward the mechanisms of tumor development, growth, and metastasis are promising and actively translated into clinical practice. Long-term lung cancer (LTLC) survivors are people who are alive 5 Years after the diagnosis. Knowledge about the health and QOL in LTLC survivors is limited because outcome research in lung cancer has been focused mainly on short-term survival. The independent or combined effects of lung cancer treatment, aging, smoking and drinking, comorbid conditions, and psychosocial factors likely cause late effects, including organ malfunction, chronic fatigue, pain, or premature death among lung cancer survivors. New knowledge to be gained should help lung cancer survivors, their healthcare providers, and their caregivers by providing evidence for establishing clinical recommendations to enhance their long-term survival and health-related QOL.

An epidemiological study of risk factors for lung cancer in Guangzhou, China.

PubMed

Du, Y X; Cha, Q; Chen, X W; Chen, Y Z; Huang, L F; Feng, Z Z; Wu, X F; Wu, J M

1996-03-01

Lung cancer has been on a rapid rise worldwide during the last three or four decades, in part due to modern social habits and unhealthy lifestyles. Although smoking, air pollution, and certain types of occupational exposure have been recognized as the major risk factors for lung cancer, the significance of each of these factors appears to vary with sex, country, and with region within a given country. In the case of nonsmoking females, some risk factors for lung cancer remain to be identified. In the city of Guangzhou, lung cancer is one of the five leading tumors and the rate has been increasing steadily in both males and females since the 1970s. In this report, more than 6000 cases of lung cancer deaths, accumulated over the past 9 years, were analyzed. The severity of air pollution and cigarette smoking were positively correlated with the incidence of lung cancer deaths. Analysis of levels of SO2 and NOx suggests that the major source of indoor air pollution came from cooking. Two studies were performed in order to determine the relative contribution and importance of smoking, indoor air pollution and occupational exposure as risk factors for the rising incidence of lung cancer. The first was a population-based case-control study involving 849 subjects (566 males and 283 females). The second study was based on the data made available by the Third National Census survey, in which the standardized mortality rate (SMR) and population attributable risk (PAR) for lung cancer due to occupational exposure for the population in Guangzhou were analyzed. Results of these two studies show that: in females, indoor air pollution, derived primarily from burning coal, was found to be a highly significant risk factor for lung cancer. In males, however, cigarette smoking and occupational exposure were significantly associated with lung cancer. To further elucidate the contribution of indoor air pollution as a risk factor for lung cancer in nonsmoking females, two additional case-control studies were performed in 1985 and 1986. The 1985 study involved 120 nonsmokers (28 males, 92 females) in which the influence of such lifestyle factors as: personal history of nonmalignant respiratory diseases, fresh vegetable consumption, lifetime occupation and occupational exposure histories, exposure to environmental tobacco smoke (ETS), degree of indoor air pollution, general conditions of home residence, cooking practices and environments, and family history of cancer were first individually assessed and then collectively subjected to multiple conditional regression analysis for evaluation as risk factors for lung cancer. The 1986 study involved 75 cases of never-smoking females in which the aim was to investigate the influence of exposure to spousal smoke as a risk factor for lung cancer. These studies suggest that consumption of fresh vegetables was a "protective" factor for lung cancer in both males and females. In females, indoor air pollution and size of the kitchen were risk factors for lung cancer, whereas ETS exposure, respiratory disease history, family history of cancer, living conditions, use of cooking fuel, and participation in cooking, were not statistically associated with female lung cancer deaths. Occupational exposure was also correlated with the incidence of female lung cancer deaths. In males, chemists had the highest SMR, whereas in females, homemakers had the highest SMR. In males, the most common lung cancer cell type was squamous cell carcinoma, whereas in females adenocarcinoma was the most predominant type. The factors affecting the distribution of histologic lung cancer cell types were also investigated and discussed.

[Massive multiplication of coffee (Coffee arabica L. cv. Catimor) through embryogenic cell suspension culture].

PubMed

Flermoso-Gallardo, L; Menóndez-Yuffá, A

2000-01-01

Cell suspensions offer several advantages as a system for massive propagation because of the high rates of multiplication, the higher homogeneity in the culture conditions and the possibility of automatization. In this study, different experimental conditions were analyzed to establish embryogenic cell suspension cultures of coffee. The best conditions to establish the embryogenic cell suspension cultures of coffee were as follows: coffee leaf sections were cultivated during 12 weeks (Stage I) in a solid medium with the Murashige and Skoog salts, 2 mg/l kinetin and 0.5 mg/l 2,4-dichlorophenoxiacetic acid (medium 1). Under these conditions the explants formed a callus tissue that was transferred to a liquid medium containing 5 mg/l of 6-benzylamlno-purine (medium 2). After 12 days in a shaking liquid medium (Stage II), the cultures were sieved and were maintained In the same media, which was renewed every eight days (Stage III). This method yielded 1884 embryos in 50 ml; placing the embryos under conditions for germination yielded plantlets of normal appearance.

A qualitative analysis of communication between members of a hospital-based multidisciplinary lung cancer team.

PubMed

Rowlands, S; Callen, J

2013-01-01

The aim of the study was to explore how patient information is communicated between health professionals within a multidisciplinary hospital-based lung cancer team and to identify mechanisms to improve these communications. A qualitative method was employed using semi-structured in-depth interviews with a representative sample (n = 22) of members of a multidisciplinary hospital-based lung cancer team including medical, nursing and allied health professionals. Analysis was undertaken using a thematic grounded theory approach to derive key themes to describe communication patterns within the team and how communication could be improved. Two themes with sub-themes were identified: (1) characteristics of communication between team members including the impact of role on direction of communications, and doctors' dominance in communications; and (2) channels of communication including, preference for face-to-face and the suboptimal roles of the Multidisciplinary Team Meeting and the hospital medical record as mediums for communication. Traditional influences of role delineation and the dominance of doctors were found to impact on communication within the multidisciplinary hospital-based lung cancer team. Existing guidelines on implementation of multidisciplinary cancer care fail to address barriers to effective team communication. The paper-based medical record does not support team communications and alternative electronic solutions need to be used. © 2012 Blackwell Publishing Ltd.

Roller-massager application to the quadriceps and knee-joint range of motion and neuromuscular efficiency during a lunge.

PubMed

Bradbury-Squires, David J; Noftall, Jennifer C; Sullivan, Kathleen M; Behm, David G; Power, Kevin E; Button, Duane C

2015-02-01

Roller massagers are used as a recovery and rehabilitative tool to initiate muscle relaxation and improve range of motion (ROM) and muscular performance. However, research demonstrating such effects is lacking. To determine the effects of applying a roller massager for 20 and 60 seconds on knee-joint ROM and dynamic muscular performance. Randomized controlled clinical trial. University laboratory. Ten recreationally active men (age = 26.6 ± 5.2 years, height = 175.3 ± 4.3 cm, mass = 84.4 ± 8.8 kg). Participants performed 3 randomized experimental conditions separated by 24 to 48 hours. In condition 1 (5 repetitions of 20 seconds) and condition 2 (5 repetitions of 60 seconds), they applied a roller massager to the quadriceps muscles. Condition 3 served as a control condition in which participants sat quietly. Visual analog pain scale, electromyography (EMG) of the vastus lateralis (VL) and biceps femoris during roller massage and lunge, and knee-joint ROM. We found no differences in pain between the 20-second and 60-second roller-massager conditions. During 60 seconds of roller massage, pain was 13.5% (5.7 ± 0.70) and 20.6% (6.2 ± 0.70) greater at 40 seconds and 60 seconds, respectively, than at 20 seconds (P < .05). During roller massage, VL and biceps femoris root mean square (RMS) EMG was 8% and 7%, respectively, of RMS EMG recorded during maximal voluntary isometric contraction. Knee-joint ROM was 10% and 16% greater in the 20-second and 60-second roller-massager conditions, respectively, than the control condition (P < .05). Finally, average lunge VL RMS EMG decreased as roller-massage time increased (P < .05). Roller massage was painful and induced muscle activity, but it increased knee-joint ROM and neuromuscular efficiency during a lunge.

SU-E-J-91: Biomechanical Deformable Image Registration of Longitudinal Lung CT Images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cazoulat, G; Owen, D; Matuszak, M

2015-06-15

Purpose: Spatial correlation of lung tissue across longitudinal images, as the patient responds to treatment, is a critical step in adaptive radiotherapy. The goal of this work is to expand a biomechanical model-based deformable registration algorithm (Morfeus) to achieve accurate registration in the presence of significant anatomical changes. Methods: Four lung cancer patients previously treated with conventionally fractionated radiotherapy that exhibited notable tumor shrinkage during treatment were retrospectively evaluated. Exhale breathhold CT scans were obtained at treatment planning (PCT) and following three weeks (W3CT) of treatment. For each patient, the PCT was registered to the W3CT using Morfeus, a biomechanicalmore » model-based deformable registration algorithm, consisting of boundary conditions on the lungs and incorporating a sliding interface between the lung and chest wall. To model the complex response of the lung, an extension to Morfeus has been developed: (i) The vessel tree was segmented by thresholding a vesselness image based on the Hessian matrix’s eigenvalues and the centerline was extracted; (ii) A 3D shape context method was used to find correspondences between the trees of the two images; (ii) Correspondences were used as additional boundary conditions (Morfeus+vBC). An expert independently identified corresponding landmarks well distributed in the lung to compute Target Registration Errors (TRE). Results: The TRE within 15mm of the tumor boundaries (on average 11 landmarks) is: 6.1±1.8, 4.6±1.1 and 3.8±2.3 mm after rigid registration, Morfeus and Morfeus+vBC, respectively. The TRE in the rest of the lung (on average 13 landmarks) is: 6.4±3.9, 4.7±2.2 and 3.6±1.9 mm, which is on the order of the 2mm isotropic dose grid vector (3.5mm). Conclusion: The addition of boundary conditions on the vessels improved the accuracy in modeling the response of the lung and tumor over the course of radiotherapy. Minimizing and modeling these geometrical uncertainties will enable future plan adaptation strategies. This work was funded in part by NIH 2P01CA059827-16.« less

RAGE and tobacco smoke: insights into modeling chronic obstructive pulmonary disease

PubMed Central

Robinson, Adam B.; Stogsdill, Jeffrey A.; Lewis, Joshua B.; Wood, Tyler T.; Reynolds, Paul R.

2012-01-01

Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by chronic airway inflammation and airspace remodeling, leading to airflow limitation that is not completely reversible. Smoking is the leading risk factor for compromised lung function stemming from COPD pathogenesis. First- and second-hand cigarette smoke contain thousands of constituents, including several carcinogens and cytotoxic chemicals that orchestrate chronic lung inflammation and destructive alveolar remodeling. Receptors for advanced glycation end-products (RAGE) are multi-ligand cell surface receptors primarily expressed by diverse lung cells. RAGE expression increases following cigarette smoke exposure and expression is elevated in the lungs of patients with COPD. RAGE is responsible in part for inducing pro-inflammatory signaling pathways that culminate in expression and secretion of several cytokines, chemokines, enzymes, and other mediators. In the current review, new transgenic mouse models that conditionally over-express RAGE in pulmonary epithelium are discussed. When RAGE is over-expressed throughout embryogenesis, apoptosis in the peripheral lung causes severe lung hypoplasia. Interestingly, apoptosis in RAGE transgenic mice occurs via conserved apoptotic pathways also known to function in advanced stages of COPD. RAGE over-expression in the adult lung models features of COPD including pronounced inflammation and loss of parenchymal tissue. Understanding the biological contributions of RAGE during cigarette smoke-induced inflammation may provide critically important insight into the pathology of COPD. PMID:22934052

An investigation into the stability of commercial versus MG63-derived hepatocyte growth factor under flow cultivation conditions.

PubMed

Meneghello, Giulia; Storm, Michael P; Chaudhuri, Julian B; De Bank, Paul A; Ellis, Marianne J

2015-03-01

The scale-up of tissue engineering cell culture must ensure that conditions are maintained while also being cost effective. Here we analyse the stability of hepatocyte growth factor (HGF) to investigate whether concentrations change under dynamic conditions, and compare commercial recombinant human HGF as an additive in 'standard medium', to HGF secreted by the osteosarcoma cell line MG63 as a 'preconditioned medium'. After 3 h under flow conditions, HGF in the standard medium degraded to 40% of its original concentration but HGF in the preconditioned medium remained at 100%. The concentration of secreted HGF was 10 times greater than the working concentration of commercially-available HGF. Thus HGF within this medium has increased stability; MG63-derived HGF should therefore be investigated as a cost-effective alternative to current lyophilised powders for use in in vitro models. Furthermore, we recommend that those intending to use HGF (or other growth factors) should consider similar stability testing before embarking on experiments with media flow.

Transformation of proanthocyanidin A2 to its isomers under different physiological pH conditions and common cell culture medium.

PubMed

Lu, Wen-Chien; Huang, Wei-Ting; Kumaran, Alaganandam; Ho, Chi-Tang; Hwang, Lucy Sun

2011-06-08

Proanthocyanidins constitute an important class of polyphenols ubiquitously found in plants. They have been extensively studied for their antioxidant capacity and bioactivity in vitro and in animal models. However, their stability under different pH conditions and in cell culture medium has not been well documented. In the present study, it was observed that proanthocyanidin A2 (PA2) was relatively more stable in acidic condition than in weak alkaline condition. PA2 was also quite unstable in basal-Dulbecco's Modified Eagle medium (b-DMEM medium) at 37 °C. The addition of PA2 to the cell culture medium accelerated its epimerization with a half-life of <15 min, and ethylenediaminetetraacetic acid (EDTA) could not stop the reaction. The results also demonstrated that the major isomers transformed in the weak alkaline condition or cell culture medium at 37 °C were identified as epicatechin-(4β→8; 2β→O→7)-ent-catechin (proanthocyanidin A4) and epicatechin-(4β→6; 2β→O→7)-ent-catechin. The rates of transformation were dependent on the pH or the components of the medium. Therefore, the results obtained for PA2 in the cell culture bioassays, which were usually carried out for 24 h, might not represent the true activity of the original PA2. The stability and transformation of PA2 should be considered when the bioactivity of PA2 is evaluated in a given cell culture system.

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

PubMed

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

2013-01-01

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

The role of the adenosinergic system in lung fibrosis.

PubMed

Della Latta, Veronica; Cabiati, Manuela; Rocchiccioli, Silvia; Del Ry, Silvia; Morales, Maria-Aurora

2013-10-01

Adenosine (ADO) is a retaliatory metabolite that is expressed in conditions of injury or stress. During these conditions ATP is released at the extracellular level and is metabolized to adenosine. For this reason, adenosine is defined as a "danger signal" for cells and organs, in addition to its important role as homeostatic regulator. Its physiological functions are mediated through interaction with four specific transmembrane receptors called ADORA1, ADORA2A, ADORA2B and ADORA3. In the lungs of mice and humans all four adenosine receptors are expressed with different roles, having pro- and anti-inflammatory roles, determining bronchoconstriction and regulating lung inflammation and airway remodeling. Adenosine receptors can also promote differentiation of lung fibroblasts into myofibroblasts, typical of the fibrotic event. This last function suggests a potential involvement of adenosine in the fibrotic lung disease processes, which are characterized by different degrees of inflammation and fibrosis. Idiopathic pulmonary fibrosis (IPF) is the pathology with the highest degree of fibrosis and is of unknown etiology and burdened by lack of effective treatments in humans. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Primitive lung abscess: an unusual situation in children].

PubMed

Bouyahia, O; Jlidi, S; Sammoud, A

2014-12-01

Lung abscess is a localized area of non tuberculosis suppurative necrosis of the parenchyma lung, resulting in formation of a cavity containing purulent material. This pathology is uncommon in childhood. A 3-year-6 month-old boy was admitted with prolonged fever and dyspnea. Chest X-ray showed a non systemized, well limited, thick walled, hydric, and excavated opacity containing an air-fluid level. Chest ultrasound examination showed a collection of 6. 8 cm of diameter in the right pulmonary field with an air-fluid level. Hemoculture showed Staphylococcus aureus. The patient received large spectrum antibiotherapy. Three days after, he presented a septic shock and surgical drainage was indicated. Histological examination confirmed the diagnosis of lung abscess. Any underlying condition such as inoculation site, local cause or immune deficiency, was noted and diagnosis of primary abscess was made. The patient demonstrated complete recovery. He is asymptomatic with normal chest X-ray and pulmonary function after 3 years of evolution. Lung abscess represent a rare cause of prolonged fever in childhood. An underlying condition must be excluded to eliminate secondary abscess. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Antioxidant Activity and Cytotoxicity Effect of Cocoa Beans Subjected to Different Processing Conditions in Human Lung Carcinoma Cells

PubMed Central

Bauer, Deborah; de Abreu, Joel Pimentel; Oliveira, Hilana Salete Silva; Goes-Neto, Aristoteles; Koblitz, Maria Gabriela Bello

2016-01-01

Lung cancer is a common malignancy in men and the second leading cause of cancer-related mortality in men in the western world. Phenolic cocoa ingredients have a strong antioxidative activity and the potential to have a protective effect against cancer. In the present study, we have evaluated the influence of cocoa beans subjected to different processing conditions on cell viability and apoptosis of human lung cancer cells (A549). We measured the viability of lung cells treated with cocoa beans, unroasted slates (US), roasted slates (RS), unroasted well fermented (UWF) cocoa, and roasted well fermented (RWF) cocoa for 24 h. Using an MTT assay, we observed a decrease in the viability of A549 cells after treatment with cocoa bean extracts. Flow cytometer analysis revealed that cocoa beans increased the percentage of cells in sub-G1 phase and promoted up to twofold increase of apoptotic cells when compared to the control group. Taken together, the present study suggests that cocoa beans may have a protective effect against lung cancer. PMID:27034742

Regional volume changes in canine lungs suspended in air

NASA Technical Reports Server (NTRS)

Abbrecht, Peter H.; Kyle, Richard R.; Bryant, Howard J.; Feuerstein, Irwin

1995-01-01

The purpose of this study was to determine the effect of the absence of a pleural pressure gradient (simulating the presumed condition found in microgravity) upon regional expansion of the lung. We attempted to produce a uniform pressure over the surface of the lung by suspending excised lungs in air. Such studies should help determine whether or not the absence of a pleural pressure gradient leads to uniform ventilation. A preparation in which there is no pleural pressure gradient should also be useful in studying non-gravitational effects on ventilation distribution.

Particulate deposition in the human lung under lunar habitat conditions.

PubMed

Darquenne, Chantal; Prisk, G Kim

2013-03-01

Lunar dust may be a toxic challenge to astronauts. While deposition in reduced gravity is less than in normal gravity (1 G), reduced gravitational sedimentation causes particles to penetrate deeper in the lung, potentially causing more harm. The likely design of the lunar habitat has a reduced pressure environment and low-density gas has been shown to reduce upper airway deposition and increase peripheral deposition. Breathing air and a reduced-density gas approximating the density of the proposed lunar habitat atmosphere, five healthy subjects inhaled 1 -microm diameter aerosol boluses at penetration volumes (V(p)) of 200 ml (central airways), 500 ml, and 1000 ml (lung periphery) in microgravity during parabolic flight, and in 1 G. Deposition in the lunar habitat was significantly less than for Earth conditions (and less than in 1 G with the low-density gas) with a relative decrease in deposition of -59.1 +/- 14.0% (-46.9 +/- 11.7%), -50.7 +/- 9.2% (-45.8 +/- 11.2%), and -46.0 +/- 8.3% (-45.3 +/- 11.1%) at V(p) = 200, 500, and 1000 ml, respectively. There was no significant effect of reduced density on deposition in 1 G. While minimally affected by gas density, deposition was significantly less in microgravity than in 1 G for both gases, with a larger portion of particles depositing in the lung periphery under lunar conditions than Earth conditions. Thus, gravity, and not gas properties, mainly affects deposition in the peripheral lung, suggesting that studies of aerosol transport in the lunar habitat need not be performed at the low density proposed for the atmosphere in that environment.

Effect of culture medium, host strain and oxygen transfer on recombinant Fab antibody fragment yield and leakage to medium in shaken E. coli cultures.

PubMed

Ukkonen, Kaisa; Veijola, Johanna; Vasala, Antti; Neubauer, Peter

2013-07-29

Fab antibody fragments in E. coli are usually directed to the oxidizing periplasmic space for correct folding. From periplasm Fab fragments may further leak into extracellular medium. Information on the cultivation parameters affecting this leakage is scarce, and the unpredictable nature of Fab leakage is problematic regarding consistent product recovery. To elucidate the effects of cultivation conditions, we investigated Fab expression and accumulation into either periplasm or medium in E. coli K-12 and E. coli BL21 when grown in different types of media and under different aeration conditions. Small-scale Fab expression demonstrated significant differences in yield and ratio of periplasmic to extracellular Fab between different culture media and host strains. Expression in a medium with fed-batch-like glucose feeding provided highest total and extracellular yields in both strains. Unexpectedly, cultivation in baffled shake flasks at 150 rpm shaking speed resulted in higher yield and accumulation of Fabs into culture medium as compared to cultivation at 250 rpm. In the fed-batch medium, extracellular fraction in E. coli K-12 increased from 2-17% of total Fab at 250 rpm up to 75% at 150 rpm. This was partly due to increased lysis, but also leakage from intact cells increased at the lower shaking speed. Total Fab yield in E. coli BL21 in glycerol-based autoinduction medium was 5 to 9-fold higher at the lower shaking speed, and the extracellular fraction increased from ≤ 10% to 20-90%. The effect of aeration on Fab localization was reproduced in multiwell plate by variation of culture volume. Yield and leakage of Fab fragments are dependent on expression strain, culture medium, aeration rate, and the combination of these parameters. Maximum productivity in fed-batch-like conditions and in autoinduction medium is achieved under sufficiently oxygen-limited conditions, and lower aeration also promotes increased Fab accumulation into extracellular medium. These findings have practical implications for screening applications and small-scale Fab production, and highlight the importance of maintaining consistent aeration conditions during scale-up to avoid changes in product yield and localization. On the other hand, the dependency of Fab leakage on cultivation conditions provides a practical way to manipulate Fab localization.

Effect of culture medium, host strain and oxygen transfer on recombinant Fab antibody fragment yield and leakage to medium in shaken E. coli cultures

PubMed Central

2013-01-01

Background Fab antibody fragments in E. coli are usually directed to the oxidizing periplasmic space for correct folding. From periplasm Fab fragments may further leak into extracellular medium. Information on the cultivation parameters affecting this leakage is scarce, and the unpredictable nature of Fab leakage is problematic regarding consistent product recovery. To elucidate the effects of cultivation conditions, we investigated Fab expression and accumulation into either periplasm or medium in E. coli K-12 and E. coli BL21 when grown in different types of media and under different aeration conditions. Results Small-scale Fab expression demonstrated significant differences in yield and ratio of periplasmic to extracellular Fab between different culture media and host strains. Expression in a medium with fed-batch-like glucose feeding provided highest total and extracellular yields in both strains. Unexpectedly, cultivation in baffled shake flasks at 150 rpm shaking speed resulted in higher yield and accumulation of Fabs into culture medium as compared to cultivation at 250 rpm. In the fed-batch medium, extracellular fraction in E. coli K-12 increased from 2-17% of total Fab at 250 rpm up to 75% at 150 rpm. This was partly due to increased lysis, but also leakage from intact cells increased at the lower shaking speed. Total Fab yield in E. coli BL21 in glycerol-based autoinduction medium was 5 to 9-fold higher at the lower shaking speed, and the extracellular fraction increased from ≤ 10% to 20-90%. The effect of aeration on Fab localization was reproduced in multiwell plate by variation of culture volume. Conclusions Yield and leakage of Fab fragments are dependent on expression strain, culture medium, aeration rate, and the combination of these parameters. Maximum productivity in fed-batch-like conditions and in autoinduction medium is achieved under sufficiently oxygen-limited conditions, and lower aeration also promotes increased Fab accumulation into extracellular medium. These findings have practical implications for screening applications and small-scale Fab production, and highlight the importance of maintaining consistent aeration conditions during scale-up to avoid changes in product yield and localization. On the other hand, the dependency of Fab leakage on cultivation conditions provides a practical way to manipulate Fab localization. PMID:23895637

Indoor air pollution and the lung in low- and medium-income countries.

PubMed

Kurmi, Om P; Lam, Kin Bong Hubert; Ayres, Jon G

2012-07-01

Over half the world's population, mostly from developing countries, use solid fuel for domestic purposes and are exposed to very high concentrations of harmful air pollutants with potential health effects such as respiratory problems, cardiovascular problems, infant mortality and ocular problems. The evidence also suggests that, although the total percentage of people using solid fuel is decreasing, the absolute number is currently increasing. Exposure to smoke from solid fuel burning increases the risk of chronic obstructive pulmonary disease (COPD) and lung cancer in adults, and acute lower respiratory tract infection/pneumonia in children. Despite the heterogeneity among studies, the association between COPD and exposure to smoke produced by burning different types of solid fuel is consistent. However, there is strong evidence that while coal burning is a risk factor for lung cancer, exposure to other biomass fuel smoke is less so. There is some evidence that reduction of smoke exposure using improved cooking stoves reduces the risk of COPD and, possibly, acute lower respiratory infection in children, so approaches to reduce biomass smoke exposure are likely to result in reductions in the global burden of respiratory disease.

Adult Lung Spheroid Cells Contain Progenitor Cells and Mediate Regeneration in Rodents With Bleomycin-Induced Pulmonary Fibrosis.

PubMed

Henry, Eric; Cores, Jhon; Hensley, M Taylor; Anthony, Shirena; Vandergriff, Adam; de Andrade, James B M; Allen, Tyler; Caranasos, Thomas G; Lobo, Leonard J; Cheng, Ke

2015-11-01

Lung diseases are devastating conditions and ranked as one of the top five causes of mortality worldwide according to the World Health Organization. Stem cell therapy is a promising strategy for lung regeneration. Previous animal and clinical studies have focused on the use of mesenchymal stem cells (from other parts of the body) for lung regenerative therapies. We report a rapid and robust method to generate therapeutic resident lung progenitors from adult lung tissues. Outgrowth cells from healthy lung tissue explants are self-aggregated into three-dimensional lung spheroids in a suspension culture. Without antigenic sorting, the lung spheroids recapitulate the stem cell niche and contain a natural mixture of lung stem cells and supporting cells. In vitro, lung spheroid cells can be expanded to a large quantity and can form alveoli-like structures and acquire mature lung epithelial phenotypes. In severe combined immunodeficiency mice with bleomycin-induced pulmonary fibrosis, intravenous injection of human lung spheroid cells inhibited apoptosis, fibrosis, and infiltration but promoted angiogenesis. In a syngeneic rat model of pulmonary fibrosis, lung spheroid cells outperformed adipose-derived mesenchymal stem cells in reducing fibrotic thickening and infiltration. Previously, lung spheroid cells (the spheroid model) had only been used to study lung cancer cells. Our data suggest that lung spheroids and lung spheroid cells from healthy lung tissues are excellent sources of regenerative lung cells for therapeutic lung regeneration. The results from the present study will lead to future human clinical trials using lung stem cell therapies to treat various incurable lung diseases, including pulmonary fibrosis. The data presented here also provide fundamental knowledge regarding how injected stem cells mediate lung repair in pulmonary fibrosis. ©AlphaMed Press.

Mechlorethamine

MedlinePlus

... leukemia (CLL) and chronic myelogenous leukemia (CML); and lung cancer. Mechlorethamine is also used to treat polycythemia vera ( ... effusions (a condition when fluid collects in the lungs or around the heart) ... It works by slowing or stopping the growth of cancer cells in your body.

Lung volumes: measurement, clinical use, and coding.

PubMed

Flesch, Judd D; Dine, C Jessica

2012-08-01

Measurement of lung volumes is an integral part of complete pulmonary function testing. Some lung volumes can be measured during spirometry; however, measurement of the residual volume (RV), functional residual capacity (FRC), and total lung capacity (TLC) requires special techniques. FRC is typically measured by one of three methods. Body plethysmography uses Boyle's Law to determine lung volumes, whereas inert gas dilution and nitrogen washout use dilution properties of gases. After determination of FRC, expiratory reserve volume and inspiratory vital capacity are measured, which allows the calculation of the RV and TLC. Lung volumes are commonly used for the diagnosis of restriction. In obstructive lung disease, they are used to assess for hyperinflation. Changes in lung volumes can also be seen in a number of other clinical conditions. Reimbursement for measurement of lung volumes requires knowledge of current procedural terminology (CPT) codes, relevant indications, and an appropriate level of physician supervision. Because of recent efforts to eliminate payment inefficiencies, the 10 previous CPT codes for lung volumes, airway resistance, and diffusing capacity have been bundled into four new CPT codes.

A feasibility study of automatic lung nodule detection in chest digital tomosynthesis with machine learning based on support vector machine

NASA Astrophysics Data System (ADS)

Lee, Donghoon; Kim, Ye-seul; Choi, Sunghoon; Lee, Haenghwa; Jo, Byungdu; Choi, Seungyeon; Shin, Jungwook; Kim, Hee-Joung

2017-03-01

The chest digital tomosynthesis(CDT) is recently developed medical device that has several advantage for diagnosing lung disease. For example, CDT provides depth information with relatively low radiation dose compared to computed tomography (CT). However, a major problem with CDT is the image artifacts associated with data incompleteness resulting from limited angle data acquisition in CDT geometry. For this reason, the sensitivity of lung disease was not clear compared to CT. In this study, to improve sensitivity of lung disease detection in CDT, we developed computer aided diagnosis (CAD) systems based on machine learning. For design CAD systems, we used 100 cases of lung nodules cropped images and 100 cases of normal lesion cropped images acquired by lung man phantoms and proto type CDT. We used machine learning techniques based on support vector machine and Gabor filter. The Gabor filter was used for extracting characteristics of lung nodules and we compared performance of feature extraction of Gabor filter with various scale and orientation parameters. We used 3, 4, 5 scales and 4, 6, 8 orientations. After extracting features, support vector machine (SVM) was used for classifying feature of lesions. The linear, polynomial and Gaussian kernels of SVM were compared to decide the best SVM conditions for CDT reconstruction images. The results of CAD system with machine learning showed the capability of automatically lung lesion detection. Furthermore detection performance was the best when Gabor filter with 5 scale and 8 orientation and SVM with Gaussian kernel were used. In conclusion, our suggested CAD system showed improving sensitivity of lung lesion detection in CDT and decide Gabor filter and SVM conditions to achieve higher detection performance of our developed CAD system for CDT.

Comparison of static end-expiratory and effective lung volumes for gas exchange in healthy and surfactant-depleted lungs.

PubMed

Albu, Gergely; Wallin, Mats; Hallbäck, Magnus; Emtell, Per; Wolf, Andrew; Lönnqvist, Per-Arne; Göthberg, Sylvia; Peták, Ferenc; Habre, Walid

2013-07-01

Effective lung volume (ELV) for gas exchange is a new measure that could be used as a real-time guide during controlled mechanical ventilation. The authors established the relationships of ELV to static end-expiratory lung volume (EELV) with varying levels of positive end-expiratory pressure (PEEP) in healthy and surfactant-depleted rabbit lungs. Nine rabbits were anesthetized and ventilated with a modified volume-controlled mode where periods of five consecutive alterations in inspiratory/expiratory ratio (1:2-1.5:1) were imposed to measure ELV from the corresponding carbon dioxide elimination traces. EELV and the lung clearance index were concomitantly determined by helium wash-out technique. Airway and tissue mechanics were assessed by using low-frequency forced oscillations. Measurements were collected at PEEP 0, 3, 6, and 9 cm H2O levels under control condition and after surfactant depletion by whole-lung lavage. ELV was greater than EELV at all PEEP levels before lavage, whereas there was no evidence for a difference in the lung volume indices after surfactant depletion at PEEP 6 or 9 cm H2O. Increasing PEEP level caused significant parallel increases in both ELV and EELV levels, decreases in ventilation heterogeneity, and improvement in airway and tissue mechanics under control condition and after surfactant depletion. ELV and EELV exhibited strong and statistically significant correlations before (r=0.84) and after lavage (r=0.87). The parallel changes in ELV and EELV with PEEP in healthy and surfactant-depleted lungs support the clinical value of ELV measurement as a bedside tool to estimate dynamic changes in EELV in children and infants.

Toxicogenomics analysis of mouse lung responses following exposure to titanium dioxide nanomaterials reveal their disease potential at high doses

PubMed Central

Rahman, Luna; Wu, Dongmei; Johnston, Michael; William, Andrew; Halappanavar, Sabina

2017-01-01

Titanium dioxide nanoparticles (TiO2NPs) induce lung inflammation in experimental animals. In this study, we conducted a comprehensive toxicogenomic analysis of lung responses in mice exposed to six individual TiO2NPs exhibiting different sizes (8, 20 and 300nm), crystalline structure (anatase, rutile or anatase/rutile) and surface modifications (hydrophobic or hydrophilic) to investigate whether the mechanisms leading to TiO2NP-induced lung inflammation are property specific. A detailed histopathological analysis was conducted to investigate the long-term disease implications of acute exposure to TiO2NPs. C57BL/6 mice were exposed to 18, 54, 162 or 486 µg of TiO2NPs/mouse via single intratracheal instillation. Controls were exposed to dispersion medium only. Bronchoalveolar lavage fluid (BALF) and lung tissue were sampled on 1, 28 and 90 days post-exposure. Although all TiO2NPs induced lung inflammation as measured by the neutrophil influx in BALF, rutile-type TiO2NPs induced higher inflammation with the hydrophilic rutile TiO2NP showing the maximum increase. Accordingly, the rutile TiO2NPs induced higher number of differentially expressed genes. Histopathological analysis of lung sections on Day 90 post-exposure showed increased collagen staining and fibrosis-like changes following exposure to the rutile TiO2NPs at the highest dose tested. Among the anatase, the smallest TiO2NP of 8nm showed the maximum response. The anatase TiO2NP of 300nm was the least responsive of all. The results suggest that the severity of lung inflammation is property specific; however, the underlying mechanisms (genes and pathways perturbed) leading to inflammation were the same for all particle types. While the particle size clearly influenced the overall acute lung responses, a combination of small size, crystalline structure and hydrophilic surface contributed to the long-term pathological effects observed at the highest dose (486 µg/mouse). Although the dose at which the pathological changes were observed is considered physiologically high, the study highlights the disease potential of certain TiO2NPs of specific properties. PMID:27760801

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paudel, M R; Beachey, D J; Sarfehnia, A

Purpose: A new commercial GPU-based Monte Carlo dose calculation algorithm (GPUMCD) developed by the vendor Elekta™ to be used in the Monaco Treatment Planning System (TPS) is capable of modeling dose for both a standard linear accelerator and for an Elekta MRI-Linear accelerator (modeling magnetic field effects). We are evaluating this algorithm in two parts: commissioning the algorithm for an Elekta Agility linear accelerator (the focus of this work) and evaluating the algorithm’s ability to model magnetic field effects for an MRI-linear accelerator. Methods: A beam model was developed in the Monaco TPS (v.5.09.06) using the commissioned beam data formore » a 6MV Agility linac. A heterogeneous phantom representing tumor-in-lung, lung, bone-in-tissue, and prosthetic was designed/built. Dose calculations in Monaco were done using the current clinical algorithm (XVMC) and the new GPUMCD algorithm (1 mm3 voxel size, 0.5% statistical uncertainty) and in the Pinnacle TPS using the collapsed cone convolution (CCC) algorithm. These were compared with the measured doses using an ionization chamber (A1SL) and Gafchromic EBT3 films for 2×2 cm{sup 2}, 5×5 cm{sup 2}, and 10×10 cm{sup 2} field sizes. Results: The calculated central axis percentage depth doses (PDDs) in homogeneous solid water were within 2% compared to measurements for XVMC and GPUMCD. For tumor-in-lung and lung phantoms, doses calculated by all of the algorithms were within the experimental uncertainty of the measurements (±2% in the homogeneous phantom and ±3% for the tumor-in-lung or lung phantoms), except for 2×2 cm{sup 2} field size where only the CCC algorithm differs from film by 5% in the lung region. The analysis for bone-in-tissue and the prosthetic phantoms are ongoing. Conclusion: The new GPUMCD algorithm calculated dose comparable to both the XVMC algorithm and to measurements in both a homogeneous solid water medium and the heterogeneous phantom representing lung or tumor-in-lung for 2×2 cm{sup 2}-10×10 cm{sup 2} field sizes. Funding support was obtained from Elekta.« less

Micromechanical model of lung parenchyma hyperelasticity

NASA Astrophysics Data System (ADS)

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

Effect of environmental and cultural conditions on medium pH and explant growth performance of Douglas-fir ( Pseudotsuga menziesii) shoot cultures

PubMed Central

Chen, Chien-Chih; Bates, Rick; Carlson, John

2015-01-01

The medium pH level of plant tissue cultures has been shown to be essential to many aspects of explant development and growth. Sensitivity or tolerance of medium pH change in vitro varies according to specific requirements of individual species. The objectives of this study are to 1) determine medium pH change over time in storage conditions and with presence of explants, 2) evaluate the effects of medium pH change on explant growth performance and 3) assess the effects of adding a pH stabilizer, 2-(N-morpholino)ethanesulfonic acid (MES) that is commonly used in Douglas-fir micropropagation medium. Vegetative buds were collected in the spring before breaking dormancy from juvenile and mature donor trees for conducting these evaluations. Medium, with or without MES, was pre-adjusted to five pH levels before adding MES, agar and autoclaving. Medium pH changes and explant growth parameters were measured at eight different incubation times. Overall, MES provided a more stable medium pH, relative to starting pH values, under both light and dark storage conditions as well as with presence of explants. A general trend of decreasing medium pH over time was found comparing explants from juvenile and mature donor genotypes. Explant height and weight growth increased over time, but differ among explants from juvenile and mature donor genotypes. Our findings suggest that a 21-day subculture practice may best sustain medium freshness, medium pH level and desirable explant growth. PMID:26535110

Antitumor Activity of Rat Mesenchymal Stem Cells during Direct or Indirect Co-Culturing with C6 Glioma Cells.

PubMed

Gabashvili, A N; Baklaushev, V P; Grinenko, N F; Mel'nikov, P A; Cherepanov, S A; Levinsky, A B; Chehonin, V P

2016-02-01

The tumor-suppressive effect of rat mesenchymal stem cells against low-differentiated rat C6 glioma cells during their direct and indirect co-culturing and during culturing of C6 glioma cells in the medium conditioned by mesenchymal stem cells was studied in an in vitro experiment. The most pronounced antitumor activity of mesenchymal stem cells was observed during direct co-culturing with C6 glioma cells. The number of live C6 glioma cells during indirect co-culturing and during culturing in conditioned medium was slightly higher than during direct co-culturing, but significantly differed from the control (C6 glioma cells cultured in medium conditioned by C6 glioma cells). The cytotoxic effect of medium conditioned by mesenchymal stem cells was not related to medium depletion by glioma cells during their growth. The medium conditioned by other "non-stem" cells (rat astrocytes and fibroblasts) produced no tumor-suppressive effect. Rat mesenchymal stem cells, similar to rat C6 glioma cells express connexin 43, the main astroglial gap junction protein. During co-culturing, mesenchymal stem cells and glioma C6 cells formed functionally active gap junctions. Gap junction blockade with connexon inhibitor carbenoxolone attenuated the antitumor effect observed during direct co-culturing of C6 glioma cells and mesenchymal stem cells to the level produced by conditioned medium. Cell-cell signaling mediated by gap junctions can be a mechanism of the tumor-suppressive effect of mesenchymal stem cells against C6 glioma cells. This phenomenon can be used for the development of new methods of cell therapy for high-grade malignant gliomas.

Predictors of lung transplant survival in eurotransplant.

PubMed

Smits, J M A; Mertens, B J A; Van Houwelingen, H C; Haverich, A; Persijn, G G; Laufer, G

2003-11-01

This study was undertaken to assess the influence of patient/donor and center factors on lung transplantation outcome. Outcomes of all consecutive first cadaveric lung transplants performed at 21 Eurotransplant centers in 1997-99 were analyzed. The risk-adjusted center effect on mortality was estimated. A Cox model was built including donor and recipient age and gender, primary disease, HLA mismatches, patient's residence, cold ischemic time, donor's cause of death, serum creatinine, type of lung transplant, respiratory support status, clinical condition and percentage predicted FEV1. The center effect was calculated (expressed as the standardized difference between the observed and expected survival rates), and empirical and full Bayes methods were applied to evaluate between-center differences. A total of 590 adults underwent lung transplantation. The primary disease (p=0.01), HLA-mismatches (p = 0.02), clinical condition(p < 0.0001) and the patient's respiratory support status (p = 0.05) were significantly associated with survival. After adjusting for case-mix, no between-center differences could be found. An in-depth empirical Bayes analysis showed the between-center variation to be zero. Similar results were obtained from the full Bayes analysis. Based on these data, there is no scientific basis to support a hypothesis of possible association between center volume and lung survival rates.

Bronchoscopic drainage of a malignant lung abscess.

PubMed

Katsenos, Stamatis; Psathakis, Konstantinos; Chatzivasiloglou, Fotini; Antonogiannaki, Elvira-Markela; Psara, Anthoula; Tsintiris, Konstantinos

2015-04-01

Bronchoscopic drainage of a pyogenic lung abscess is an established therapeutic approach in selected patients in whom conventional antibiotic therapy fails. This intervention has also been undertaken in patients with abscess owing to underlying lung cancer and prior combined radiochemotherapy. However, this procedure has rarely been performed in cavitary lesions of advanced tumor origin before initiating any chemotherapy/radiotherapy scheme. Herein, we describe a case of a 68-year-old woman with lung adenocarcinoma stage IIIB, who underwent bronchoscopic drainage of necrotizing tumor lesion, thus improving her initial poor clinical condition and rendering other treatment modalities, such as radiotherapy, more effective and beneficial. Bronchoscopic drainage of a symptomatic cancerous lung abscess should be considered as an alternative and palliative treatment approach in patients with advanced inoperable non-small cell lung cancer.

Dynamic prognostication using conditional survival analysis for patients with operable lung adenocarcinoma

PubMed Central

Kim, Wooil; Lee, Ho Yun; Jung, Sin-Ho; Woo, Min-Ah; Kim, Hong Kwan; Choi, Yong Soo; Kim, Jhingook; Zo, Jae Ill; Shim, Young Mog; Han, Joungho; Jeong, Ji Yun; Choi, Joon Young; Lee, Kyung Soo

2017-01-01

Purpose To evaluate conditional survival among patients with surgically resected stage I-IIIa lung adenocarcinoma and identify changes in prognostic contributions for various prognostic factors over time. Patients and Methods We performed conditional survival analysis at each t0 (=0, 1, 2, 3, 4, 5 years) for 723 consecutive patients who underwent surgical resection for lung adenocarcinoma, stratified by various clinico-demographic features, as well as pathologic and imaging (tumor-shadow disappearance ratio [TDR] on CT and maximum standardized uptake value [SUVmax] on PET) characteristics. Uni- and multivariableCox regression analyses were performed to evaluate relationships between those variables and conditional survival. Results Three-year conditional overall survival (OS) and disease-free survival (DFS) were 92.12% and 75.51% at baseline, but improved steadily up to 98.33% and 95.95% at 5 years after surgery. In contrast to demographic factors, pathologic (stage, subtype, pathologic grade and differentiation) and radiologic factors (TDR and SUVmax) maintained a statistically significant association with subseqeunt 3-year OS until 3 years after surgery. According to the multivariableanalysis, high SUVmax and low TDR value were independent predictors of subsequent 3-year OS and DFS at baseline, 1 and 2 years after surgery, respectively. Conclusion Our findings based on CS provide theoretical background for clinicians to plan longer period of surveillance following lung adenocarcinoma resection in survivors with preoperatively high SUVmax and low TDR on PET-CT and chest CT, respectively. PMID:27793026

Lung Cancer in Patients with Severe Idiopathic Pulmonary Fibrosis: Critical Aspects.

PubMed

Bargagli, Elena; Bonti, Viola; Ferrari, Katia; Rosi, Elisabetta; Bindi, Alessandra; Bartolucci, Maurizio; Chiara, Moroni; Voltolini, Luca

2017-01-01

Idiopathic pulmonary fibrosis (IPF) is a rare interstitial lung disease limited to the lung with an undefined etiopathogenesis and a very short life expectancy (less than 5 years). IPF susceptibility has been associated with several genetic and environmental risk factors and the prognosis is conditioned by comorbidities such as gastro-esophageal reflux, depression, venous thromboembolism, pulmonary hypertension and lung cancer. At 5 years follow-up, 15% of IPF patients develop lung cancer, which can significantly reduce their survival. Because diagnostic or therapeutic procedures such as surgical, radiation or pharmacological treatments may induce acute exacerbations and increase mortality, the management of lung cancer in IPF patients is a very difficult task. This study discusses advantages and disadvantages of lung cancer treatments in patients with severe IPF, highlighting several controversial aspects on this topic, including potential nintedanib treatment. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

In Vitro Toxicity Screening Technique for Volatile Substances ...

EPA Pesticide Factsheets

In 2007 the National Research Council envisioned the need for inexpensive, high throughput, cell based toxicity testing methods relevant to human health. High Throughput Screening (HTS) in vitro screening approaches have addressed these problems by using robotics. However the challenge is that many of these chemicals are volatile and not amenable to HTS robotic liquid handling applications. We assembled an in vitro cell culture apparatus capable of screening volatile chemicals for toxicity with potential for miniaturization for high throughput. BEAS-2B lung cells were grown in an enclosed culture apparatus under air-liquid interface (ALI) conditions, and exposed to an array of xenobiotics in 5% CO2. Use of ALI conditions allows direct contact of cells with a gas xenobiotic, as well as release of endogenous gaseous molecules without interference by medium on the apical surface. To identify potential xenobiotic-induced perturbations in cell homeostasis, we monitored for alterations of endogenously-produced gaseous molecules in air directly above the cells, termed “headspace”. Alterations in specific endogenously-produced gaseous molecules (e.g., signaling molecules nitric oxide (NO) and carbon monoxide (CO) in headspace is indicative of xenobiotic-induced perturbations of specific cellular processes. Additionally, endogenously produced volatile organic compounds (VOCs) may be monitored in a nonspecific, discovery manner to determine whether cell processes are

[Pulmonary rehabilitation after total laryngectomy using a heat and moisture exchanger (HME)].

PubMed

Lorenz, K J; Maier, H

2009-08-01

A complete removal of the larynx has profound consequences for a patient. Since laryngectomy involves the separation of the upper airway from the lower airway, it not only implies a loss of the voice organ but also leads to chronic lung problems such as increased coughing, mucus production and expectoration. In addition, laryngectomees complain of fatigue, sleeping problems, a reduced sense of smell and taste, and a loss of social contact. A heat and moisture exchanger (HME) cassette can replace a function of the upper airway which consists in conditioning inspired air. It can improve pulmonary symptoms in three ways. 1. An HME cassette heats and moisturises inhaled air and thus creates nearly physiological conditions in the region of the deep airway. 2. The use of an HME cassette leads to an increase in breathing resistance, thereby reducing dynamic airway compression and improving lung ventilation. 3. An HME cassette acts as a filter and removes larger particles from incoming air. This review examines the current understanding of lung physiology after laryngectomy and assesses the effects of HME cassettes on the conditioning of respiratory air, lung function and psychosocial problems. Georg Thieme Verlag KG Stuttgart, New York.

A tree-parenchyma coupled model for lung ventilation simulation.

PubMed

Pozin, Nicolas; Montesantos, Spyridon; Katz, Ira; Pichelin, Marine; Vignon-Clementel, Irene; Grandmont, Céline

2017-11-01

In this article, we develop a lung ventilation model. The parenchyma is described as an elastic homogenized media. It is irrigated by a space-filling dyadic resistive pipe network, which represents the tracheobronchial tree. In this model, the tree and the parenchyma are strongly coupled. The tree induces an extra viscous term in the system constitutive relation, which leads, in the finite element framework, to a full matrix. We consider an efficient algorithm that takes advantage of the tree structure to enable a fast matrix-vector product computation. This framework can be used to model both free and mechanically induced respiration, in health and disease. Patient-specific lung geometries acquired from computed tomography scans are considered. Realistic Dirichlet boundary conditions can be deduced from surface registration on computed tomography images. The model is compared to a more classical exit compartment approach. Results illustrate the coupling between the tree and the parenchyma, at global and regional levels, and how conditions for the purely 0D model can be inferred. Different types of boundary conditions are tested, including a nonlinear Robin model of the surrounding lung structures. Copyright © 2017 John Wiley & Sons, Ltd.

X-irradiation of human bronchial cancer cells causes the bystander effects in normal bronchial cells in vitro.

PubMed

Konopacka, M; Rogoliński, J

2010-01-01

Using X radiation commonly used in radiotherapy of cancers we investigated bystander interactions between human cells: irradiated A549 bronchial carcinoma human cells and non irradiated BEAS-2B normal bronchial epithelial cells. Non irradiated cells were incubated in medium transferred from irradiated A549 cells (ICM-irradiation conditioned medium) for 48h and next the chromosomal damage and apoptosis were estimated. Conditioned medium collected from irradiated cancer cells induced in non irradiated cells of the same line as well as in BEAS-2B normal cells genetic changes such as micronuclei, chromatid and chromosomal breaks and condensation of chromatin characteristic for processes of apoptosis. Addition of only 1% of conditioned medium to fresh medium was sufficient to induction of bystander response to normal bronchial cells. The presented results in this study could have implications for human radiation risk and in evaluating the secondary effects of radiotherapy.

An invisible medium for circularly polarized electromagnetic waves.

PubMed

Tamayama, Y; Nakanishi, T; Sugiyama, K; Kitano, M

2008-12-08

We study the no reflection condition for a planar boundary between vacuum and an isotropic chiral medium. In general chiral media, elliptically polarized waves incident at a particular angle satisfy the no reflection condition. When the wave impedance and wavenumber of the chiral medium are equal to the corresponding parameters of vacuum, one of the circularly polarized waves is transmitted to the medium without reflection or refraction for all angles of incidence. We propose a circular polarizing beam splitter as a simple application of the no reflection effect. (c) 2008 Optical Society of America

Outcomes of lung transplantation in patients with scleroderma.

PubMed

Massad, Malek G; Powell, Charles R; Kpodonu, Jacques; Tshibaka, Cimenga; Hanhan, Ziad; Snow, Norman J; Geha, Alexander S

2005-11-01

Patients with pulmonary insufficiency due to scleroderma have long been considered suboptimal candidates for lung transplantation. This has been supported by small single-center experiences that did not reflect the entire U.S. experience. We sought to evaluate the outcome of patients with scleroderma who underwent lung transplantation. We conducted a retrospective review of 47 patients with scleroderma who underwent lung transplantation at 23 U.S. centers between 1987 and 2004 and were reported to the United Network for Organ Sharing. Women constituted 57% of the patients. The mean age was 46 years. Twenty-seven patients received single lung transplants (57%), and the remaining received double lung transplants. The mean cold ischemia time was 4.1 hours. There were 7 early deaths (< or =30 days) and 17 late deaths (> 30 days). The causes of early death were primary graft failure and a cardiac event in two patients each and bacterial infection and stroke in one patient each. Late mortality was due to infection in seven patients, respiratory failure in three, malignancy in two, and multisystem organ failure, rejection, pulmonary hypertension, and a cardiac event in one patient each. The causes of early and late death were not recorded for two patients. One patient received a second transplant owing to graft failure of the first. Twenty-three patients (49%) were alive at a mean follow-up of 24 months. The Kaplan-Meier 1- and 3-year survival rates were 67.6% and 45.9% respectively, which are not significantly different from those of 10,070 patients given transplants for other lung conditions during the same period (75.5% and 58.8% respectively, P = 0.25). Donor gender, recipient's age, and type of transplant did not affect survival. In carefully selected patients with scleroderma who have end-stage lung disease, lung transplantation is a valid life-saving therapeutic option. Available data suggest acceptable short-term morbidity and mortality and a long-term survival similar to that of patients given transplants for other lung conditions.

Recurrent Recruitment Manoeuvres Improve Lung Mechanics and Minimize Lung Injury during Mechanical Ventilation of Healthy Mice

PubMed Central

Reiss, Lucy Kathleen; Kowallik, Anke; Uhlig, Stefan

2011-01-01

Introduction Mechanical ventilation (MV) of mice is increasingly required in experimental studies, but the conditions that allow stable ventilation of mice over several hours have not yet been fully defined. In addition, most previous studies documented vital parameters and lung mechanics only incompletely. The aim of the present study was to establish experimental conditions that keep these parameters within their physiological range over a period of 6 h. For this purpose, we also examined the effects of frequent short recruitment manoeuvres (RM) in healthy mice. Methods Mice were ventilated at low tidal volume VT = 8 mL/kg or high tidal volume VT = 16 mL/kg and a positive end-expiratory pressure (PEEP) of 2 or 6 cmH2O. RM were performed every 5 min, 60 min or not at all. Lung mechanics were followed by the forced oscillation technique. Blood pressure (BP), electrocardiogram (ECG), heart frequency (HF), oxygen saturation and body temperature were monitored. Blood gases, neutrophil-recruitment, microvascular permeability and pro-inflammatory cytokines in bronchoalveolar lavage (BAL) and blood serum as well as histopathology of the lung were examined. Results MV with repetitive RM every 5 min resulted in stable respiratory mechanics. Ventilation without RM worsened lung mechanics due to alveolar collapse, leading to impaired gas exchange. HF and BP were affected by anaesthesia, but not by ventilation. Microvascular permeability was highest in atelectatic lungs, whereas neutrophil-recruitment and structural changes were strongest in lungs ventilated with high tidal volume. The cytokines IL-6 and KC, but neither TNF nor IP-10, were elevated in the BAL and serum of all ventilated mice and were reduced by recurrent RM. Lung mechanics, oxygenation and pulmonary inflammation were improved by increased PEEP. Conclusions Recurrent RM maintain lung mechanics in their physiological range during low tidal volume ventilation of healthy mice by preventing atelectasis and reduce the development of pulmonary inflammation. PMID:21935418

Black Lung Program: Further Improvements Can Be Made in Claims Adjudication

DTIC Science & Technology

1990-03-21

Law Judges SS Social Security Administration S I ction Miners sometimes develop black lung disease ( neumoconiosis or a chronic respiratory condition res...the identifica- tion and measurement of impairments involving the lung’s efficiency in exchanging oxygen and carbon dioxide. When these test results...and carbon dioxide. When these test results, judged by criteria established by the Secretary of Labor, demonstrate the miner’s inability to perform

Occupational pulmonary aluminosis: a case report.

PubMed

Smolková, Petra; Nakládalová, Marie; Tichý, Tomáš; Hampalová, Marie; Kolek, Vítězslav

2014-01-01

The authors present a case of occupational lung damage from exposure to dust containing aluminium. The first detected objective pathological finding was that of dispersed micronodules in the lungs seen in a chest radiograph. The final diagnosis of pulmonary aluminosis was established after three years of gradual exclusion of other interstitial lung diseases. The diagnosis was supported by the occupational history confirmed by hygiene assessment of the patient's workplace and especially by histological examination with elemental analysis of the lung tissue. The possibility of development of this rare condition should not be underestimated in workers at high-risk jobs.

Lung function requirements in flying duty the problem of bronchial hyperresponsiveness in military aircrew.

PubMed

Hartmann, C M; Steinhoff-Lankes, D; Maya-Pelzer, P

1999-09-09

Uncompromised lung function is essential for fitness to fly. Under hypobaric conditions there is an increased risk of hypoxemia. G-forces, positive pressure breathing and anti-G maneuvers cause physical stress to the lung tissue and altered pulmonary blood flow. Breathing with pure oxygen, dry cabin air and ozone can cause airway irritation. Chemically and physically by irritating agents may be present. Emergencies such as smoke in the cockpit or inhalation of tear gas can rapidly compromise the pulmonary system in susceptible persons. Sudden incapacitation may occur. Trapped gases may cause overinflation and lung rupture in rapid decompression. Applicants for military duty have to pass basic lung function tests routinely. Preselection of aircrew candidates tends to be even stricter. Asthma and obstructive lung disease are disqualifying. Trained aircrew with late onset of pulmonary problems can be waived under certain restrictions in many cases. Some national regulations exclude even applicants with allergies. Due to aeromedical experience we should always be aware of the latent unspecific bronchial hyperresponsiveness (BHR). BHR is one of the characteristics of asthma bronchiale. If BHR exists there is an increased risk of later development of asthma bronchiale, especially together with perennial allergies such as against house dust mite. Under certain conditions BHR can become symptomatic and aeromedically relevant. In some cases we saw an exacerbation under medication, mostly under beta-receptor-blockers. In one case even under betablocker-containing eye drops. In the Gulf War 1991 a number of allied military personnel had to be withdrawn because of bronchospastic symptoms. This can be explained among others by medication with physostigmine. Physostigmine is a systemically active cholinergic drug which is prophylactically used under threat of chemically warfare agents. In individuals with latent BHR physostigmine will lower the threshold for bronchial reactions considerably and even cause manifest bronchospasm. We recommend an unspecific bronchial challenge test in the selection of personnel for duties where uncompromised lung function under all environmental conditions is essential.

Asthma and lung cancer, after accounting for co-occurring respiratory diseases and allergic conditions: a systematic review protocol.

PubMed

Denholm, Rachel; Crellin, Elizabeth; Arvind, Ashwini; Quint, Jennifer

2017-01-16

Asthma is one of the most frequently diagnosed respiratory diseases in the UK, and commonly co-occurs with other respiratory and allergic diseases, such as chronic obstructive pulmonary disease (COPD) and atopic dermatitis. Previous studies have shown an increased risk of lung cancer related to asthma, but the evidence is mixed when accounting for co-occurring respiratory diseases and allergic conditions. A systematic review of published data that investigate the relationship between asthma and lung cancer, accounting for co-occurring respiratory and allergic diseases, will be conducted to investigate the independent association of asthma with lung cancer. A systematic review will be conducted, and include original reports of cohort, cross-sectional and case-control studies of the association of asthma with lung cancer after accounting for co-occurring respiratory diseases. Articles published up to June 2016 will be included, and their selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A standardised data extraction form will be developed and pretested, and descriptive analyses will be used to summarise the available literature. If appropriate, pooled effect estimates of the association between asthma and lung cancer, given adjustment for a specific co-occurring condition will be estimated using random effects models. Potential sources of heterogeneity and between study heterogeneity will also be investigated. The study will be a review of published data and does not require ethical approval. Results will be disseminated through a peer-reviewed publication. International Prospective Register for Systematic Reviews (PROSPERO) number CRD42016043341. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Impact of Obesity on Heart and Lung Transplantation: Does Pre-Transplant Obesity Affect Outcomes?

PubMed

Bozso, S J; Nagendran, Je; Gill, R S; Freed, D H; Nagendran, Ja

2017-03-01

Increasing prevalence of obesity has led to a rise in the number of prospective obese heart and lung transplant recipients. The optimal management strategy of obese patients with end-stage heart and lung failure remains controversial. This review article discusses and provides a summary of the literature surrounding the impact of obesity on outcomes in heart and lung transplantation. Studies on transplant obesity demonstrate controversy in terms of morbidity and mortality outcomes and obesity pre-transplantation. However, the impact of obesity on outcomes seems to be more consistently demonstrated in lung rather than heart transplantation. The ultimate goal in heart and lung transplantation in the obese patient is to identify those at highest risk of complication that may warrant therapies to mitigate risk by addressing comorbid conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2012-01-01

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

Human periodontal ligament stem cells secretome from multiple sclerosis patients suppresses NALP3 inflammasome activation in experimental autoimmune encephalomyelitis

PubMed Central

Soundara Rajan, Thangavelu; Giacoppo, Sabrina; Diomede, Francesca; Bramanti, Placido; Trubiani, Oriana; Mazzon, Emanuela

2017-01-01

Research in recent years has largely explored the immunomodulatory effects of mesenchymal stem cells (MSCs) and their secretory products, called “secretome,” in the treatment of neuroinflammatory diseases. Here, we examined whether such immunosuppressive effects might be elicited due to inflammasome inactivation. To this end, we treated experimental autoimmune encephalomyelitis (EAE) mice model of multiple sclerosis (MS) with the conditioned medium or purified exosomes/microvesicles (EMVs) obtained from relapsing-remitting-MS patients human periodontal ligament stem cells (hPDLSCs) and investigated the regulation of NALP3 inflammasome. We noticed enhanced expression of NALP3, Cleaved Caspase 1, interleukin (IL)-1β, and IL-18 in EAE mouse spinal cord. Conversely, hPDLSCs-conditioned medium and EMVs significantly blocked NALP3 inflammasome activation and provided protection from EAE. Reduction in NALP3, Cleaved Caspase 1, IL-1β, and IL-18 level was noticed in conditioned medium and EMVs-treated EAE mice. Pro-inflammatory Toll-like receptor (TLR)-4 and nuclear factor (NF)-κB were elevated in EAE, while hPDLSCs-conditioned medium and EMVs treatment reduced their expression and increased IκB-α expression. Characterization of hPDLSCs-conditioned medium showed substantial level of anti-inflammatory IL-10, transforming growth factor (TGF)-β, and stromal cell–derived factor 1α (SDF-1α). We propose that the immunosuppressive role of hPDLSCs-derived conditioned medium and EMVs in EAE mice may partly attribute to the presence of soluble immunomodulatory factors, NALP3 inflammasome inactivation, and NF-κB reduction. PMID:28764573

Encapsulated microsensors for reservoir interrogation

DOEpatents

Scott, Eddie Elmer; Aines, Roger D.; Spadaccini, Christopher M.

2016-03-08

In one general embodiment, a system includes at least one microsensor configured to detect one or more conditions of a fluidic medium of a reservoir; and a receptacle, wherein the receptacle encapsulates the at least one microsensor. In another general embodiment, a method include injecting the encapsulated at least one microsensor as recited above into a fluidic medium of a reservoir; and detecting one or more conditions of the fluidic medium of the reservoir.

Effects of vascular flow and PEEP in a multiple hit model of lung injury in isolated perfused rabbit lungs.

PubMed

Piacentini, Enrique; López-Aguilar, Josefina; García-Martín, Carolina; Villagrá, Ana; Saenz-Valiente, Alicia; Murias, Gastón; Fernández-Segoviano, Pilar; Hotchkiss, John R; Blanch, Lluis

2008-07-01

High vascular flow aggravates lung damage in animal models of ventilator-induced lung injury. Positive end-expiratory pressure (PEEP) can attenuate ventilator-induced lung injury, but its continued effectiveness in the setting of antecedent lung injury is unclear. The objective of the present study was to evaluate whether the application of PEEP diminishes lung injury induced by concurrent high vascular flow and high alveolar pressures in normal lungs and in a preinjury lung model. Two series of experiments were performed. Fifteen sets of isolated rabbit lungs were randomized into three groups (n = 5): low vascular flow/low PEEP; high vascular flow/low PEEP, and high vascular flow/high PEEP. Subsequently, the same protocol was applied in an additional 15 sets of isolated rabbit lungs in which oleic acid was added to the vascular perfusate to produce mild to moderate lung injury. All lungs were ventilated with peak airway pressure of 30 cm H2O for 30 minutes. Outcome measures included frequency of gross structural failure, pulmonary hemorrhage, edema formation, changes in static compliance, pulmonary vascular resistance, and pulmonary ultrafiltration coefficient. In the context of high vascular flow, application of a moderate level of PEEP reduced pulmonary rupture, edema formation, and lung hemorrhage. The protective effects of PEEP were not observed in lungs concurrently injured with oleic acid. Under these experimental conditions, PEEP attenuates lung injury in the setting of high vascular flow. The protective effect of PEEP is lost in a two-hit model of lung injury.

A new mechanism for DNA alterations induced by alpha particles such as those emitted by radon and radon progeny.

PubMed Central

Lehnert, B E; Goodwin, E H

1997-01-01

The mechanism(s) by which alpha (alpha) particles like those emitted from inhaled radon and radon progeny cause their carcinogenic effects in the lung remains unclear. Although direct nuclear traversals by alpha-particles may be involved in mediating these outcomes, increasing evidence indicates that a particles can cause alterations in DNA in the absence of direct hits to cell nuclei. Using the occurrence of excessive sister chromatid exchanges (SCE) as an index of DNA damage in human lung fibroblasts, we investigated the hypothesis that alpha-particles may induce DNA damage through the generation of extracellular factors. We have found that a relatively low dose of alpha-particles can result in the generation of extracellular factors, which, upon transfer to unexposed normal human cells, can cause excessive SCE to an extent equivalent to that observed when the cells are directly irradiated with the same irradiation dose. A short-lived, SCE-inducing factor(s) is generated in alpha-irradiated culture medium containing serum in the absence of cells. A more persistent SCE-inducing factor(s), which can survive freeze-thaw and is heat labile is produced by fibroblasts after exposure to the alpha-particles. These results indicate that the initiating target for alpha-particle-induced genetic changes can be larger than a cell's nucleus or even a whole cell. How transmissible factors like those observed here in vitro may extend to the in vivo condition in the context of a-particle-induced carcinogenesis in the respiratory tract remains to be determined. PMID:9400706

Pulmonary Veno-Occlusive Disease: A Newly Recognized Cause of Severe Pulmonary Hypertension in Dogs.

PubMed

Williams, K; Andrie, K; Cartoceti, A; French, S; Goldsmith, D; Jennings, S; Priestnall, S L; Wilson, D; Jutkowitz, A

2016-07-01

Pulmonary hypertension is a well-known though poorly characterized disease in veterinary medicine. In humans, pulmonary veno-occlusive disease (PVOD) is a rare cause of severe pulmonary hypertension with a mean survival time of 2 years without lung transplantation. Eleven adult dogs (5 males, 6 females; median age 10.5 years, representing various breeds) were examined following the development of severe respiratory signs. Lungs of affected animals were evaluated morphologically and with immunohistochemistry for alpha smooth muscle actin, desmin, CD31, CD3, CD20, and CD204. All dogs had pulmonary lesions consistent with PVOD, consisting of occlusive remodeling of small- to medium-sized pulmonary veins, foci of pulmonary capillary hemangiomatosis (PCH), and accumulation of hemosiderophages; 6 of 11 dogs had substantial pulmonary arterial medial and intimal thickening. Ultrastructural examination and immunohistochemistry showed that smooth muscle cells contributed to the venous occlusion. Increased expression of CD31 was evident in regions of PCH indicating increased numbers of endothelial cells in these foci. Spindle cells strongly expressing alpha smooth muscle actin and desmin co-localized with foci of PCH; similar cells were present but less intensely labeled elsewhere in non-PCH alveoli. B cells and macrophages, detected by immunohistochemistry, were not co-localized with the venous lesions of canine PVOD; small numbers of CD3-positive T cells were occasionally in and around the wall of remodeled veins. These findings indicate a condition in dogs with clinically severe respiratory disease and pathologic features resembling human PVOD, including foci of pulmonary venous remodeling and PCH. © The Author(s) 2016.

The physiological basis of bird flight

PubMed Central

Butler, Patrick J.

2016-01-01

Flapping flight is energetically more costly than running, although it is less costly to fly a given body mass a given distance per unit time than it is for a similar mass to run the same distance per unit time. This is mainly because birds can fly faster than they can run. Oxygen transfer and transport are enhanced in migrating birds compared with those in non-migrators: at the gas-exchange regions of the lungs the effective area is greater and the diffusion distance smaller. Also, migrating birds have larger hearts and haemoglobin concentrations in the blood, and capillary density in the flight muscles tends to be higher. Species like bar-headed geese migrate at high altitudes, where the availability of oxygen is reduced and the energy cost of flapping flight increased compared with those at sea level. Physiological adaptations to these conditions include haemoglobin with a higher affinity for oxygen than that in lowland birds, a greater effective ventilation of the gas-exchange surface of the lungs and a greater capillary-to-muscle fibre ratio. Migrating birds use fatty acids as their source of energy, so they have to be transported at a sufficient rate to meet the high demand. Since fatty acids are insoluble in water, birds maintain high concentrations of fatty acid–binding proteins to transport fatty acids across the cell membrane and within the cytoplasm. The concentrations of these proteins, together with that of a key enzyme in the β-oxidation of fatty acids, increase before migration. This article is part of the themed issue ‘Moving in a moving medium: new perspectives on flight’. PMID:27528774

The cancer secretome, current status and opportunities in the lung, breast and colorectal cancer context.

PubMed

Schaaij-Visser, Tieneke B M; de Wit, Meike; Lam, Siu W; Jiménez, Connie R

2013-11-01

Despite major improvements on the knowledge and clinical management, cancer is still a deadly disease. Novel biomarkers for better cancer detection, diagnosis and treatment prediction are urgently needed. Proteins secreted, shed or leaking from the cancer cell, collectively termed the cancer secretome, are promising biomarkers since they might be detectable in blood or other biofluids. Furthermore, the cancer secretome in part represents the tumor microenvironment that plays a key role in tumor promoting processes such as angiogenesis and invasion. The cancer secretome, sampled as conditioned medium from cell lines, tumor/tissue interstitial fluid or tumor proximal body fluids, can be studied comprehensively by nanoLC-MS/MS-based approaches. Here, we outline the importance of current cancer secretome research and describe the mass spectrometry-based analysis of the secretome. Further, we provide an overview of cancer secretome research with a focus on the three most common cancer types: lung, breast and colorectal cancer. We conclude that the cancer secretome research field is a young, but rapidly evolving research field. Up to now, the focus has mainly been on the discovery of novel promising secreted cancer biomarker proteins. An interesting finding that merits attention is that in cancer unconventional secretion, e.g. via vesicles, seems increased. Refinement of current approaches and methods and progress in clinical validation of the current findings are vital in order to move towards applications in cancer management. This article is part of a Special Issue entitled: An Updated Secretome. Copyright © 2013 Elsevier B.V. All rights reserved.

Isolation of Actinobacillus suis from a cat's lung.

PubMed Central

Daignault, D; Chouinard, L; Møller, K; Ahrens, P; Messier, S; Higgins, R

1999-01-01

Actinobacillus suis has been isolated from the lungs of 9-month-old cat. The bacterium was characterized biochemically as well as genetically, and its sensitivity profile to different antimicrobial agents was established. The role of this isolate in the cat's condition is discussed. PMID:9919368

Congenital Lobar Emphysema: An Approach of Anesthetic Management.

PubMed

Mourya, Meenakshi; Meena, Dharam Singh

2016-08-01

Congenital Lobar Emphysema (CLE) is a medical condition which is quiet rarely seen especially in neonates. The disease is characterized by over inflation of lungs which is produced due to inhibition of escape of inspired air from lungs. This condition usually occurs in infants due to partial obstruction of the bronchus and can be reversed with timely and planned anaesthetic management. Here in, we are presenting a case of an infant who was merely four months of age. CLE was affecting his left upper lobe since birth which was being treated as lobar pneumonia outside at some peripheral health center. The case presented to hospital with the symptoms acute respiratory distress and was taken up for urgent surgical management. Left upper lobectomy was performed which relived his symptoms. Case was discharged from hospital after 10 days of uneventful hospital stay. The case was challenging, as it involved careful and planned anaesthetic management of lung separation as well as prevention of hyperventilation of the un-involved lung.

A rare case of pulmonary toxoplasmosis in a patient with undifferentiated inflammatory arthritis on chronic methotrexate and corticosteroid therapy.

PubMed

Abdulkareem, Abdullateef; D'Souza, Ryan Steven; Patel, Nitin; Donato, Anthony A

2017-08-23

Pulmonary toxoplasmosis is a serious pulmonary condition caused by the protozoan Toxoplasma gondii It typically affects immunocompromised patients presenting acutely with cough, fever, myalgias, arthralgias and lymphadenopathy, and chronically with persistent cough and dyspnoea. Because of its protean features, it can mimic many more common lung conditions in the immunocompromised patient, including atypical pneumonia, Pneumocystis pneumonia and interstitial lung disease. In this article, we present the case of a 55-year-old woman who presented to our hospital with persistent dyspnoea and cough, initially suspected to have an arthritis-related interstitial lung disease. She received a final diagnosis of pulmonary toxoplasmosis after lung biopsy demonstrated Toxoplasma cysts, later confirmed by serology. Treatment with trimethoprim-sulfamethoxazole resulted in significant improvement of her respiratory symptoms after 3 months. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effects of biomaterial-derived fibroblast conditioned medium on the α-amylase expression of parotid gland acinar cells.

PubMed

Chou, Ya-Shuan; Young, Tai-Horng; Lou, Pei-Jen

2015-11-01

Salivary gland cells are surrounded by a complex stromal environment, in which fibroblasts are the main cells in proximity to the gland cells. In this study, the interaction between parotid gland acinar cells (PGACs), fibroblasts, and biomaterials was investigated. We prepared different biomaterials, including chitosan, polyvinyl alcohol (PVA), poly (ethylene-co-vinyl alcohol) (EVAL), polyvinylidene fluoride (PVDF), and tissue culture polystyrene (TCPS) to culture fibroblasts and then collect their conditioned media to culture PGACs. We observed no difference in AQP3, AQP5, and E-cadherin expression among different fibroblast conditioned medium treatments. Interestingly, α-amylase expression was obviously enhanced in PGACs cultured in the presence of conditioned medium from fibroblasts cultured on PVDF. Higher neurotrophin-4 (NT-4) expression was observed in PVDF-derived fibroblast conditioned medium using a growth factor protein array assay. In addition, directly adding NT-4 into the culture medium significantly promoted α-amylase expression by PGACs. Finally, nestin and βIII-tubulin expression by fibroblasts cultured on PVDF was also enhanced. Together, these results suggest that PVDF could promote α-amylase expression by PGACs via the NT-4 produced by fibroblasts. To date, there is no effective therapy for patients with dry mouth with persistent salivary hypofunction. The study made use of different biomaterials to culture fibroblasts and then collect their conditioned media to culture PGACs. It was found that the effect of fibroblast conditioned medium from PVDF on the α-amylase expression of PGACs was obviously enhanced and higher neurotrophin-4 (NT-4) expression was found in PVDF-derived fibroblast conditioned medium. In addition, directly adding NT-4 into the culture medium significantly promoted the expression of α-amylase by PGACs and the expression of nestin and βIII-tubulin of fibroblasts after being cultured on PVDF was enhanced. Therefore, the present study represents the first description of the role of NT-4 in the expression of α-amylase of PGACs and the role of PVDF in the reprogramming fibroblasts into neural progenitor-like cells, indicating that PVDF could promote the expression of α-amylase by PGACs via the NT-4 produced by fibroblasts. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Biotin deficiency inhibits heme synthesis and impairs mitochondria in human lung fibroblasts.

PubMed

Atamna, Hani; Newberry, Justin; Erlitzki, Ronit; Schultz, Carla S; Ames, Bruce N

2007-01-01

Four of the 5 biotin-dependent carboxylases (BDC) are in the mitochondria. BDC replace intermediates in the Krebs [tricarboxylic acid (TCA)] cycle that are regularly removed for the synthesis of key metabolites such as heme or amino acids. Heme, unlike amino acids, is not recycled to regenerate these intermediates, is not utilized from the diet, and must be synthesized in situ. We studied whether biotin deficiency (BD) lowers heme synthesis and whether mitochondria would be disrupted. Biotin-deficient medium was prepared by using bovine serum stripped of biotin with charcoal/dextran or avidin. Biotin-deficient primary human lung fibroblasts (IMR90) lost their BDC and senesced before biotin-sufficient cells. BD caused heme deficiency; there was a decrease in heme content and heme synthesis, and biotin-deficient cells selectively lost mitochondrial complex IV, which contains heme-a. Loss of complex IV, which is part of the electron transport chain, triggered oxidant release and oxidative damage, hallmarks of heme deficiency. Restoring biotin to the biotin-deficient medium prevented the above changes. Old cells were more susceptible to biotin shortage than young cells. These findings highlight the biochemical connection among biotin, heme, and iron metabolism, and the mitochondria, due to the role of biotin in maintaining the biochemical integrity of the TCA cycle. The findings are discussed in relation to aging and birth defects in humans.

CO2 clearance by membrane lungs.

PubMed

Sun, Liqun; Kaesler, Andreas; Fernando, Piyumindri; Thompson, Alex J; Toomasian, John M; Bartlett, Robert H

2018-05-01

Commercial membrane lungs are designed to transfer a specific amount of oxygen per unit of venous blood flow. Membrane lungs are much more efficient at removing CO 2 than adding oxygen, but the range of CO 2 transfer is rarely reported. Commercial membrane lungs were studied with the goal of evaluating CO 2 removal capacity. CO 2 removal was measured in 4 commercial membrane lungs under standardized conditions. CO 2 clearance can be greater than 4 times that of oxygen at a given blood flow when the gas to blood flow ratio is elevated to 4:1 or 8:1. The CO 2 clearance was less dependent on surface area and configuration than oxygen transfer. Any ECMO system can be used for selective CO 2 removal.

Relation between lower respiratory tract microbiota and type of immune response against tuberculosis.

PubMed

Nakhaee, Maede; Rezaee, Abdolrahim; Basiri, Reza; Soleimanpour, Saman; Ghazvini, Kiarash

2018-05-01

In this study, the interaction between the microbiota of the lower respiratory tract and the type of immune response against Mycobacterium tuberculosis were studied. Bronchoalveolar lavage (BAL) samples of 10 tuberculosis (TB) patients and 5 cases suspected of lung cancer as control were obtained. Clinical symptoms were recorded for the TB patients. Serial dilutions of samples were prepared and cultured on a selective medium in order to count Streptococcus spp., Neisseria spp., Haemophilus spp. and Veillonella in the lung. To determine the type of immune response of Th1/Th2, Real Time-PCR method was used. The prevalence of Streptococcus spp. in the lungs of patients with TB increased when compared with the control group and the Th1-response in this group may be influenced by Neisseria and Haemophilus. However, reducing the number of Streptococcus and Neisseria can be involved in the development of Th1-response in the control group. Prevalence of Neisseria and Veillonella of the lung microbiota in this group may be associated with fever. The chest x-ray influenced both Th1 and Th2-responses in the lung, but only Th1-response was involved in reducing the weight of patients. The relationship between each of the clinical symptoms with immune response and with each genus of microbiota were reviewed separately, and these data are the new information on TB disease and can be the beginning of the study on the impact of genus, different species and strains of microbiota on the clinical signs of disease. Copyright © 2018 Elsevier Ltd. All rights reserved.

Four-dimensional optical coherence tomography imaging of total liquid ventilated rats

NASA Astrophysics Data System (ADS)

Kirsten, Lars; Schnabel, Christian; Gaertner, Maria; Koch, Edmund

2013-06-01

Optical coherence tomography (OCT) can be utilized for the spatially and temporally resolved visualization of alveolar tissue and its dynamics in rodent models, which allows the investigation of lung dynamics on the microscopic scale of single alveoli. The findings could provide experimental input data for numerical simulations of lung tissue mechanics and could support the development of protective ventilation strategies. Real four-dimensional OCT imaging permits the acquisition of several OCT stacks within one single ventilation cycle. Thus, the entire four-dimensional information is directly obtained. Compared to conventional virtual four-dimensional OCT imaging, where the image acquisition is extended over many ventilation cycles and is triggered on pressure levels, real four-dimensional OCT is less vulnerable against motion artifacts and non-reproducible movement of the lung tissue over subsequent ventilation cycles, which widely reduces image artifacts. However, OCT imaging of alveolar tissue is affected by refraction and total internal reflection at air-tissue interfaces. Thus, only the first alveolar layer beneath the pleura is visible. To circumvent this effect, total liquid ventilation can be carried out to match the refractive indices of lung tissue and the breathing medium, which improves the visibility of the alveolar structure, the image quality and the penetration depth and provides the real structure of the alveolar tissue. In this study, a combination of four-dimensional OCT imaging with total liquid ventilation allowed the visualization of the alveolar structure in rat lung tissue benefiting from the improved depth range beneath the pleura and from the high spatial and temporal resolution.

Metabolic cooperation between co-cultured lung cancer cells and lung fibroblasts.

PubMed

Koukourakis, Michael I; Kalamida, Dimitra; Mitrakas, Achilleas G; Liousia, Maria; Pouliliou, Stamatia; Sivridis, Efthimios; Giatromanolaki, Alexandra

2017-11-01

Cooperation of cancer cells with stromal cells, such as cancer-associated fibroblasts (CAFs), has been revealed as a mechanism sustaining cancer cell survival and growth. In the current study, we focus on the metabolic interactions of MRC5 lung fibroblasts with lung cancer cells (A549 and H1299) using co-culture experiments and studying changes of the metabolic protein expression profile and of their growth and migration abilities. Using western blotting, confocal microscopy and RT-PCR, we observed that in co-cultures MRC5 respond by upregulating pyruvate dehydrogenase (PDH) and the monocarboxylate transporter MCT1. In contrast, cancer cells increase the expression of glucose transporters (GLUT1), LDH5, PDH kinase and the levels of phosphorylated/inactivated pPDH. H1299 cells growing in the same culture medium with fibroblasts exhibit a 'metastasis-like' phenomenon by forming nests within the fibroblast area. LDH5 and pPDH were drastically upregulated in these nests. The growth rate of both MRC5 and cancer cells increased in co-cultures. Suppression of LDHA or PDK1 in cancer cells abrogates the stimulatory signal from cancer cells to fibroblasts. Incubation of MRC5 fibroblasts with lactate resulted in an increase of LDHB and of PDH expression. Silencing of PDH gene in fibroblasts, or silencing of PDK1 or LDHA gene in tumor cells, impedes cancer cell's migration ability. Overall, a metabolic cooperation between lung cancer cells and fibroblasts has been confirmed in the context of direct Warburg effect, thus the fibroblasts reinforce aerobic metabolism to support the intensified anaerobic glycolytic pathways exploited by cancer cells.

Purification of Legiobactin and importance of this siderophore in lung infection by Legionella pneumophila.

PubMed

Allard, Kimberly A; Dao, Jenny; Sanjeevaiah, Prakash; McCoy-Simandle, Kessler; Chatfield, Christa H; Crumrine, David S; Castignetti, Domenic; Cianciotto, Nicholas P

2009-07-01

When cultured in a low-iron medium, Legionella pneumophila secretes a siderophore (legiobactin) that is both reactive in the chrome azurol S (CAS) assay and capable of stimulating the growth of iron-starved legionellae. Using anion-exchange high-pressure liquid chromatography (HPLC), we purified legiobactin from culture supernatants of a virulent strain of L. pneumophila. In the process, we detected the ferrated form of legiobactin as well as other CAS-reactive substances. Purified legiobactin had a yellow-gold color and absorbed primarily from 220 nm and below. In accordance, nuclear magnetic resonance spectroscopy revealed that legiobactin lacks aromatic carbons, and among the 13 aliphatics present, there were 3 carbonyls. When examined by HPLC, supernatants from L. pneumophila mutants inactivated for lbtA and lbtB completely lacked legiobactin, indicating that the LbtA and LbtB proteins are absolutely required for siderophore activity. Independently derived lbtA mutants, but not a complemented derivative, displayed a reduced ability to infect the lungs of A/J mice after intratracheal inoculation, indicating that legiobactin is required for optimal intrapulmonary survival by L. pneumophila. This defect, however, was not evident when the lbtA mutant and its parental strain were coinoculated into the lung, indicating that legiobactin secreted by the wild type can promote growth of the mutant in trans. Legiobactin mutants grew normally in murine lung macrophages and alveolar epithelial cells, suggesting that legiobactin promotes something other than intracellular infection of resident lung cells. Overall, these data represent the first documentation of a role for siderophore expression in the virulence of L. pneumophila.

Successful extracorporeal membrane oxygenation therapy as a bridge to sequential bilateral lung transplantation for a patient after severe paraquat poisoning.

PubMed

Tang, Xiao; Sun, Bing; He, Hangyong; Li, Hui; Hu, Bin; Qiu, Zewu; Li, Jie; Zhang, Chunyan; Hou, Shengcai; Tong, Zhaohui; Dai, Huaping

2015-11-01

Paraquat is a widely used herbicide that can cause severe to fatal poisoning in humans. The irreversible and rapid progression of pulmonary fibrosis associated with respiratory failure is the main cause of death in the later stages of poisoning. There are infrequent reports of successful lung transplants for cases of severe paraquat poisoning. We expect that this successful case will provide a reference for other patients in similar circumstances. A 24-year-old female was sent to the hospital approximately 2 hours after ingesting 50 ml of paraquat. She experienced rapidly aggravated pulmonary fibrosis and severe respiratory failure. On the 34th day after ingestion, she underwent intubation and invasive mechanical ventilation. The patient was evaluated for lung transplantation, and veno-venous extracorporeal membrane oxygenation (ECMO) was established as a bridge to lung transplantation on the 44th day. On the 56th day, she successfully underwent a bilateral sequential lung transplantation. Through respiratory and physical rehabilitation and nutrition support, the patient was weaned from mechanical ventilation and extubated on the 66th day. On the 80th day, she was discharged. During the 1-year follow-up, the patient was found to be in good condition, and her pulmonary function improved gradually. We suggest that lung transplantation may be an effective treatment in the end stages of paraquat-induced pulmonary fibrosis and consequential respiratory failure. For patients experiencing a rapid progression to a critical condition in whom lung transplantation cannot be performed immediately (e.g., while awaiting a viable donor or toxicant clearance), ECMO should be a viable bridge to lung transplantation.

Is Chronic Obstructive Pulmonary Disease an Accelerated Aging Disease?

PubMed

MacNee, William

2016-12-01

Aging is one of the most important risk factors for most chronic diseases. The worldwide increase in life expectancy has been accompanied by an increase in the prevalence of age-related diseases that result in significant morbidity and mortality and place an enormous burden on healthcare and resources. Aging is a progressive degeneration of the tissues that has a negative impact on the structure and function of vital organs. The lung ages, resulting in decreased function and reduced capacity to respond to environmental stresses and injury. Many of the changes that occur in the lungs with normal aging, such as decline in lung function, increased gas trapping, loss of lung elastic recoil, and enlargement of the distal air spaces, also are present in chronic obstructive pulmonary disease (COPD). The prevalence of COPD is two to three times higher in people over the age of 60 years than in younger age groups. Indeed, COPD has been considered a condition of accelerated lung aging. Several mechanisms associated with aging are present in the lungs of patients with COPD. Cell senescence is present in emphysematous lungs and is associated with shortened telomeres and decreased antiaging molecules, suggesting accelerated aging in the lungs of patients with COPD. Increasing age leads to elevated basal levels of inflammation and oxidative stress (inflammaging) and to increased immunosenescence associated with changes in both the innate and adaptive immune responses. These changes are similar to those that occur in COPD and may enhance the activity of the disease as well as increase susceptibility to exacerbations in patients with COPD. Understanding the mechanism of age-related changes in COPD may identify novel therapies for this condition.

Protective effects of puerarin on acute lung and cerebrum injury induced by hypobaric hypoxia via the regulation of aquaporin (AQP) via NF-κB signaling pathway.

PubMed

Wang, Chi; Yan, Muyang; Jiang, Hui; Wang, Qi; Guan, Xu; Chen, Jingwen; Wang, Chengbin

2016-11-01

Hypobaric hypoxia, frequently encountered at high altitude, may lead to lung and cerebrum injury. Our study aimed to investigate whether puerarin could exert ameliorative effects on rats exposed to hypobaric hypoxia via regulation of aquaporin (AQP) and NF-κB signaling pathway in lung and cerebrum. 40 Sprague Dawley rats were divided into four groups (normal control group, hypobaric hypoxia group, puerarin group and dexamethasone group). Wet/dry ratio, blood gas, pathological changes of lung and cerebrum and spatial memory were observed in each group. Inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were determined with ELISA and expression of AQP1, AQP4, NF-κB signaling pathway in lung and cerebrum with western blot RESULTS: Puerarin showed significant preventative effects on tissue injury and behavioral changes, as evidenced by histopathological findings and Morris water maze. In addition, levels of inflammatory cytokines in BALF decreased in the two preventative groups compared with those of hypobaric hypoxia group. AQP in lung and cerebrum increased under the condition of hypobaric hypoxia while was down regulated in both two preventative groups. NF-κB and IκB was also inhibited by puerarin. Our study suggested that lung and cerebrum injury, increased inflammatory cytokines in BALF and increased AQP1, AQP4 and NF-κB signaling pathway occurred under the condition of hypobaric hypoxia. Moreover, puerarin could prevent lung and cerebrum injury of rats exposed to hypobaric hypoxia via down-regulation of inflammatory cytokines, AQP1 and AQP4 expression and NF-κB signaling pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

[Supportive care during chemotherapy for lung cancer in daily practice].

PubMed

Müller, Veronika; Tamási, Lilla; Gálffy, Gabriella; Losonczy, György

2012-09-01

Active oncotherapy, combination chemotherapy of lung cancer is accompanied with many side effects which may impair patients' quality of life and compromise the effectiveness of chemotherapy. Most side effects of chemotherapy are preventable or treatable with optimal supportive care which enhances success in patient care and treatment. The aim of this review is to summarize the most important conditions that may be associated with combined chemotherapy of lung cancer from the practical point of view.

Enhanced expression of PKM2 associates with the biological properties of cancer stem cells from A549 human lung cancer cells.

PubMed

Guo, Chang-Ying; Yan, Chen; Luo, Lan; Goto, Shinji; Urata, Yoshishige; Xu, Jian-Jun; Wen, Xiao-Ming; Kuang, Yu-Kang; Tou, Fang-Fang; Li, Tao-Sheng

2017-04-01

Cancer cells express the M2 isoform of glycolytic enzyme pyruvate kinase (PKM2) for favoring the survival under a hypoxic condition. Considering the relative low oxygen microenvironment in stem cell niche, we hypothesized that an enhanced PKM2 expression associates with the biological properties of cancer stem cells. We used A549 human lung cancer cell line and surgical resected lung cancer tissue samples from patients for experiments. We confirmed the co-localization of PKM2 and CD44, a popular marker for cancer stem cells in lung cancer tissue samples from patients. The expression of PKM2 was clearly observed in approximately 80% of the A549 human lung cancer cells. Remarkably, enhanced expression of PKM2 was specially observed in these cells that also positively expressed CD44. Downregulation of PKM2 in CD44+ cancer stem cells by siRNA significantly impaired the potency for spheroid formation, decreased the cell survival under fetal bovine serum deprivation and hypoxic conditions, but increased their sensitivity to anti-cancer drug of cisplatin and γ-ray. The enhanced expression of PKM2 seems to associate with the biological properties of cancer stem cells from A549 human lung cancer cells. Selective targeting of PKM2 may provide a new strategy for cancer therapy, especially for patients with therapeutic resistance.

Brain stem slice conditioned medium contains endogenous BDNF and GDNF that affect neural crest boundary cap cells in co-culture.

PubMed

Kaiser, Andreas; Kale, Ajay; Novozhilova, Ekaterina; Siratirakun, Piyaporn; Aquino, Jorge B; Thonabulsombat, Charoensri; Ernfors, Patrik; Olivius, Petri

2014-05-30

Conditioned medium (CM), made by collecting medium after a few days in cell culture and then re-using it to further stimulate other cells, is a known experimental concept since the 1950s. Our group has explored this technique to stimulate the performance of cells in culture in general, and to evaluate stem- and progenitor cell aptitude for auditory nerve repair enhancement in particular. As compared to other mediums, all primary endpoints in our published experimental settings have weighed in favor of conditioned culture medium, where we have shown that conditioned culture medium has a stimulatory effect on cell survival. In order to explore the reasons for this improved survival we set out to analyze the conditioned culture medium. We utilized ELISA kits to investigate whether brain stem (BS) slice CM contains any significant amounts of brain-derived neurotrophic factor (BDNF) and glial cell derived neurotrophic factor (GDNF). We further looked for a donor cell with progenitor characteristics that would be receptive to BDNF and GDNF. We chose the well-documented boundary cap (BC) progenitor cells to be tested in our in vitro co-culture setting together with cochlear nucleus (CN) of the BS. The results show that BS CM contains BDNF and GDNF and that survival of BC cells, as well as BC cell differentiation into neurons, were enhanced when BS CM were used. Altogether, we conclude that BC cells transplanted into a BDNF and GDNF rich environment could be suitable for treatment of a traumatized or degenerated auditory nerve. Copyright © 2014 Elsevier B.V. All rights reserved.

GERMINATION, VIABILITY AND CLEARANCE OF STACHYBOTRYS CHARTARUM IN THE LUNGS OF INFANT RATS

EPA Science Inventory

The fungus Stachybotrys chartarum has been associated with many adverse health effects including the condition known as idiopathic pulmonary hemorrhage in infants. In order to gain some insight into possible mechanisms, viable conidia of S. chartarum were instilled into the lung...

Application of Low cost Spirulina growth medium using Deep sea water

NASA Astrophysics Data System (ADS)

Lim, Dae-hack; Kim, Bong-ju; Lee, Sung-jae; Choi, Nag-chul; Park, Cheon-young

2017-04-01

Deep-sea water has a relatively constant temperature, abundant nutrients such as calcium, magnesium, nitrates, and phosphates, etc., and stable water quality, even though there might be some variations of their compositions according to collection places. Thus, deep-sea water would be a good substrate for algal growth and biomass production since it contains various nutrients, including a fluorescent red pigment, and β-carotene, etc. The aim of this study was to investigate the economics of a culture condition through comparative analysis to Spirulina platensis growth characteristic under various medium conditions for cost-effective production of Spirulina sp.. Growth experiments were performed with S. platensis under various culture medium conditions (deep sea water + SP medium). Growth tests for culture medium demonstrated that the deep sea water to SP medium ratio of 50:50(W/W) was effective in S. platensis with the maximum biomass (1.35g/L) and minimum medium making cost per production mass (133.28 KRW/g). Parameter estimation of bio-kinetics (maximum growth rate and yield) for low cost medium results showed that the maximum growth rate and yield of N, P, K were obtained under deep sea water to SP medium ratio of 50:50(W/W) of 0.057 1/day and 0.151, 0.076, 0.123, respectively. Acknowledgment : "This research was a part of the project titled 'Development of microalgae culture technique for cosmetic materials based on ocean deep sea water(20160297)', funded by the Ministry of Oceans and Fisheries, Korea."

[Improving Primary Culture of Pulmonary Microvascular Endothelial Cells of Rats].

PubMed

Jiang, Ling; Hu, Yuan-Dong; Xu, Fei-Fei; Wang, Ting-Hua

2016-09-01

To improve the culturing method of pulmonary microvascular endothelial cells (PMEVCs) of SD rats. The culturing processes in regard to obtaining peripheral lung tissue, attaching tissue block,preparing medium and subculturing were modified.These included an injection of heparin sodium before anesthesia, abdominal bleeding, opening of chest when breathing stopped, improvement of operational details, reduction of pollution by adding penicillin and streptomycin, discard of tissues after 48 h of primary culturing, remove of fibroblasts by a second digestion, and identification of cells using a fluorescence microscope for binding with lectin from BSI (FITC-BSI).An inverted microscope was used to observe the morphological characteristics of PMEVCs. Purified PMEVCs were obtained,which displayed a polygon or short fusiform, exhibiting a typical cobblestone-like morphology. The morphology of PMVECs turned into swirling or long fusiform following subculture or changes in culture conditions. The results of FITC-BSI assay showed that more than 90% cells were stained with green fluorescence. Purified PMEVCs with a good growth state and subculture stability can be obtained using the modified method.

A Synthetic Analogue of Neopeltolide, 8,9-Dehydroneopeltolide, Is a Potent Anti-Austerity Agent against Starved Tumor Cells.

PubMed

Fuwa, Haruhiko; Sato, Mizuho

2017-10-20

Neopeltolide, an antiproliferative marine macrolide, is known to specifically inhibit complex III of the mitochondrial electron transport chain (mETC). However, details of the biological mode-of-action(s) remain largely unknown. This work demonstrates potent cytotoxic activity of synthetic neopeltolide analogue, 8,9-dehydroneopeltolide (8,9-DNP), against starved human pancreatic adenocarcinoma PANC-1 cells and human non-small cell lung adenocarcinoma A549 cells. 8,9-DNP induced rapid dissipation of the mitochondrial membrane potential and depletion of intracellular ATP level in nutrient-deprived medium. Meanwhile, in spite of mTOR inhibition under starvation conditions, impairment of cytoprotective autophagy was observed as the lipidation of LC3-I to form LC3-II and the degradation of p62 were suppressed. Consequently, cells were severely deprived of energy sources and underwent necrotic cell death. The autophagic flux inhibited by 8,9-DNP could be restored by glucose, and this eventually rescued cells from necrotic death. Thus, 8,9-DNP is a potent anti-austerity agent that impairs mitochondrial ATP synthesis and cytoprotective autophagy in starved tumor cells.

A Synthetic Analogue of Neopeltolide, 8,9-Dehydroneopeltolide, Is a Potent Anti-Austerity Agent against Starved Tumor Cells

PubMed Central

Sato, Mizuho

2017-01-01

Neopeltolide, an antiproliferative marine macrolide, is known to specifically inhibit complex III of the mitochondrial electron transport chain (mETC). However, details of the biological mode-of-action(s) remain largely unknown. This work demonstrates potent cytotoxic activity of synthetic neopeltolide analogue, 8,9-dehydroneopeltolide (8,9-DNP), against starved human pancreatic adenocarcinoma PANC-1 cells and human non-small cell lung adenocarcinoma A549 cells. 8,9-DNP induced rapid dissipation of the mitochondrial membrane potential and depletion of intracellular ATP level in nutrient-deprived medium. Meanwhile, in spite of mTOR inhibition under starvation conditions, impairment of cytoprotective autophagy was observed as the lipidation of LC3-I to form LC3-II and the degradation of p62 were suppressed. Consequently, cells were severely deprived of energy sources and underwent necrotic cell death. The autophagic flux inhibited by 8,9-DNP could be restored by glucose, and this eventually rescued cells from necrotic death. Thus, 8,9-DNP is a potent anti-austerity agent that impairs mitochondrial ATP synthesis and cytoprotective autophagy in starved tumor cells. PMID:29053565

Optimization of culture conditions and medium composition for the production of micrococcin GO5 by Micrococcus sp. GO5.

PubMed

Kim, Mi-Hee; Kong, Yoon-Jung; Baek, Hong; Hyun, Hyung-Hwan

2006-01-02

To enhance the production of micrococcin GO5, a bacteriocin produced by Micrococcus sp. GO5, cultivation conditions and medium composition were optimized. The optimal initial pH and temperature for bacteriocin production were 7.0-9.0 and 37 degrees C, respectively. Micrococcus sp. GO5 displayed the highest micrococcin GO5 activity when grown in modified MRS medium that contained lactose or sucrose, rather than glucose, as a carbon source. The maximum bacteriocin activity was obtained in modified MRS medium containing 0.5% tryptone and 1.0% yeast extract as nitrogen sources instead of the other nitrogen sources present in MRS medium. Bacteriocin production was greatly affected by the concentration of K(2)HPO(4); strain GO5 produced eight-fold more bacteriocin in medium containing 2.0-2.5% K(2)HPO(4) than in medium containing 0.2% K(2)HPO(4). The optimal concentration of MgSO(4).7H(2)O for bacteriocin production was 0.5%. The production of micrococcin GO5 was increased 32-fold in shake flask culture and 16-fold in a bioreactor using the optimized medium (TY medium), compared with culturing in MRS medium.

Lung abscess-etiology, diagnostic and treatment options.

PubMed

Kuhajda, Ivan; Zarogoulidis, Konstantinos; Tsirgogianni, Katerina; Tsavlis, Drosos; Kioumis, Ioannis; Kosmidis, Christoforos; Tsakiridis, Kosmas; Mpakas, Andrew; Zarogoulidis, Paul; Zissimopoulos, Athanasios; Baloukas, Dimitris; Kuhajda, Danijela

2015-08-01

Lung abscess is a type of liquefactive necrosis of the lung tissue and formation of cavities (more than 2 cm) containing necrotic debris or fluid caused by microbial infection. It can be caused by aspiration, which may occur during altered consciousness and it usually causes a pus-filled cavity. Moreover, alcoholism is the most common condition predisposing to lung abscesses. Lung abscess is considered primary (60%) when it results from existing lung parenchymal process and is termed secondary when it complicates another process, e.g., vascular emboli or follows rupture of extrapulmonary abscess into lung. There are several imaging techniques which can identify the material inside the thorax such as computerized tomography (CT) scan of the thorax and ultrasound of the thorax. Broad spectrum antibiotic to cover mixed flora is the mainstay of treatment. Pulmonary physiotherapy and postural drainage are also important. Surgical procedures are required in selective patients for drainage or pulmonary resection. In the current review we will present all current information from diagnosis to treatment.

Lung abscess-etiology, diagnostic and treatment options

PubMed Central

Kuhajda, Ivan; Zarogoulidis, Konstantinos; Tsirgogianni, Katerina; Tsavlis, Drosos; Kioumis, Ioannis; Kosmidis, Christoforos; Tsakiridis, Kosmas; Mpakas, Andrew; Zissimopoulos, Athanasios; Baloukas, Dimitris; Kuhajda, Danijela

2015-01-01

Lung abscess is a type of liquefactive necrosis of the lung tissue and formation of cavities (more than 2 cm) containing necrotic debris or fluid caused by microbial infection. It can be caused by aspiration, which may occur during altered consciousness and it usually causes a pus-filled cavity. Moreover, alcoholism is the most common condition predisposing to lung abscesses. Lung abscess is considered primary (60%) when it results from existing lung parenchymal process and is termed secondary when it complicates another process, e.g., vascular emboli or follows rupture of extrapulmonary abscess into lung. There are several imaging techniques which can identify the material inside the thorax such as computerized tomography (CT) scan of the thorax and ultrasound of the thorax. Broad spectrum antibiotic to cover mixed flora is the mainstay of treatment. Pulmonary physiotherapy and postural drainage are also important. Surgical procedures are required in selective patients for drainage or pulmonary resection. In the current review we will present all current information from diagnosis to treatment. PMID:26366400

Lung Oxidative Damage by Hypoxia

PubMed Central

Araneda, O. F.; Tuesta, M.

2012-01-01

One of the most important functions of lungs is to maintain an adequate oxygenation in the organism. This organ can be affected by hypoxia facing both physiological and pathological situations. Exposure to this condition favors the increase of reactive oxygen species from mitochondria, as from NADPH oxidase, xanthine oxidase/reductase, and nitric oxide synthase enzymes, as well as establishing an inflammatory process. In lungs, hypoxia also modifies the levels of antioxidant substances causing pulmonary oxidative damage. Imbalance of redox state in lungs induced by hypoxia has been suggested as a participant in the changes observed in lung function in the hypoxic context, such as hypoxic vasoconstriction and pulmonary edema, in addition to vascular remodeling and chronic pulmonary hypertension. In this work, experimental evidence that shows the implied mechanisms in pulmonary redox state by hypoxia is reviewed. Herein, studies of cultures of different lung cells and complete isolated lung and tests conducted in vivo in the different forms of hypoxia, conducted in both animal models and humans, are described. PMID:22966417

Cysts mark the early stage of metastatic tumor development in non-small cell lung cancer

PubMed Central

Thakur, Chitra; Rapp, Ulf R.; Rudel, Thomas

2018-01-01

Identifying metastatic tumor growth at an early stage has been one of the biggest challenges in the treatment of lung cancer. By genetic lineage tracing approach in a conditional model of Non-Small Cell Lung Cancer (NSCLC) in mice, we demonstrate that cystic lesions represent an early stage of metastatic invasion. We generated a mouse model for NSCLC which incorporated a heritable DsRed fluorescent tag driven by the ubiquitous CAG promoter in the alveolar type II cells of the lung. We found early cystic lesions in a secondary organ (liver) that lacked the expression of bona fide lung makers namely Scgb1a1 and surfactant protein C Sftpc and were DsRed positive hence identifying lung as their source of origin. This demonstrates the significant potential of alveolar type II cells in orchestrating the process of metastasis, rendering it as one of the target cell types of the lung of therapeutic importance in human NSCLC. PMID:29464089

Idiopathic Pulmonary Fibrosis and Myasthenia Gravis: An Unusual Association

PubMed Central

Chogtu, Bharti; Malik, Daliparty Vasudev

2016-01-01

Idiopathic Pulmonary Fibrosis (IPF) is a chronic fibrosing lung condition with high morbidity and mortality, accounting for about 25% of the cases of interstitial lung diseases. It usually has a progressive course resulting in death due to respiratory failure. Myasthenia Gravis (MG) is an autoimmune neuromuscular disease, caused by antibody mediated activity against acetylcholine receptor at the neuromuscular junction. It is characterized by fluctuating muscle weakness and fatigue. Extensive literature search did not reveal any case report of an association between these two conditions. Here we present a case of a patient with IPF who also developed MG. The diagnosis of IPF was based on High Resolution Computed Tomography (HRCT) of the lung and that of MG was based on clinical criteria and electrophysiological testing. The case was successfully managed. PMID:27190866

Developing Physiologic Models for Emergency Medical Procedures Under Microgravity

NASA Technical Reports Server (NTRS)

Parker, Nigel; O'Quinn, Veronica

2012-01-01

Several technological enhancements have been made to METI's commercial Emergency Care Simulator (ECS) with regard to how microgravity affects human physiology. The ECS uses both a software-only lung simulation, and an integrated mannequin lung that uses a physical lung bag for creating chest excursions, and a digital simulation of lung mechanics and gas exchange. METI s patient simulators incorporate models of human physiology that simulate lung and chest wall mechanics, as well as pulmonary gas exchange. Microgravity affects how O2 and CO2 are exchanged in the lungs. Procedures were also developed to take into affect the Glasgow Coma Scale for determining levels of consciousness by varying the ECS eye-blinking function to partially indicate the level of consciousness of the patient. In addition, the ECS was modified to provide various levels of pulses from weak and thready to hyper-dynamic to assist in assessing patient conditions from the femoral, carotid, brachial, and pedal pulse locations.

Developing Physiologic Models for Emergency Medical Procedures Under Microgravity

NASA Technical Reports Server (NTRS)

Parker, Nigel; OQuinn, Veronica

2012-01-01

Several technological enhancements have been made to METI's commercial Emergency Care Simulator (ECS) with regard to how microgravity affects human physiology. The ECS uses both a software-only lung simulation, and an integrated mannequin lung that uses a physical lung bag for creating chest excursions, and a digital simulation of lung mechanics and gas exchange. METI's patient simulators incorporate models of human physiology that simulate lung and chest wall mechanics, as well as pulmonary gas exchange. Microgravity affects how O2 and CO2 are exchanged in the lungs. Procedures were also developed to take into affect the Glasgow Coma Scale for determining levels of consciousness by varying the ECS eye-blinking function to partially indicate the level of consciousness of the patient. In addition, the ECS was modified to provide various levels of pulses from weak and thready to hyper-dynamic to assist in assessing patient conditions from the femoral, carotid, brachial, and pedal pulse locations.

A new medium for Caenorhabditis elegans toxicology and nanotoxicology studies designed to better reflect natural soil solution conditions.

PubMed

Tyne, William; Lofts, Stephen; Spurgeon, David J; Jurkschat, Kerstin; Svendsen, Claus

2013-08-01

A new toxicity test medium for Caenorhabditis elegans is presented. The test solution is designed to provide a better representation of natural soil pore water conditions than currently available test media. The medium has a composition that can readily be modified to allow for studies of the influences of a range of environmentally relevant parameters on nematode biology and toxicology. Tests conducted in the new medium confirmed that nematodes' reproduction was possible at a range of solution pH levels, offering the potential to conduct toxicity studies under a variety of conditions. A test to establish silver nanoparticle and dissolved silver nitrate toxicity, a study type not feasible in M9 or agar media due to precipitation and nanoparticle agglomeration, indicated lower silver nanoparticle (median effective concentration [EC50] of 6.5 mg Ag/L) than silver nitrate (EC50 0.28 mg Ag/L) toxicity. Characterization identified stable nanoparticle behavior in the new test medium. Copyright © 2013 SETAC.

The Nitrated Fatty Acid 10-Nitro-oleate Diminishes Severity of LPS-Induced Acute Lung Injury in Mice

PubMed Central

Reddy, Aravind T.; Lakshmi, Sowmya P.; Reddy, Raju C.

2012-01-01

Acute lung injury (ALI) is an inflammatory condition culminating in respiratory failure. There is currently no effective pharmacological treatment. Nitrated fatty acids (NFAs) have been shown to exert anti-inflammatory effects. We therefore hypothesized that delivery of NFAs directly to the site of inflammation would reduce the severity of ALI. Pulmonary delivery of 10-nitro-oleate following endotoxin-induced ALI in mice reduced markers of lung inflammation and injury, including capillary leakage, lung edema, infiltration of neutrophils into the lung, and oxidant stress, as well as plasma levels of proinflammatory cytokines. Nitro-oleate delivery likewise downregulated expression of proinflammatory genes by alveolar macrophages, key cells in regulation of lung inflammation. These effects may be accounted for by the observed increases in the activity of PPAR-γ and the PPAR-γ-induced antioxidant transcription factor Nrf2, together with the decreased activity of NF-κB. Our results demonstrate that pulmonary delivery of NFAs reduces severity of acute lung injury and suggest potential utility of these molecules in other inflammatory lung diseases. PMID:22919366

Heavy metals found in the breathing zone, toenails and lung function of welders working in an air-conditioned welding workplace.

PubMed

Hariri, Azian; Mohamad Noor, Noraishah; Paiman, Nuur Azreen; Ahmad Zaidi, Ahmad Mujahid; Zainal Bakri, Siti Farhana

2017-09-22

Welding operations are rarely conducted in an air-conditioned room. However, a company would set its welding operations in an air-conditioned room to maintain the humidity level needed to reduce hydrogen cracks in the specimen being welded. This study intended to assess the exposure to metal elements in the welders' breathing zone and toenail samples. Heavy metal concentration was analysed using inductively coupled plasma mass spectrometry. The lung function test was also conducted and analysed using statistical approaches. Chromium and manganese concentrations in the breathing zone exceeded the permissible exposure limit stipulated by Malaysian regulations. A similar trend was obtained in the concentration of heavy metals in the breathing zone air sampling and in the welders' toenails. Although there was no statistically significant decrease in the lung function of welders, it is suggested that exposure control through engineering and administrative approaches should be considered for workplace safety and health improvement.

[The value of bedside lung ultrasound in emergency-plus protocol for the assessment of lung consolidation and atelectasis in critical patients].

PubMed

Wang, Xiao-ting; Liu, Da-wei; Zhang, Hong-min; He, Huai-wu; Liu, Ye; Chai, Wen-zhao; Du, Wei

2012-12-01

To investigate the effect of the bedside lung ultrasound in emergency(BLUE)-plus lung ultrasound protocol on lung consolidation and atelectasis of critical patients. All patients who need to receive mechanical ventilation for more than 48 hours in ICU from June 2010 to December 2011 in Peking Union Medical College Hospital were included in the study. BLUE-plus and BLUE lung ultrasound, bedside X-ray, lung CT examination were performed on all patients at the same time. The condition of lung consolidation and atelectasis discovered by BLUE-plus lung ultrasound protocol was recorded and compared with bedside X-ray or lung CT. The difference in assessment of lung consolidation and atelectasis between BLUE-plus lung ultrasound protocol and BLUE protocol was compared. A total of 78 patients were finally enrolled in the study. The lung CT found 70 cases (89.74%) had different degrees of lung consolidation and atelectasis. The sensitivity, specificity and diagnostic accuracy of lung consolidation and atelectasis by the bedside chest X-ray were 31.29%, 75.00% and 38.46%, respectively. BLUE-plus lung ultrasound protocol found 68 cases with lung consolidation and atelectasis, and its sensitivity, specificity, and diagnostic accuracy were 95.71%, 87.50% and 94.87%, respectively, which were significantly higher than those of lung CT. BLUE protocol found 48 cases of lung consolidation and atelectasis, and its sensitivity, specificity, and diagnostic accuracy were 65.71%, 75.00% and 66.67%, respectively. The position of lung consolidation and atelectasis which hadn't been found by BLUE protocol was mainly proved to be located in the basement of lung by lung CT. The incidence of lung consolidation and atelectasis in critical patients who received mechanical ventilation is high. The BLUE-plus lung ultrasound protocol has a relatively higher sensitivity, specificity and diagnostic accuracy for consolidation and atelectasis, which can find majority of consolidation and atelectasis. As BLUE-plus lung ultrasound is a bedside noninvasive method allowing immediate assessment of most lung consolidation and atelectasis, it will be likely the alternative of the CT and play a key role in assessment of lung consolidation and atelectasis.

Idiopathic pulmonary fibrosis in a Staffordshire bull terrier with hypothyroidism.

PubMed

Corcoran, B M; Dukes-McEwan, J; Rhind, S; French, A

1999-04-01

Radiographic evidence of chronic interstitial lung changes, usually believed to be attributable to lung fibrosis, is readily recognised in canine practice. Furthermore, there is a body of anecdotal evidence suggesting that a specific clinical entity consistent with chronic lung fibrosis occurs in specific breeds of terrier dogs. However, there is little pathological data to confirm these radiographic and clinical findings and, therefore, chronic interstitial lung disease of dogs is poorly characterised. In this report, a case of chronic pulmonary fibrosis is described in which histopathological confirmation was possible, and suggested that the condition might be analogous to idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) in humans.

[Work capacity evaluation in nonspecific lung diseases in a polyclinic section for lung diseases and tuberculosis].

PubMed

Herlík, J; Kos, S

1991-01-01

Describing the structure of a chest clinic in a large city requirements for a high level on the field of medical assessing in patients with non-specific lung diseases are formulated. 1. It must be sure, that all patients suffering from lung diseases are referred to a pneumologist. 2. Opportunities for optimal diagnosis must be given (knowledge and experiences of physicians and nurses; medical equipments of a high technical standard). 3. A scientific-based treatment must be guaranteed. Under optimal conditions it is possible to shorten the duration of disablement and to avoid the hospitalization in some cases.

A new needle on the block: EchoTip ProCore endobronchial ultrasound needle

PubMed Central

Dincer, H Erhan; Andrade, Rafael; Zamora, Felix; Podgaetz, Eitan

2016-01-01

Endobronchial ultrasound has become the first choice standard of care procedure to diagnose benign or malignant lesions involving mediastinum and lung parenchyma adjacent to the airways owing to its characteristics of being real-time and minimally invasive. Although the incidence of lung cancer has been decreasing, it is and will be the leading cause of cancer-related mortality in the next few decades. When compared to other cancers, lung cancer kills more females than breast and colon cancers combined and more males than colon and prostate cancers combined. The type of lung cancer has changed in recent decades and adenocarcinoma has become the most frequent cell type. Prognosis of lung cancer depends upon the cell type and the staging at the time of diagnosis. The cell type and molecular characteristics of adenocarcinoma may allow individualized targeted treatment. Other malignant conditions in the mediastinum and lung (eg, metastatic lung cancers and lymphoma) can be biopsied using endobronchial ultrasound needles. Endobronchial ultrasound needle biopsies provides mostly cytology specimens due to its small sizes of needles (22 gauge or larger) which may not give enough tissue to make a definitive diagnosis in malignant (eg, lymphoma) or benign conditions (eg, sarcoidosis). EchoTip ProCore endobronchial needle released in early 2014 provides histologic biopsy material. Larger tissue biopsies may potentially provide a higher diagnostic yield and it eliminates mediastinoscopy or other surgical interventions. Here we aim to review bronchoscopic approach in the diagnosis of mediastinal lesions with emphasis of EchoTip ProCore needles. PMID:27099535

Oxidative stress differentially impacts male and female bovine embryos depending on the culture medium and the stress condition.

PubMed

Dallemagne, Matthew; Ghys, Emmanuelle; De Schrevel, Catalina; Mwema, Ariane; De Troy, Delphine; Rasse, Catherine; Donnay, Isabelle

2018-09-01

Male and female embryos are known to differ for their metabolism and response to environmental factors very early in development. The present study aimed to evaluate the response to oxidative stress of male and female bovine embryos at the morula-blastocyst stages in terms of developmental rates, total cell number and apoptotic rates in two culture conditions. Embryos where cultured in a medium supplemented with either 5% fetal calf serum (FCS) or 4 mg/mL bovine serum albumin and a mixture of insulin, transferrin and selenium (BSA-ITS). Oxidative stress was applied at Day-5 post insemination (pi) by adding either AAPH or menadione to the culture medium, and blastocysts were analyzed at Day-7pi. The impact on development and blastocyst quality was dependent on the culture medium and the stress inducer but differed between male and female embryos. Male embryos resisted better to oxidative stress in FCS supplemented medium, no matter the stress inducer. Accordingly, the impact on blastocyst cell number tended to be higher in female blastocysts after stress induction with AAPH in FCS supplemented medium. On the other hand, in BSA-ITS supplemented medium, female embryos were more resistant to AAPH induced stress, while menadione had no impact on sex ratio. The weaker resistance of males to AAPH in this medium is in accordance with their trend to show a higher increase in apoptotic rates than females in this condition. In conclusion, this study shows that oxidative stress has differential impact on male and female bovine blastocysts depending on the culture condition and on the way oxidative stress is induced. Copyright © 2018 Elsevier Inc. All rights reserved.

Characterization of Cancer Stem-Like Cells Derived from Mouse Induced Pluripotent Stem Cells Transformed by Tumor-Derived Extracellular Vesicles

PubMed Central

Yan, Ting; Mizutani, Akifumi; Chen, Ling; Takaki, Mai; Hiramoto, Yuki; Matsuda, Shuichi; Shigehiro, Tsukasa; Kasai, Tomonari; Kudoh, Takayuki; Murakami, Hiroshi; Masuda, Junko; Hendrix, Mary J. C.; Strizzi, Luigi; Salomon, David S.; Fu, Li; Seno, Masaharu

2014-01-01

Several studies have shown that cancer niche can perform an active role in the regulation of tumor cell maintenance and progression through extracellular vesicles-based intercellular communication. However, it has not been reported whether this vesicle-mediated communication affects the malignant transformation of normal stem cells/progenitors. We have previously reported that the conditioned medium derived from the mouse Lewis Lung Carcinoma (LLC) cell line can convert mouse induced pluripotent stem cells (miPSCs) into cancer stem cells (CSCs), indicating that normal stem cells when placed in an aberrant microenvironment can give rise to functionally active CSCs. Here, we focused on the contribution of tumor-derived extracellular vesicles (tEVs) that are secreted from LLC cells to induce the transformation of miPSCs into CSCs. We isolated tEVs from the conditioned medium of LLC cells, and then the differentiating miPSCs were exposed to tEVs for 4 weeks. The resultant tEV treated cells (miPS-LLCev) expressed Nanog and Oct3/4 proteins comparable to miPSCs. The frequency of sphere formation of the miPS-LLCev cells in suspension culture indicated that the self-renewal capacity of the miPS-LLCev cells was significant. When the miPS-LLCev cells were subcutaneously transplanted into Balb/c nude mice, malignant liposarcomas with extensive angiogenesis developed. miPS-LLCevPT and miPS-LLCevDT, the cells established from primary site and disseminated liposarcomas, respectively, showed their capacities to self-renew and differentiate into adipocytes and endothelial cells. Moreover, we confirmed the secondary liposarcoma development when these cells were transplanted. Taken together, these results indicate that miPS-LLCev cells possess CSC properties. Thus, our current study provides the first evidence that tEVs have the potential to induce CSC properties in normal tissue stem cells/progenitors. PMID:25057308

STUDIES ON LUNG INJURIES FOLLOWING ROENTGEN TREATMENT OF BREAST CANCER

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ichikawa, H.; Arai, T.

1960-01-01

Of 102 cases of breast cancer treated by x rays, 46 (45%) showed rcentgenographic evidence of lung flbrosis. A special chest phantom was constructed to measure the dose distribution within the lungs. The highest dose in the lung, by McWhirter's technique of radiation, was 150-160% of the surface. The parts of the lung where the tlssue received the highest dose were the upper, anterior, and outside parts of the radiated lung. This result was the same as indicated in the roentgenographic study. The lung radiation reaction was parallel to the skin reaction. The age had no relation to the fibrosis,more » but 4 cases, who had marked tuberculous calcification in their lung fields, seemed to have a tendency to produce considerable fibrosis by radiation. The sympton of pneumonitis was generally slight, and the general condition of the patients was not greatly influenced as a rule. The functional lung test showed almost normal results in the cases of grade I and grade II, but considerable injury in the cases of grade III, independent of their subjective symptoms. (Abstr. Japan Med., 1: No. 10, 1961)« less

Lemna paucicostata Hegelm. 6746

PubMed Central

Datko, Anne H.; Mudd, S. Harvey; Giovanelli, John

1980-01-01

Photoautotrophic and mixotrophic growth of Lemna paucicostata Hegelm. 6746 (formerly Lemna perpusilla Torr. 6746) was investigated to establish standardized conditions for biochemical studies. Optimal temperature for growth was 29 to 30 C. The medium used previously (Datko AH, Mudd SH, Giovanelli J 1977 J Biol Chem 252: 3436-3445) was modified by inclusion of NH4Cl, decreasing macronutrient and ethylenediamine tetraacetate concentration, increasing micronutrient concentration, and inclusion of bicarbonate (for photoautotrophic growth) or 2-(N-morpholino)ethanesulfonic acid (for mixotrophic growth) buffers. Varying the sulfate concentration between 14 and 1 millimolar had no effect on growth. For photoautotrophic growth in the new medium (medium 4), the effects of CO2 concentration, light intensity, and pH were measured. Under the optimal conditions, a multiplication rate (MR) of 300 to 315, equivalent to a doubling time of 23 to 24 hours was obtained. Addition of glutamine or asparagine did not increase this MR. For mixotrophic growth in low light, the effects of sucrose concentration and pH were determined. Under optimal conditions, MR was 210. A concentration of sucrose less than maximal for growth was chosen for the medium for experiments which will include 14C-labeling of intermediates. MR under these conditions was 184. Growth was equally good in medium 4 and in half-strength Hutner's medium when sulfate was high (0.4 to 1 millimolar), but better in medium 4 when sulfate was low (20 micromolar). Growth rates could be restored to normal in half-strength Hutner's with low sulfate by decreasing the molybdate concentration. By modifying medium 4 to contain very low amounts of sulfate, and by preconditioning medium and plants, it was shown that there was an increment in plant protein of approximately 2.5 micrograms per nanomole of added MgSO4. Colonies undergoing sulfur limitation exhibited a slow growth rate and a high frond to colony ratio. Molybdate and selenate produced growth inhibition reversible by sulfate. Conditions were developed in which the plants could be maintained indefinitely in the presence of either molybdate or selenate in altered metabolic steady-states with lowered growth rates and protein per frond. Images PMID:16661306

[The influence of spray drying process conditions on physical, chemical properties and lung inhaling performance of Panax notoginseng saponins - tanshinone II A composite particles].

PubMed

Wang, Hua-Mei; Fu, Ting-Ming; Guo, Li-Wei

2013-06-01

This study is to report the influence of conditions in spray drying process on physical and chemical properties and lung inhaling performance of Panax notoginseng Saponins - Tanshinone II A composite particles. According to the physical and chemical properties of the two types of components within the composite particles, three solvent systems were selected including ethanol, ethanol : acetone (9 : 1, v/v) and ethanol : acetone (4 : 1, v/v), and three inlet temperature: 110 degrees C, 120 degrees C, 130 degrees C to prepare seven different composite particle samples; each sample was characterized using laser diffraction, scanning electron microscopy (SEM), dynamic vapour sorption (DVS) and atomic force microscope (AFM), and their aerodynamic behavior was evaluated by a Next Generation Impactor (NGI). The results indicate that under the conditions of using the mixed solvent system of ethanol--acetone volume ratio of 9 : 1, and the inlet temperature of 110 degrees C, the resulting composite particles showed rough surface, with more tanshinone II A distributing in the outer layer, such composite particles have the best lung inhaling performance and the fine particle fraction (FPF) close to 60%. Finally it is concluded that by adjusting the conditions in co-spray drying process, the distribution amount and existence form of tanshinone II A in the outer layer of the particles can be changed so that to enhance lung inhaling performance of the drug composite particles.

Percutaneous Radiofrequency Ablation of Lung Tumors in Contact with the Aorta: Dangerous and Difficult but Efficient: A Report of Two Cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thanos, Loukas, E-mail: loutharad@yahoo.co; Mylona, Sofia; Giannoulakos, Nikolaos

Percutaneous imaging-guided tumor ablation is a widely accepted method for the treatment of primary and secondary lung tumors. Although it is generally feasible and effective for local tumor control, some conditions may affect its feasibility and effectiveness. Herein the authors report their experience with two patients with lung malignancies contiguous to the aorta who were successfully treated with radiofrequency ablation, even though it initially appeared highly risky due to the possible fatal complications.

[Creation of experimental emphysema by the intratracheal administration of papain].

PubMed

Basmadzhieva, K; Kolev, K; Balabaeva, L

1981-01-01

The authors formed lung emphysema in white rats under experimental conditions by intratracheal application of various concentrations of papaine at different intervals. In the performed experiment the most suitable dose for formation of emphysema was two fold administration of 2 milligrams of papaine. The following indices were observed in the experimental and control animals: body weight, weight coefficient of the internal organs, indices of lipid and nucleinic metabolism in homogenates of lung as well as histomorphologic examination of lung.

Towards a Biohybrid Lung: Endothelial Cells Promote Oxygen Transfer through Gas Permeable Membranes.

PubMed

Menzel, Sarah; Finocchiaro, Nicole; Donay, Christine; Thiebes, Anja Lena; Hesselmann, Felix; Arens, Jutta; Djeljadini, Suzana; Wessling, Matthias; Schmitz-Rode, Thomas; Jockenhoevel, Stefan; Cornelissen, Christian Gabriel

2017-01-01

In patients with respiratory failure, extracorporeal lung support can ensure the vital gas exchange via gas permeable membranes but its application is restricted by limited long-term stability and hemocompatibility of the gas permeable membranes, which are in contact with the blood. Endothelial cells lining these membranes promise physiological hemocompatibility and should enable prolonged application. However, the endothelial cells increase the diffusion barrier of the blood-gas interface and thus affect gas transfer. In this study, we evaluated how the endothelial cells affect the gas exchange to optimize performance while maintaining an integral cell layer. Human umbilical vein endothelial cells were seeded on gas permeable cell culture membranes and cultivated in a custom-made bioreactor. Oxygen transfer rates of blank and endothelialized membranes in endothelial culture medium were determined. Cell morphology was assessed by microscopy and immunohistochemistry. Both setups provided oxygenation of the test fluid featuring small standard deviations of the measurements. Throughout the measuring range, the endothelial cells seem to promote gas transfer to a certain extent exceeding the blank membranes gas transfer performance by up to 120%. Although the underlying principles hereof still need to be clarified, the results represent a significant step towards the development of a biohybrid lung.

Urinary metabolomic study of non-small cell lung carcinoma based on ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

PubMed

Wu, Qian; Wang, Yan; Gu, Xue; Zhou, Junyi; Zhang, Huiping; Lv, Wang; Chen, Zhe; Yan, Chao

2014-07-01

Metabolic profiles from human urine reveal the significant difference of carnitine and acylcarnitines levels between non-small cell lung carcinoma patients and healthy controls. Urine samples from cancer patients and healthy individuals were assayed in this metabolomic study using ultra high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. The data were normalized by the sum of all intensities and creatinine calibration, respectively, before orthogonal partial least squares discriminant analysis. Twenty differential metabolites were identified based on standard compounds or tandem mass spectrometry fragments. Among them, some medium-/long-chain acylcarnitines, for example, cis-3,4-methylene heptanoylcarnitine, were found to be downregulated while carnitine was upregulated in urine samples from the cancer group compared to the control group. Receiver operating characteristic analysis of the two groups showed that the area under curve for the combination of carnitine and 11 selected acylcarnitines was 0.958. This study suggests that the developed carnitine and acylcarnitines profiling method has the potential to be used for screening non-small cell lung carcinoma. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Plasticity of lung development in the amphibian, Xenopus laevis

PubMed Central

Rose, Christopher S.; James, Brandon

2013-01-01

Summary Contrary to previous studies, we found that Xenopus laevis tadpoles raised in normoxic water without access to air can routinely complete metamorphosis with lungs that are either severely stunted and uninflated or absent altogether. This is the first demonstration that lung development in a tetrapod can be inhibited by environmental factors and that a tetrapod that relies significantly on lung respiration under unstressed conditions can be raised to forego this function without adverse effects. This study compared lung development in untreated, air-deprived (AD) and air-restored (AR) tadpoles and frogs using whole mounts, histology, BrdU labeling of cell division and antibody staining of smooth muscle actin. We also examined the relationship of swimming and breathing behaviors to lung recovery in AR animals. Inhibition and recovery of lung development occurred at the stage of lung inflation. Lung recovery in AR tadpoles occurred at a predictable and rapid rate and correlated with changes in swimming and breathing behavior. It thus presents a new experimental model for investigating the role of mechanical forces in lung development. Lung recovery in AR frogs was unpredictable and did not correlate with behavioral changes. Its low frequency of occurrence could be attributed to developmental, physical and behavioral changes, the effects of which increase with size and age. Plasticity of lung inflation at tadpole stages and loss of plasticity at postmetamorphic stages offer new insights into the role of developmental plasticity in amphibian lung loss and life history evolution. PMID:24337117

Plasticity of lung development in the amphibian, Xenopus laevis.

PubMed

Rose, Christopher S; James, Brandon

2013-12-15

Contrary to previous studies, we found that Xenopus laevis tadpoles raised in normoxic water without access to air can routinely complete metamorphosis with lungs that are either severely stunted and uninflated or absent altogether. This is the first demonstration that lung development in a tetrapod can be inhibited by environmental factors and that a tetrapod that relies significantly on lung respiration under unstressed conditions can be raised to forego this function without adverse effects. This study compared lung development in untreated, air-deprived (AD) and air-restored (AR) tadpoles and frogs using whole mounts, histology, BrdU labeling of cell division and antibody staining of smooth muscle actin. We also examined the relationship of swimming and breathing behaviors to lung recovery in AR animals. Inhibition and recovery of lung development occurred at the stage of lung inflation. Lung recovery in AR tadpoles occurred at a predictable and rapid rate and correlated with changes in swimming and breathing behavior. It thus presents a new experimental model for investigating the role of mechanical forces in lung development. Lung recovery in AR frogs was unpredictable and did not correlate with behavioral changes. Its low frequency of occurrence could be attributed to developmental, physical and behavioral changes, the effects of which increase with size and age. Plasticity of lung inflation at tadpole stages and loss of plasticity at postmetamorphic stages offer new insights into the role of developmental plasticity in amphibian lung loss and life history evolution.

Aspiration lung disorders in bovines: a case report and review.

PubMed

Shakespeare, Anthony S

2012-11-01

Lung aspiration disorders in bovines are invariably diagnosed as infectious aspiration pneumonias. There is a distinct differentiation between aspiration pneumonia and aspiration pneumonitis in humans that can be applied to bovines. The nature and quantity of the aspirate can result in differing pathogeneses which can require differing therapeutic approaches. Whilst blood gases were important in detecting and prognosticating lung problems, changes in barometric pressure with altitude have to be considered when interpreting partial pressures of oxygen. Anatomical differences in the lungs of bovines can explain why this species is more prone to certain pneumonic problems. Pulmonary physiotherapy is important in treating lung disorders in humans and should be considered as an adjunct therapy in bovine respiratory conditions. A case work-up was used to highlight some of the points discussed in this article.

Stimulation of GABA-Induced Ca2+ Influx Enhances Maturation of Human Induced Pluripotent Stem Cell-Derived Neurons

PubMed Central

Rushton, David J.; Mattis, Virginia B.; Svendsen, Clive N.; Allen, Nicholas D.; Kemp, Paul J.

2013-01-01

Optimal use of patient-derived, induced pluripotent stem cells for modeling neuronal diseases is crucially dependent upon the proper physiological maturation of derived neurons. As a strategy to develop defined differentiation protocols that optimize electrophysiological function, we investigated the role of Ca2+ channel regulation by astrocyte conditioned medium in neuronal maturation, using whole-cell patch clamp and Ca2+ imaging. Standard control medium supported basic differentiation of induced pluripotent stem cell-derived neurons, as assayed by the ability to fire simple, single, induced action potentials. In contrast, treatment with astrocyte conditioned medium elicited complex and spontaneous neuronal activity, often with rhythmic and biphasic characteristics. Such augmented spontaneous activity correlated with astrocyte conditioned medium-evoked hyperpolarization and was dependent upon regulated function of L-, N- and R-type Ca2+ channels. The requirement for astrocyte conditioned medium could be substituted by simply supplementing control differentiation medium with high Ca2+ or γ-amino butyric acid (GABA). Importantly, even in the absence of GABA signalling, opening Ca2+ channels directly using Bay K8644 was able to hyperpolarise neurons and enhance excitability, producing fully functional neurons. These data provide mechanistic insight into how secreted astrocyte factors control differentiation and, importantly, suggest that pharmacological modulation of Ca2+ channel function leads to the development of a defined protocol for improved maturation of induced pluripotent stem cell-derived neurons. PMID:24278369

Measurements of bovine sperm velocities under true anaerobic and aerobic conditions.

PubMed

Krzyzosiak, J; Molan, P; Vishwanath, R

1999-04-30

Velocities of bovine spermatozoa in a medium containing glucose were similar under true anaerobic and aerobic conditions. Spermatozoa were not able to sustain motility under anaerobic conditions when glycolysis was inhibited, but regained motility when re-aerated. This demonstrates that immobilisation was due to lack of oxygen and that conditions under which motility was analysed were truly anaerobic. Sperm motility parameters were not significantly different in the presence and absence of 4 microM antimycin A and 4 microM rotenone when glucose was present in the medium. After each incubation, functionality of sperm mitochondria was assayed by washing sperm into the medium which supported respiration but not glycolysis, and motility was visually assessed. All sperm samples were highly motile in this medium indicating that their mitochondria were functional. When glycolysis was inhibited, antimycin and rotenone abolished sperm motility immediately after addition. Bovine sperm can maintain similar levels of motility aerobically and anaerobically if a glycolysable substrate is available. Available data on bovine sperm energetics support this view.

Role of ATM in bystander signaling between human monocytes and lung adenocarcinoma cells.

PubMed

Ghosh, Somnath; Ghosh, Anu; Krishna, Malini

2015-12-01

The response of a cell or tissue to ionizing radiation is mediated by direct damage to cellular components and indirect damage mediated by radiolysis of water. Radiation affects both irradiated cells and the surrounding cells and tissues. The radiation-induced bystander effect is defined by the presence of biological effects in cells that were not themselves in the field of irradiation. To establish the contribution of the bystander effect in the survival of the neighboring cells, lung carcinoma A549 cells were exposed to gamma-irradiation, 2Gy. The medium from the irradiated cells was transferred to non-irradiated A549 cells. Irradiated A549 cells as well as non-irradiated A549 cells cultured in the presence of medium from irradiated cells showed decrease in survival and increase in γ-H2AX and p-ATM foci, indicating a bystander effect. Bystander signaling was also observed between different cell types. Phorbol-12-myristate-13-acetate (PMA)-stimulated and gamma-irradiated U937 (human monocyte) cells induced a bystander response in non-irradiated A549 (lung carcinoma) cells as shown by decreased survival and increased γ-H2AX and p-ATM foci. Non-stimulated and/or irradiated U937 cells did not induce such effects in non-irradiated A549 cells. Since ATM protein was activated in irradiated cells as well as bystander cells, it was of interest to understand its role in bystander effect. Suppression of ATM with siRNA in A549 cells completely inhibited bystander effect in bystander A549 cells. On the other hand suppression of ATM with siRNA in PMA stimulated U937 cells caused only a partial inhibition of bystander effect in bystander A549 cells. These results indicate that apart from ATM, some additional factor may be involved in bystander effect between different cell types. Copyright © 2015 Elsevier B.V. All rights reserved.

Application of a neutral community model to assess structuring of the human lung microbiome.

PubMed

Venkataraman, Arvind; Bassis, Christine M; Beck, James M; Young, Vincent B; Curtis, Jeffrey L; Huffnagle, Gary B; Schmidt, Thomas M

2015-01-20

DNA from phylogenetically diverse microbes is routinely recovered from healthy human lungs and used to define the lung microbiome. The proportion of this DNA originating from microbes adapted to the lungs, as opposed to microbes dispersing to the lungs from other body sites and the atmosphere, is not known. We use a neutral model of community ecology to distinguish members of the lung microbiome whose presence is consistent with dispersal from other body sites and those that deviate from the model, suggesting a competitive advantage to these microbes in the lungs. We find that the composition of the healthy lung microbiome is consistent with predictions of the neutral model, reflecting the overriding role of dispersal of microbes from the oral cavity in shaping the microbial community in healthy lungs. In contrast, the microbiome of diseased lungs was readily distinguished as being under active selection. We also assessed the viability of microbes from lung samples by cultivation with a variety of media and incubation conditions. Bacteria recovered by cultivation from healthy lungs represented species that comprised 61% of the 16S rRNA-encoding gene sequences derived from bronchoalveolar lavage samples. Neutral distribution of microbes is a distinguishing feature of the microbiome in healthy lungs, wherein constant dispersal of bacteria from the oral cavity overrides differential growth of bacteria. No bacterial species consistently deviated from the model predictions in healthy lungs, although representatives of many of the dispersed species were readily cultivated. In contrast, bacterial populations in diseased lungs were identified as being under active selection. Quantification of the relative importance of selection and neutral processes such as dispersal in shaping the healthy lung microbiome is a first step toward understanding its impacts on host health. Copyright © 2015 Venkataraman et al.

Effects of E-Cigarette Health Warnings and Modified Risk Ad Claims on Adolescent E-Cigarette Craving and Susceptibility.

PubMed

Andrews, J Craig; Mays, Darren; Netemeyer, Richard G; Burton, Scot; Kees, Jeremy

2018-04-16

A between-subjects experiment examines the effects of different warning types and modified risk e-cigarette ad claims on adolescent e-cigarette craving and future e-cigarette susceptibility for two different themes. One theme focuses on nicotine and addiction, and the other on the effects of potentially harmful constituents (e.g., flavored chemicals and lung disease). The effects of warning type (control, text-only, graphic health warning (GHW) and text) and modified risk e-cigarette ad claims (control, exposure reduction, risk reduction) are tested experimentally with two different arms (themes) for a sample of 1,011 adolescents who had tried either e-cigarettes or cigarettes. For addiction, the text-only warning led to significantly less e-cigarette susceptibility than the no warning control condition. As expected, there were no differences between the GHW + text condition and text-only or control conditions for e-cigarette craving. An interaction between warning type and modified risk claims revealed significantly fewer e-cigarette cravings and less susceptibility for the text-only warning and no claim (control) condition than for any other condition. For fatal lung disease, the GHW + text condition led to fewer e-cigarette cravings and less susceptibility than the text-only warning and no warning (control) conditions. Warning type effects can be very different under different themes (e.g., addiction, fatal lung disease). In general, our results point to the effectiveness of the text-only warning for addiction and GHW + text for fatal lung disease. Relative exposure and risk modification claims (e.g., less nicotine; less addicting) tend to undercut addiction warnings. More than one type of e-cigarette warning may be necessary as e-cigarette research evolves. Our results show different warning type effects (e.g., text-only; GHW + text) on e-cigarette craving and future susceptibility for adolescent experimenters depending on the risk theme (e.g., addiction; lung disease) and presence of ad claims (e.g., exposure and risk reduction). As research emerges on risks associated with e-cigarette use, it is important to first know what at-risk populations (e.g., adolescents) believe about such risks. Such research will aid our understanding of what types of warnings might be most effective, especially in the presence of ad claims.

FGF1 and IGF1-conditioned 3D culture system promoted the amplification and cancer stemness of lung cancer cells.

PubMed

Liu, Pengpeng; Zhang, Rui; Yu, Wenwen; Ye, Yingnan; Cheng, Yanan; Han, Lei; Dong, Li; Chen, Yongzi; Wei, Xiyin; Yu, Jinpu

2017-12-01

Lung cancer stem cells (LCSCs) are considered as the cellular origins of metastasis and relapse of lung cancer. However, routine two-dimensional culture system (2D-culture) hardly mimics the growth and functions of LCSCs in vivo and therefore significantly decreases the stemness activity of LCSCs. In this study, we constructed a special BME-based three-dimensional culture system (3D-culture) to amplify LCSCs in human lung adenocarcinoma cell line A549 cells and found 3D-culture promoted the enrichment and amplification of LCSCs in A549 cells displaying higher proliferation potential and invasion activity, but lower apoptosis. The expression and secretion levels of FGF1 and IGF1 were dramatically elevated in 3D-culture compared to 2D-culture. After growing in FGF1 and IGF1-conditioned 3D-culture, the proportion of LCSCs with specific stemness phenotypes in A549 cells significantly increased compared to that in conventional 3D suspension culture system. Further results indicated that FGF1 and IGF1 promoted the amplification and cancer stemness of LCSCs dependent on MAPK signaling pathway. Our data firstly established a growth factors-conditioned 3D-culture for LCSCs and demonstrated the effects of FGF1 and IGF1 in promoting the enrichment and amplification of LCSCs which might provide a feasible cell model in vitro for both mechanism study and translational research on lung cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bioengineered Lungs: A Challenge and An Opportunity.

PubMed

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.

Robust lung identification in MSCT via controlled flooding and shape constraints: dealing with anatomical and pathological specificity

NASA Astrophysics Data System (ADS)

Fetita, Catalin; Tarando, Sebastian; Brillet, Pierre-Yves; Grenier, Philippe A.

2016-03-01

Correct segmentation and labeling of lungs in thorax MSCT is a requirement in pulmonary/respiratory disease analysis as a basis for further processing or direct quantitative measures: lung texture classification, respiratory functional simulations, intrapulmonary vascular remodeling evaluation, detection of pleural effusion or subpleural opacities, are only few clinical applications related to this requirement. Whereas lung segmentation appears trivial for normal anatomo-pathological conditions, the presence of disease may complicate this task for fully-automated algorithms. The challenges come either from regional changes of lung texture opacity or from complex anatomic configurations (e.g., thin septum between lungs making difficult proper lung separation). They make difficult or even impossible the use of classic algorithms based on adaptive thresholding, 3-D connected component analysis and shape regularization. The objective of this work is to provide a robust segmentation approach of the pulmonary field, with individualized labeling of the lungs, able to overcome the mentioned limitations. The proposed approach relies on 3-D mathematical morphology and exploits the concept of controlled relief flooding (to identify contrasted lung areas) together with patient-specific shape properties for peripheral dense tissue detection. Tested on a database of 40 MSCT of pathological lungs, the proposed approach showed correct identification of lung areas with high sensitivity and specificity in locating peripheral dense opacities.

[A case-control study of the risk factors for lung cancer among Chinese women who have never smoked].

PubMed

Fang, Jun; Gan, De-kun; Zheng, Su-hua; Zhang, Hong-wei

2006-07-01

To investigate the risk factors for lung cancer among women who had never smoked. Methods A 1:2 matched case-control study was carried out. The cases are the no-smoking female patients with the primary lung cancer diagnosed by pathology mothed from hospitals in Beijing, Shanghai and Chengdu between September 2001 and February 2004. One hospital control and one population control matched for age, sex and no-smoking et al., were enrolled. The case and control were interviewed about the exposure information of related factors using the uniform questionnaire. Statistical analysis of single-factor and multivariate conditional Logistic regression were performed to screen the risk factors of lung cancer. During the single-factoranalysis, 28 exposure factors were identified as risk factors for lung cancer. The multivariate conditional Logistic regression show that passive smoking index > or = 50 person * year (OR = 1.77,95% CI, 1.07 - 2.92), consumption of internal organs of animals (OR = 1.85,95% CI, 1.06 - 3.22), and occupational exposure to dust (OR = 2.47,95% CI, 1.21 - 5.03) and bad ventilation in workplace( OR = 4.02,95% CI, 1.74 - 9.29) are risk factors for lung cancer, but consumption of vegetables( OR = 0.26, 95% CI, 0.12 - 0.59), taking vitamins often (OR = 0.53, 95% CI, 0.30 - 0.93), average month income per person after married > or = 500 yuan ( OR = 0.50, 95% CI, 0.28 - 0.91) and the first procreation occurred between 24 and 30 years old (OR = 0.53, 95% CI, 0.32 - 0.90) are the protective factors for lung cancer. The dose-response were observed between passive smoking and risk rate of lung cancer by trend test. Some factors such as passive smoking, consumption of internal organs of animals, occupational exposure to dust and bad ventilation in workplace can increase the risk of lung cancer for women who had never smoked. Other factors such as consumption of vegetables, taking vitamins, and so on, can reduce the risk of lung cancer for women who had never smoked.

Hydroxyl Radical Formation from HULIS and Fe(II) Interactions: Fulvic Acid-Fe(II) Complexes in Simulated and Human Lung Fluids

NASA Astrophysics Data System (ADS)

Gonzalez, D.

2017-12-01

Inhalation of fine particulate matter (PM2.5) has long been associated with adverse health outcomes. However, the causative agents and underlying mechanisms for these health effects have yet to be identified. One hypothesis is that PM2.5 deposited in the alveoli produce an excess of highly reactive radicals, leading to oxidative stress. The OH radical may be the most physiologically damaging, capable of oxidizing of lipids, proteins and DNA. Due to the variability and uncertainty in PM2.5 composition, the components that contribute to OH formation are not well understood. Soluble Fe is a component of PM2.5that produces OH under physiological conditions. Humic-like substances are water soluble organics found in biomass burning and tobacco smoke. Humic-like substances are capable of binding to Fe and enhancing OH formation, but this chemistry is not well understood. In this work, we use soil derived fulvic acid as a surrogate for Humic-like substances and investigate its effect on OH formation from Fe(II) under conditions relevant to the lungs. We use a fluorescent OH trapping probe, chemical kinetics and thermodynamic modeling to investigate OH formation from fulvic acid and Fe(II) dissolved in simulated and human lung fluids. In simulated lung fluid, we find that fulvic acid binds to Fe(II) and enhances the rate of key reactions that form OH. When fulvic acid is added to human lung fluids containing Fe(II), an enhancement of OH formation is observed. In human lung fluid, fulvic acid and metal binding proteins compete for Fe binding. These metal binding proteins are typically not found in simulated lung fluids. Results show that fulvic acid strongly binds Fe(II) and catalyzes key reactions that form OH in both simulated and human lung fluids. These results may help explain the role of Humic-like substances and Fe in oxidative stress and adverse health outcomes. Furthermore, we suggest that future studies employ simulated lung fluids containing metal binding proteins to better reflect human lung fluids.

Cryptococcus Neoformans Modulates Extracellular Killing by Neutrophils

PubMed Central

Qureshi, Asfia; Grey, Angus; Rose, Kristie L.; Schey, Kevin L.; Del Poeta, Maurizio

2011-01-01

We recently established a key role for host sphingomyelin synthase (SMS) in regulating the killing activity of neutrophils against Cryptococcus neoformans. In this paper, we studied the effect of C. neoformans on the killing activity of neutrophils and whether SMS would still be a player against C. neoformans in immunocompromised mice lacking T and natural killer (NK) cells (Tgε26 mice). To this end, we analyzed whether C. neoformans would have any effect on neutrophil survival and killing in vitro and in vivo. We show that unlike Candida albicans, neither the presence nor the capsule size of C. neoformans cells have any effect on neutrophil viability. Interestingly, melanized C. neoformans cells totally abrogated the killing activity of neutrophils. We monitored how exposure of neutrophils to C. neoformans cells would interfere with any further killing activity of the conditioned medium and found that pre-incubation with live but not “heat-killed” fungal cells significantly inhibits further killing activity of the medium. We then studied whether activation of SMS at the site of C. neoformans infection is dependent on T and NK cells. Using matrix-assisted laser desorption–ionization tissue imaging in infected lung we found that similar to previous observations in the isogenic wild-type CBA/J mice, SM 16:0 levels are significantly elevated at the site of infection in mice lacking T and NK cells, but only at early time points. This study highlights that C. neoformans may negatively regulate the killing activity of neutrophils and that SMS activation in neutrophils appears to be partially independent of T and/or NK cells. PMID:21960987

Conditioned medium as a strategy for human stem cells chondrogenic differentiation.

PubMed

Alves da Silva, M L; Costa-Pinto, A R; Martins, A; Correlo, V M; Sol, P; Bhattacharya, M; Faria, S; Reis, R L; Neves, Nuno M

2015-06-01

Paracrine signalling from chondrocytes has been reported to increase the synthesis and expression of cartilage extracellular matrix (ECM) by stem cells. The use of conditioned medium obtained from chondrocytes for stimulating stem cells chondrogenic differentiation may be a very interesting alternative for moving into the clinical application of these cells, as chondrocytes could be partially replaced by stem cells for this type of application. In the present study we aimed to achieve chondrogenic differentiation of two different sources of stem cells using conditioned medium, without adding growth factors. We tested both human bone marrow-derived mesenchymal stem cells (hBSMCs) and human Wharton's jelly-derived stem cells (hWJSCs). Conditioned medium obtained from a culture of human articular chondrocytes was used to feed the cells during the experiment. Cultures were performed in previously produced three-dimensional (3D) scaffolds, composed of a blend of 50:50 chitosan:poly(butylene succinate). Both types of stem cells were able to undergo chondrogenic differentiation without the addition of growth factors. Cultures using hWJSCs showed significantly higher GAGs accumulation and expression of cartilage-related genes (aggrecan, Sox9 and collagen type II) when compared to hBMSCs cultures. Conditioned medium obtained from articular chondrocytes induced the chondrogenic differentiation of MSCs and ECM formation. Obtained results showed that this new strategy is very interesting and should be further explored for clinical applications. Copyright © 2013 John Wiley & Sons, Ltd.

Assisting the Adult with a Respiratory Condition. Care of the Adult.

ERIC Educational Resources Information Center

Anoka-Hennepin Area Vocational Technical Inst., MN.

These three units for students in a practical nursing program provide supplemental instruction in caring for adult patients with respiratory conditions. Unit titles are Introduction to Care of the Patient with a Respiratory Condition, Infectious Respiratory Conditions, and Chronic Lung Conditions. Each unit contains the following: objectives, an…

[Occupational and non-occupational factors influencing health state of small and medium business workers].

PubMed

Fasikov, R M; Khuzhakhmetova, I B; Stepanov, E G

2010-01-01

Complex study of work conditions and health parameters of workers engaged into small and medium business proved that preserved and better health of these workers, prevention of occupational and occupationally mediated diseases necessitate federal and regional complex system of measures including legal basis, database on work conditions and their influence on small and medium business workers' health, occupational medicine training for employers and employees, more active involvement of medical institutioins into screening for occupational diseases.

Early identification of patients at risk of acute lung injury: evaluation of lung injury prediction score in a multicenter cohort study.

PubMed

Gajic, Ognjen; Dabbagh, Ousama; Park, Pauline K; Adesanya, Adebola; Chang, Steven Y; Hou, Peter; Anderson, Harry; Hoth, J Jason; Mikkelsen, Mark E; Gentile, Nina T; Gong, Michelle N; Talmor, Daniel; Bajwa, Ednan; Watkins, Timothy R; Festic, Emir; Yilmaz, Murat; Iscimen, Remzi; Kaufman, David A; Esper, Annette M; Sadikot, Ruxana; Douglas, Ivor; Sevransky, Jonathan; Malinchoc, Michael

2011-02-15

Accurate, early identification of patients at risk for developing acute lung injury (ALI) provides the opportunity to test and implement secondary prevention strategies. To determine the frequency and outcome of ALI development in patients at risk and validate a lung injury prediction score (LIPS). In this prospective multicenter observational cohort study, predisposing conditions and risk modifiers predictive of ALI development were identified from routine clinical data available during initial evaluation. The discrimination of the model was assessed with area under receiver operating curve (AUC). The risk of death from ALI was determined after adjustment for severity of illness and predisposing conditions. Twenty-two hospitals enrolled 5,584 patients at risk. ALI developed a median of 2 (interquartile range 1-4) days after initial evaluation in 377 (6.8%; 148 ALI-only, 229 adult respiratory distress syndrome) patients. The frequency of ALI varied according to predisposing conditions (from 3% in pancreatitis to 26% after smoke inhalation). LIPS discriminated patients who developed ALI from those who did not with an AUC of 0.80 (95% confidence interval, 0.78-0.82). When adjusted for severity of illness and predisposing conditions, development of ALI increased the risk of in-hospital death (odds ratio, 4.1; 95% confidence interval, 2.9-5.7). ALI occurrence varies according to predisposing conditions and carries an independently poor prognosis. Using routinely available clinical data, LIPS identifies patients at high risk for ALI early in the course of their illness. This model will alert clinicians about the risk of ALI and facilitate testing and implementation of ALI prevention strategies. Clinical trial registered with www.clinicaltrials.gov (NCT00889772).

The diagnosis of neonatal pulmonary atelectasis using lung ultrasonography.

PubMed

Liu, Jing; Chen, Shui-Wen; Liu, Fang; Li, Qiu-Ping; Kong, Xiang-Yong; Feng, Zhi-Chun

2015-04-01

Ultrasonography has been used for the diagnosis of many kinds of lung conditions, but few studies have investigated ultrasound for the diagnosis of neonatal pulmonary atelectasis (NAP). In this study, we evaluated the usefulness of lung ultrasonography for the diagnosis of NPA. From May 2012 to December 2013, 80 neonates with NPA and 50 neonates without lung disease were enrolled in this study. Each lung of every infant was divided into the anterior, lateral, and posterior regions by the anterior and posterior axillary lines. Each region was scanned carefully with the probe perpendicular or parallel to the ribs. The ultrasound findings were confirmed by chest radiograph (CXR) or CT scan. Sixty of the 80 patients with signs of NPA on lung ultrasound also had signs of NPA on CXR (termed focal-type atelectasis), and the other 20 patients had signs of NPA on chest CT scan while there were no abnormal findings on CXR (termed occult lung atelectasis). In patients with NPA, the main ultrasound findings were large areas of lung consolidation with clearly demarcated borders, air bronchograms, pleural line abnormalities, and absence of A-lines, as well as the presence of lung pulse and absence of lung sliding on real-time ultrasound. The sensitivity of lung ultrasonography for the diagnosis of NPA was 100%, whereas the sensitivity of CXR was 75%. Large areas of lung consolidation with clearly demarcated borders were only observed in patients with NPA. Lung ultrasonography is an accurate and reliable method for diagnosing NPA; most importantly, it can find those occult lung atelectasis that could not be detected on CXR. Routine lung ultrasonography is a useful method of diagnosing or excluding NPA in neonates.

Initial observations of cell-mediated drug delivery to the deep lung.

PubMed

Kumar, Arun; Glaum, Mark; El-Badri, Nagwa; Mohapatra, Shyam; Haller, Edward; Park, Seungjoo; Patrick, Leslie; Nattkemper, Leigh; Vo, Dawn; Cameron, Don F

2011-01-01

Using current methodologies, drug delivery to small airways, terminal bronchioles, and alveoli (deep lung) is inefficient, especially to the lower lungs. Urgent lung pathologies such as acute respiratory distress syndrome (ARDS) and post-lung transplantation complications are difficult to treat, in part due to the methodological limitations in targeting the deep lung with high efficiency drug distribution to the site of pathology. To overcome drug delivery limitations inhibiting the optimization of deep lung therapy, isolated rat Sertoli cells preloaded with chitosan nanoparticles were use to obtain a high-density distribution and concentration (92%) of the nanoparticles in the lungs of mice by way of the peripheral venous vasculature rather than the more commonly used pulmonary route. Additionally, Sertoli cells were preloaded with chitosan nanoparticles coupled with the anti-inflammatory compound curcumin and then injected intravenously into control or experimental mice with deep lung inflammation. By 24 h postinjection, most of the curcumin load (∼90%) delivered in the injected Sertoli cells was present and distributed throughout the lungs, including the perialveloar sac area in the lower lungs. This was based on the high-density, positive quantification of both nanoparticles and curcumin in the lungs. There was a marked positive therapeutic effect achieved 24 h following curcumin treatment delivered by this Sertoli cell nanoparticle protocol (SNAP). Results identify a novel and efficient protocol for targeted delivery of drugs to the deep lung mediated by extratesticular Sertoli cells. Utilization of SNAP delivery may optimize drug therapy for conditions such as ARDS, status asthmaticus, pulmonary hypertension, lung cancer, and complications following lung transplantation where the use of high concentrations of anti-inflammatory drugs is desirable, but often limited by risks of systemic drug toxicity.

UNIVERSAL RELATIONSHIP OF TOTAL LUNG DEPOSITION OF PARTICLES IN NORMAL ADULTS WITH PARTICLE SIZE AND BREATHING PATTERN

EPA Science Inventory

Particulate matter in the air is known for causing adverse health effects and yet estimating lung deposition dose is difficult because exposure conditions vary widely. We measured total deposition fraction (TDF) of monodisperse aerosols in the size range of 0.04 - 5 micron in dia...

Inflammatory Monocytes Orchestrate Innate Antifungal Immunity in the Lung

PubMed Central

Dutta, Orchi; Kasahara, Shinji; Donnelly, Robert; Du, Peicheng; Rosenfeld, Jeffrey; Leiner, Ingrid; Chen, Chiann-Chyi; Ron, Yacov; Hohl, Tobias M.; Rivera, Amariliz

2014-01-01

Aspergillus fumigatus is an environmental fungus that causes invasive aspergillosis (IA) in immunocompromised patients. Although -CC-chemokine receptor-2 (CCR2) and Ly6C-expressing inflammatory monocytes (CCR2+Mo) and their derivatives initiate adaptive pulmonary immune responses, their role in coordinating innate immune responses in the lung remain poorly defined. Using conditional and antibody-mediated cell ablation strategies, we found that CCR2+Mo and monocyte-derived dendritic cells (Mo-DCs) are essential for innate defense against inhaled conidia. By harnessing fluorescent Aspergillus reporter (FLARE) conidia that report fungal cell association and viability in vivo, we identify two mechanisms by which CCR2+Mo and Mo-DCs exert innate antifungal activity. First, CCR2+Mo and Mo-DCs condition the lung inflammatory milieu to augment neutrophil conidiacidal activity. Second, conidial uptake by CCR2+Mo temporally coincided with their differentiation into Mo-DCs, a process that resulted in direct conidial killing. Our findings illustrate both indirect and direct functions for CCR2+Mo and their derivatives in innate antifungal immunity in the lung. PMID:24586155

Exploring candidate biomarkers for lung and prostate cancers using gene expression and flux variability analysis.

PubMed

Asgari, Yazdan; Khosravi, Pegah; Zabihinpour, Zahra; Habibi, Mahnaz

2018-02-19

Genome-scale metabolic models have provided valuable resources for exploring changes in metabolism under normal and cancer conditions. However, metabolism itself is strongly linked to gene expression, so integration of gene expression data into metabolic models might improve the detection of genes involved in the control of tumor progression. Herein, we considered gene expression data as extra constraints to enhance the predictive powers of metabolic models. We reconstructed genome-scale metabolic models for lung and prostate, under normal and cancer conditions to detect the major genes associated with critical subsystems during tumor development. Furthermore, we utilized gene expression data in combination with an information theory-based approach to reconstruct co-expression networks of the human lung and prostate in both cohorts. Our results revealed 19 genes as candidate biomarkers for lung and prostate cancer cells. This study also revealed that the development of a complementary approach (integration of gene expression and metabolic profiles) could lead to proposing novel biomarkers and suggesting renovated cancer treatment strategies which have not been possible to detect using either of the methods alone.

Bacterial lung sepsis in patients with febrile neutropenia.

PubMed

Lanoix, Jean-Philippe; Schmit, Jean-Luc; Douadi, Youcef

2012-05-01

This review provides an update on microbiological and therapeutic data in febrile neutropenic patients in general and those with bacterial lung sepsis in particular. Although the Infectious Diseases Society of America updated its guidelines on febrile neutropenia in 2010, changing epidemiological factors and the spread of new drug resistance constitutes challenges for initial treatment of this condition. Lung sepsis stands out because of the frequent absence of microbiological identification. We review the use of newly available, novel, broad-spectrum antibiotics (linezolid, tigecycline, daptomycin, etc.) in this indication. Although the incidence of Gram-negative infections in neutropenic fever is leveling off, there is a worrying increase in resistance. New drugs are available but not well studied in febrile neutropenia; daptomycin and tigecycline should not be used in suspected lung sepsis in these patients. New diagnostic tools (such as the procalcitonin assay and the LightCycler SeptiFast assay, Roche Molecular Systems) appear to be unhelpful in febrile neutropenia, although more data on fungal sepsis are required. There are no specific features of the treatment of pneumonia or septic shock in neutropenic fever, but both conditions increase the mortality rate.

Carcinogenic and Cocarcinogenic Effects of Radon and Radon Daughters in Rats.

PubMed Central

Monchaux, G; Morlier, JP; Morin, M; Chameaud, J; Lafuma, J; Masse, R

1994-01-01

It has been previously established that lung cancer could be induced in rats by exposure to radon and radon daughters. Although the oat-cell carcinomas that are common in humans were not found in rats, other histological types of lung carcinomas, especially squamous cell carcinomas and primitive lung adenocarcinomas, were similar to those observed in humans. A dose-effect relationship was established for cumulative doses varying from 25 to 3000 working-level-months (WLM), which was similar for medium and high cumulative doses to that observed in uranium miners. This experimental protocol was also used to study the potential cocarcinogenic effects of other environmental or industrial airborne pollutants such as tobacco smoke, mineral fibers, diesel exhausts, or minerals from metallic mine ores that may act synergistically with radon exposure. In rats exposed to radon and tobacco smoke combined, the incidence of lung cancers was higher by a factor of 2-4 according to the cumulative radon exposure and the duration of tobacco smoke exposure. When mineral fibers were injected intrapleurally, an increased incidence of malignant thoracic tumors was observed in rats exposed to radon and fibers combined, but synergistic effects resulted in additivity. With diesel exhausts or minerals from metallic ores, a slight, nonsignificant increase in the incidence of lung carcinomas was observed compared with rats exposed to radon alone. These results demonstrated that it is possible to establish the potential cocarcinogenic action, showing either multiplicative, additive, or no effect of various environmental or industrial airborne pollutants combined with radon exposure. This radon model is valid for investigating possible interactions between two occupational exposures. Images p64-a Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. PMID:9719670

Rapid learning in practice: A lung cancer survival decision support system in routine patient care data

PubMed Central

Dekker, Andre; Vinod, Shalini; Holloway, Lois; Oberije, Cary; George, Armia; Goozee, Gary; Delaney, Geoff P.; Lambin, Philippe; Thwaites, David

2016-01-01

Background and purpose A rapid learning approach has been proposed to extract and apply knowledge from routine care data rather than solely relying on clinical trial evidence. To validate this in practice we deployed a previously developed decision support system (DSS) in a typical, busy clinic for non-small cell lung cancer (NSCLC) patients. Material and methods Gender, age, performance status, lung function, lymph node status, tumor volume and survival were extracted without review from clinical data sources for lung cancer patients. With these data the DSS was tested to predict overall survival. Results 3919 lung cancer patients were identified with 159 eligible for inclusion, due to ineligible histology or stage, non-radical dose, missing tumor volume or survival. The DSS successfully identified a good prognosis group and a medium/poor prognosis group (2 year OS 69% vs. 27/30%, p < 0.001). Stage was less discriminatory (2 year OS 47% for stage I–II vs. 36% for stage IIIA–IIIB, p = 0.12) with most good prognosis patients having higher stage disease. The DSS predicted a large absolute overall survival benefit (~40%) for a radical dose compared to a non-radical dose in patients with a good prognosis, while no survival benefit of radical radiotherapy was predicted for patients with a poor prognosis. Conclusions A rapid learning environment is possible with the quality of clinical data sufficient to validate a DSS. It uses patient and tumor features to identify prognostic groups in whom therapy can be individualized based on predicted outcomes. Especially the survival benefit of a radical versus non-radical dose predicted by the DSS for various prognostic groups has clinical relevance, but needs to be prospectively validated. PMID:25241994

Lung Cancer Attributable to Indoor Radon Exposures in Two Radon--Prone Areas, Stei (Romania) and Torrelodones (Spain)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dinu, Alexandra; Cosma, Constantin; Vasiliniuc, Stefan

2009-05-22

Radon and radon progeny are present indoors, in houses and others dwellings, representing the most important contribution to dose from natural sources of radiation. Most studies have demonstrated an increased risk of lung cancer at high concentration of radon for both smokers and nonsmokers. For medium and low concentrations which are the typical residential radon levels, recent researches have also demonstrated increased risks of lung cancer for people exposed. The work presents a comparative analysis of the radon exposure data in the two radon--prone areas, Stei, Transylvania, (Romania), in the near of old Romanian uranium mines and in the graniticmore » area of Torrelodones town, Sierra de Guadarrama (Spain). One important difference between the two studied areas is related to the houses built using uranium waste as construction material in Stei area. Measurements of indoor radon were performed in 280 dwellings (Romania) and 91 dwellings (Spain) by using nuclear track detectors, CR 39. The highest value measured in Stei area was 2650 Bq{center_dot}m{sup -3}. and 366 Bq{center_dot}m{sup -3} in the Spanish region. The results are compute with the BEIR VI report estimates using the age-duration model at an exposure rate below 2650 Bq{center_dot}m{sup -3}. A total of 233 lung cancer deaths were calculated in the Stei area for a period of 13 years (1994-2006), which is 116.82% higher than observed from the national statistics. In comparison, in Torrelodones area, a number of 276 deaths caused by lung cancer were estimated along a period of 13 years, which is 2.09 times higher than the number observed by authorities. This represents a significantly evidence that elevated risk can strongly be associated with cumulated radon exposure.« less

Decreased Dissolution of ZnO by Iron Doping Yields Nanoparticles with Reduced Toxicity in the Rodent Lung and Zebrafish Embryos

PubMed Central

Xia, Tian; Zhao, Yan; Sager, Tina; George, Saji; Pokhrel, Suman; Li, Ning; Schoenfeld, David; Meng, Huan; Lin, Sijie; Wang, Xiang; Wang, Meiying; Ji, Zhaoxia; Zink, Jeffrey I.; Mädler, Lutz; Castranova, Vincent; Lin, Shuo; Nel, Andre E.

2014-01-01

We have recently shown that the dissolution of ZnO nanoparticles and Zn2+ shedding leads to a series of sub-lethal and lethal toxicological responses at cellular level that can be alleviated by iron-doping. Iron-doping changes the particle matrix and slows the rate of particle dissolution. To determine whether iron doping of ZnO also leads to lesser toxic effects in vivo, toxicity studies were performed in rodent and zebrafish models. First, we synthesized a fresh batch of ZnO nanoparticles doped with 1–10 wt % of Fe. These particles were extensively characterized to confirm their doping status, reduced rate of dissolution in an exposure medium and reduced toxicity in a cellular screen. Subsequent studies compared the effects of undoped to doped particles in the rat lung, mouse lung and the zebrafish embryo. The zebrafish studies looked at embryo hatching and mortality rates as well as the generation of morphological defects, while the endpoints in the rodent lung included an assessment of inflammatory cell infiltrates, LDH release and cytokine levels in the bronchoalveolar lavage fluid. Iron doping, similar to the effect of the metal chelator, DTPA, interfered in the inhibitory effects of Zn2+ on zebrafish hatching. In the oropharyngeal aspiration model in the mouse, iron doping was associated with decreased polymorphonuclear cell counts and IL-6 mRNA production. Doped particles also elicited decreased heme oxygenase 1 expression in the murine lung. In the intratracheal instillation studies in the rat, Fe-doping was associated with decreased polymorphonuclear cell counts, LDH and albumin levels. All considered, the above data show that Fe-doping is a possible safe design strategy for preventing ZnO toxicity in animals and the environment. PMID:21250651

Correlation between in vivo and in vitro pulmonary responses to jet propulsion fuel-8 using precision-cut lung slices and a dynamic organ culture system.

PubMed

Hays, Allison M; Lantz, R Clark; Witten, Mark L

2003-01-01

In tissue slice models, interactions between the heterogeneous cell types comprising the lung parenchyma are maintained thus providing a controlled system for the study of pulmonary toxicology in vitro. However, validation of the model in vitro system must be affirmed. Previous reports, in in vivo systems, have demonstrated that Clara cells and alveolar type II cells are the targets following inhalation of JP-8 jet fuel. We have utilized the lung slice model to determine if cellular targets are similar following in vitro exposure to JP-8. Agar-filled adult rat lung explants were cored and precision cut, using the Brende/Vitron tissue slicer. Slices were cultured on titanium screens located as half-cylinders in cylindrical Teflon cradles that were loaded into standard scintillation vials and incubated at 37 degrees C. Slices were exposed to JP-8 jet fuel (0.5 mg/ml, 1.0 mg/ml, and 1.5 mg/ml in medium) for up to 24 hours. We determined ATP content using a luciferin-luciferase bioluminescent assay. No significant difference was found between the JP-8 jet fuel doses or time points, when compared to controls. Results were correlated with structural alterations following aerosol inhalation of JP-8. As a general observation, ultrastructural evaluation of alveolar type cells revealed an apparent increase in the number and size of surfactant secreting lamellar bodies that was JP-8 jet fuel-dose dependent. These results are similar to those observed following aerosol inhalation exposure. Thus, the lung tissue slice model appears to mimic in vivo effects of JP-8 and therefore is a useful model system for studying the mechanisms of lunginjury following JP-8 exposure.

COSMOS 2044: Lung morphology study, experiment K-7-28

NASA Technical Reports Server (NTRS)

Elliott, Ann R.; Mathieu-Costello, Odile; West, John B.

1991-01-01

Researchers examined the effect of microgravity during spaceflight on lung tissue. The ultrastructure of the left lungs of 5 Czechoslovakian Wister rats flown on the 13 day, 19+ hour Cosmos 2044 mission was examined and compared to 5 vivarium and 5 synchronous controls at 1-g conditions, and 5 rats exposed to 14 days of tail suspension. Pulmonary hemorrage and alveolar adema of unknown origin occurred to a greater extent in the flight, tail-suspended, and synchronous control animals, and in the dorsal regions of the lung when compared with the vivarium controls. The cause of these changes, which are possibly due to an increase in pulmonary vascular pressure, requires further investigation.

40 CFR Table 1 to Subpart Hhh of... - Emission Limits for Small Rural, Small, Medium, and Large HMIWI

Code of Federal Regulations, 2011 CFR

2011-07-01

..., Medium, and Large HMIWI 1 Table 1 to Subpart HHH of Part 62 Protection of Environment ENVIRONMENTAL... 62—Emission Limits for Small Rural, Small, Medium, and Large HMIWI Pollutant Units (7 percent oxygen, dry basis at standard conditions) Emission limits HMIWI size Small rural Small Medium Large...

40 CFR Table 1 to Subpart Hhh of... - Emission Limits for Small Rural, Small, Medium, and Large HMIWI

Code of Federal Regulations, 2012 CFR

2012-07-01

..., Medium, and Large HMIWI 1 Table 1 to Subpart HHH of Part 62 Protection of Environment ENVIRONMENTAL... 62—Emission Limits for Small Rural, Small, Medium, and Large HMIWI Pollutant Units (7 percent oxygen, dry basis at standard conditions) Emission limits HMIWI size Small rural Small Medium Large...

40 CFR Table 1 to Subpart Hhh of... - Emission Limits for Small Rural, Small, Medium, and Large HMIWI

Code of Federal Regulations, 2010 CFR

2010-07-01

..., Medium, and Large HMIWI 1 Table 1 to Subpart HHH of Part 62 Protection of Environment ENVIRONMENTAL... 62—Emission Limits for Small Rural, Small, Medium, and Large HMIWI Pollutant Units (7 percent oxygen, dry basis at standard conditions) Emission limits HMIWI size Small rural Small Medium Large...

Dietary inflammatory index and risk of lung cancer and other respiratory conditions among heavy smokers in the COSMOS screening study.

PubMed

Maisonneuve, Patrick; Shivappa, Nitin; Hébert, James R; Bellomi, Massimo; Rampinelli, Cristiano; Bertolotti, Raffaella; Spaggiari, Lorenzo; Palli, Domenico; Veronesi, Giulia; Gnagnarella, Patrizia

2016-04-01

To test whether the inflammatory potential of diet, as measured using the dietary inflammatory index (DII), is associated with risk of lung cancer or other respiratory conditions and to compare results obtained with those based on the aMED score, an established dietary index that measures adherence to the traditional Mediterranean diet. In 4336 heavy smokers enrolled in a prospective, non-randomized lung cancer screening program, we measured participants' diets at baseline using a self-administered food frequency questionnaire from which dietary scores were calculated. Cox proportional hazards and logistic regression models were used to assess association between the dietary indices and lung cancer diagnosed during annual screening, and other respiratory outcomes that were recorded at baseline, respectively. In multivariable analysis, adjusted for baseline lung cancer risk (estimated from age, sex, smoking history, and asbestos exposure) and total energy, both DII and aMED scores were associated with dyspnoea (p trend = 0.046 and 0.02, respectively) and radiological evidence of emphysema (p trend = 0.0002 and 0.02). After mutual adjustment of the two dietary scores, only the association between DII and radiological evidence of emphysema (Q4 vs. Q1, OR 1.30, 95 % CI 1.01-1.67, p trend = 0.012) remained statistically significant. At univariate analysis, both DII and aMED were associated with lung cancer risk, but in fully adjusted multivariate analysis, only the association with aMED remained statistically significant (p trend = 0.04). Among heavy smokers, a pro-inflammatory diet, as indicated by increasing DII score, is associated with dyspnoea and radiological evidence of emphysema. A traditional Mediterranean diet, which is associated with a lower DII, may lower lung cancer risk.

Dietary inflammatory index and risk of lung cancer and other respiratory conditions among heavy smokers in the COSMOS screening study

PubMed Central

Shivappa, Nitin; Hébert, James R.; Bellomi, Massimo; Rampinelli, Cristiano; Bertolotti, Raffaella; Spaggiari, Lorenzo; Palli, Domenico; Veronesi, Giulia; Gnagnarella, Patrizia

2016-01-01

Purpose To test whether the inflammatory potential of diet, as measured using the dietary inflammatory index (DII), is associated with risk of lung cancer or other respiratory conditions and to compare results obtained with those based on the aMED score, an established dietary index that measures adherence to the traditional Mediterranean diet. Methods In 4336 heavy smokers enrolled in a prospective, non-randomized lung cancer screening program, we measured participants’ diets at baseline using a self-administered food frequency questionnaire from which dietary scores were calculated. Cox proportional hazards and logistic regression models were used to assess association between the dietary indices and lung cancer diagnosed during annual screening, and other respiratory outcomes that were recorded at baseline, respectively. Results In multivariable analysis, adjusted for baseline lung cancer risk (estimated from age, sex, smoking history, and asbestos exposure) and total energy, both DII and aMED scores were associated with dyspnoea (p trend = 0.046 and 0.02, respectively) and radiological evidence of emphysema (p trend = 0.0002 and 0.02). After mutual adjustment of the two dietary scores, only the association between DII and radiological evidence of emphysema (Q4 vs. Q1, OR 1.30, 95 % CI 1.01–1.67, p trend = 0.012) remained statistically significant. At univariate analysis, both DII and aMED were associated with lung cancer risk, but in fully adjusted multivariate analysis, only the association with aMED remained statistically significant (p trend = 0.04). Conclusions Among heavy smokers, a pro-inflammatory diet, as indicated by increasing DII score, is associated with dyspnoea and radiological evidence of emphysema. A traditional Mediterranean diet, which is associated with a lower DII, may lower lung cancer risk. PMID:25953452

Impact assessment of repeated exposure of organotypic 3D bronchial and nasal tissue culture models to whole cigarette smoke.

PubMed

Kuehn, Diana; Majeed, Shoaib; Guedj, Emmanuel; Dulize, Remi; Baumer, Karine; Iskandar, Anita; Boue, Stephanie; Martin, Florian; Kostadinova, Radina; Mathis, Carole; Ivanov, Nikolai V; Frentzel, Stefan; Hoeng, Julia; Peitsch, Manuel C

2015-02-12

Cigarette smoke (CS) has a major impact on lung biology and may result in the development of lung diseases such as chronic obstructive pulmonary disease or lung cancer. To understand the underlying mechanisms of disease development, it would be important to examine the impact of CS exposure directly on lung tissues. However, this approach is difficult to implement in epidemiological studies because lung tissue sampling is complex and invasive. Alternatively, tissue culture models can facilitate the assessment of exposure impacts on the lung tissue. Submerged 2D cell cultures, such as normal human bronchial epithelial (NHBE) cell cultures, have traditionally been used for this purpose. However, they cannot be exposed directly to smoke in a similar manner to the in vivo exposure situation. Recently developed 3D tissue culture models better reflect the in vivo situation because they can be cultured at the air-liquid interface (ALI). Their basal sides are immersed in the culture medium; whereas, their apical sides are exposed to air. Moreover, organotypic tissue cultures that contain different type of cells, better represent the physiology of the tissue in vivo. In this work, the utilization of an in vitro exposure system to expose human organotypic bronchial and nasal tissue models to mainstream CS is demonstrated. Ciliary beating frequency and the activity of cytochrome P450s (CYP) 1A1/1B1 were measured to assess functional impacts of CS on the tissues. Furthermore, to examine CS-induced alterations at the molecular level, gene expression profiles were generated from the tissues following exposure. A slight increase in CYP1A1/1B1 activity was observed in CS-exposed tissues compared with air-exposed tissues. A network-and transcriptomics-based systems biology approach was sufficiently robust to demonstrate CS-induced alterations of xenobiotic metabolism that were similar to those observed in the bronchial and nasal epithelial cells obtained from smokers.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sudhyadhom, A; McGuinness, C; Descovich, M

Purpose: To develop a methodology for validation of a Monte-Carlo dose calculation model for robotic small field SRS/SBRT deliveries. Methods: In a robotic treatment planning system, a Monte-Carlo model was iteratively optimized to match with beam data. A two-part analysis was developed to verify this model. 1) The Monte-Carlo model was validated in a simulated water phantom versus a Ray-Tracing calculation on a single beam collimator-by-collimator calculation. 2) The Monte-Carlo model was validated to be accurate in the most challenging situation, lung, by acquiring in-phantom measurements. A plan was created and delivered in a CIRS lung phantom with film insert.more » Separately, plans were delivered in an in-house created lung phantom with a PinPoint chamber insert within a lung simulating material. For medium to large collimator sizes, a single beam was delivered to the phantom. For small size collimators (10, 12.5, and 15mm), a robotically delivered plan was created to generate a uniform dose field of irradiation over a 2×2cm{sup 2} area. Results: Dose differences in simulated water between Ray-Tracing and Monte-Carlo were all within 1% at dmax and deeper. Maximum dose differences occurred prior to dmax but were all within 3%. Film measurements in a lung phantom show high correspondence of over 95% gamma at the 2%/2mm level for Monte-Carlo. Ion chamber measurements for collimator sizes of 12.5mm and above were within 3% of Monte-Carlo calculated values. Uniform irradiation involving the 10mm collimator resulted in a dose difference of ∼8% for both Monte-Carlo and Ray-Tracing indicating that there may be limitations with the dose calculation. Conclusion: We have developed a methodology to validate a Monte-Carlo model by verifying that it matches in water and, separately, that it corresponds well in lung simulating materials. The Monte-Carlo model and algorithm tested may have more limited accuracy for 10mm fields and smaller.« less

Callus induction and flavonoid production on the immature seed of Stelechocarpus burahol

NASA Astrophysics Data System (ADS)

Habibah, N. A.; Moeljopawiro, S.; Dewi, K.; Indrianto, A.

2018-03-01

Stelechocarpus burahol [(Bl.) Hook. f. & Th.] is one of the medicinal plants. In vitro callus induction studies on S. burahol were carried out to determine phytohormone requirement for optimum callus induction. Immature seed explants were cultured on MS medium by adding different kinds and different concentrations of plant growth regulators (picloram and 2,4-D) under light and dark conditions. The results showed that callus formation was initiated on the 18,50th to the 55th days. The best condition for optimum callus induction was found on MS medium, which was supplemented with 7.5 mg/L picloram and was maintained in the dark condition. The callus induction varied from 60% to 100%. The callus that produced the highest flavonoid was grown on the medium with the addition of 10 mg/L of 2,4-D. In conclusion, the results represented a suitable medium for S.burahol callus induction.

Lung Involvement in Systemic Sclerosis

PubMed Central

Hassoun, Paul M.

2011-01-01

Summary Scleroderma is a multisystem disease characterized by a severe inflammatory process and exuberant fibrosis. Lung involvement is a frequent complication and a leading cause of morbidity and mortality in this syndrome. Two major pulmonary syndromes are associated with scleroderma; a pulmonary vascular disorder evolving over time into relatively isolated pulmonary arterial hypertension (PAH), and interstitial lung disease (ILD). Each syndrome, when present, is a cause of morbidity and significantly reduces survival of scleroderma patients when compared to patients free of lung complication. When pulmonary hypertension and ILD are combined, survival is further reduced. Current therapy appears to have no meaningful effect on either condition and, thus, there is a need for better understanding of underlying pathogenic mechanisms. This review focuses on clinical, diagnostic, and therapeutic features of PAH and ILD as well as other frequent but less debilitating lung complications of scleroderma. PMID:21195581

Effect of SO/sub 2/ on the clearance of Listeria monocytogenes from the lungs of emphysematous hamsters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trimpe, K.L.; Weiss, H.; Zwilling, B.S.

1986-10-01

The effect of sulfur dioxide on the clearance of Listeria monocytogenes from normal and emphysematous hamsters was assessed by measuring the number of colony forming units recovered from whole lung homogenates. Continuous exposure to SO/sub 2/ after intratracheal instillation of Listeria significantly altered the clearance of viable bacteria from the lungs of emphysematous but not normal hamsters. Pre-exposure of hamsters to SO/sub 2/ for 2 weeks prior to respiratory infection had similar effects. The emphysematous hamsters exposed to SO/sub 2/ had a lower average number of Listeria in the lungs after the first week of infection than control groups. Thismore » effect appears to result from the combined influence of the SO/sub 2/, the Listeria infection, and the emphysematous condition within the lungs.« less

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

PubMed

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

2016-04-01

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

Aspergillus spp. colonization in exhaled breath condensate of lung cancer patients from Puglia Region of Italy.

PubMed

Carpagnano, Giovanna E; Lacedonia, Donato; Palladino, Grazia Pia; Logrieco, Giuseppe; Crisetti, Elisabetta; Susca, Antonia; Logrieco, Antonio; Foschino-Barbaro, Maria P

2014-02-18

Airways of lung cancer patients are often colonized by fungi. Some of these colonizing fungi, under particular conditions, produce cancerogenic mycotoxins. Given the recent interest in the infective origin of lung cancer, with this preliminary study we aim to give our small contribution to this field of research by analysing the fungal microbiome of the exhaled breath condensate of lung cancer patients from Puglia, a region of Italy. We enrolled 43 lung cancer patients and 21 healthy subjects that underwent exhaled breath condensate and bronchial brushing collection. The fungal incidence and nature of sample collected were analysed by using a selected media for Aspergillus species. For the first time we were able to analyse the fungal microbioma of the exhaled breath condensate. 27.9% of lung cancer patients showed a presence of Aspergillus niger, or A. ochraceus or Penicillium ssp. while none of the healthy subjects did so. The results confirmed the high percentage of fungal colonization of the airways of lung cancer patients from Puglia, suggesting the need to conduct further analyses in this field in order to evaluate the exact pathogenetic role of these fungi in lung cancer as well as to propose efficient, empirical therapy.

CXCR3 Signaling Is Required for Restricted Homing of Parenteral Tuberculosis Vaccine-Induced T Cells to Both the Lung Parenchyma and Airway.

PubMed

Jeyanathan, Mangalakumari; Afkhami, Sam; Khera, Amandeep; Mandur, Talveer; Damjanovic, Daniela; Yao, Yushi; Lai, Rocky; Haddadi, Siamak; Dvorkin-Gheva, Anna; Jordana, Manel; Kunkel, Steven L; Xing, Zhou

2017-10-01

Although most novel tuberculosis (TB) vaccines are designed for delivery via the muscle or skin for enhanced protection in the lung, it has remained poorly understood whether systemic vaccine-induced memory T cells can readily home to the lung mucosa prior to and shortly after pathogen exposure. We have investigated this issue by using a model of parenteral TB immunization and intravascular immunostaining. We find that systemically induced memory T cells are restricted to the blood vessels in the lung, unable to populate either the lung parenchymal tissue or the airway under homeostatic conditions. We further find that after pulmonary TB infection, it still takes many days before such T cells can enter the lung parenchymal tissue and airway. We have identified the acquisition of CXCR3 expression by circulating T cells to be critical for their entry to these lung mucosal compartments. Our findings offer new insights into mucosal T cell biology and have important implications in vaccine strategies against pulmonary TB and other intracellular infections in the lung. Copyright © 2017 by The American Association of Immunologists, Inc.

Human Lung Small Airway-on-a-Chip Protocol.

PubMed

Benam, Kambez H; Mazur, Marc; Choe, Youngjae; Ferrante, Thomas C; Novak, Richard; Ingber, Donald E

2017-01-01

Organs-on-chips are microfluidic cell culture devices created using microchip manufacturing techniques that contain hollow microchannels lined by living cells, which recreate specialized tissue-tissue interfaces, physical microenvironments, and vascular perfusion necessary to recapitulate organ-level physiology in vitro. Here we describe a protocol for fabrication, culture, and operation of a human lung "small airway-on-a-chip," which contains a differentiated, mucociliary bronchiolar epithelium exposed to air and an underlying microvascular endothelium that experiences fluid flow. First, microengineering is used to fabricate a multilayered microfluidic device that contains two parallel elastomeric microchannels separated by a thin rigid porous membrane; this requires less than 1 day to complete. Next, primary human airway bronchiolar epithelial cells isolated from healthy normal donors or patients with respiratory disease are cultured on the porous membrane within one microchannel while lung microvascular endothelial cells are cultured on the opposite side of the same membrane in the second channel to create a mucociliated epithelium-endothelium interface; this process take about 4-6 weeks to complete. Finally, culture medium containing neutrophils isolated from fresh whole human blood are flowed through the microvascular channel of the device to enable real-time analysis of capture and recruitment of circulating leukocytes by endothelium under physiological shear; this step requires less than 1 day to complete. The small airway-on-a-chip represents a new microfluidic tool to model complex and dynamic inflammatory responses of healthy and diseased lungs in vitro.

Cannabis-induced bullous lung disease leading to pneumothorax: Case report and literature review.

PubMed

Mishra, Rashmi; Patel, Ravi; Khaja, Misbahuddin

2017-05-01

Marijuana use has been increasing in the United States among college students and young adults. Marijuana use has been associated with bullous lung disease which can lead to pneumothorax. There are other recreational drugs like methylphenidate, cocaine and heroin which have been associated with pneumothorax. We present a case of a 30-year-old man with spontaneous pneumothorax associated with marijuana use. The patient had no medical conditions and presented to the emergency room with chest pain. The physical examination revealed decreased breath sound on the right side of the chest. Bed side ultrasound of chest showed stratosphere sign, absent lung sliding; consistent with right-sided pneumothorax. The patient underwent placement of a chest tube. Computed tomography chest scans performed on day two also showed bullous lung disease in the right lung. Serial x-rays of the chest showed re-expansion of the lung. Despite the beneficial effects of Marijuana there are deleterious effects which are emphasized here. This case highlights the need for further studies to establish the relationship between marijuana use and lung diseases in the absence of nicotine use.

Effects of Aspergillus fumigatus colonization on lung function in cystic fibrosis.

PubMed

Speirs, Jennifer J; van der Ent, Cornelis K; Beekman, Jeffrey M

2012-11-01

Aspergillus fumigatus is frequently isolated from cystic fibrosis (CF) patients and is notorious for its role in the debilitating condition of allergic bronchopulmonary aspergillosis (ABPA). Although CF patients suffer from perpetual microorganism-related lung disease, it is unclear whether A. fumigatus colonization has a role in causing accelerated lung function decline and whether intervention is necessary. A. fumigatus morbidity appears to be related to cystic fibrosis transmembrane conductance regulator-dependant function of the innate immune system. A. fumigatus-colonized patients have a lower lung capacity, more frequent hospitalizations and more prominent radiological abnormalities than noncolonized patients. Treatment with antifungal agents can be of value but has several drawbacks and a direct effect on lung function is yet to be shown. A. fumigatus appears to have an important role in CF lung disease, not exclusive to the context of ABPA. However, a causal relationship still needs to be confirmed. Study observations and trends indicate a need to further elucidate the mechanisms of A. fumigatus interactions with the host innate immune system and its role in CF lung morbidity.

Development of conditioning programs for dressage horses based on time-motion analysis of competitions.

PubMed

Clayton, H M

1993-05-01

The time-motion characteristics of Canadian basic- and medium-level dressage competitions are described, and the results are applied in formulating sport-specific conditioning programs. One competition was analyzed at the six levels from basic 1 to medium 3. Each test was divided into a series of sequences based on the type and speed of activity. The durations of the sequences were measured from videotapes. The basic-level tests had fewer sequences, and they were shorter in distance and duration than the medium tests (P < 0.10), but the average speed did not differ between the two levels. It is recommended that horses competing at the basic levels be conditioned using 5-min exercise periods, with short (10-s) bursts of lengthened trot and canter included at basic 2 and above. In preparation for medium-level competitions, the duration of the work periods increases to 7 min, 10- to 12-s bursts of medium or extended trot and canter are included, and transitions are performed frequently to simulate the energy expenditure in overcoming inertia.

The extracellular calcium-sensing receptor regulates human fetal lung development via CFTR

PubMed Central

Brennan, Sarah C.; Wilkinson, William J.; Tseng, Hsiu-Er; Finney, Brenda; Monk, Bethan; Dibble, Holly; Quilliam, Samantha; Warburton, David; Galietta, Luis J.; Kemp, Paul J.; Riccardi, Daniela

2016-01-01

Optimal fetal lung growth requires anion-driven fluid secretion into the lumen of the developing organ. The fetus is hypercalcemic compared to the mother and here we show that in the developing human lung this hypercalcaemia acts on the extracellular calcium-sensing receptor, CaSR, to promote fluid-driven lung expansion through activation of the cystic fibrosis transmembrane conductance regulator, CFTR. Several chloride channels including TMEM16, bestrophin, CFTR, CLCN2 and CLCA1, are also expressed in the developing human fetal lung at gestational stages when CaSR expression is maximal. Measurements of Cl−-driven fluid secretion in organ explant cultures show that pharmacological CaSR activation by calcimimetics stimulates lung fluid secretion through CFTR, an effect which in humans, but not mice, was also mimicked by fetal hypercalcemic conditions, demonstrating that the physiological relevance of such a mechanism appears to be species-specific. Calcimimetics promote CFTR opening by activating adenylate cyclase and we show that Ca2+-stimulated type I adenylate cyclase is expressed in the developing human lung. Together, these observations suggest that physiological fetal hypercalcemia, acting on the CaSR, promotes human fetal lung development via cAMP-dependent opening of CFTR. Disturbances in this process would be expected to permanently impact lung structure and might predispose to certain postnatal respiratory diseases. PMID:26911344

Computationally efficient analysis of particle transport and deposition in a human whole-lung-airway model. Part II: Dry powder inhaler application.

PubMed

Kolanjiyil, Arun V; Kleinstreuer, Clement; Sadikot, Ruxana T

2017-05-01

Pulmonary drug delivery is becoming a favored route for administering drugs to treat both lung and systemic diseases. Examples of lung diseases include asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD) as well as respiratory distress syndrome (ARDS) and pulmonary fibrosis. Special respiratory drugs are administered to the lungs, using an appropriate inhaler device. Next to the pressurized metered-dose inhaler (pMDI), the dry powder inhaler (DPI) is a frequently used device because of the good drug stability and a minimal need for patient coordination. Specific DPI-designs and operations greatly affect drug-aerosol formation and hence local lung deposition. Simulating the fluid-particle dynamics after use of a DPI allows for the assessment of drug-aerosol deposition and can also assist in improving the device configuration and operation. In Part I of this study a first-generation whole lung-airway model (WLAM) was introduced and discussed to analyze particle transport and deposition in a human respiratory tract model. In the present Part II the drug-aerosols are assumed to be injected into the lung airways from a DPI mouth-piece, forming the mouth-inlet. The total as well as regional particle depositions in the WLAM, as inhaled from a DPI, were successfully compared with experimental data sets reported in the open literature. The validated modeling methodology was then employed to study the delivery of curcumin aerosols into lung airways using a commercial DPI. Curcumin has been implicated to possess high therapeutic potential as an antioxidant, anti-inflammatory and anti-cancer agent. However, efficacy of curcumin treatment is limited because of the low bioavailability of curcumin when ingested. Hence, alternative drug administration techniques, e.g., using inhalable curcumin-aerosols, are under investigation. Based on the present results, it can be concluded that use of a DPI leads to low lung deposition efficiencies because large amounts of drugs are deposited in the oral cavity. Hence, the output of a modified DPI has been evaluated to achieve improved drug delivery, especially needed when targeting the smaller lung airways. This study is the first to utilize CF-PD methodology to simulate drug-aerosol transport and deposition under actual breathing conditions in a whole lung model, using a commercial dry-powder inhaler for realistic inlet conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mechanisms for the target patterns formation in a stochastic bistable excitable medium

NASA Astrophysics Data System (ADS)

Verisokin, Andrey Yu.; Verveyko, Darya V.; Postnov, Dmitry E.

2018-04-01

We study the features of formation and evolution of spatiotemporal chaotic regime generated by autonomous pacemakers in excitable deterministic and stochastic bistable active media using the example of the FitzHugh - Nagumo biological neuron model under discrete medium conditions. The following possible mechanisms for the formation of autonomous pacemakers have been studied: 1) a temporal external force applied to a small region of the medium, 2) geometry of the solution region (the medium contains regions with Dirichlet or Neumann boundaries). In our work we explore the conditions for the emergence of pacemakers inducing target patterns in a stochastic bistable excitable system and propose the algorithm for their analysis.

FIBER AND INTEGRATED OPTICS. OTHER TOPICS IN QUANTUM ELECTRONICS: Determination of the saturation parameter in a fast-flow CO2 active medium

NASA Astrophysics Data System (ADS)

Lebedev, V. F.; Lysikov, A. Yu; Ryazanova, A. V.; Shalygin, S. V.

1990-05-01

A diagnostic method was developed for determination of such an important characteristic of a CO2 active medium as the energy stored in the vibrational degrees of freedom of molecules, which can be determined directly from the experimentally measured powers of probe beams without the need for any additional information on the medium and without any numerical calculations. Measurements were carried out using a real fast-flow system, which satisfied the conditions of validity of the proposed diagnostic method, and the correctness of the approach was confirmed. The results obtained demonstrated the efficiency of the excitation of the medium when the pump conditions were varied.

Hair Loss (Alopecia)

MedlinePlus

... Pediatrician Health Issues Conditions Abdominal ADHD Allergies & Asthma Autism Cancer Chest & Lungs Chronic Conditions Cleft & Craniofacial Developmental ... with certain abnormalities of the nails and the teeth. Later in childhood, hair loss may be due ...

[The respiratory effects of smoking].

PubMed

Peiffer, G; Underner, M; Perriot, J

2018-06-01

A marked increase in the morbidity and mortality of a large number of broncho-pulmonary diseases has been documented in relation to smoking. The influence of tobacco smoking on various respiratory conditions. is discussed: incidence, severity or natural history modification of some respiratory illnesses: obstructive lung diseases (COPD, asthma), lung cancer, bacterial, viral respiratory infections, with the impact of smoking on tuberculosis. Finally, the relationship of tobacco with diffuse interstitial lung disease: protective role of smoking (controversial in sarcoidosis, real in hypersensitivity pneumonitis). The benefits of smoking cessation are described. Copyright © 2018. Published by Elsevier Masson SAS.

Lung cancer risk among construction workers in California, 1988-2007.

PubMed

Calvert, Geoffrey M; Luckhaupt, Sara; Lee, Soo-Jeong; Cress, Rosemary; Schumacher, Pam; Shen, Rui; Tak, SangWoo; Deapen, Dennis

2012-05-01

Although lung cancer risks can vary by race/ethnicity and by construction occupation, these risks have not been examined extensively. This study analyzed 110,937 lung cancer cases identified from the California Cancer Registry between 1988 and 2007. Mean age at diagnosis, proportion diagnosed at an advanced stage, and proportion with 3-year survival were calculated for lung cancer cases employed in the construction industry. Case-control methodology was also used to assess the risk of lung cancer. Morbidity odds ratios (MORs) were estimated by conditional logistic regression. Construction workers were found to have a significantly elevated risk for all lung cancer combined (MOR = 1.57) and for each lung cancer histologic subtype examined. All construction occupations, except managers/engineers and supervisors, had a significantly elevated risk for all lung cancer combined. Roofers and welders had the highest risks for total lung cancer and for each of the histologic subtypes. Construction workers in each of the four race/ethnicity groups also had significantly increased lung cancer risks. Compared to non-construction workers, construction workers were diagnosed at an earlier age, at a more advanced stage, and had significantly lower 3-year survival, though differences were modest. These findings justify additional reductions in carcinogenic exposures in construction, and increased support for smoking cessation programs at construction sites. Copyright © 2012 Wiley Periodicals, Inc.

WNTLESS IS REQUIRED FOR PERIPHERAL LUNG DIFFERENTIATION AND PULMONARY VASCULAR DEVELOPMENT

PubMed Central

Cornett, Bridget; Snowball, John; Varisco, Brian M.; Lang, Richard; Whitsett, Jeffrey; Sinner, Debora

2013-01-01

Wntless (Wls), a gene highly conserved across the animal kingdom, encodes for a transmembrane protein that mediates Wnt ligand secretion. Wls is expressed in developing lung, wherein Wnt signaling is necessary for pulmonary morphogenesis. We hypothesize that Wls plays a critical role in modulating Wnt signaling during lung development and therefore affects processes critical for pulmonary morphogenesis. We generated conditional Wls mutant mice utilizing Shh-Cre and Dermo1-Cre mice to delete Wls in the embryonic respiratory epithelium and mesenchyme, respectively. Epithelial deletion of Wls disrupted lung branching morphogenesis, peripheral lung development and pulmonary endothelial differentiation. Epithelial Wls mutant mice died at birth due to respiratory failure caused by lung hypoplasia and pulmonary hemorrhage. In the lungs of these mice, VEGF and Tie2-angiopoietin signaling pathways, which mediate vascular development, were downregulated from early stages of development. In contrast, deletion of Wls in mesenchymal cells of the developing lung did not alter branching morphogenesis or early mesenchymal differentiation. In vitro assays support the concept that Wls acts in part via Wnt5a to regulate pulmonary vascular development. We conclude that epithelial Wls modulates Wnt ligand activities critical for pulmonary vascular differentiation and peripheral lung morphogenesis. These studies provide a new framework for understanding the molecular mechanisms underlying normal pulmonary vasculature formation and the dysmorphic pulmonary vasculature development associated with congenital lung disease. PMID:23523683

Wntless is required for peripheral lung differentiation and pulmonary vascular development.

PubMed

Cornett, Bridget; Snowball, John; Varisco, Brian M; Lang, Richard; Whitsett, Jeffrey; Sinner, Debora

2013-07-01

Wntless (Wls), a gene highly conserved across the animal kingdom, encodes for a transmembrane protein that mediates Wnt ligand secretion. Wls is expressed in developing lung, wherein Wnt signaling is necessary for pulmonary morphogenesis. We hypothesize that Wls plays a critical role in modulating Wnt signaling during lung development and therefore affects processes critical for pulmonary morphogenesis. We generated conditional Wls mutant mice utilizing Shh-Cre and Dermo1-Cre mice to delete Wls in the embryonic respiratory epithelium and mesenchyme, respectively. Epithelial deletion of Wls disrupted lung branching morphogenesis, peripheral lung development and pulmonary endothelial differentiation. Epithelial Wls mutant mice died at birth due to respiratory failure caused by lung hypoplasia and pulmonary hemorrhage. In the lungs of these mice, VEGF and Tie2-angiopoietin signaling pathways, which mediate vascular development, were downregulated from early stages of development. In contrast, deletion of Wls in mesenchymal cells of the developing lung did not alter branching morphogenesis or early mesenchymal differentiation. In vitro assays support the concept that Wls acts in part via Wnt5a to regulate pulmonary vascular development. We conclude that epithelial Wls modulates Wnt ligand activities critical for pulmonary vascular differentiation and peripheral lung morphogenesis. These studies provide a new framework for understanding the molecular mechanisms underlying normal pulmonary vasculature formation and the dysmorphic pulmonary vasculature development associated with congenital lung disease. Copyright © 2013 Elsevier Inc. All rights reserved.

Creb1 regulates late stage mammalian lung development via respiratory epithelial and mesenchymal-independent mechanisms

PubMed Central

Antony, N.; McDougall, A. R.; Mantamadiotis, T.; Cole, T. J.; Bird, A. D.

2016-01-01

During mammalian lung development, the morphological transition from respiratory tree branching morphogenesis to a predominantly saccular architecture, capable of air-breathing at birth, is dependent on physical forces as well as molecular signaling by a range of transcription factors including the cAMP response element binding protein 1 (Creb1). Creb1−/− mutant mice exhibit complete neonatal lethality consistent with a lack of lung maturation beyond the branching phase. To further define its role in the developing mouse lung, we deleted Creb1 separately in the respiratory epithelium and mesenchyme. Surprisingly, we found no evidence of a morphological lung defect nor compromised neonatal survival in either conditional Creb1 mutant. Interestingly however, loss of mesenchymal Creb1 on a genetic background lacking the related Crem protein showed normal lung development but poor neonatal survival. To investigate the underlying requirement for Creb1 for normal lung development, Creb1−/− mice were re-examined for defects in both respiratory muscles and glucocorticoid hormone signaling, which are also required for late stage lung maturation. However, these systems appeared normal in Creb1−/− mice. Together our results suggest that the requirement of Creb1 for normal mammalian lung morphogenesis is not dependent upon its expression in lung epithelium or mesenchyme, nor its role in musculoskeletal development. PMID:27150575

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

NASA Astrophysics Data System (ADS)

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

2017-03-01

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

Accurate segmentation of lung fields on chest radiographs using deep convolutional networks

NASA Astrophysics Data System (ADS)

Arbabshirani, Mohammad R.; Dallal, Ahmed H.; Agarwal, Chirag; Patel, Aalpan; Moore, Gregory

2017-02-01

Accurate segmentation of lung fields on chest radiographs is the primary step for computer-aided detection of various conditions such as lung cancer and tuberculosis. The size, shape and texture of lung fields are key parameters for chest X-ray (CXR) based lung disease diagnosis in which the lung field segmentation is a significant primary step. Although many methods have been proposed for this problem, lung field segmentation remains as a challenge. In recent years, deep learning has shown state of the art performance in many visual tasks such as object detection, image classification and semantic image segmentation. In this study, we propose a deep convolutional neural network (CNN) framework for segmentation of lung fields. The algorithm was developed and tested on 167 clinical posterior-anterior (PA) CXR images collected retrospectively from picture archiving and communication system (PACS) of Geisinger Health System. The proposed multi-scale network is composed of five convolutional and two fully connected layers. The framework achieved IOU (intersection over union) of 0.96 on the testing dataset as compared to manual segmentation. The suggested framework outperforms state of the art registration-based segmentation by a significant margin. To our knowledge, this is the first deep learning based study of lung field segmentation on CXR images developed on a heterogeneous clinical dataset. The results suggest that convolutional neural networks could be employed reliably for lung field segmentation.

Effects of neural stem cell media on hypoxic injury in rat hippocampal slice cultures.

PubMed

Lee, Na Mi; Chae, Soo Ahn; Lee, Hong Jun

2017-12-15

Neonatal hypoxic-ischemic brain injuries cause serious neurological sequelae, yet there is currently no effective treatment for them. We hypothesized that neurotrophic factors released into the medium by stem cells could supply hypoxia-damaged organotypic hippocampal slice cultures with regenerative abilities. We prepared organotypic slice cultures of the hippocampus of 7-day-old Sprague-Dawley rats based on the modified Stoppini method; slices were cultured for 14days in vitro using either Gahwiler's medium (G-medium) or stem cell-conditioned medium (S-medium) as culture medium. At day 14 in vitro, hippocampal slice cultures were exposed to 95% N 2 and 5% CO 2 for 3h to induce hypoxic damage, the extent of which was then measured using propidium iodide fluorescence and immunohistochemistry images. We performed dot blotting to estimate neurotrophic/growth factor levels in the G- and S-media. Organotypic hippocampal slices cultured using S-medium after hypoxic injury were significantly less damaged than those cultured using G-medium. GLUT1, NGF, GDNF, VEGF, GCSF, and IGF2 levels were higher in S-medium than in G-medium, whereas FGF1, HIF, and MCP3 levels were not significantly different between media. In conclusion, we found that stem cell-conditioned medium had a neuroprotective effect against hypoxic injury, and that, of the various neurotrophic factors in S-medium, NGF, GDNF, and VEGF can contribute to neuroprotection. Copyright © 2017 Elsevier B.V. All rights reserved.

[Phylogeny of gas exchange systems].

PubMed

Jürgens, K D; Gros, G

2002-04-01

Several systems of gas transport have developed during evolution, all of which are able to sufficiently supply oxygen to the tissues and eliminate the CO2 produced by the metabolism, in spite of great distances between the environment and the individual cells of the tissues. Almost all these systems utilize a combination of convection and diffusion steps. Convection achieves an efficient transport of gas over large distances, but requires energy and cannot occur across tissue barriers. Diffusion, on the other hand, achieves gas transport across barriers, but requires optimization of diffusion paths and diffusion areas. When two convectional gas flows are linked via a diffusional barrier (gas/fluid in the case of the avian lung, fluid/fluid in the case of gills), the directions in which the respective convectional movements pass each other are important determinants of gas exchange efficiency (concurrent, countercurrent and cross-current systems). The tracheal respiration found in insects has the advantage of circumventing the convective gas transport step in the blood, thereby avoiding the high energy expenditure of circulatory systems. This is made possible by a system of tracheae, ending in tracheoles, that reaches from the body surface to every cell within the body. The last step of gas transfer in these animals occurs by diffusion from the tracheoles ("air capillaries") to the mitochondria of cells. The disadvantage is that the tracheal system occupies a substantial fraction of body volume and that, due to limited mechanical stability of tracheal walls, this system would not be able to operate under conditions of high hydrostatic pressures, i. e. in large animals. Respiration in an "open" system, i. e. direct exposure of the diffusional barrier to the environmental air, eliminates the problem of bringing the oxygen to the barrier by convection, as is necessary in the avian and mammalian lung, in the insects' tracheal system and in the gills. An open system is found in the respiration via the skin, which is of significance in some amphibians, but is limited by the thickness of the skin that constitutes a substantial diffusion path for O2 and CO2. The thick skin, on the other hand, provides mechanical protection as well as flexibility for the animals' body and helps avoid massive water loss via the body surface. The gills of fishes, in contrast, exhibit rather short diffusion distances, are located in a mechanically protected space, and the problem of water loss does not exist. The flows of blood and water occur in opposite direction (countercurrent flow) and this situation makes an arterial PO2 approaching the environmental PO2 possible. A major disadvantage is constituted by the environmental medium since water contains little O2 compared to air and, to compensate this, much energy is expended to maintain a high flow rate of water through the gills. In the mammalian lung ("pool system"), the presence of a dead space and the rhythmic ventilation that replaces only a small fraction of the gas volume of the lung per breath, are responsible for an arterial PO2 (2/3 of the atmospheric PO2) that cannot reach the expiratory PO2. However, an advantage of this feature is the constantly high alveolar and arterial PCO2, which provides a highly effective H(+) buffer system in the entire body. The apparent disadvantage of the mammalian lung is avoided by the avian lung, which uses an extended system of airways to establish continuous equilibration of a part of the capillary blood with fresh air (cross current system), during inspiration as well as during expiration. In this system, arterial PO2 can significantly exceed expiratory PO2. A disadvantage here is the enormous amount of space taken up by the avian lung, in animals of 1 kg body weight three times as much as taken up by the mammalian lung. All respiratory exchange systems considered here exhibit high degrees of optimization - yet follow highly diverse construction principles. There is no such thing as an ideal gas exchange system. The system that has evolved in each species depends to an impressive extent on environmental conditions, on body build and size, on the animal's patterns of movement and on its energy consumption.

[Method of culturing microorganisms at constant concentrations of the nutrient components].

PubMed

Markvichev, N S; Manakov, M N

1985-01-01

A method for batch cultivation of microorganisms in a flow medium is described, characterized by slight changes in concentrations of medium components in time and by the absence of products of vital activity of microorganisms in the fermentation medium. The conditions are achieved due to application of a fermentation installation with a microfiltrative membrane that separates the cells of cultivated microorganisms from the culture fluid and due to increasing the flow rate to a value at which the inlet and outlet concentrations of the medium components are almost equal. The cells of cultivated microorganisms under such conditions remain in the fermentation medium volume. The system was called "Ekostat". If the process is performed in "Ekostat" system, a positive deviation from the logarithmic law is observed for the growth rate of the yeast Candida utilis VSB-651 on ethanol cultivation.

Differential respirable dust related lung function effects between current and former South African coal miners.

PubMed

Naidoo, Rajen N; Robins, Thomas G; Seixas, Noah; Lalloo, Umesh G; Becklake, Margaret

2005-05-01

Dust-related dose-response decrements in lung function among coal miners have been reported in several studies, with varying magnitudes across populations. Few studies have compared differences between current and former coal miners. No studies on dose response relationships with lung function have been conducted in South African coal mines, one of the top three producers of coal internationally. The objectives of this study were (1) to describe the relationship between respirable dust exposure and lung function among current and former South African coal miners and to determine whether differential dust related effects were present between these employment categories; (2) to examine dust related dose response relationships, controlling for potential confounding by smoking and a history of tuberculosis (TB). Six hundred and eighty-four current and 188 ex-miners from three bituminous coal mines in Mpumalanga Province were studied. Interviews assessing work histories, smoking profiles and other risk factors were conducted. Work histories were also obtained from company records. Standardised spirometry was performed by trained technicians. Cumulative respirable dust exposure (CDE) estimates were constructed from company-collected sampling and measurements conducted by the researchers. Regression models examined the associations of CDE with per cent predicted FEV(1) and FVC, controlling for smoking, past history of TB and employment status. A statistically significant decline in FEV(1) of 1.1 and 2.2 ml/mg-year/m(3) was found in representative 40-year-old, 1.7-m tall current and former miners, respectively. Significant differences were found between the highest and medium exposure categories. Ex-miners had a lower mean per cent predicted lung function than current miners for each cumulative exposure category, suggesting a "healthy worker" effect. Past history of TB contributed to 21 and 14% declines in per cent predicted FEV(1) and FVC, respectively. Thus, in this cohort, a dose-related decline in lung function was associated with respirable dust exposure, with a magnitude of effect similar to that seen in other studies and important differences between current and former employees. A "healthy worker" effect may have attenuated the magnitude of this relationship. TB was a significant contributor to lung function loss.

SU-E-T-454: Dosimetric Comparison between Pencil Beam and Monte Carlo Algorithms for SBRT Lung Treatment Using IPlan V4.1 TPS and CIRS Thorax Phantom.

PubMed

Fernandez, M Castrillon; Venencia, C; Garrigó, E; Caussa, L

2012-06-01

To compare measured and calculated doses using Pencil Beam (PB) and Monte Carlo (MC) algorithm on a CIRS thorax phantom for SBRT lung treatments. A 6MV photon beam generated by a Primus linac with an Optifocus MLC (Siemens) was used. Dose calculation was done using iPlan v4.1.2 TPS (BrainLAB) by PB and MC (dose to water and dose to medium) algorithms. The commissioning of both algorithms was done reproducing experimental measurements in water. A CIRS thorax phantom was used to compare doses using a Farmer type ion chamber (PTW) and EDR2 radiographic films (KODAK). The ionization chamber, into a tissue equivalent insert, was placed in two position of lung tissue and was irradiated using three treatments plans. Axial dose distributions were measured for four treatments plans using conformal and IMRT technique. Dose distribution comparisons were done by dose profiles and gamma index (3%/3mm). For the studied beam configurations, ion chamber measurements shows that PB overestimate the dose up to 8.5%, whereas MC has a maximum variation of 1.6%. Dosimetric analysis using dose profiles shows that PB overestimates the dose in the region corresponding to the lung up to 16%. For axial dose distribution comparison the percentage of pixels with gamma index bigger than one for MC and PB was, plan 1: 95.6% versus 87.4%, plan 2: 91.2% versus 77.6%, plan 3: 99.7% versus 93.1% and for plan 4: 98.8% versus 91.7%. It was confirmed that the lower dosimetric errors calculated applying MC algorithm appears when the spatial resolution and variance decrease at the expense of increased computation time. The agreement between measured and calculated doses, in a phantom with lung heterogeneities, is better with MC algorithm. PB algorithm overestimates the doses in lung tissue, which could have a clinical impact in SBRT lung treatments. © 2012 American Association of Physicists in Medicine.

SU-E-T-101: Determination and Comparison of Correction Factors Obtained for TLDs in Small Field Lung Heterogenous Phantom Using Acuros XB and EGSnrc

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soh, R; Lee, J; Harianto, F

Purpose: To determine and compare the correction factors obtained for TLDs in 2 × 2cm{sup 2} small field in lung heterogenous phantom using Acuros XB (AXB) and EGSnrc. Methods: This study will simulate the correction factors due to the perturbation of TLD-100 chips (Harshaw/Thermoscientific, 3 × 3 × 0.9mm{sup 3}, 2.64g/cm{sup 3}) in small field lung medium for Stereotactic Body Radiation Therapy (SBRT). A physical lung phantom was simulated by a 14cm thick composite cork phantom (0.27g/cm{sup 3}, HU:-743 ± 11) sandwiched between 4cm thick Plastic Water (CIRS,Norfolk). Composite cork has been shown to be a good lung substitute materialmore » for dosimetric studies. 6MV photon beam from Varian Clinac iX (Varian Medical Systems, Palo Alto, CA) with field size 2 × 2cm{sup 2} was simulated. Depth dose profiles were obtained from the Eclipse treatment planning system Acuros XB (AXB) and independently from DOSxyznrc, EGSnrc. Correction factors was calculated by the ratio of unperturbed to perturbed dose. Since AXB has limitations in simulating actual material compositions, EGSnrc will also simulate the AXB-based material composition for comparison to the actual lung phantom. Results: TLD-100, with its finite size and relatively high density, causes significant perturbation in 2 × 2cm{sup 2} small field in a low lung density phantom. Correction factors calculated by both EGSnrc and AXB was found to be as low as 0.9. It is expected that the correction factor obtained by EGSnrc wlll be more accurate as it is able to simulate the actual phantom material compositions. AXB have a limited material library, therefore it only approximates the composition of TLD, Composite cork and Plastic water, contributing to uncertainties in TLD correction factors. Conclusion: It is expected that the correction factors obtained by EGSnrc will be more accurate. Studies will be done to investigate the correction factors for higher energies where perturbation may be more pronounced.« less

Respiratory mechanics and fluid dynamics after lung resection surgery.

PubMed

Miserocchi, Giuseppe; Beretta, Egidio; Rivolta, Ilaria

2010-08-01

Thoracic surgery that requires resection of a portion of lung or of a whole lung profoundly alters the mechanical and fluid dynamic setting of the lung-chest wall coupling, as well as the water balance in the pleural space and in the remaining lung. The most frequent postoperative complications are of a respiratory nature, and their incidence increases the more the preoperative respiratory condition seems compromised. There is an obvious need to identify risk factors concerning mainly the respiratory function, without neglecting the importance of other comorbidities, such as coronary disease. At present, however, a satisfactory predictor of postoperative cardiopulmonary complications is lacking; postoperative morbidity and mortality have remained unchanged in the last 10 years. The aim of this review is to provide a pathophysiologic interpretation of the main respiratory complications of a respiratory nature by relying on new concepts relating to lung fluid dynamics and mechanics. New parameters are proposed to improve evaluation of respiratory function from pre- to the early postoperative period when most of the complications occur. Published by Elsevier Inc.

All the “RAGE” in lung disease: The receptor for advanced glycation endproducts (RAGE) is a major mediator of pulmonary inflammatory responses

PubMed Central

Oczypok, Elizabeth A.; Perkins, Timothy N.; Oury, Tim D.

2017-01-01

SUMMARY The receptor for advanced glycation endproducts (RAGE) is a pro-inflammatory pattern recognition receptor (PRR) that has been implicated in the pathogenesis of numerous inflammatory diseases. It was discovered in 1992 on endothelial cells and was named for its ability to bind advanced glycation endproducts and promote vascular inflammation in the vessels of patients with diabetes. Further studies revealed that RAGE is most highly expressed in lung tissue and spurred numerous explorations into RAGE’s role in the lung. These studies have found that RAGE is an important mediator in allergic airway inflammation (AAI) and asthma, pulmonary fibrosis, lung cancer, chronic obstructive pulmonary disease (COPD), acute lung injury, pneumonia, cystic fibrosis, and bronchopulmonary dysplasia. RAGE has not yet been targeted in the lungs of paediatric or adult clinical populations, but the development of new ways to inhibit RAGE is setting the stage for the emergence of novel therapeutic agents for patients suffering from these pulmonary conditions. PMID:28416135

Algorithm of pulmonary emphysema extraction using thoracic 3-D CT images

NASA Astrophysics Data System (ADS)

Saita, Shinsuke; Kubo, Mitsuru; Kawata, Yoshiki; Niki, Noboru; Nakano, Yasutaka; Ohmatsu, Hironobu; Tominaga, Keigo; Eguchi, Kenji; Moriyama, Noriyuki

2008-03-01

Emphysema patients have the tendency to increase due to aging and smoking. Emphysematous disease destroys alveolus and to repair is impossible, thus early detection is essential. CT value of lung tissue decreases due to the destruction of lung structure. This CT value becomes lower than the normal lung- low density absorption region or referred to as Low Attenuation Area (LAA). So far, the conventional way of extracting LAA by simple thresholding has been proposed. However, the CT value of CT image fluctuates due to the measurement conditions, with various bias components such as inspiration, expiration and congestion. It is therefore necessary to consider these bias components in the extraction of LAA. We removed these bias components and we proposed LAA extraction algorithm. This algorithm has been applied to the phantom image. Then, by using the low dose CT(normal: 30 cases, obstructive lung disease: 26 cases), we extracted early stage LAA and quantitatively analyzed lung lobes using lung structure.

Inorganic particulates in pneumoconiotic lungs of hard metal grinders.

PubMed Central

Rüttner, J R; Spycher, M A; Stolkin, I

1987-01-01

Data from the analysis of lung dust in 16 metal grinders who had been exposed to hard metals between five and 44 years is reported. The mean latent time between the first exposure and analysis in biopsy or necropsy specimens was 33.6 years. Mineralogical and elementary analysis by a variety of techniques showed small or trace amounts of hard metal in all lungs. Many specimens, however, did not contain all hard metal components, cobalt, for example, being detected in four cases only. All the lungs contained quartz and silicates and in most of the necropsy cases carborundum and corundum could also be shown. Histologically no specific pattern was found. The appearances included mixed dust nodular pneumoconiosis, diffuse interstitial lung fibrosis, and foreign body and sarcoid like granulomatous changes. In view of the mixed dust exposure of the hard metal grinders and the variable histological appearance we think that the term "mixed dust pneumoconiosis in hard metal grinders" is more appropriate than "hard metal lung" to describe this condition. PMID:3676118

[New toxicity of fotemustine: diffuse interstitial lung disease].

PubMed

Bertrand, M; Wémeau-Stervinou, L; Gauthier, S; Auffret, M; Mortier, L

2012-04-01

Fotemustine is an alkylating cytostatic drug belonging to the nitrosourea family and is used in particular in the treatment of disseminated malignant melanoma. Herein, we report a case of interstitial lung disease associated with fotemustine. An 81-year-old man treated with fotemustine for metastatic melanoma presented acute interstitial lung disease 20 days after a fourth course of fotemustine monotherapy. The condition regressed spontaneously, with the patient returning to the clinical, radiological and blood gas status that had preceded fotemustine treatment. After other potential aetiologies had been ruled out, acute fotemustine-induced lung toxicity was considered and this treatment was definitively withdrawn. Other cytostatic agents belonging to the nitrosourea family can cause similar pictures, with a number of cases of interstitial lung disease thus being ascribed to fotemustine and dacarbazine. To our knowledge, this is the first case of interstitial lung disease induced by fotemustine monotherapy. This diagnosis should be considered where respiratory signs appear in melanoma patients undergoing fotemustine treatment. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

CD109 is a component of exosome secreted from cultured cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakakura, Hiroki; Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya; Mii, Shinji

Exosomes are 50–100-nm-diameter membrane vesicles released from various types of cells. Exosomes retain proteins, mRNAs and miRNAs, which can be transported to surrounding cells. CD109 is a glycosylphosphatidylinositol-anchored glycoprotein, and is released from the cell surface to the culture medium in vitro. Recently, it was reported that secreted CD109 from the cell surface downregulates transforming growth factor-β signaling in human keratinocytes. In this study, we revealed that CD109 is a component of the exosome in conditioned medium. FLAG-tagged human CD109 (FLAG-CD109) in conditioned medium secreted from HEK293 cells expressing FLAG-CD109 (293/FLAG-CD109) was immunoprecipitated with anti-FLAG affinity gel, and the co-precipitated proteins weremore » analyzed by mass spectrometry and western blotting. Exosomal proteins were associated with CD109. We revealed the presence of CD109 in exosome fractions from conditioned medium of 293/FLAG-CD109. Moreover, the localization of CD109 in the exosome was demonstrated using immuno-electron microscopy. When we used HEK293 cells expressing FLAG-tagged truncated CD109, which does not contain the C-terminal region, the association of truncated CD109 with exosomes was not detected in conditioned medium. These findings indicate that CD109 is an exosomal protein and that the C-terminal region of CD109 is required for its presence in the exosome. - Highlights: • CD109 is an exosomal protein. • The C-terminal region of CD109 is required for its presence in the exosome. • Part of the secreted CD109 is present in the exosome-free fraction in the conditioned medium.« less

Epidermal regulation of dermal fibroblast activity.

PubMed

Garner, W L

1998-07-01

Although the association between delayed burn wound healing and subsequent hypertrophic scar formation is well-established, the mechanism for this relationship is unknown. Unhealed burn wounds lack an epidermis, suggesting a possible regulatory role for the epidermis in controlling dermal fibroblast matrix synthesis. Therefore, we examined the effect of epidermal cells and media conditioned by epidermal cells on fibroblast collagen synthesis and replication. Purified fibroblast and keratinocyte cell strains were developed from discarded normal adult human skin. Conditioned media were created by incubation of cytokine-free and serum-free medium with either confluent fibroblast or keratinocyte cultures for 18 hours (n = 3). Nearly confluent fibroblast cultures were exposed for 48 hours to graded concentrations of either unconditioned medium (control), conditioned medium, or varying numbers of keratinocytes. Replication was quantified by the incorporation of 3H-thymidine. Collagen synthesis was measured by the incorporation of 3H-proline into collagenase-sensitive protein. Data were compared using analysis of variance (ANOVA) and linear regression. Keratinocyte conditioned medium induced a significant increase in replication (n = 3) (p = 0.004) and a decrease in collagen synthesis (n = 6) (p < 0.001). In contrast, neither fibroblast conditioned medium nor control medium had an effect on fibroblast replication or collagen synthesis. Co-culture of fibroblast with a graded number of keratinocytes similarly decreased collagen synthesis (n = 6) (p < 0.001). Dermal fibroblast collagen synthesis appears to be regulated by a soluble keratinocyte product. This result suggests a mechanism for the clinical observation that unhealed burn wounds, which lack the epidermis, demonstrate excess collagen production and scar. Clinical strategies to decrease hypertrophic scar should include an attempt at early wound closure with skin grafting or the application of cultured epithelial autografts.

CXCR4-mediated osteosarcoma growth and pulmonary metastasis is promoted by mesenchymal stem cells through VEGF.

PubMed

Zhang, Peng; Dong, Ling; Yan, Kang; Long, Hua; Yang, Tong-Tao; Dong, Ming-Qing; Zhou, Yong; Fan, Qing-Yu; Ma, Bao-An

2013-10-01

Chemokines and chemokine receptor 4 (CXCR4) play an important role in metastasis. CXCR4 is also expressed in the human osteosarcoma cell line 9607-F5M2 (F5M2), which has a high tumorigenic ability and potential for spontaneous pulmonary metastasis. Mesenchymal stem cells (MSCs) contribute to the formation of the tumor stroma and promote metastasis. However, mechanisms underlying the promotion of osteosarcoma growth and pulmonary metastasis by MSCs are still elusive. Our study co-injected the human MSCs and F5M2 cells into the caudal vein of nude mice. The total number of tumor nodules per lung was significantly increased in the F5M2+MSC group compared to the other groups (control, F5M2 cells alone and MSCs alone) at week six. Moreover, a high number of Dil-labeled MSCs was present also at the osteosarcoma metastasis sites in the lung. Using Transwell assays, we found that F5M2 cells migrate towards MSCs, while the CXCR4 inhibitor AMD3100 decreased the migration potential of F5M2 cells towards MSCs. Furthermore, upon treatment with F5M2-conditioned medium, MSCs expressed and secreted higher levels of VEGF as determined by immunohistochemistry, western blotting and ELISA, respectively. Importantly, co-cultured with F5M2 cells, MSCs expressed and secreted higher VEGF levels, while AMD3100 dramatically decreased the VEGF secretion by MSCs. However, CXCR4 expression on F5M2 cells was not significantly increased in the co-culture system. Additionally, VEGF increased the proliferation of both MSCs and F5M2 cells. These findings suggest that CXCR4-mediated osteosarcoma growth and pulmonary metastasis are promoted by MSCs through VEGF.

CREB- and NF-κB-Regulated CXC Chemokine Gene Expression in Lung Carcinogenesis

PubMed Central

Sun, Hongxia; Chung, Wen-Cheng; Ryu, Seung-Hee; Ju, Zhenlin; Tran, Hai T.; Kim, Edward; Kurie, Jonathan M.; Koo, Ja Seok

2009-01-01

The recognition of the importance of angiogenesis in tumor progression has led to the development of antiangiogenesis as a new strategy for cancer treatment and prevention. By modulating tumor microenvironment and inducing angiogenesis, the proinflammatory cytokine interleukine (IL)-1 β has been reported to promote tumor development. However, the factors mediating IL-1β-induced angiogenesis in non-small cell lung cancer (NSCLC) and the regulation of these angiogenic factors by IL-1β are less clear. Here, we report that IL-1β upregulated an array of proangiogenic CXC chemokine genes in NSCLC cell line A549 and in normal human tracheobronchial epithelium (NHTBE) cells, as determined by microarray analysis. Further analysis revealed that IL-1β induced much higher protein levels of CXC chemokines in NSCLC cells than in NHTBE cells. Conditioned medium from IL-1β treated A549 cells markedly increased endothelial cell migration, which was suppressed by neutralizing antibodies against CXCL5 and CXCR2. We also found that IL-1β-induced CXC chemokine gene overexpression in NSCLC cells was abrogated with the knockdown of CREB or NF-κB. Moreover, the expression of the CXC chemokine genes as well as CREB and NF-κB activities were greatly increased in tumorigenic NSCLC cell line compared with normal, premalignant immortalized or non-tumorigenic cell lines. A disruptor of the interaction between CREB-binding protein (CBP) and transcription factors such as CREB and NF-κB, 2-naphthol-AS-E-phosphate (KG-501), inhibited IL-1β-induced CXC chemokine gene expression and angiogenic activity in NSCLC. We propose that targeting CREB or NF-κB using small molecule inhibitors, such as KG-501, holds promise as a preventive and/or therapeutic approach for NSCLC. PMID:19138976

Administration of nicotinamide riboside prevents oxidative stress and organ injury in sepsis.

PubMed

Hong, Guangliang; Zheng, Dong; Zhang, Lulu; Ni, Rui; Wang, Grace; Fan, Guo-Chang; Lu, Zhongqiu; Peng, Tianqing

2018-08-01

Sepsis-caused multiple organ failure remains the major cause of morbidity and mortality in intensive care units. Nicotinamide riboside (NR) is a precursor of nicotinamide adenine dinucleotide (NAD + ), which is important in regulating oxidative stress. This study investigated whether administration of NR prevented oxidative stress and organ injury in sepsis. Mouse sepsis models were induced by injection of lipopolysaccharides (LPS) or feces-injection-in-peritoneum. NR was given before sepsis onset. Cultured macrophages and endothelial cells were incubated with various agents. Administration of NR elevated the NAD + levels, and elicited a reduction of oxidative stress, inflammation and caspase-3 activity in lung and heart tissues, which correlated with attenuation of pulmonary microvascular permeability and myocardial dysfunction, leading to less mortality in sepsis models. These protective effects of NR were associated with decreased levels of plasma high mobility group box-1 (HMGB1) in septic mice. Consistently, pre-treatment of macrophages with NR increased NAD + content and reduced HMGB1 release upon LPS stimulation. NR also prevented reactive oxygen species (ROS) production and apoptosis in endothelial cells induced by a conditioned-medium collected from LPS-treated macrophages. Furthermore, inhibition of SIRT1 by EX527 offset the negative effects of NR on HMGB1 release in macrophages, and ROS and apoptosis in endothelial cells. Administration of NR prevents lung and heart injury, and improves the survival in sepsis, likely by inhibiting HMGB1 release and oxidative stress via the NAD + /SIRT1 signaling. Given NR has been used as a health supplement, it may be a useful agent to prevent organ injury in sepsis. Copyright © 2018 Elsevier Inc. All rights reserved.

Shrinking lung syndrome as a manifestation of pleuritis: a new model based on pulmonary physiological studies.

PubMed

Henderson, Lauren A; Loring, Stephen H; Gill, Ritu R; Liao, Katherine P; Ishizawar, Rumey; Kim, Susan; Perlmutter-Goldenson, Robin; Rothman, Deborah; Son, Mary Beth F; Stoll, Matthew L; Zemel, Lawrence S; Sandborg, Christy; Dellaripa, Paul F; Nigrovic, Peter A

2013-03-01

The pathophysiology of shrinking lung syndrome (SLS) is poorly understood. We sought to define the structural basis for this condition through the study of pulmonary mechanics in affected patients. Since 2007, most patients evaluated for SLS at our institutions have undergone standardized respiratory testing including esophageal manometry. We analyzed these studies to define the physiological abnormalities driving respiratory restriction. Chest computed tomography data were post-processed to quantify lung volume and parenchymal density. Six cases met criteria for SLS. All presented with dyspnea as well as pleurisy and/or transient pleural effusions. Chest imaging results were free of parenchymal disease and corrected diffusing capacities were normal. Total lung capacities were 39%-50% of predicted. Maximal inspiratory pressures were impaired at high lung volumes, but not low lung volumes, in 5 patients. Lung compliance was strikingly reduced in all patients, accompanied by increased parenchymal density. Patients with SLS exhibited symptomatic and/or radiographic pleuritis associated with 2 characteristic physiological abnormalities: (1) impaired respiratory force at high but not low lung volumes; and (2) markedly decreased pulmonary compliance in the absence of identifiable interstitial lung disease. These findings suggest a model in which pleural inflammation chronically impairs deep inspiration, for example through neural reflexes, leading to parenchymal reorganization that impairs lung compliance, a known complication of persistently low lung volumes. Together these processes could account for the association of SLS with pleuritis as well as the gradual symptomatic and functional progression that is a hallmark of this syndrome.

Alveolar Edema Fluid Clearance and Acute Lung Injury

PubMed Central

Berthiaume, Yves; Matthay, Michael A.

2009-01-01

Although lung-protective ventilation strategies have substantially reduced mortality of acute lung injury patients there is still a need for new therapies that can further decrease mortality in patients with acute lung injury. Studies of epithelial ion and fluid transport across the distal pulmonary epithelia have provided important new concepts regarding potential new therapies for acute lung injury. Overall, there is convincing evidence that the alveolar epithelium is not only a tight epithelial barrier that resists the movement of edema fluid into the alveoli, but it is also actively involved in the transport of ions and solutes, a process that is essential for edema fluid clearance and the resolution of acute lung injury. The objective of this article is to consider some areas of recent progress in the field of alveolar fluid transport under normal and pathologic conditions. Vectorial ion transport across the alveolar and distal airway epithelia is the primary determinant of alveolar fluid clearance. The general paradigm is that active Na+ and Cl− transport drives net alveolar fluid clearance, as demonstrated in several different species, including the human lung. Although these transport processes can be impaired in severe lung injury, multiple experimental studies suggest that upregulation of Na+ and Cl− transport might be an effective therapy in acute lung injury. We will review mechanisms involved in pharmacological modulation of ion transport in lung injury with a special focus on the use of β-adrenergic agonists which has generated considerable interest and is a promising therapy for clinical acute lung injury. PMID:17604701

Modelling of the Nutrient Medium for Plants Cultivation in Spaceflight

NASA Astrophysics Data System (ADS)

Nechitailo, Galina S.

2016-07-01

MODELLING OF THE NUTRIENT MEDIUM FOR PLANTS CULTIVATION IN SPACEFLIGHT Nechitajlo G.S.*, Rakhmetova A.A.**, Bogoslovskaja O.A.**, Ol'hovskay I.P.**, Glushchenko N.N.** *Emanuel Institute of Biochemical Physics of Russian Academy of Sciences (IBCP RAS) mail: spacemal@mail.ru **V.L. Talrose Institute for Energy Problems of Chemical Physics of Russian Academy of Science (INEPCP RAS) mail: nnglu@ mail.ru The valuable life and fruitful activity of cosmonauts and researchers in conditions of spaceflights and prolonged work at space stations are only possible with creating life area providing fresh air, natural food, comfortable psychological conditions, etc. The solution of that problem under space conditions seems impossible without use of high nano- and biotechnologies for plants growth. A priority should be given not only to choose species of growth plants in space, but also to improve conditions for their growth which includes optimal nourishing components for plants, preparation of nutrient mediums, illumination and temperature. We are deeply convinced that just manipulations with growing conditions for cultivated plants, but not genes changes, is a guarantee of success in the decision of this problem. For improving the method of plants growing on the artificial nutrient medium with balanced content of components, being necessary for growth and development of plants, we added essential metal elements: Fe, Zn, Cu - in an electroneutral state in the form of nanoparticles instead of sulfates or other easily dissolving salts. Nanoparticulated metals are known to have a number of advantages in comparison with salts: metals in an electroneutral form are characterized with the prolonged and multifunctional action, low toxicity per se and appearing to be much below the toxicity of the same metals in the ionic forms, accumulation as a reserve being used in biotic dozes, active distribution in bodies and organs of plants and stimulation of vital processes. A high reactivity of nanoparticles and their active interactions with components of a nutrient medium demands development of certain technological solutions for conservation of activity potential of nanoparticles in nutrient mediums. Thus, we have elaborated and created the artificial nutrient medium having balanced structure of components and assuring successful plants cultivation in conditions of spaceflight.

Accumulation and chemical states of radiocesium by fungus Saccharomyces cerevisiae

NASA Astrophysics Data System (ADS)

Ohnuki, Toshihiko; Sakamoto, Fuminori; Kozai, Naofumi; Yamasaki, Shinya; Yu, Qianqian

2014-05-01

After accident of Fukushima Daiichi Nuclear Power Plant, the fall-out radiocesium was deposited on the ground. Filamentous fungus is known to accumulate radiocesium in environment, even though many minerals are involved in soil. These facts suggest that fungus affect the migration behavior of radiocesium in the environment. However, accumulation mechanism of radiocesium by fungus is not understood. In the present study, accumulation and chemical states change of Cs by unicellular fungus of Saccharomyces cerevisiae have been studied to elucidate the role of microorganisms in the migration of radiocesium in the environment. Two different experimental conditions were employed; one is the accumulation experiments of radiocesium by S. cerevisiae from the agar medium containing 137Cs and a mineral of zeolite, vermiculite, smectite, mica, or illite. The other is the experiments using stable cesium to examine the chemical states change of Cs. In the former experiment, the cells were grown on membrane filter of 0.45 μm installed on the agar medium. After the grown cells were weighed, radioactivity in the cells was measured by an autoradiography technique. The mineral weight contents were changed from 0.1% to 1% of the medium. In the latter experiment, the cells were grown in the medium containing stable Cs between 1 mM and 10mM. The Cs accumulated cells were analyzed by SEM-EDS and EXAFS. The adsorption experiments of cesium by the cells under resting condition were also conducted to test the effect of cells metabolic activity. Without mineral in the medium, cells of S. cerevisiae accumulated 1.5x103 Bq/g from the medium containing 137Cs of 2.6x102 Bq/g. When mineral was added in the medium, concentration of 137Cs in the cells decreased. The concentration of 137Cs in the cells from the medium containing different minerals were in the following order; smectite, illite, mica > vermiculite > zeolite. This order was nearly the same as the inverse of distribution coefficient of mineral for 137Cs in the medium solution. The concentration of 137Cs in the cells lowered in the medium containing higher mineral content. These results indicate that radiocesium was competively accumulated in the cells with minerals in the soil. Higher concentration of stable Cs was accumulated in the cells in the metabolically active condition than in the resting cells condition. XAFS analyses showed that the k3-weighted extended-XAFS functions and the radial structural function of Cs accumulated by the cells in the metabolically active condition were similar to those in the resting condition, indicating that chemical states of the accumulated Cs were nearly the same between both conditions. These results indicate that the fungus accumulates radiocesium by competitively with minerals in the soils, and performs higher retardation of the migration of Cs in the metabolically active condition than the resting one. A part of this study is the results of "Multidisciplinary investigation on radiocesium fate and transport for safety assessment for interim storage and disposal of heterogeneous waste" carried out under the Initiatives for Atomic Energy Basic and Generic Strategic Research by the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Genetics Home Reference: lymphangioleiomyomatosis

MedlinePlus

... Genetics Share: Email Facebook Twitter Home Health Conditions LAM Lymphangioleiomyomatosis Printable PDF Open All Close All Enable ... to view the expand/collapse boxes. Description Lymphangioleiomyomatosis ( LAM ) is a condition that affects the lungs , the ...

Experimental and Computational Studies of Sound Transmission in a Branching Airway Network Embedded in a Compliant Viscoelastic Medium

PubMed Central

Dai, Zoujun; Peng, Ying; Mansy, Hansen A.; Sandler, Richard H.; Royston, Thomas J.

2015-01-01

Breath sounds are often used to aid in the diagnosis of pulmonary disease. Mechanical and numerical models could be used to enhance our understanding of relevant sound transmission phenomena. Sound transmission in an airway mimicking phantom was investigated using a mechanical model with a branching airway network embedded in a compliant viscoelastic medium. The Horsfield self-consistent model for the bronchial tree was adopted to topologically couple the individual airway segments into the branching airway network. The acoustics of the bifurcating airway segments were measured by microphones and calculated analytically. Airway phantom surface motion was measured using scanning laser Doppler vibrometry. Finite element simulations of sound transmission in the airway phantom were performed. Good agreement was achieved between experiments and simulations. The validated computational approach can provide insight into sound transmission simulations in real lungs. PMID:26097256

Experimental and computational studies of sound transmission in a branching airway network embedded in a compliant viscoelastic medium

NASA Astrophysics Data System (ADS)

Dai, Zoujun; Peng, Ying; Mansy, Hansen A.; Sandler, Richard H.; Royston, Thomas J.

2015-03-01

Breath sounds are often used to aid in the diagnosis of pulmonary disease. Mechanical and numerical models could be used to enhance our understanding of relevant sound transmission phenomena. Sound transmission in an airway mimicking phantom was investigated using a mechanical model with a branching airway network embedded in a compliant viscoelastic medium. The Horsfield self-consistent model for the bronchial tree was adopted to topologically couple the individual airway segments into the branching airway network. The acoustics of the bifurcating airway segments were measured by microphones and calculated analytically. Airway phantom surface motion was measured using scanning laser Doppler vibrometry. Finite element simulations of sound transmission in the airway phantom were performed. Good agreement was achieved between experiments and simulations. The validated computational approach can provide insight into sound transmission simulations in real lungs.

Astrocytes produce an insulin-like neurotrophic factor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kadle, R.; Suksang, C.; Fellows, R.E.

1986-05-01

They have previously reported that survival of dissociated neurons from fetal rat telencephalon plated at low density in serum-free, hormone-free defined medium is enhanced in the presence of insulin. In the absence of insulin a similar effect on neuronal survival is observed if cells are grown in medium conditioned by glial cells. The present study was carried out to characterize the insulin-like neurotrophic activity present in the glial conditioned medium (GLCM). Conditioned medium from confluent cultures of astrogial cells maintained in a serum free defined medium without insulin was collected every two or three days. A 5 to 30kDa fractionmore » of this medium was obtained by filtering it sequentially through YM30 and YM5 membrane filters. Binding of /sup 125/I-insulin to high density neuronal cultures was inhibited 43% by this fraction. Radioimmunoassay for insulin indicated that 1-2 ng of immuno-reactive insulin were present per ml of GLCM. Immunosequestration of the factor by insulin antibodies bound to protein A agarose gel resulted in loss of neurotrophic activity of the 5 to 30 kDa fraction. These results indicate that cultured astrocytes produce a factor immunologically and biochemically similar to insulin. This factor enhances the survival of neurons in culture and may be important for their normal development and differentiation.« less

OMARC: An online multimedia application for training health care providers in the assessment of respiratory conditions.

PubMed

Meruvia-Pastor, Oscar; Patra, Pranjal; Andres, Karen; Twomey, Creina; Peña-Castillo, Lourdes

2016-05-01

OMARC, a multimedia application designed to support the training of health care providers for the identification of common lung sounds heard in a patient's thorax as part of a health assessment, is described and its positive contribution to user learning is assessed. The main goal of OMARC is to effectively help health-care students become familiar with lung sounds as part of the assessment of respiratory conditions. In addition, the application must be easy to use and accessible to students and practitioners over the internet. OMARC was developed using an online platform to facilitate access to users in remote locations. OMARC's unique contribution as an educational software tool is that it presents a narrative about normal and abnormal lung sounds using interactive multimedia and sample case studies designed by professional health-care providers and educators. Its interface consists of two distinct components: a sounds glossary and a rich multimedia interface which presents clinical case studies and provides access to lung sounds placed on a model of a human torso. OMARC's contents can be extended through the addition of sounds and case studies designed by health-care educators and professionals. To validate OMARC and determine its efficacy in improving learning and capture user perceptions about it, we performed a pilot study with ten nursing students. Participants' performance was measured through an evaluation of their ability to identify several normal and adventitious/abnormal sounds prior and after exposure to OMARC. Results indicate that participants are able to better identify different lung sounds, going from an average of 63% (S.D. 18.3%) in the pre-test evaluation to an average of 90% (S.D. of 11.5%) after practising with OMARC. Furthermore, participants indicated in a user satisfaction questionnaire that they found the application helpful, easy to use and that they would recommend it to other persons in their field. OMARC is an online multimedia application for training health care students in the assessment of respiratory conditions. The software integrates multimedia technology and health-care education concepts to facilitate learning, while being useful and easy to use. Results from a pilot study indicate that OMARC significantly helps to improve the capacity of the users to correctly identify lung sounds for different respiratory conditions. In addition, participants' opinions about OMARC were quite positive: users were likely to recommend the application to other persons in their field and found the application easy to use and helpful to better identify lung sounds. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Chemical characterization of indoor air of homes from communes in Xuan Wei, China, with high lung cancer mortality rates

EPA Science Inventory

In a rural county, Xuan Wei, China, the lung cancer mortality rate is among China's highest, especially in women. This mortality rate is more associated with indoor air burning of smoky coal, as opposed to smokeless coal or wood, for cooking and heating under unvented conditions....

Enhanced inflammation and attenuated tumor suppressor pathways are associated with oncogene-induced lung tumors in aged mice

USDA-ARS?s Scientific Manuscript database

Aging is often accompanied by a dramatic increase in cancer susceptibility. To gain insights into how aging affects tumor susceptibility, we generated a conditional mouse model in which oncogenic KrasG12D was activated specifically in lungs of young (3-5 months) and old (19-24 months) mice. Activati...

Adult hippocampus derived soluble factors induce a neuronal-like phenotype in mesenchymal stem cells.

PubMed

Rivera, Francisco J; Sierralta, Walter D; Minguell, Jose J; Aigner, Ludwig

2006-10-02

Bone marrow-derived mesenchymal stem cells (MSCs) are not restricted in their differentiation fate to cells of the mesenchymal lineage. They acquire a neural phenotype in vitro and in vivo after transplantation in the central nervous system. Here we investigated whether soluble factors derived from different brain regions are sufficient to induce a neuronal phenotype in MSCs. We incubated bone marrow-derived MSCs in conditioned medium (CM) derived from adult hippocampus (HCM), cortex (CoCM) or cerebellum (CeCM) and analyzed the cellular morphology and the expression of neuronal and glial markers. In contrast to muscle derived conditioned medium, which served as control, conditioned medium derived from the different brain regions induced a neuronal morphology and the expression of the neuronal markers GAP-43 and neurofilaments in MSCs. Hippocampus derived conditioned medium had the strongest activity. It was independent of NGF or BDNF; and it was restricted to the neuronal differentiation fate, since no induction of the astroglial marker GFAP was observed. The work indicates that soluble factors present in the brain are sufficient to induce a neuronal phenotype in MSCs.

PR-Set7 is degraded in a conditional Cul4A transgenic mouse model of lung cancer

DOE PAGES

Wang, Yang; Xu, Zhidong; Mao, Jian -Hua; ...

2015-06-01

Background and objective. Maintenance of genomic integrity is essential to ensure normal organismal development and to prevent diseases such as cancer. PR-Set7 (also known as Set8) is a cell cycle regulated enzyme that catalyses monomethylation of histone 4 at Lys20 (H4K20me1) to promote chromosome condensation and prevent DNA damage. Recent studies show that CRL4CDT2-mediated ubiquitylation of PR-Set7 leads to its degradation during S phase and after DNA damage. This might occur to ensure appropriate changes in chromosome structure during the cell cycle or to preserve genome integrity after DNA damage. Methods. We developed a new model of lung tumor developmentmore » in mice harboring a conditionally expressed allele of Cul4A. We have therefore used a mouse model to demonstrate for the first time that Cul4A is oncogenic in vivo. With this model, staining of PR-Set7 in the preneoplastic and tumor lesions in AdenoCre-induced mouse lungs was performed. Meanwhile we identified higher protein level changes of γ-tubulin and pericentrin by IHC. Results. The level of PR-Set7 down-regulated in the preneoplastic and adenocarcinomous lesions following over-expression of Cul4A. We also identified higher levels of the proteins pericentrin and γ-tubulin in Cul4A mouse lungs induced by AdenoCre. Conclusion. PR-Set7 is a direct target of Cul4A for degradation and involved in the formation of lung tumors in the conditional Cul4A transgenic mouse model.« less

GSK-3Beta-Dependent Activation of GEF-H1/ROCK Signaling Promotes LPS-Induced Lung Vascular Endothelial Barrier Dysfunction and Acute Lung Injury.

PubMed

Yi, Lei; Huang, Xiaoqin; Guo, Feng; Zhou, Zengding; Chang, Mengling; Huan, Jingning

2017-01-01

The bacterial endotoxin or lipopolysaccharide (LPS) leads to the extensive vascular endothelial cells (EC) injury under septic conditions. Guanine nucleotide exchange factor-H1 (GEF-H1)/ROCK signaling not only involved in LPS-induced overexpression of pro-inflammatory mediator in ECs but also implicated in LPS-induced endothelial hyper-permeability. However, the mechanisms behind LPS-induced GEF-H1/ROCK signaling activation in the progress of EC injury remain incompletely understood. GEF-H1 localized on microtubules (MT) and is suppressed in its MT-bound state. MT disassembly promotes GEF-H1 release from MT and stimulates downstream ROCK-specific GEF activity. Since glycogen synthase kinase (GSK-3beta) participates in regulating MT dynamics under pathologic conditions, we examined the pivotal roles for GSK-3beta in modulating LPS-induced activation of GEF-H1/ROCK, increase of vascular endothelial permeability and severity of acute lung injury (ALI). In this study, we found that LPS induced human pulmonary endothelial cell (HPMEC) monolayers disruption accompanied by increase in GSK-3beta activity, activation of GEF-H1/ROCK signaling and decrease in beta-catenin and ZO-1 expression. Inhibition of GSK-3beta reduced HPMEC monolayers hyper-permeability and GEF-H1/ROCK activity in response to LPS. GSK-3beta/GEF-H1/ROCK signaling is implicated in regulating the expression of beta-catenin and ZO-1. In vivo , GSK-3beta inhibition attenuated LPS-induced activation of GEF-H1/ROCK pathway, lung edema and subsequent ALI. These findings present a new mechanism of GSK-3beta-dependent exacerbation of lung micro-vascular hyper-permeability and escalation of ALI via activation of GEF-H1/ROCK signaling and disruption of intracellular junctional proteins under septic condition.

PR-Set7 is degraded in a conditional Cul4A transgenic mouse model of lung cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yang; Xu, Zhidong; Mao, Jian -Hua

Background and objective. Maintenance of genomic integrity is essential to ensure normal organismal development and to prevent diseases such as cancer. PR-Set7 (also known as Set8) is a cell cycle regulated enzyme that catalyses monomethylation of histone 4 at Lys20 (H4K20me1) to promote chromosome condensation and prevent DNA damage. Recent studies show that CRL4CDT2-mediated ubiquitylation of PR-Set7 leads to its degradation during S phase and after DNA damage. This might occur to ensure appropriate changes in chromosome structure during the cell cycle or to preserve genome integrity after DNA damage. Methods. We developed a new model of lung tumor developmentmore » in mice harboring a conditionally expressed allele of Cul4A. We have therefore used a mouse model to demonstrate for the first time that Cul4A is oncogenic in vivo. With this model, staining of PR-Set7 in the preneoplastic and tumor lesions in AdenoCre-induced mouse lungs was performed. Meanwhile we identified higher protein level changes of γ-tubulin and pericentrin by IHC. Results. The level of PR-Set7 down-regulated in the preneoplastic and adenocarcinomous lesions following over-expression of Cul4A. We also identified higher levels of the proteins pericentrin and γ-tubulin in Cul4A mouse lungs induced by AdenoCre. Conclusion. PR-Set7 is a direct target of Cul4A for degradation and involved in the formation of lung tumors in the conditional Cul4A transgenic mouse model.« less

Conditioned medium: a new alternative for cryopreservation of equine umbilical cord mesenchymal stem cells.

PubMed

Maia, Leandro; Dias, Marianne Camargos; de Moraes, Carolina Nogueira; de Paula Freitas-Dell'Aqua, Camila; da Mota, Ligia S L Silveira; Santiloni, Valquíria; da Cruz Landim-Alvarenga, Fernanda

2017-03-01

Cryopreservation is a feasible alternative to maintaining several cell lines, particularly for immediate therapeutic use, transportation of samples, and implementation of new in vitro studies. This work parts from the hypothesis that the medium of cryopreservation composed by 90% of conditioned medium (CM) supports cryopreservation of equine umbilical cord intervascular matrix mesenchymal stem cells (UCIM-MSCs), allowing the maintenance of the biological properties for the establishment of cell banks intended for therapeutic use and in vitro studies. Thus, we evaluated the viability, apoptosis/necrosis rates, immunophenotypic profile (IP), chromosomal stability, clonicity, and differentiation potential of UCIM-MSCs cryopreserved with four different mediums (with FBS: M1, M3, M4 and without FBS: M2). After 3 months of cryopreservation, samples were thawed and analyzed. The potential of differentiation in the mesodermal lineages, clonicity, and the chromosomal stability were maintained after cryopreservation of UCIM-MSCs with medium containing FBS. Changes (P < 0.05) at IP for some markers were observed at cells cryopreserved with medium M1-M3. Only the UCIM-MSCs cryopreserved with the CM (M4) had similar viability post-thaw (P = 0.23) when compared with fresh cells. We proved the hypothesis that the medium of cryopreservation containing CM supports the cryopreservation of UCIM-MSCs, at the experimental conditions, being the medium that better maintains the biological characteristics observed at fresh cells. Thus, future studies of UCIM-MSCs secretome should be conducted to better understand the beneficial and protective effects of the CM during the freezing process. © 2017 International Federation for Cell Biology.

[Laboratory simulation study on the influence of resuspension on the release of mercury from Yangtze estuarine tidal flat].

PubMed

Li, Meng; Bi, Chun-Juan; Zhang, Jing-Jing; Lü, Jin-Gang; Chen, Zhen-Lou

2011-11-01

Using a Particle Environment Simulator, laboratory simulation experiment on the influence of resuspension on the release of mercury from sediments collected from medium tidal flat and low tidal flat in Chongming Dongtan was conducted. Results indicated that the conditions of overlying water changed significantly during resuspension. The concentrations of HgD and HgP were mainly in the rang of 0.152-2.657 microg x L(-1), 0.080-2.722 microg x L(-1) separately. In the resuspension processes, mercury was released from the medium intertidal sediments under the salinity condition of 4.1 per thousand, 8.0 per thousand, 10.0 per thousand, 13.0 per thousand, and from the low intertidal sediments under the salinity condition of 13.0 per thousand. However, the release of mercury from the medium intertidal sediments is not significant under the salinity condition of 4.1 per thousand, 8.0 per thousand, 10.0 per thousand. The salinity of overlying water had an important effect on resuspension. In different salinity condition, the release of mercury was different. And the release of mercury from medium tidal flat and low tidal flat was different during the resuspension periods, the release of mercury from the medium intertidal sediment was significantly higher than the release from the low intertidal sediment. When the rotate speed was (210 +/- 5) r x min(-1), the desorption of mercury significantly increased, thereby the rotate speed had an effect on the release of mercury.

Pericellular oxygen concentration of cultured primary human trophoblasts

PubMed Central

Chen, Baosheng; Longtine, Mark S.; Nelson, D. Michael

2012-01-01

Introduction Oxygen is pivotal in placental development and function. In vitro culture of human trophoblasts provides a useful model to study this phenomenon, but a hotly debated issue is whether or not the oxygen tension of the culture conditions mimics in vivo conditions. We tested the hypothesis that ambient oxygen tensions in culture reflect the pericellular oxygen levels. Methods We used a microelectrode oxygen sensor to measure the concentration of dissolved oxygen in the culture medium equilibrated with 21%, 8% or <0.5% oxygen. Results The concentration of oxygen in medium without cells resembled that in the ambient atmosphere. The oxygen concentration present in medium bathing trophoblasts was remarkably dependent on the depth within the medium where sampling occurred, and the oxygen concentration within the overlying atmosphere was not reflected in medium immediately adjacent to the cells. Indeed, the pericellular oxygen concentration was in a range that most would consider severe hypoxia, at ≤ 0.6% oxygen or about 4.6 mm Hg, when the overlying atmosphere was 21% oxygen. Conclusions We conclude that culture conditions of 21% oxygen are unable to replicate the pO2 of 40–60 mm Hg commonly attributed to the maternal blood in the intervillous space in the second and third trimesters of pregnancy. We further surmise that oxygen atmospheres in culture conditions between 0.5% and 21% provide different oxygen fluxes in the immediate pericellular environment yet can still yield insights into the responses of human trophoblast to different oxygen conditions. PMID:23211472

Basic FGF Support of Human Embryonic Stem Cell Self-Renewal

PubMed Central

Levenstein, Mark E.; Ludwig, Tenneille E.; Xu, Ren-He; Llanas, Rachel A.; VanDenHeuvel-Kramer, Kaitlyn; Manning, Daisy; Thomson, James A.

2015-01-01

Human embryonic stem (ES) cells have most commonly been cultured in the presence of basic FGF (FGF2) either on fibroblast feeder layers or in fibroblast-conditioned medium. Recently, it has been reported that elevated concentrations of FGF2 permit the culture of human ES cells in the absence of fibroblasts or fibroblast-conditioned medium. Here we compare the ability of unconditioned medium (UM) supplemented with 4, 24, 40, 80, 100 and 250 ng/ml FGF2 to sustain low-density human ES cell cultures through multiple passages. In these stringent culture conditions, 4, 24, and 40 ng/ml FGF2 failed to sustain human ES cells through three passages, but 100 ng/ml sustained human ES cells with an effectiveness comparable to conditioned medium (CM). Two human ES cell lines (H1 and H9) were maintained for up to 164 population doublings (7 and 4 months) in UM supplemented with 100 ng/ml FGF2. After prolonged culture the cells formed teratomas when injected into SCID-beige mice, and expressed markers characteristic of undifferentiated human ES cells. We also demonstrate that FGF2 is degraded more rapidly in UM than in CM, partly explaining the need for higher concentrations of FGF2 in UM. These results further facilitate the large-scale, routine culture of human ES cells, and suggest that fibroblasts and fibroblast-conditioned medium sustain human ES cells in part by stabilizing FGF signaling above a critical threshold. PMID:16282444

Abolished ventilation and perfusion of lung caused by blood clot in the left main bronchus: auto-downregulation of pulmonary arterial blood supply.

PubMed

Afzelius, P; Bergmann, A; Henriksen, J H

2015-09-15

It is generally assumed that the lungs possess arterial autoregulation associated with bronchial obstruction. A patient with pneumonia and congestive heart failure unexpectedly developed frequent haemoptysis. High-resolution CT and diagnostic CT were performed as well as ventilation/perfusion (V/Q) scintigraphy with single-photon emission CT (SPECT)/CT. V/Q SPECT/CT demonstrated abolished ventilation due to obstruction of the left main bronchus and markedly reduced perfusion of the entire left lung, a condition that was completely reversed after removal of a blood clot. We present the first pictorially documented case of hypoxia-induced pulmonary vasoconstriction and flow shift in a main pulmonary artery due to a complete intrinsic obstruction of the ipsilateral main bronchus. The condition is reversible, contingent on being relieved within a few days. 2015 BMJ Publishing Group Ltd.

Tics, Tourette Syndrome, and OCD

MedlinePlus

... AAP Find a Pediatrician Health Issues Conditions Abdominal ADHD Allergies & Asthma Autism Cancer Chest & Lungs Chronic Conditions ... In children who eventually develop tic disorders and ADHD, the ADHD usually develops 2 to 3 years ...

Oxidative Lung Damage Resulting from Repeated Exposure to Radiation and Hyperoxia Associated with Space Exploration.

PubMed

Pietrofesa, Ralph A; Turowski, Jason B; Arguiri, Evguenia; Milovanova, Tatyana N; Solomides, Charalambos C; Thom, Stephen R; Christofidou-Solomidou, Melpo

2013-09-30

Spaceflight missions may require crewmembers to conduct Extravehicular Activities (EVA) for repair, maintenance or scientific purposes. Pre-breathe protocols in preparation for an EVA entail 100% hyperoxia exposure that may last for a few hours (5-8 hours), and may be repeated 2-3 times weekly. Each EVA is associated with additional challenges such as low levels of total body cosmic/galactic radiation exposure that may present a threat to crewmember health and therefore, pose a threat to the success of the mission. We have developed a murine model of combined, hyperoxia and radiation exposure (double-hit) in the context of evaluating countermeasures to oxidative lung damage associated with space flight. In the current study, our objective was to characterize the early and chronic effects of repeated single and double-hit challenge on lung tissue using a novel murine model of repeated exposure to low-level total body radiation and hyperoxia. This is the first study of its kind evaluating lung damage relevant to space exploration in a rodent model. Mouse cohorts (n=5-15/group) were exposed to repeated: a) normoxia; b) >95% O 2 (O 2 ); c) 0.25Gy single fraction gamma radiation (IR); or d) a combination of O 2 and IR (O 2 +IR) given 3 times per week for 4 weeks. Lungs were evaluated for oxidative damage, active TGFβ1 levels, cell apoptosis, inflammation, injury, and fibrosis at 1, 2, 4, 8, 12, 16, and 20 weeks post-initiation of exposure. Mouse cohorts exposed to all challenge conditions displayed decreased bodyweight compared to untreated controls at 4 and 8 weeks post-challenge initiation. Chronic oxidative lung damage to lipids (malondialdehyde levels), DNA (TUNEL, cleaved Caspase 3, cleaved PARP positivity) leading to apoptotic cell death and to proteins (nitrotyrosine levels) was elevated all treatment groups. Importantly, significant systemic oxidative stress was also noted at the late phase in mouse plasma, BAL fluid, and urine. Importantly, however, late oxidative damage across all parameters that we measured was significantly higher than controls in all cohorts but was exacerbated by the combined exposure to O 2 and IR. Additionally, impaired levels of arterial blood oxygenation were noted in all exposure cohorts. Significant but transient elevation of lung tissue fibrosis ( p <0.05), determined by lung hydroxyproline content, was detected as early as 2 week in mice exposed to challenge conditions and persisted for 4-8 weeks only. Interestingly, active TGFβ1 levels in +BAL fluid was also transiently elevated during the exposure time only (1-4 weeks). Inflammation and lung edema/lung injury was also significantly elevated in all groups at both early and late time points, especially the double-hit group. We have characterized significant, early and chronic lung changes consistent with oxidative tissue damage in our murine model of repeated radiation and hyperoxia exposure relevant to space travel. Lung tissue changes, detectable several months after the original exposure, include significant oxidative lung damage (lipid peroxidation, DNA damage and protein nitrosative stress) and increased pulmonary fibrosis. These findings, along with increased oxidative stress in diverse body fluids and the observed decreases in blood oxygenation levels in all challenge conditions (whether single or in combination), lead us to conclude that in our model of repeated exposure to oxidative stressors, chronic tissue changes are detected that persist even months after the exposure to the stressor has ended. This data will provide useful information in the design of countermeasures to tissue oxidative damage associated with space exploration.

Oxidative Lung Damage Resulting from Repeated Exposure to Radiation and Hyperoxia Associated with Space Exploration

PubMed Central

Pietrofesa, Ralph A; Turowski, Jason B; Arguiri, Evguenia; Milovanova, Tatyana N; Solomides, Charalambos C; Thom, Stephen R; Christofidou-Solomidou, Melpo

2013-01-01

Background Spaceflight missions may require crewmembers to conduct Extravehicular Activities (EVA) for repair, maintenance or scientific purposes. Pre-breathe protocols in preparation for an EVA entail 100% hyperoxia exposure that may last for a few hours (5-8 hours), and may be repeated 2-3 times weekly. Each EVA is associated with additional challenges such as low levels of total body cosmic/galactic radiation exposure that may present a threat to crewmember health and therefore, pose a threat to the success of the mission. We have developed a murine model of combined, hyperoxia and radiation exposure (double-hit) in the context of evaluating countermeasures to oxidative lung damage associated with space flight. In the current study, our objective was to characterize the early and chronic effects of repeated single and double-hit challenge on lung tissue using a novel murine model of repeated exposure to low-level total body radiation and hyperoxia. This is the first study of its kind evaluating lung damage relevant to space exploration in a rodent model. Methods Mouse cohorts (n=5-15/group) were exposed to repeated: a) normoxia; b) >95% O2 (O2); c) 0.25Gy single fraction gamma radiation (IR); or d) a combination of O2 and IR (O2+IR) given 3 times per week for 4 weeks. Lungs were evaluated for oxidative damage, active TGFβ1 levels, cell apoptosis, inflammation, injury, and fibrosis at 1, 2, 4, 8, 12, 16, and 20 weeks post-initiation of exposure. Results Mouse cohorts exposed to all challenge conditions displayed decreased bodyweight compared to untreated controls at 4 and 8 weeks post-challenge initiation. Chronic oxidative lung damage to lipids (malondialdehyde levels), DNA (TUNEL, cleaved Caspase 3, cleaved PARP positivity) leading to apoptotic cell death and to proteins (nitrotyrosine levels) was elevated all treatment groups. Importantly, significant systemic oxidative stress was also noted at the late phase in mouse plasma, BAL fluid, and urine. Importantly, however, late oxidative damage across all parameters that we measured was significantly higher than controls in all cohorts but was exacerbated by the combined exposure to O2 and IR. Additionally, impaired levels of arterial blood oxygenation were noted in all exposure cohorts. Significant but transient elevation of lung tissue fibrosis (p<0.05), determined by lung hydroxyproline content, was detected as early as 2 week in mice exposed to challenge conditions and persisted for 4-8 weeks only. Interestingly, active TGFβ1 levels in +BAL fluid was also transiently elevated during the exposure time only (1-4 weeks). Inflammation and lung edema/lung injury was also significantly elevated in all groups at both early and late time points, especially the double-hit group. Conclusion We have characterized significant, early and chronic lung changes consistent with oxidative tissue damage in our murine model of repeated radiation and hyperoxia exposure relevant to space travel. Lung tissue changes, detectable several months after the original exposure, include significant oxidative lung damage (lipid peroxidation, DNA damage and protein nitrosative stress) and increased pulmonary fibrosis. These findings, along with increased oxidative stress in diverse body fluids and the observed decreases in blood oxygenation levels in all challenge conditions (whether single or in combination), lead us to conclude that in our model of repeated exposure to oxidative stressors, chronic tissue changes are detected that persist even months after the exposure to the stressor has ended. This data will provide useful information in the design of countermeasures to tissue oxidative damage associated with space exploration. PMID:24358450

Microarray Meta-Analysis Identifies Acute Lung Injury Biomarkers in Donor Lungs That Predict Development of Primary Graft Failure in Recipients

PubMed Central

Haitsma, Jack J.; Furmli, Suleiman; Masoom, Hussain; Liu, Mingyao; Imai, Yumiko; Slutsky, Arthur S.; Beyene, Joseph; Greenwood, Celia M. T.; dos Santos, Claudia

2012-01-01

Objectives To perform a meta-analysis of gene expression microarray data from animal studies of lung injury, and to identify an injury-specific gene expression signature capable of predicting the development of lung injury in humans. Methods We performed a microarray meta-analysis using 77 microarray chips across six platforms, two species and different animal lung injury models exposed to lung injury with or/and without mechanical ventilation. Individual gene chips were classified and grouped based on the strategy used to induce lung injury. Effect size (change in gene expression) was calculated between non-injurious and injurious conditions comparing two main strategies to pool chips: (1) one-hit and (2) two-hit lung injury models. A random effects model was used to integrate individual effect sizes calculated from each experiment. Classification models were built using the gene expression signatures generated by the meta-analysis to predict the development of lung injury in human lung transplant recipients. Results Two injury-specific lists of differentially expressed genes generated from our meta-analysis of lung injury models were validated using external data sets and prospective data from animal models of ventilator-induced lung injury (VILI). Pathway analysis of gene sets revealed that both new and previously implicated VILI-related pathways are enriched with differentially regulated genes. Classification model based on gene expression signatures identified in animal models of lung injury predicted development of primary graft failure (PGF) in lung transplant recipients with larger than 80% accuracy based upon injury profiles from transplant donors. We also found that better classifier performance can be achieved by using meta-analysis to identify differentially-expressed genes than using single study-based differential analysis. Conclusion Taken together, our data suggests that microarray analysis of gene expression data allows for the detection of “injury" gene predictors that can classify lung injury samples and identify patients at risk for clinically relevant lung injury complications. PMID:23071521

Regulation of alveolar macrophage death in acute lung inflammation.

PubMed

Fan, Erica K Y; Fan, Jie

2018-03-27

Acute lung injury (ALI) and its severe form, known as acute respiratory distress syndrome (ARDS), are caused by direct pulmonary insults and indirect systemic inflammatory responses that result from conditions such as sepsis, trauma, and major surgery. The reciprocal influences between pulmonary and systemic inflammation augments the inflammatory process in the lung and promotes the development of ALI. Emerging evidence has revealed that alveolar macrophage (AM) death plays important roles in the progression of lung inflammation through its influence on other immune cell populations in the lung. Cell death and tissue inflammation form a positive feedback cycle, ultimately leading to exaggerated inflammation and development of disease. Pharmacological manipulation of AM death signals may serve as a logical therapeutic strategy for ALI/ARDS. This review will focus on recent advances in the regulation and underlying mechanisms of AM death as well as the influence of AM death on the development of ALI.

A squamous cell lung carcinoma with abscess-like distant metastasis.

PubMed

Dursunoğlu, Neşe; Başer, Sevin; Evyapan, Fatma; Kiter, Göksel; Ozkurt, Sibel; Polat, Bahattin; Karabulut, Nevzat

2007-01-01

This is a metastatic spread of squamous cell lung carcinoma to lungs, liver, lymph node, bone and subcutanous region as multiple abscess-like lesions. A fifty-five years old man admitted to the out-patient clinic with fever, cough, hemopthysis, night sweats, chest pain, abdominal pain and weight loss. In a short period of time abcess like lesions developed in his lungs, liver, lymph node, bone and subcutanous region. Though the clinical presentation is suggestive for an infectious condition, no success to antimicrobial treatment and negative results of microbiological studies have arised a need to further investigations. Histopathological studies of the abscess wall ultimately gave the definitive diagnosis as metastatic squamous cell carcinoma. We believe that case report is interesting because of the uncommon metastatic lesions masquerading the abscesses and also wide-spread multiple distant invasions of a squamous cell lung carcinoma in a short time period.

Respiratory Distress

NASA Technical Reports Server (NTRS)

1976-01-01

The University of Miami School of Medicine asked the Research Triangle Institute for assistance in improvising the negative pressure technique to relieve respiratory distress in infants. Marshall Space Flight Center and Johnson Space Center engineers adapted this idea to the lower-body negative-pressure system seals used during the Skylab missions. Some 20,000 babies succumb to respiratory distress in the U.S. each year, a condition in which lungs progressively lose their ability to oxygenate blood. Both positive and negative pressure techniques have been used - the first to force air into lungs, the second to keep infant's lungs expanded. Negative pressure around chest helps the baby expand his lungs and maintain proper volume of air. If doctors can keep the infant alive for four days, the missing substance in the lungs will usually form in sufficient quantity to permit normal breathing. The Skylab chamber and its leakproof seals were adapted for medical use.

Alveolar macrophage activation and an emphysema-like phenotype in adiponectin-deficient mice

PubMed Central

Summer, R.; Little, F. F.; Ouchi, N.; Takemura, Y.; Aprahamian, T.; Dwyer, D.; Fitzsimmons, K.; Suki, B.; Parameswaran, H.; Fine, A.; Walsh, K.

2013-01-01

Adiponectin is an adipocyte-derived collectin that acts on a wide range of tissues including liver, brain, heart, and vascular endothelium. To date, little is known about the actions of adiponectin in the lung. Herein, we demonstrate that adiponectin is present in lung lining fluid and that adiponectin deficiency leads to increases in proinflammatory mediators and an emphysema-like phenotype in the mouse lung. Alveolar macrophages from adiponectin-deficient mice spontaneously display increased production of tumor necrosis factor-α (TNF-α) and matrix metalloproteinase (MMP-12) activity. Consistent with these observations, we found that pretreatment of alveolar macrophages with adiponectin leads to TNF-α and MMP-12 suppression. Together, our findings show that adiponectin leads to macrophage suppression in the lung and suggest that adiponectin-deficient states may contribute to the pathogenesis of inflammatory lung conditions such as emphysema. PMID:18326826

Inflammasome Activity in Non-Microbial Lung Inflammation

PubMed Central

Ather, Jennifer L.; Martin, Rebecca A.; Ckless, Karina; Poynter, Matthew E.

2015-01-01

The understanding of interleukin-1 (IL-1) family cytokines in inflammatory disease has rapidly developed, due in part to the discovery and characterization of inflammasomes, which are multi-subunit intracellular protein scaffolds principally enabling recognition of a myriad of cellular stimuli, leading to the activation of caspase-1 and the processing of IL-1β and IL-18. Studies continue to elucidate the role of inflammasomes in immune responses induced by both microbes and environmental factors. This review focuses on the current understanding of inflammasome activity in the lung, with particular focus on the non-microbial instigators of inflammasome activation, including inhaled antigens, oxidants, cigarette smoke, diesel exhaust particles, mineral fibers, and engineered nanomaterials, as well as exposure to trauma and pre-existing inflammatory conditions such as metabolic syndrome. Inflammasome activity in these sterile inflammatory states contribute to diseases including asthma, chronic obstructive disease, acute lung injury, ventilator-induced lung injury, pulmonary fibrosis, and lung cancer. PMID:25642415

The Role of Interventional Oncology in the Management of Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duka, Ejona, E-mail: ejonaduka@hotmail.com; Ierardi, Anna Maria, E-mail: amierardi@yahoo.it; Floridi, Chiara, E-mail: chiara.floridi@gmail.com

Interventional radiological procedures for diagnosis and treatment of lung cancer have become increasingly important. Imaging-guided percutaneous biopsy has become the modality of choice for diagnosing lung cancer, and in the era of target therapies, it is an useful tool to define earlier patient-specific tumor phenotypes. In functionally inoperable patients, especially the ablative procedures are potentially curative alternatives to surgery. In addition to thermally ablative treatment, selective chemoembolization by a vascular access allows localized therapy. These treatments are considered for patients in a reduced general condition which does not allow systemic chemotherapy. The present article reviews the role of interventional oncologymore » in the management of primary lung cancer, focusing on the state of the art for each procedure.« less

A case of systemic arterial supply to the right lower lobe of the lung: imaging findings and review of the literature.

PubMed

Mautone, Marcela; Naidoo, Parm

2014-03-01

Systemic arterialization of the lung without pulmonary sequestration is the rarest form of anomalous systemic arterial supply to the lung. This condition is characterised by an aberrant arterial branch arising from the aorta which supplies an area of lung parenchyma with normal bronchopulmonary anatomy. It is often diagnosed following investigation of an incidental cardiac murmur or based on abnormal imaging, as most patients are asymptomatic or minimally symptomatic. Thoracic computed tomography and computed tomography angiography are generally the most useful diagnostic tests. We present a case of a 22-year old female who was diagnosed with systemic arterial supply to a portion of otherwise normal right lower lobe following investigation of low volume haemoptysis.

Recovery of rat alveolar macrophages by bronchoalveolar lavage under normal and activated conditions.

PubMed Central

Rehn, B; Bruch, J; Zou, T; Hobusch, G

1992-01-01

When rat (female Wistar) lungs were lavaged (bronchoalveolar lavage, BAL) six times with physiological saline, approximately the same number of alveolar macrophages (AM) were found in the first and second BAL, whereas in the third fourth, fifth, and sixth BAL, the number of AM decreased exponentially. Morphometric counting of the number of AM in histological sections of lung tissue showed that only 14% of the AM population had been recovered by BAL. Although additives to the BAL fluid such as lidocaine and/or fetal calf serum increased the AM count in the first washing considerably, the total number of AM washed out remained unaltered. Addition of the phagocytosis stimulant zymosan increased the AM count in BAL by a factor of more than 2. On stimulation of the lungs with an inert dust (silicon carbide), the AM count in the BAL and the lung was only slightly increased 8 weeks after intratracheal instillation. In contrast, after exposure to fibrogenic and cytotoxic quartz, the AM count in BAL and lung was significantly increased, and the recovery of AM had also increased by a factor of approximately 2. The experiments show that it is the micromilieu of the alveoli and the condition of the AM (certain physiological activation states, such as phagocytic activity) that essentially determine the degree of recovery. PMID:1396444

Expression of profibrotic growth factors and their receptors by mouse lung macrophages and fibroblasts under conditions of acute viral inflammation in influenza A/H5N1 virus.

PubMed

Anikina, A G; Shkurupii, V A; Potapova, O V; Kovner, A V; Shestopalov, A M

2014-04-01

Morphological signs of early interstitial fibrosis, developing under conditions of acute viral inflammation (postinfection days 1-14), were observed in C57Bl/6 mice infected with influenza A/H5N1 A/goose/Krasnoozerskoye/627/05 virus. The development of fibrosis was confirmed by an increase in the number of lung cells expressing TNF-α. These changes were recorded in the presence of a many-fold increase in the counts of macrophages and fibroblasts expressing FGF, EGF, and their receptors.

The alveolar surface network: a new anatomy and its physiological significance.

PubMed

Scarpelli, E M

1998-08-01

It is generally held that the terminal lung unit (TLU) is an agglomeration of alveoli that opens into the branching air spaces of respiratory bronchioles, alveolar ducts, and alveolar sacs and that these structures are covered by a continuous thin liquid layer bearing a monomolecular film of surfactants at the open gas-liquid interface. The inherent structural and functional instability given TLUs by a broad liquid surface layer of this nature has been mitigated by the discovery that the TLU surface is in fact an agglomeration of bubbles, a foam (the alveolar surface network) that fills the TLU space and forms ultrathin foam films that 1) impart infrastructural stability to sustain aeration, 2) modulate circulation of surface liquid, both in series and in parallel, throughout the TLU and between TLUs and the liquid surface of conducting airways, 3) modulate surface liquid volume and exchange with interstitial liquid, and 4) sustain gas transfer between conducting airways and pulmonary capillaries throughout the respiratory cycle. The experimental evidence, from discovery to the present, is addressed in this report. Lungs were examined in thorax by stereomicroscopy immediately from the in vivo state at volumes ranging from functional residual capacity to maximal volume (Vmax). Lungs were then excised; bubble topography of all anterior and anterolateral surfaces was reaffirmed and also confirmed for all posterior and posterolateral surfaces. The following additional criteria verify the ubiquitous presence of normal intraalveolar bubbles. 1) Bubbles are absent in conducting airways. 2) Bubbles are stable and stationary in TLUs but can be moved individually by gentle microprobe pressure. 3) Adjoining bubbles move into the external medium through subpleural microincisions; there is no free gas, and vacated spaces are rendered airless. Adjacent bubbles may shift position in situ, while more distal bubbles remain stationary. 4) The position and movement of "large" bubbles identifies them as intraductal bubbles. 5) Transection of the lung reveals analogous bubble occurrence and history in central lung regions. 6) Bubbles become fixed in place and change shape when the lung is dried in air; the original shape and movement are restored when the lung is rewet. 7) All exteriorized bubbles are stable with lamellar (film) surface tension near zero. 8) Intact lungs prepared and processed by the new double-embedding technique reveal the intact TLU bubbles and bubble films. Lungs were also monitored directly by stereomicroscopy to establish their presence, transformations, and apparent function from birth through adulthood, as summarized in the following section. Intraalveolar bubbles and bubble films (the unit structures of the alveolar surface network) have been found in all mammalian species examined to date, including lambs, kids, and rabbit pups and adult mice, rats, rabbits, cats, and pigs. Rabbits were used for the definitive studies. 1) A unit bubble occupies each alveolus and branching airway of the TLU; unit bubbles in clusters correspond with alveolar clusters. 2) The appositions of unit bubble lamellae (films) form a network of liquid channels within the TLUs. The appositions are bubble to bubble (near alveolar entrances, at pores of Kohn, and between ductal bubbles), bubble to epithelial cell surface, and bubble to surface liquid of conducting airways. They rapidly form stable Newtonian black foam films (approximately 7 nm thick) under hydrodynamic conditions expected in vivo. 3) Lamellae of the foam films and bubbles tend to exclude bulk liquid and thus maintain near-zero surface tension. At the same time, the foam film formations--abetted by the constant but small retractive force of tissue recoil--stabilize unit bubble position within the network. 4) Unit bubble mobility in response to applied force increases as liquid accumulates within the network (e.g. (ABSTRACT TRUNCATED)

Nasal airflow simulations suggest convergent adaptation in Neanderthals and modern humans.

PubMed

de Azevedo, S; González, M F; Cintas, C; Ramallo, V; Quinto-Sánchez, M; Márquez, F; Hünemeier, T; Paschetta, C; Ruderman, A; Navarro, P; Pazos, B A; Silva de Cerqueira, C C; Velan, O; Ramírez-Rozzi, F; Calvo, N; Castro, H G; Paz, R R; González-José, R

2017-11-21

Both modern humans (MHs) and Neanderthals successfully settled across western Eurasian cold-climate landscapes. Among the many adaptations considered as essential to survival in such landscapes, changes in the nasal morphology and/or function aimed to humidify and warm the air before it reaches the lungs are of key importance. Unfortunately, the lack of soft-tissue evidence in the fossil record turns difficult any comparative study of respiratory performance. Here, we reconstruct the internal nasal cavity of a Neanderthal plus two representatives of climatically divergent MH populations (southwestern Europeans and northeastern Asians). The reconstruction includes mucosa distribution enabling a realistic simulation of the breathing cycle in different climatic conditions via computational fluid dynamics. Striking across-specimens differences in fluid residence times affecting humidification and warming performance at the anterior tract were found under cold/dry climate simulations. Specifically, the Asian model achieves a rapid air conditioning, followed by the Neanderthals, whereas the European model attains a proper conditioning only around the medium-posterior tract. In addition, quantitative-genetic evolutionary analyses of nasal morphology provided signals of stabilizing selection for MH populations, with the removal of Arctic populations turning covariation patterns compatible with evolution by genetic drift. Both results indicate that, departing from important craniofacial differences existing among Neanderthals and MHs, an advantageous species-specific respiratory performance in cold climates may have occurred in both species. Fluid dynamics and evolutionary biology independently provided evidence of nasal evolution, suggesting that adaptive explanations regarding complex functional phenotypes require interdisciplinary approaches aimed to quantify both performance and evolutionary signals on covariation patterns.

Bronchiolitis

MedlinePlus

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A simple and cost effective liquid culture system for the micropropagation of two commercially important apple rootstocks.

PubMed

Mehta, Mohina; Ram, Raja; Bhattacharya, Amita

2014-07-01

The two commercially important apple rootstocks i.e., MM106 and B9 were micropropagated using a liquid culture system. Three different strengths of 0.8% agar solidified PGR free basal MS medium were first tested to optimize the culture media for both the rootstocks. Full strength medium (MS0) supported maximum in vitro growth, multiplication, rooting and survival under field conditions as opposed to quarter and half strength media. When three different volumes of liquid MS0 were tested, highest in vitro growth, multiplication, rooting and also survival under field conditions were achieved in 20 mL liquid MS0. The cost of one litre of liquid medium was also reduced by 8 times to Rs. 6.29 as compared to solid medium. The cost of 20 mL medium was further reduced to Rs. 0.125.

Functional Investigation of NCI-H460-Inducible Myofibroblasts on the Chemoresistance to VP-16 with a Microfluidic 3D Co-Culture Device

PubMed Central

He, Jiarui; Guo, Zhe; Ying, Li; Xu, Zhiyun; Zhang, Jianing; Lu, Jianxin; Wang, Qi

2013-01-01

Fibroblasts, the major cell type in tumor stroma, are essential for tumor growth and survival, and represent an important therapeutic target for cancers. Here we presented a microfluidic co-culture device in which the three-dimensional (3D) matrix was employed to reconstruct an in vivo-like fibroblast-tumor cell microenvironment for investigation of the role of myofibroblasts induced by lung cancer cells in the chemoresistance to VP-16. Composed of a double-layer chip and an injection pump, the device houses fibroblasts and lung cancer cells co-cultured in 3D matrix and 2D mode to induce fibroblasts to become myofibroblasts with the supplement of the medium continuously. With this device, we verified that the cytokines secreted by lung cancer cells could effectively transform the fibroblasts into myofibroblasts. Moreover, compared to fibroblasts, the myofibroblasts showed higher resistance to anticancer drug VP-16. We also demonstrated that this kind of acquired resistance in myofibroblasts was associated with the expression of Glucose-regulated protein 78 (GP78). We concluded that this device allows for the assay to characterize various cellular events in a single device sequentially, facilitating a better understanding of the interactions among heterotypic cells in a sophisticated microenvironment. PMID:23613925

Exploring Radiotherapy Targeting Strategy and Dose: A Pooled Analysis of Cooperative Group Trials of Combined Modality Therapy for Stage III Non-Small Cell Lung Cancer.

PubMed

Schild, Steven E; Fan, Wen; Stinchcombe, Thomas E; Vokes, Everett E; Ramalingam, Suresh S; Bradley, Jeffrey D; Kelly, Karen; Pang, Herbert H; Wang, Xiaofei

2018-04-21

Concurrent chemoradiotherapy(CRT) is standard therapy for locally-advanced non-small-cell lung cancer(LA-NSCLC)patients. This study was performed to examine thoracic radiotherapy(TRT) parameters and their impact on patient survival. We collected Individual patient data(IPD) from 3600LA-NSCLC patients participating in 16 cooperative group trials of concurrent CRT. The primary TRT parameters examined included field design strategy(elective nodal irradiation(ENI) compared to involved field TRT(IF-TRT)), total dose, and biologically effective dose(BED). Hazard ratios(HRs) for overall survival were calculated with univariable and multivariable Cox models. TRT doses ranged from 60 to 74 Gy with most treatments administered once-daily. ENI was associated with poorer survival than IF-TRT(univariable HR,1.37;95%CI,1.24-1.51,p<0.0001;multivariable HR,1.31;95%CI,1.08-1.59,p=0.002). The median survival of the IF and ENI patients were 24 and 16 months, respectively. Patients were divided into 3 dose groups: low total dose(60 Gy), medium total dose(>60Gy-66Gy) and high total dose(>66Gy-74 Gy). With reference to the low dose group, the multivariable HR's were 1.08 for the medium dose group(95%CI=0.93-1.25) and 1.12 for the high dose group(CI=0.97-1.30).The univariate p=0.054 and multivariable p=0.17. BED was grouped as follows: low(<55.5Gy 10 ), medium(=55.5 Gy 10) , or high(>55.5 Gy 10 ). With reference to the low BED group, the HR was 1.00(95%CI=0.85-1.18) for the medium BED group and 1.10(95%CI=0.93-1.31) for the high BED group. The univariable p=0.076 and multivariable p=0.16. For LA-NSCLC patients treated with concurrent CRT, IF-TRT was associated with significantly better survival than ENI-TRT. TRT total and BED dose levels were not significantly associated with patient survival. Future progress will require research focusing on better systemic therapy and TRT. Copyright © 2018. Published by Elsevier Inc.

Gamma-ray line afterglow from burst environments

NASA Technical Reports Server (NTRS)

Fencl, H. S.; Boyd, R. N.; Hartmann, Dieter

1992-01-01

We consider photoerosion and direct pair production in a medium surrounding a gamma-ray burst. The resulting secondary gamma-rays may provide diagnostic tools of these environments and, in turn, of the nature of the bursters themselves. In some instances short-lived nuclides are formed; the beta-delayed gamma-rays produced from their decays provide the signatures of the photoerosion. In addition, annihilation radiation produced from positrons resulting from direct pair production is related to the plasma conditions in the medium. We investigate the plausibility of detecting the various radiations. Under extremely favorable conditions, the photoerosion afterglow might be detectable with the present generation of detectors. However, the positron annihilation line should be detectable under a fairly wide range in the conditions of the medium.

Stimulation of plasmin activity in cultured human fibroblast cells by Porphyromonas endodontalis.

PubMed

Oikawa, T; Ogura, N; Akiba, M; Abiko, Y; Takiguchi, H; Izumi, H

1993-09-01

1. Plasmin activity in the conditioned medium of Gin-1 cells, a human gingival fibroblast cell line, was stimulated by Porphyromonas endodontalis, a putative pathogen of oral submucous abscesses, in a time- and dose-dependent manner. 2. P. endodontalis stimulated the activity of plasminogen activator in both the conditioned medium and the cell lysate. The plasminogen activator in Gin-1 cells was approx. 50 kDa by zymography. 3. The conditioned medium of Gin-1 cells exposed to P. endodontalis stimulated the conversion of human serum prekallikrein to kallikrein. 4. These results suggested that P. endodontalis stimulates the plasminogen activator-plasmin system in Gin-1 cells, and that activated plasmin plays a role in the progress of periodontal tissue inflammation.

Optimization of flask culture medium and conditions for hyaluronic acid production by a Streptococcus equisimilis mutant nc2168.

PubMed

Chen, Yong-Hao; Li, Jun; Liu, Li; Liu, Hong-Zhi; Wang, Qiang

2012-10-01

A mutant designated NC2168, which was selected from wild-type Streptococcus equisimilis CVCC55116 by ultraviolet ray combined with(60)Co-γ ray treatment and does not produce streptolysin, was employed to produce hyaluronic acid (HA). In order to increase the output of HA in a flask, the culture medium and conditions for NC2168 were optimized in this study. The influence of culture medium ingredients including carbon sources, nitrogen sources and metal ions on HA production was evaluated using factional factorial design. The mathematical model, which represented the effect of each medium component and their interaction on the yield of HA, was established by the quadratic rotary combination design and response surface method. The model estimated that, a maximal yield of HA could be obtained when the concentrations of yeast extract, peptone, glucose, and MgSO4 were set at 3 g/100 mL, 2 g/100 mL, 0.5 g/100 mL and 0.15 g/100 mL, respectively. Compared with the values obtained by other runs in the experimental design, the optimized medium resulted in a remarkable increase in the output of HA and the maximum of the predicted HA production was 174.76 mg/L. The model developed was accurate and reliable for predicting the production of HA by NC2168.Cultivation conditions were optimized by an orthogonal experimental design and the optimal conditions were as follows: temperature 33°C, pH 7.8, agitation speed 200 rpm, medium volume 20 mL.

Suppressed translation as a mechanism of initiation of CASP8 (caspase 8)-dependent apoptosis in autophagy-deficient NSCLC cells under nutrient limitation.

PubMed

Allavena, Giulia; Cuomo, Francesca; Baumgartner, Georg; Bele, Tadeja; Sellgren, Alexander Yarar; Oo, Kyaw Soe; Johnson, Kaylee; Gogvadze, Vladimir; Zhivotovsky, Boris; Kaminskyy, Vitaliy O

2018-01-01

Macroautophagy/autophagy inhibition under stress conditions is often associated with increased cell death. We found that under nutrient limitation, activation of CASP8/caspase-8 was significantly increased in autophagy-deficient lung cancer cells, which precedes mitochondria outer membrane permeabilization (MOMP), CYCS/cytochrome c release, and activation of CASP9/caspase-9, indicating that under such conditions the activation of CASP8 is a primary event in the initiation of apoptosis as well as essential to reduce clonogenic survival of autophagy-deficient cells. Starvation leads to suppression of CFLAR proteosynthesis and accumulation of CASP8 in SQSTM1 puncta. Overexpression of CFLARs reduces CASP8 activation and apoptosis during starvation, while its silencing promotes efficient activation of CASP8 and apoptosis in autophagy-deficient U1810 lung cancer cells even under nutrient-rich conditions. Similar to starvation, inhibition of protein translation leads to efficient activation of CASP8 and cell death in autophagy-deficient lung cancer cells. Thus, here for the first time we report that suppressed translation leads to activation of CASP8-dependent apoptosis in autophagy-deficient NSCLC cells under conditions of nutrient limitation. Our data suggest that targeting translational machinery can be beneficial for elimination of autophagy-deficient cells via the CASP8-dependent apoptotic pathway.

Anatomy and bronchoscopy of the porcine lung. A model for translational respiratory medicine.

PubMed

Judge, Eoin P; Hughes, J M Lynne; Egan, Jim J; Maguire, Michael; Molloy, Emer L; O'Dea, Shirley

2014-09-01

The porcine model has contributed significantly to biomedical research over many decades. The similar size and anatomy of pig and human organs make this model particularly beneficial for translational research in areas such as medical device development, therapeutics and xenotransplantation. In recent years, a major limitation with the porcine model was overcome with the successful generation of gene-targeted pigs and the publication of the pig genome. As a result, the role of this model is likely to become even more important. For the respiratory medicine field, the similarities between pig and human lungs give the porcine model particular potential for advancing translational medicine. An increasing number of lung conditions are being studied and modeled in the pig. Genetically modified porcine models of cystic fibrosis have been generated that, unlike mouse models, develop lung disease similar to human cystic fibrosis. However, the scientific literature relating specifically to porcine lung anatomy and airway histology is limited and is largely restricted to veterinary literature and textbooks. Furthermore, methods for in vivo lung procedures in the pig are rarely described. The aims of this review are to collate the disparate literature on porcine lung anatomy, histology, and microbiology; to provide a comparison with the human lung; and to describe appropriate bronchoscopy procedures for the pig lungs to aid clinical researchers working in the area of translational respiratory medicine using the porcine model.

Single lung transplantation and fatal fat embolism acquired from the donor: management and literature review.

PubMed

López-Sánchez, Marta; Alvarez-Antoñán, Carlos; Arce-Mateos, Félix P; Gómez-Román, José; Quesada-Suescun, Antonio; Zurbano-Goñi, Felipe

2010-01-01

Fat embolism (FE) is a consequence of skeletal trauma that occurs in more than 90% of cases of severe trauma. However, most of these emboli are clinically insignificant. We report the case of a 59-yr-old man with massive progressive fibrosis who died from widespread FE after a single-lung transplantation (SLT). The lung donor was a 22-yr-old woman who died from traumatic cerebral injury. She had sustained a closed fracture of the tibia, fibula and pelvis. The PaO(2)/FiO(2) before procurement was 452 mmHg. A left SLT using cardiopulmonary bypass was performed. In the immediate postoperative period, profound pulmonary edema in the transplanted lung developed, with overinflation of the native lung and systemic hypotension. Severe Primary Graft Dysfunction (PGD) was suspected and nitric oxide (NO) and independent lung ventilation (ILV) initiated. Over the next 24 h the patient's condition deteriorated and extracorporeal membrane oxygenation (ECMO) was initiated. The patient died 45 h after transplantation as cardiovascular and respiratory function continued to decline and massive thoracic bleeding secondary to coagulopathy appeared. Post-mortem examination revealed both massive FE in the non-transplanted donor lung and in the allograft lung. Only two previous cases of donor-acquired FE and PGD after lung transplantation (LT) have been reported. Occult pulmonary FE in a traumatized donor should be considered a cause of PGD.

Lung cancer in patients with idiopathic pulmonary fibrosis.

PubMed

Karampitsakos, Theodoros; Tzilas, Vasilios; Tringidou, Rodoula; Steiropoulos, Paschalis; Aidinis, Vasilis; Papiris, Spyros A; Bouros, Demosthenes; Tzouvelekis, Argyris

2017-08-01

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease of unknown etiology. With a gradually increasing worldwide prevalence and a mortality rate exceeding that of many cancers, IPF diagnosis and management are critically important and require a comprehensive multidisciplinary approach. This approach also involves assessment of comorbid conditions, such as lung cancer, that exerts a dramatic impact on disease survival. Emerging evidence suggests that progressive lung scarring in the context of IPF represents a risk factor for lung carcinogenesis. Both disease entities present with major similarities in terms of pathogenetic pathways, as well as potential causative factors, such as smoking and viral infections. Besides disease pathogenesis, anti-cancer agents, including nintedanib, have been successfully applied in the treatment of patients with IPF while an oncologic approach with a cocktail of several pleiotropic anti-fibrotic agents is currently in the therapeutic pipeline of IPF. Nevertheless, epidemiologic association between IPF and lung cancer does not prove causality. Currently there is significant lack of knowledge supporting a direct association between lung fibrosis and cancer reflecting to disappointing therapeutic algorithms. An optimal therapeutic strategy for patients with both IPF and lung cancer represents an amenable need. This review article synthesizes the current state of knowledge regarding pathogenetic commonalities between IPF and lung cancer and focuses on clinical and therapeutic data that involve both disease entities. Copyright © 2017. Published by Elsevier Ltd.

Aspergillus spp. colonization in exhaled breath condensate of lung cancer patients from Puglia Region of Italy

PubMed Central

2014-01-01

Background Airways of lung cancer patients are often colonized by fungi. Some of these colonizing fungi, under particular conditions, produce cancerogenic mycotoxins. Given the recent interest in the infective origin of lung cancer, with this preliminary study we aim to give our small contribution to this field of research by analysing the fungal microbiome of the exhaled breath condensate of lung cancer patients from Puglia, a region of Italy. Methods We enrolled 43 lung cancer patients and 21 healthy subjects that underwent exhaled breath condensate and bronchial brushing collection. The fungal incidence and nature of sample collected were analysed by using a selected media for Aspergillus species. Results For the first time we were able to analyse the fungal microbioma of the exhaled breath condensate. 27.9% of lung cancer patients showed a presence of Aspergillus niger, or A. ochraceus or Penicillium ssp. while none of the healthy subjects did so. Conclusion The results confirmed the high percentage of fungal colonization of the airways of lung cancer patients from Puglia, suggesting the need to conduct further analyses in this field in order to evaluate the exact pathogenetic role of these fungi in lung cancer as well as to propose efficient, empirical therapy. PMID:24548615

Skeletal muscle strength and endurance in recipients of lung transplants.

PubMed

Mathur, Sunita; Levy, Robert D; Reid, W Darlene

2008-09-01

Exercise limitation in recipients of lung transplant may be a result of abnormalities in the skeletal muscle. However, it is not clear whether these abnormalities are merely a reflection of the changes observed in the pretransplant condition. The purpose of this paper was to compare thigh muscle volume and composition, strength, and endurance in lung transplant recipients to people with chronic obstructive pulmonary disease (COPD). Single lung transplant recipients (n=6) and people with COPD (n=6), matched for age, sex, and BMI participated in the study. Subjects underwent MRI to determine muscle size and composition, lower extremity strength testing and an isometric endurance test of the quadriceps. Lung transplant recipients had similar muscle volumes and intramuscular fat infiltration of their thigh muscles and similar strength of the quadriceps and hamstrings to people with COPD who had not undergone transplant. However, quadriceps endurance tended to be lower in transplant recipients compared to people with COPD (15 +/- 7 seconds in transplant versus 31 +/- 12 seconds in COPD, p = 0.08). Recipients of lung transplant showed similar changes in muscle size and strength as people with COPD, however muscle endurance tended to be lower in people with lung transplants. Impairments in muscle endurance may reflect the effects of immunosuppressant medications on skeletal muscle in people with lung transplant.

Mechanobiology in Lung Epithelial Cells: Measurements, Perturbations, and Responses

PubMed Central

Waters, Christopher M.; Roan, Esra; Navajas, Daniel

2015-01-01

Epithelial cells of the lung are located at the interface between the environment and the organism and serve many important functions including barrier protection, fluid balance, clearance of particulate, initiation of immune responses, mucus and surfactant production, and repair following injury. Because of the complex structure of the lung and its cyclic deformation during the respiratory cycle, epithelial cells are exposed to continuously varying levels of mechanical stresses. While normal lung function is maintained under these conditions, changes in mechanical stresses can have profound effects on the function of epithelial cells and therefore the function of the organ. In this review, we will describe the types of stresses and strains in the lungs, how these are transmitted, and how these may vary in human disease or animal models. Many approaches have been developed to better understand how cells sense and respond to mechanical stresses, and we will discuss these approaches and how they have been used to study lung epithelial cells in culture. Understanding how cells sense and respond to changes in mechanical stresses will contribute to our understanding of the role of lung epithelial cells during normal function and development and how their function may change in diseases such as acute lung injury, asthma, emphysema, and fibrosis. PMID:23728969

The lung is a site of platelet biogenesis and a reservoir for hematopoietic progenitors

PubMed Central

Lefrançais, Emma; Ortiz-Muñoz, Guadalupe; Caudrillier, Axelle; Mallavia, Beñat; Liu, Fengchun; Sayah, David M.; Thornton, Emily E.; Headley, Mark B.; David, Tovo; Coughlin, Shaun R.; Krummel, Matthew F.; Leavitt, Andrew D.; Passegué, Emmanuelle; Looney, Mark R.

2017-01-01

Platelets are critical for hemostasis, thrombosis, and inflammatory responses1,2, yet the events leading to mature platelet production remain incompletely understood3. The bone marrow (BM) is proposed to be a major site of platelet production although indirect evidence points towards a potential pulmonary contribution to platelet biogenesis4-7. By directly imaging the lung microcirculation in mice8, we discovered that a large number of megakaryocytes (MKs) circulate through the lungs where they dynamically release platelets. MKs releasing platelets in the lung are of extrapulmonary origin, such as the BM, where we observed large MKs migrating out of the BM space. The lung contribution to platelet biogenesis is substantial with approximately 50% of total platelet production or 10 million platelets per hour. Furthermore, we identified populations of mature and immature MKs along with hematopoietic progenitors that reside in the extravascular spaces of the lung. Under conditions of thrombocytopenia and relative stem cell deficiency in the BM9, these progenitors can migrate out of the lung, repopulate the BM, completely reconstitute blood platelet counts, and contribute to multiple hematopoietic lineages. These results position the lung as a primary site of terminal platelet production and an organ with considerable hematopoietic potential. PMID:28329764

Human Umbilical Cord Mesenchymal Stem Cells Reduce Fibrosis of Bleomycin-Induced Lung Injury

PubMed Central

Moodley, Yuben; Atienza, Daniel; Manuelpillai, Ursula; Samuel, Chrishan S.; Tchongue, Jorge; Ilancheran, Sivakami; Boyd, Richard; Trounson, Alan

2009-01-01

Acute respiratory distress syndrome is characterized by loss of lung tissue as a result of inflammation and fibrosis. Augmenting tissue repair by the use of mesenchymal stem cells may be an important advance in treating this condition. We evaluated the role of term human umbilical cord cells derived from Wharton’s jelly with a phenotype consistent with mesenchymal stem cells (uMSCs) in the treatment of a bleomycin-induced mouse model of lung injury. uMSCs were administered systemically, and lungs were harvested at 7, 14, and 28 days post-bleomycin. Injected uMSCs were located in the lung 2 weeks later only in areas of inflammation and fibrosis but not in healthy lung tissue. The administration of uMSCs reduced inflammation and inhibited the expression of transforming growth factor-β, interferon-γ, and the proinflammatory cytokines macrophage migratory inhibitory factor and tumor necrosis factor-α. Collagen concentration in the lung was significantly reduced by uMSC treatment, which may have been a consequence of the simultaneous reduction in Smad2 phosphorylation (transforming growth factor-β activity). uMSCs also increased matrix metalloproteinase-2 levels and reduced their endogenous inhibitors, tissue inhibitors of matrix metalloproteinases, favoring a pro-degradative milieu following collagen deposition. Notably, injected human lung fibroblasts did not influence either collagen or matrix metalloproteinase levels in the lung. The results of this study suggest that uMSCs have antifibrotic properties and may augment lung repair if used to treat acute respiratory distress syndrome. PMID:19497992

Extracellular ATP mediates the late phase of neutrophil recruitment to the lung in murine models of acute lung injury.

PubMed

Shah, Dilip; Romero, Freddy; Stafstrom, William; Duong, Michelle; Summer, Ross

2014-01-01

Acute lung injury (ALI) is a severe inflammatory condition whose pathogenesis is irrevocably linked to neutrophil emigration to the lung. Activation and recruitment of neutrophils to the lung is mostly attributable to local production of the chemokines. However, much of our understanding of neutrophil recruitment to the lung is based on studies focusing on early time points after initiation of injury. In this study, we sought to evaluate the extended temporal relationship between neutrophil chemotactic factor expression and influx of neutrophils into the lung after intratracheal administration of either LPS or bleomycin. In both models, results demonstrated two phases of neutrophil chemotactic factor expression; first, an early phase characterized by high levels of CXCL1/keratinocyte-derived chemokine, CXCL2/monocyte-inhibitory protein-2, and CXCL5/LPS-induced chemokine expression, and second, a late phase distinguished by increases in extracellular ATP. Furthermore, we show that strategies aimed at either enhancing ATP catabolism (ip ecto-5'-nucleotidase administration) or inhibiting glycolytic ATP production (ip 2-deoxy-d-glucose treatment) reduce extracellular ATP accumulation, limit vascular leakage, and effectively block the late, but not the early, stages of neutrophil recruitment to the lung after LPS instillation. In conclusion, this study illustrates that neutrophil recruitment to the lung is mediated by the time-dependent expression of chemotactic factors and suggests that novel strategies, which reduce extracellular ATP accumulation, may attenuate late neutrophil recruitment and limit lung injury during ALI.

Extracellular ATP mediates the late phase of neutrophil recruitment to the lung in murine models of acute lung injury

PubMed Central

Shah, Dilip; Romero, Freddy; Stafstrom, William; Duong, Michelle

2013-01-01

Acute lung injury (ALI) is a severe inflammatory condition whose pathogenesis is irrevocably linked to neutrophil emigration to the lung. Activation and recruitment of neutrophils to the lung is mostly attributable to local production of the chemokines. However, much of our understanding of neutrophil recruitment to the lung is based on studies focusing on early time points after initiation of injury. In this study, we sought to evaluate the extended temporal relationship between neutrophil chemotactic factor expression and influx of neutrophils into the lung after intratracheal administration of either LPS or bleomycin. In both models, results demonstrated two phases of neutrophil chemotactic factor expression; first, an early phase characterized by high levels of CXCL1/keratinocyte-derived chemokine, CXCL2/monocyte-inhibitory protein-2, and CXCL5/LPS-induced chemokine expression, and second, a late phase distinguished by increases in extracellular ATP. Furthermore, we show that strategies aimed at either enhancing ATP catabolism (ip ecto-5′-nucleotidase administration) or inhibiting glycolytic ATP production (ip 2-deoxy-d-glucose treatment) reduce extracellular ATP accumulation, limit vascular leakage, and effectively block the late, but not the early, stages of neutrophil recruitment to the lung after LPS instillation. In conclusion, this study illustrates that neutrophil recruitment to the lung is mediated by the time-dependent expression of chemotactic factors and suggests that novel strategies, which reduce extracellular ATP accumulation, may attenuate late neutrophil recruitment and limit lung injury during ALI. PMID:24285266

Maresin 1 Ameliorates Lung Ischemia/Reperfusion Injury by Suppressing Oxidative Stress via Activation of the Nrf-2-Mediated HO-1 Signaling Pathway

PubMed Central

Wu, You; Zhao, Feng

2017-01-01

Lung ischemia/reperfusion (I/R) injury occurs in various clinical conditions and heavily damaged lung function. Oxidative stress reaction and antioxidant enzymes play a pivotal role in the etiopathogenesis of lung I/R injury. In the current study, we investigated the impact of Maresin 1 on lung I/R injury and explored the possible mechanism involved in this process. MaR 1 ameliorated I/R-induced lung injury score, wet/dry weight ratio, myeloperoxidase, tumor necrosis factor, bronchoalveolar lavage fluid (BALF) leukocyte count, BALF neutrophil ratio, and pulmonary permeability index levels in lung tissue. MaR 1 significantly reduced ROS, methane dicarboxylic aldehyde, and 15-F2t-isoprostane generation and restored antioxidative enzyme (superoxide dismutase, glutathione peroxidase, and catalase) activities. Administration of MaR 1 improved the expression of nuclear Nrf-2 and cytosolic HO-1 in I/R-treated lung tissue. Furthermore, we also found that the protective effects of MaR 1 on lung tissue injury and oxidative stress were reversed by HO-1 activity inhibitor, Znpp-IX. Nrf-2 transcription factor inhibitor, brusatol, significantly decreased MaR 1-induced nuclear Nrf-2 and cytosolic HO-1 expression. In conclusion, these results indicate that MaR 1 protects against lung I/R injury through suppressing oxidative stress. The mechanism is partially explained by activation of the Nrf-2-mediated HO-1 signaling pathway. PMID:28751936

Changes in Functional Lung Regions During the Course of Radiation Therapy and Their Potential Impact on Lung Dosimetry for Non-Small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meng, Xue; Department of Radiation Oncology, Shandong Cancer Hospital, Shandong University, Jinan; Frey, Kirk

2014-05-01

Purpose: To study changes in functional activity on ventilation (V)/perfusion (Q) single-photon emission computed tomography (SPECT) during radiation therapy (RT) and explore the impact of such changes on lung dosimetry in patients with non-small cell lung cancer (NSCLC). Methods and Materials: Fifteen NSCLC patients with centrally located tumors were enrolled. All patients were treated with definitive RT dose of ≥60 Gy. V/Q SPECT-CT scans were performed prior to and after delivery of 45 Gy of fractionated RT. SPECT images were used to define temporarily dysfunctional regions of lung caused by tumor or other potentially reversible conditions as B3. The functional lung (FL)more » was defined on SPECT by 2 separate approaches: FL1, a threshold of 30% of the maximum uptake of the patient's lung; and FL2, FL1 plus B3 region. The impact of changes in FL between initiation of RT and delivery of 45 Gy on lung dosimetry were analyzed. Results: Fourteen patients (93%) had larger FL2 volumes than FL1 pre-RT (P<.001). Dysfunctional lung became functional in 11 patients (73%) on V SPECT and in 10 patients (67%) on Q SPECT. The dosimetric parameters generated from CT-based anatomical lung had significantly lower values in FL1 than FL2, with a median reduction in the volume of lung receiving a dose of at least 20 Gy (V{sub 20}) of 3%, 5.6%, and mean lung dose of 0.95 and 1.55 on V and Q SPECT respectively. Conclusions: Regional ventilation and perfusion function improve significantly during RT in centrally located NSCLC. Lung dosimetry values vary notably between different definitions of functional lung.« less

Gross pulmonary thrombosis in a greyhound.

PubMed

Baines, E A; Watson, P J; Stidworthy, M F; Herrtage, M E

2001-09-01

A two-year-old greyhound was presented with progressive dyspnoea. Radiography showed a hypovascular lung pattern with hyperlucent lung fields and echocardiography revealed a large thrombus in the main pulmonary artery. Blood results showed azotaemia and marked hypoalbuminaemia. The dog's clinical condition continued to deteriorate and it was euthanased. Postmortem examination confirmed the presence of the pulmonary thrombus and revealed idiopathic membranous glomerulonephritis.

Aeromonas hydrophila as cause of hemorrhagic septicemia in a ground-hornbill (Bucorvus abyssinicus).

PubMed

Ocholi, R A; Kalejaiye, J O

1990-01-01

An acute hemorrhagic septicemia in a captive ground-hornbill (Bucorvus abyssinicus) is reported. Aeromonas hydrophila was isolated from lungs, liver, kidney, and intestines. Postmortem lesions were characterized by hemorrhages in the internal organs. Microscopically, necrotic lesions were found in the liver, lungs, and kidney. Factors that might have contributed to the clinical disease condition are discussed.

Liquid Therapy Delivery Models Using Microfluidic Airways

NASA Astrophysics Data System (ADS)

Mulligan, Molly K.; Grotberg, James B.; Waisman, Dan; Filoche, Marcel; Sznitman, Josué

2013-11-01

The propagation and break-up of viscous and surfactant-laden liquid plugs in the lungs is an active area of research in view of liquid plug installation in the lungs to treat a host of different pulmonary conditions. This includes Infant Respiratory Distress Syndrome (IRDS) the primary cause of neonatal death and disability. Until present, experimental studies of liquid plugs have generally been restricted to low-viscosity Newtonian fluids along a single bifurcation. However, these fluids reflect poorly the actual liquid medication therapies used to treat pulmonary conditions. The present work attempts to uncover the propagation, rupture and break-up of liquid plugs in the airway tree using microfluidic models spanning three or more generations of the bronchiole tree. Our approach allows the dynamics of plug propagation and break-up to be studied in real-time, in a one-to-one scale in vitro model, as a function of fluid rheology, trailing film dynamics and bronchial tree geometry. Understanding these dynamics are a first and necessary step to deliver more effectively boluses of liquid medication to the lungs while minimizing the injury caused to epithelial cells lining the lungs from the rupture of such liquid plugs.

Medium components and culture conditions affect the thermotolerance of aerial conidia of fungal biocontrol agent Beauveria bassiana.

PubMed

Ying, S-H; Feng, M-G

2006-09-01

To produce more thermotolerable conidia of Beauveria bassiana, a well-known fungal biocontrol agent, by optimizing the medium components and culture conditions. The conidia produced on media including 0.5-6% glucose, sucrose or starch as carbon source and 50-300-microg ml(-1) Cu2+, Zn2+, Mn2+ or Fe3+ as additive to Sabouraud dextrose medium at 15-30 degrees C, pH 4-8 or KCl-adjusted water availabilities were exposed to 30-min wet heat stress at 48 degrees C. The medium components for conidial production with greatly enhanced thermotolerance included 4% glucose as optimum or 1% starch as alternative for the carbon source and < or =50-microg ml(-1) Mn2+ for the metal additive. The culture conditions were optimized as 25 degrees C and pH 5-6. Conidial thermotolerance decreased remarkably when sucrose and Fe3+ or Cu2+ were used in the cultures, but altered slightly when 50-200-microg ml(-1) Zn2+ were included. The tolerance of B. bassiana conidia to the thermal stress was significantly affected by the medium composition and culture conditions under which the conidia were produced. Proper treatment of small grains as mass production substrates for more glucose release and supplement of glucose or 50-microg ml(-1) Mn2+ are possible means to enhancing conidial thermotolerance and field persistence for improved insect control.

Long-term viability and differentiation of bovine oviductal monolayers: bidimensional versus three-dimensional culture.

PubMed

Gualtieri, R; Mollo, V; Braun, S; Barbato, V; Fiorentino, I; Talevi, R

2012-10-15

Different in vitro models have been developed to study the interaction of gametes and embryos with the maternal tract. In cattle, the interaction of the oviduct with gametes and embryos have been classically studied using oviductal explants or monolayers (OMs). Explants are well differentiated but have to be used within 24 h after collection, whereas OMs can be used for a longer time after cell confluence but dedifferentiate during culture, losing cell polarity and ciliation. Herein, OMs were cultured either in M199 plus 10% fetal calf serum or in a semidefined culture medium (Gray's medium), in an immersed condition on collagen-coated coated microporous polyester or polycarbonate inserts under air-liquid interface conditions. The influence of culture conditions on long-term viability and differentiation of OMs was evaluated through scanning electron microscopy, localization of centrin and tubulin at the confocal laser scanning microscope, and assessment of maintenance of viability of sperm bound to OMs. Findings demonstrated that OMs cultured in an immersed condition with Gray's medium retain a better morphology, do not exhibit signs of crisis at least until 3 wks postconfluence, and maintain the viability of bound sperm significantly better than parallel OMs cultured in M199 plus 10% fetal calf serum. OM culture with Gray's medium in air-liquid interface conditions on porous inserts promotes cell polarity, ciliation, and maintenance of bound sperm viability at least until 3 wks postconfluence. In conclusion, oviduct culture in Gray's medium in an immersed or air-liquid condition allows long-term culture and, in the latter case, also ciliation of bovine OMs, and may represent in vitro systems that mimick more closely the biological processes modulated by the oviduct in vivo. Copyright © 2012 Elsevier Inc. All rights reserved.

Practical methods for handling human periodontal ligament stem cells in serum-free and serum-containing culture conditions under hypoxia: implications for regenerative medicine.

PubMed

Murabayashi, Dai; Mochizuki, Mai; Tamaki, Yuichi; Nakahara, Taka

2017-07-01

Stem cell-based therapies depend on the reliable expansion of patient-derived mesenchymal stem cells (MSCs) in vitro. The supplementation of cell culture media with serum is associated with several risks; accordingly, serum-free media are commercially available for cell culture. Furthermore, hypoxia is known to accelerate the expansion of MSCs. The present study aimed to characterize the properties of periodontal ligament-derived MSCs (PDLSCs) cultivated in serum-free and serum-containing media, under hypoxic and normoxic conditions. Cell growth, gene and protein expression, cytodifferentiation potential, genomic stability, cytotoxic response, and in vivo hard tissue generation of PDLSCs were examined. Our findings indicated that cultivation in serum-free medium does not affect the MSC phenotype or chromosomal stability of PDLSCs. PDLSCs expanded in serum-free medium exhibited more active growth than in fetal bovine serum-containing medium. We found that hypoxia does not alter the cell growth of PDLSCs under serum-free conditions, but inhibits their osteogenic and adipogenic cytodifferentiation while enabling maintenance of their multidifferentiation potential regardless of the presence of serum. PDLSCs expanded in serum-free medium were found to retain common MSC characteristics, including the capacity for hard tissue formation in vivo. However, PDLSCs cultured in serum-free culture conditions were more susceptible to damage following exposure to extrinsic cytotoxic stimuli than those cultured in medium supplemented with serum, suggesting that serum-free culture conditions do not exert protective effects against cytotoxicity on PDLSC cultures. The present work provides a comparative evaluation of cell culture in serum-free and serum-containing media, under hypoxic and normoxic conditions, for applications in regenerative medicine.

Lung perfusion measured using magnetic resonance imaging: New tools for physiological insights into the pulmonary circulation.

PubMed

Hopkins, Susan R; Prisk, G Kim

2010-12-01

Since the lung receives the entire cardiac output, sophisticated imaging techniques are not required in order to measure total organ perfusion. However, for many years studying lung function has required physiologists to consider the lung as a single entity: in imaging terms as a single voxel. Since imaging, and in particular functional imaging, allows the acquisition of spatial information important for studying lung function, these techniques provide considerable promise and are of great interest for pulmonary physiologists. In particular, despite the challenges of low proton density and short T2* in the lung, noncontrast MRI techniques to measure pulmonary perfusion have several advantages including high reliability and the ability to make repeated measurements under a number of physiologic conditions. This brief review focuses on the application of a particular arterial spin labeling (ASL) technique, ASL-FAIRER (flow sensitive inversion recovery with an extra radiofrequency pulse), to answer physiologic questions related to pulmonary function in health and disease. The associated measurement of regional proton density to correct for gravitational-based lung deformation (the "Slinky" effect (Slinky is a registered trademark of Pauf-Slinky incorporated)) and issues related to absolute quantification are also discussed. Copyright © 2010 Wiley-Liss, Inc.

Occupational lung diseases in Australia.

PubMed

Hoy, Ryan F; Brims, Fraser

2017-11-20

Occupational exposures are an important determinant of respiratory health. International estimates note that about 15% of adult-onset asthma, 15% of chronic obstructive pulmonary disease and 10-30% of lung cancer may be attributable to hazardous occupational exposures. One-quarter of working asthmatics either have had their asthma caused by work or adversely affected by workplace conditions. Recently, cases of historical occupational lung diseases have been noted to occur with new exposures, such as cases of silicosis in workers fabricating kitchen benchtops from artificial stone products. Identification of an occupational cause of a lung disease can be difficult and requires maintaining a high index of suspicion. When an occupational lung disease is identified, this may facilitate a cure and help to protect coworkers. Currently, very little information is collected regarding actual cases of occupational lung diseases in Australia. Most assumptions about many occupational lung diseases are based on extrapolation from overseas data. This lack of information is a major impediment to development of targeted interventions and timely identification of new hazardous exposures. All employers, governments and health care providers in Australia have a responsibility to ensure that the highest possible standards are in place to protect workers' respiratory health.

Modeling of lung cancer risk due to radon exhalation of granite stone in dwelling houses.

PubMed

Abbasi, Akbar

2017-01-01

Due to increasing occurrences of lung cancer, radon exhalation rates, radon concentrations, and lung cancer risks in several types of commonly used granite stone, samples used for flooring in buildings, have been investigated. We measured the radon exhalation rates due to granite stones by means of an AlphaGUARD Model PQ2000 in a cube container with changeable floor by various granite stones. The lung cancer risk and percentage of lung cancer deaths (LCRn) due to those conditions were calculated using Darby's model. The radon exhalation rates ranged from 1.59 ± 0.41 to 9.43 ± 0.74 Bq/m 2/h. The radon concentrations in the standard room with poor and normal ventilation were calculated 20.10-71.09 Bq/m 3 and 16.12-47.01 Bq/m 3, respectively. 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.

Ocular complications in patients with lung transplants.

PubMed

Tarabishy, Ahmad B; Khatib, Omar F; Nocero, John R; Budev, Marie; Kaiser, Peter K

2011-09-01

To describe infectious and non-infectious ocular complications found in patients with lung transplants. 545 patients underwent lung transplantation from January 1998 to September 2008 at the Cleveland Clinic. Patients who underwent ophthalmic examination at the Cole Eye Institute after lung transplantation were included in the study. Diagnoses, treatments, surgeries, laboratory parameters of immune status and patient survival were examined. Of the 545 patients who received a lung transplant during the study period at the Cleveland Clinic, 46 (8.4%) patients underwent ophthalmology examination after a lung transplant. The most common ocular finding was posterior subcapsular cataract, found in 13/46 (28.3%) patients. Infectious ocular complications were present in 6/46 patients (13.0%) including fungal infections (rhino-orbital mucormycosis (n=1), disseminated Pseudallescheria boydii infection (n=2)), cytomegalovirus retinitis (n=1), varicella-zoster virus keratouveitis (n=1) and herpes zoster ophthalmicus (n=1). Five of six patients with infectious ocular complications died within 6 months of evaluation. Decreased absolute lymphocyte count was associated with infectious ocular complications (p=0.014). Many ocular conditions can occur in patients with lung transplants. Ocular infectious complications were uncommon but may be associated with increased mortality.

Restoration of longitudinal laser tomography target image from inhomogeneous medium degradation under common conditions.

PubMed

Yi, WenJun; Wang, Ping; Fu, MeiCheng; Tan, JiChun; Zhu, Jubo; Li, XiuJian

2017-07-10

In order to overcome the shortages of the target image restoration method for longitudinal laser tomography using self-calibration, a more general restoration method through backscattering medium images associated with prior parameters is developed for common conditions. The system parameters are extracted from pre-calibration, and the LIDAR ratio is estimated according to the medium types. Assisted by these prior parameters, the degradation caused by inhomogeneous turbid media can be established with the backscattering medium images, which can further be used for removal of the interferences of turbid media. The results of simulations and experiments demonstrate that the proposed image restoration method can effectively eliminate the inhomogeneous interferences of turbid media and achieve exactly the reflectivity distribution of targets behind inhomogeneous turbid media. Furthermore, the restoration method can work beyond the limitation of the previous method that only works well under the conditions of localized turbid attenuations and some types of targets with fairly uniform reflectivity distributions.

The emerging role of myeloid-derived suppressor cells in lung diseases.

PubMed

Kolahian, Saeed; Öz, Hasan Halit; Zhou, Benyuan; Griessinger, Christoph M; Rieber, Nikolaus; Hartl, Dominik

2016-03-01

Myeloid-derived suppressor cells (MDSCs) are innate immune cells characterised by their potential to control T-cell responses and to dampen inflammation. While the role of MDSCs in cancer has been studied in depth, our understanding of their relevance for infectious and inflammatory disease conditions has just begun to evolve. Recent studies highlight an emerging and complex role for MDSCs in pulmonary diseases. In this review, we discuss the potential contribution of MDSCs as biomarkers and therapeutic targets in lung diseases, particularly lung cancer, tuberculosis, chronic obstructive pulmonary disease, asthma and cystic fibrosis. Copyright ©ERS 2016.