Comparison of cell counting methods in rodent pulmonary toxicity studies: automated and manual protocols and considerations for experimental design

PubMed Central

Zeidler-Erdely, Patti C.; Antonini, James M.; Meighan, Terence G.; Young, Shih-Houng; Eye, Tracy J.; Hammer, Mary Ann; Erdely, Aaron

2016-01-01

Pulmonary toxicity studies often use bronchoalveolar lavage (BAL) to investigate potential adverse lung responses to a particulate exposure. The BAL cellular fraction is counted, using automated (i.e. Coulter Counter®), flow cytometry or manual (i.e. hemocytometer) methods, to determine inflammatory cell influx. The goal of the study was to compare the different counting methods to determine which is optimal for examining BAL cell influx after exposure by inhalation or intratracheal instillation (ITI) to different particles with varying inherent pulmonary toxicities in both rat and mouse models. General findings indicate that total BAL cell counts using the automated and manual methods tended to agree after inhalation or ITI exposure to particle samples that are relatively nontoxic or at later time points after exposure to a pneumotoxic particle when the response resolves. However, when the initial lung inflammation and cytotoxicity was high after exposure to a pneumotoxic particle, significant differences were observed when comparing cell counts from the automated, flow cytometry and manual methods. When using total BAL cell count for differential calculations from the automated method, depending on the cell diameter size range cutoff, the data suggest that the number of lung polymorphonuclear leukocytes (PMN) varies. Importantly, the automated counts, regardless of the size cutoff, still indicated a greater number of total lung PMN when compared with the manual method, which agreed more closely with flow cytometry. The results suggest that either the manual method or flow cytometry would be better suited for BAL studies where cytotoxicity is an unknown variable. PMID:27251196

Comparison of cell counting methods in rodent pulmonary toxicity studies: automated and manual protocols and considerations for experimental design.

PubMed

Zeidler-Erdely, Patti C; Antonini, James M; Meighan, Terence G; Young, Shih-Houng; Eye, Tracy J; Hammer, Mary Ann; Erdely, Aaron

2016-08-01

Pulmonary toxicity studies often use bronchoalveolar lavage (BAL) to investigate potential adverse lung responses to a particulate exposure. The BAL cellular fraction is counted, using automated (i.e. Coulter Counter®), flow cytometry or manual (i.e. hemocytometer) methods, to determine inflammatory cell influx. The goal of the study was to compare the different counting methods to determine which is optimal for examining BAL cell influx after exposure by inhalation or intratracheal instillation (ITI) to different particles with varying inherent pulmonary toxicities in both rat and mouse models. General findings indicate that total BAL cell counts using the automated and manual methods tended to agree after inhalation or ITI exposure to particle samples that are relatively nontoxic or at later time points after exposure to a pneumotoxic particle when the response resolves. However, when the initial lung inflammation and cytotoxicity was high after exposure to a pneumotoxic particle, significant differences were observed when comparing cell counts from the automated, flow cytometry and manual methods. When using total BAL cell count for differential calculations from the automated method, depending on the cell diameter size range cutoff, the data suggest that the number of lung polymorphonuclear leukocytes (PMN) varies. Importantly, the automated counts, regardless of the size cutoff, still indicated a greater number of total lung PMN when compared with the manual method, which agreed more closely with flow cytometry. The results suggest that either the manual method or flow cytometry would be better suited for BAL studies where cytotoxicity is an unknown variable.

Specificity and sensitivity of noninvasive measurement of pulmonary vascular protein leak.

PubMed

Dauber, I M; Pluss, W T; VanGrondelle, A; Trow, R S; Weil, J V

1985-08-01

Noninvasive techniques employing external counting of radiolabeled protein have the potential for measuring pulmonary vascular protein permeability, but their specificity and sensitivity remain unclear. We tested the specificity and sensitivity of a double-radioisotope method by injecting radiolabeled albumin (131I) and erythrocytes (99mTc) into anesthetized dogs and measuring the counts of each isotope for 150 min after injection with an external gamma probe fixed over the lung. We calculated the rate of increase of albumin counts measured by the probe (which reflects the rate at which protein leaks into the extravascular space). To assess permeability we normalized the rate of increase in albumin counts for changes in labeled erythrocyte signal to minimize influence of changes in vascular surface area and thus derived an albumin leak index. We measured the albumin leak index and gravimetric lung water during hydrostatic edema (acutely elevating left atrial pressure by left atrial balloon inflation: mean pulmonary arterial wedge pressure = 22.6 Torr) and in lung injury edema induced by high- (1.0 g/kg) and low-dose (0.25 g/kg) intravenous thiourea. To test specificity we compared hydrostatic and high-dose thiourea edema. The albumin leak index increased nearly fourfold from control after thiourea injury (27.2 +/- 2.3 X 10-4 vs. 7.6 +/- 0.9 X 10-4 min-1) but did not change from control levels after elevating left atrial pressure (8.9 +/- 1.2 X 10-4 min-1) despite comparable increases in gravimetric lung water. To test sensitivity we compared low-dose thiourea with controls. Following low-dose thiourea, the albumin leak index nearly doubled despite the absence of a measurable increase in lung water. We conclude that a noninvasive double radioisotope measurement of pulmonary vascular protein leak, employing external counting techniques and a simplified method of calculation, is specific for lung injury and is also sensitive enough to detect lung injury insufficient to produce detectable pulmonary edema.

Deposition in the distal parts of the bovine respiratory tract: assessment of equipment suitable for drug inhalation.

PubMed

Genicot, B; Votion, D; Munsters, K; Close, R; Lindsey, J K; Lekeux, P

1996-03-30

The efficiency of equipment suitable for the inhalation of drugs by calves was assessed in six animals which inhaled radioisotopically labelled particles while suffering from reversible diffuse bronchoconstriction induced experimentally with 5-hydroxytryptamine and while they were breathing normally. Respiratory rates and data from pulmonary function tests and scintiscans were recorded during both investigations. After the first investigation, a mean (se) wash-out period of 9.8 (3.2) days was allowed. Under diffuse bronchoconstriction, the respiratory rate, the oscillatory resistance and the compliance of the respiratory system reached 282.1 (22.0), 161.1 (10.8) and 68.8 (2.7) per cent of their respective baseline values. When the calves were breathing normally these parameters did not change over time. The ratios (Cp/Ct) of the counts of gamma-disintegrations in the peripheral part (Cp) of the lungs and in the total lung area (Ct) were not significantly different when comparing the results from the two investigations. The ratios of Cp/Ct in the left lungs did not differ significantly from those in the right lungs.

Association Between White Blood Cell Count Following Radiation Therapy With Radiation Pneumonitis in Non-Small Cell Lung Cancer

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

Tang, Chad; Gomez, Daniel R.; Wang, Hongmei

Purpose: Radiation pneumonitis (RP) is an inflammatory response to radiation therapy (RT). We assessed the association between RP and white blood cell (WBC) count, an established metric of systemic inflammation, after RT for non-small cell lung cancer. Methods and Materials: We retrospectively analyzed 366 patients with non-small cell lung cancer who received ≥60 Gy as definitive therapy. The primary endpoint was whether WBC count after RT (defined as 2 weeks through 3 months after RT completion) was associated with grade ≥3 or grade ≥2 RP. Median lung volume receiving ≥20 Gy (V{sub 20}) was 31%, and post-RT WBC counts rangedmore » from 1.7 to 21.2 × 10{sup 3} WBCs/μL. Odds ratios (ORs) associating clinical variables and post-RT WBC counts with RP were calculated via logistic regression. A recursive-partitioning algorithm was used to define optimal post-RT WBC count cut points. Results: Post-RT WBC counts were significantly higher in patients with grade ≥3 RP than without (P<.05). Optimal cut points for post-RT WBC count were found to be 7.4 and 8.0 × 10{sup 3}/μL for grade ≥3 and ≥2 RP, respectively. Univariate analysis revealed significant associations between post-RT WBC count and grade ≥3 (n=46, OR=2.6, 95% confidence interval [CI] 1.4‒4.9, P=.003) and grade ≥2 RP (n=164, OR=2.0, 95% CI 1.2‒3.4, P=.01). This association held in a stepwise multivariate regression. Of note, V{sub 20} was found to be significantly associated with grade ≥2 RP (OR=2.2, 95% CI 1.2‒3.4, P=.01) and trended toward significance for grade ≥3 RP (OR=1.9, 95% CI 1.0-3.5, P=.06). Conclusions: Post-RT WBC counts were significantly and independently associated with RP and have potential utility as a diagnostic or predictive marker for this toxicity.« less

Heterogeneity of Particle Deposition by Pixel Analysis of 2D Gamma Scintigraphy Images

PubMed Central

Xie, Miao; Zeman, Kirby; Hurd, Harry; Donaldson, Scott

2015-01-01

Abstract Background: Heterogeneity of inhaled particle deposition in airways disease may be a sensitive indicator of physiologic changes in the lungs. Using planar gamma scintigraphy, we developed new methods to locate and quantify regions of high (hot) and low (cold) particle deposition in the lungs. Methods: Initial deposition and 24 hour retention images were obtained from healthy (n=31) adult subjects and patients with mild cystic fibrosis lung disease (CF) (n=14) following inhalation of radiolabeled particles (Tc99m-sulfur colloid, 5.4 μm MMAD) under controlled breathing conditions. The initial deposition image of the right lung was normalized to (i.e., same median pixel value), and then divided by, a transmission (Tc99m) image in the same individual to obtain a pixel-by-pixel ratio image. Hot spots were defined where pixel values in the deposition image were greater than 2X those of the transmission, and cold spots as pixels where the deposition image was less than 0.5X of the transmission. The number ratio (NR) of the hot and cold pixels to total lung pixels, and the sum ratio (SR) of total counts in hot pixels to total lung counts were compared between healthy and CF subjects. Other traditional measures of regional particle deposition, nC/P and skew of the pixel count histogram distribution, were also compared. Results: The NR of cold spots was greater in mild CF, 0.221±0.047(CF) vs. 0.186±0.038 (healthy) (p<0.005) and was significantly correlated with FEV1 %pred in the patients (R=−0.70). nC/P (central to peripheral count ratio), skew of the count histogram, and hot NR or SR were not different between the healthy and mild CF patients. Conclusions: These methods may provide more sensitive measures of airway function and localization of deposition that might be useful for assessing treatment efficacy in these patients. PMID:25393109

Radiolabel ratio method for measuring pulmonary clearance of intratracheal bacterial challenges

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

LaForce, F.M.; Boose, D.S.

Calculation of bacterial clearance is a fundamental step in any study of in situ lung antibacterial defenses. A method is described whereby about 85% of a radiolabeled bacterial inoculum was consistently introduced into the bronchopulmonary tree of a mouse by the intratracheal route. Mice were then killed 1 and 4 hours later; their lungs were removed aseptically and homogenized, and viable bacteria and radiolabel counts were determined. Radiolabel counts fell slowly, and more than 80% of the original radiolabel was still present in homogenized lung samples from animals sacrificed 4 hours after challenge. Bacteria/isotope ratios for the bacterial inoculum andmore » homogenized lung samples from animals sacrificed immediately after challenge were very similar. Bacterial clearance values were the same whether computed from bacterial counts alone or according to a radiolabel ratio method whereby the change in the bacteria/isotope ratio in ground lung aliquots was divided by a similar ratio from bacteria used to inoculate animals. Some contamination resulted from oral streptococci being swept into the bronchopulmonary free during the aspiration process. This contamination was not a problem when penicillin was incorporated into the agar and penicillin-resistant strains were used for the bacterial challenges.« less

Risk Factors Associated with Quantitative Evidence of Lung Emphysema and Fibrosis in an HIV-infected Cohort

PubMed Central

Leader, Joseph K.; Crothers, Kristina; Huang, Laurence; King, Mark A.; Morris, Alison; Thompson, Bruce W.; Flores, Sonia C.; Drummond, M. Bradley; Rom, William N.; Diaz, Philip T.

2015-01-01

Introduction The disease spectrum for HIV-infected individuals has shifted towards co-morbid non-AIDS conditions including chronic lung disease, but quantitative image analysis of lung disease has not been performed. Objectives To quantify the prevalence of structural changes of the lung indicating emphysema or fibrosis on radiographic examination. Methods A cross-sectional analysis of 510 HIV-infected participants in the multi-center Lung-HIV study was performed. Data collected included: demographics, biological markers of HIV, pulmonary function testing, and chest CT examinations. Emphysema and fibrosis-like changes were quantified on CT images based on threshold approaches. Results In our cohort: 69% was on antiretroviral therapy, 13% had a current CD4 cell count less than 200 cells/μL, 39% had an HIV viral load greater than 500 copies/mL, 25% had at least a trace level of emphysema (defined as >2.5% of voxels <-950HU). Trace emphysema was significantly correlated with age, smoking, and pulmonary function. Neither current CD4 cell count nor HIV viral load was significantly correlated with emphysema. Fibrosis-like changes were detected in 29% of the participants and were significantly correlated with HIV viral load (Pearson correlation coefficient = 0.210, p<0.05); current CD4 cell count was not associated with fibrosis. In multivariable analyses including age, race, and smoking status, HIV viral load remained significantly correlated with fibrosis-like changes (coefficient = 0.107, P = 0.03). Conclusion A higher HIV viral load was significantly associated with fibrosis-like changes possibly indicating early interstitial lung disease, but emphysematous changes were not related to current CD4 cell count or HIV viral load. PMID:26914911

Role of circulating granulocytes in sheep lung injury produced by phorbol myristate acetate.

PubMed

Dyer, E L; Snapper, J R

1986-02-01

Phorbol myristate acetate (PMA) and endotoxin cause pulmonary granulocyte sequestration and alteration in lung fluid and solute exchange in awake sheep that are felt to be analogous to the adult respiratory distress syndrome in humans. The basic hypothesis that PMA causes lung injury by activating circulating granulocytes has never been tested. The effects of infused PMA on lung mechanics and the cellular constituents of lung lymph have also not been reported. We therefore characterized the effects of intravenous PMA, 5 micrograms/kg, on lung mechanics, pulmonary hemodynamics, lung fluid and solute exchange, pulmonary gas exchange, blood and lymph leukocyte counts, and plasma and lymph cyclooxygenase products of arachidonate metabolism in 10 awake sheep with normal granulocyte counts and after granulocyte depletion with hydroxyurea. PMA significantly altered lung mechanics from base line in both nongranulocyte depleted and granulocyte-depleted sheep. Dynamic compliance decreased by over 50% and resistance to airflow across the lungs increased over threefold acutely following PMA infusion in both sets of experiments. Changes in lung mechanics, pulmonary hemodynamics, lung fluid and solute exchange, pulmonary gas exchange, and plasma and lymph arachidonate metabolites were not significantly affected by greater than 99% depletion of circulating granulocytes. We conclude that the lung injury caused by PMA in chronically instrumented awake sheep probably is not a result of activation of circulating granulocytes.

Gallium-67 activity in bronchoalveolar lavage fluid in sarcoidosis

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

Trauth, H.A.; Heimes, K.; Schubotz, R.

1986-01-01

Roentgenograms and gallium-67 scans and gallium-67 counts of BAL fluid samples, together with differential cell counts, have proved to be useful in assessing activity and lung involvement in sarcoidosis. In active pulmonary sarcoidosis gallium-67 scans are usually positive. Quantitation of gallium-67 uptake in lung scans, however, may be difficult. Because gallium-67 uptake and cell counts in BAL fluid may be correlated, we set out to investigate gallium-67 activity in BAL fluid recovered from patient of different groups. Sixteen patients with recently diagnosed and untreated sarcoidosis, nine patients with healthy lungs, and five patients with CFA were studied. Gallium-67 uptake ofmore » the lung, gallium-67 activity in the lavage fluid, SACE and LACE levels, and alpha 1-AT activity were measured. Significantly more gallium-67 activity was found in BAL fluid from sarcoidosis patients than in that from CFA patients (alpha = .001) or patients with healthy lungs (alpha = .001). Gallium-67 activity in BAL fluid could be well correlated with the number of lymphocytes in BAL fluid, but poorly with the number of macrophages. Subjects with increased levels of SACE or serum alpha 1-AT showed higher lavage gallium-67 activity than did normals, but no correlation could be established. High gallium-67 activity in lavage fluid may be correlated with acute sarcoidosis or physiological deterioration; low activity denotes change for the better. The results show that gallium-67 counts in BAL fluid reflects the intensity of gallium-67 uptake and thus of activity of pulmonary sarcoidosis.« less

Growth of alveoli during postnatal development in humans based on stereological estimation.

PubMed

Herring, Matt J; Putney, Lei F; Wyatt, Gregory; Finkbeiner, Walter E; Hyde, Dallas M

2014-08-15

Alveolarization in humans and nonhuman primates begins during prenatal development. Advances in stereological counting techniques allow accurate assessment of alveolar number; however, these techniques have not been applied to the developing human lung. Based on the recent American Thoracic Society guidelines for stereology, lungs from human autopsies, ages 2 mo to 15 yr, were fractionated and isometric uniform randomly sampled to count the number of alveoli. The number of alveoli was compared with age, weight, and height as well as growth between right and left lungs. The number of alveoli in the human lung increased exponentially during the first 2 yr of life but continued to increase albeit at a reduced rate through adolescence. Alveolar numbers also correlated with the indirect radial alveolar count technique. Growth curves for human alveolarization were compared using historical data of nonhuman primates and rats. The alveolar growth rate in nonhuman primates was nearly identical to the human growth curve. Rats were significantly different, showing a more pronounced exponential growth during the first 20 days of life. This evidence indicates that the human lung may be more plastic than originally thought, with alveolarization occurring well into adolescence. The first 20 days of life in rats implies a growth curve that may relate more to prenatal growth in humans. The data suggest that nonhuman primates are a better laboratory model for studies of human postnatal lung growth than rats. Copyright © 2014 the American Physiological Society.

[Effect of intravenous treatment with OK-432 on the bone marrow in patients with lung cancer].

PubMed

Fujii, M; Ishikawa, M; Toki, H

1984-03-01

We studied effects of OK-432 on the bone marrow and peripheral blood cells of lung cancer patients. The nuclear cell count of bone marrow increased in 5 to 7 patients upon intravenous treatment with OK-432 compared with 3 of 6 patients who were intramuscularly treated with OK-432. Serial neutrophil counts of bone marrow increased in all 7 patients treated intravenously compared with 3 of 6 patients treated intramuscularly. The mean nuclear cell count or the serial neutrophil count of bone marrow in intravenously treated patients was significantly higher than the pretreatment values (p less than 0.001). In the peripheral blood picture, the difference in white blood cells or neutrophils before and after intravenous treatment was also statistically significant (p less than 0.01). There was no change in the erythrocytic series count of bone marrow and the hemoglobin count. Our results support the superiority of intravenous OK-432 treatment over intramuscular treatment in the growth-accelerating effect on bone marrow cells, especially regarding the neutrophil series.

Prediction of post-operative pulmonary function after lobectomy for primary lung cancer: A comparison among counting method, effective lobar volume, and lobar collapsibility using inspiratory/expiratory CT.

PubMed

Yabuuchi, Hidetake; Kawanami, Satoshi; Kamitani, Takeshi; Yonezawa, Masato; Yamasaki, Yuzo; Yamanouchi, Torahiko; Nagao, Michinobu; Okamoto, Tatsuro; Honda, Hiroshi

2016-11-01

To compare the predictabilities of postoperative pulmonary function after lobectomy for primary lung cancer among counting method, effective lobar volume, and lobar collapsibility. Forty-nine patients who underwent lobectomy for primary lung cancer were enrolled. All patients underwent inspiratory/expiratory CT and pulmonary function tests 2 weeks before surgery and postoperative pulmonary function tests 6-7 months after surgery. Pulmonary function losses (ΔFEV 1.0 and ΔVC) were calculated from the pulmonary function tests. Predictive postoperative pulmonary function losses (ppoΔFEV 1.0 and ppoΔVC) were calculated using counting method, effective volume, and lobar collapsibility. Correlations and agreements between ΔFEV 1.0 and ppoFEV 1.0 and those between ΔVC and ppoΔVC were tested among three methods using Spearman's correlation coefficient and Bland-Altman plots. ΔFEV 1.0 and ppoΔFEV 1.0insp-exp were strongly correlated (r=0.72), whereas ΔFEV 1.0 and ppoΔFEV 1.0count and ΔFEV 1.0 and Pred. ΔFEV 1.0eff.vol. were moderately correlated (r=0.50, 0.56). ΔVC and ppoΔVC eff.vol. (r=0.71) were strongly correlated, whereas ΔVC and ppoΔVC count , and ΔVC and ppoΔVC insp-exp were moderately correlated (r=0.55, 0.42). Volumetry from inspiratory/expiratory CT data could be useful to predict postoperative pulmonary function after lobectomy for primary lung cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Variations in neutrophil count in preterm infants with respiratory distress syndrome who subsequently developed chronic lung disease.

PubMed

Kohelet, D; Arbel, E; Ballin, A; Goldberg, M

2000-01-01

Neutrophil counts were studied in 62 preterm infants receiving mechanical ventilation for neonatal respiratory distress syndrome (NRDS). Exploratory analysis indicated that the severity of NRDS, as demonstrated by fractional inspired oxygen (FiO2), mean airway pressure (MAP), arterial-alveolar PO2 ratio (a/APO2) and oxygenation index (OI), was correlated with percentage change of neutrophil counts during the first 5 days of life. Further analysis demonstrated that infants with NRDS who subsequently developed chronic lung disease (CLD) (n = 21) had statistically significant differences in variation of neutrophil counts when compared with the remainder (n = 41) without CLD (-35.0% +/- 4.3 vs. -16.9% +/- 5.8, p < 0.02). It is concluded that significant variations in neutrophil counts during the first 5 days of life may be found in infants with NRDS who subsequently develop CLD and that these changes may have predictive value regarding the development of CLD.

Hemodynamic and inflammatory responses following transumbilical and transthoracic lung wedge resection in a live canine model.

PubMed

Lu, Hung-Yi; Chu, Yen; Wu, Yi-Cheng; Liu, Chien-Ying; Hsieh, Ming-Ju; Chao, Yin-Kai; Wu, Ching-Yang; Yuan, Hsu-Chia; Ko, Po-Jen; Liu, Yun-Hen; Liu, Hui-Ping

2015-04-01

Single-port transumbilical surgery is a well-established platform for minimally invasive abdominal surgery. The aim of this study was to compare the hemodynamics and inflammatory response of a novel transumbilical technique with that of a conventional transthoracic technique in thoracic exploration and lung resection in a canine model. Sixteen dogs were randomly assigned to undergo transumbilical thoracoscopy (n = 8) or standard thoracoscopy (n = 8). Animals in the umbilical group received lung resection via a 3-cm transumbilical incision in combination with a 2.5-cm transdiaphragmatic incision. Animals in the standard thoracoscopy group underwent lung resection via a 3-cm thoracic incision. Hemodynamic parameters (e.g., mean arterial pressure, heart rate, cardiac index, systemic vascular resistance, and global end-diastolic volume index) and inflammatory parameters (e.g., neutrophil count, neutrophil 2',7' -dichlorohydrofluorescein [DCFH] expression, monocyte count, monocyte inducible nitric oxide synthase expression, total lymphocyte count, CD4+ and CD8+ lymphocyte counts, the CD4+/CD8+ratio, plasma Creactive protein level, interleukin-6 level) were evaluated before surgery, during the operation, and on postoperative days 1, 3, 7, and 14. Lung resections were successfully performed in all 16 animals. There were 2 surgery-related mortality complications (1 animal in each group). In the transumbilical group, 1 death was caused by early extubation before the animal fully recovered from the anesthesia. In the thoracoscopic group, 1 death was caused by respiratory distress and the complication of sepsis at 5 days after surgery. There was no significant difference between the two techniques with regard to the hemodynamic and immunologic impact of the surgeries. This study suggests that the hemodynamic and inflammatory changes with endoscopic lung resection performed by the transumbilical approach are comparable to those after using the conventional transthoracic approach. This information is novel and relevant for surgeons interested in developing new surgical techniques in minimally invasive surgery. Copyright © 2015 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Diverse Profiles of Ricin-Cell Interactions in the Lung Following Intranasal Exposure to Ricin

PubMed Central

Sapoznikov, Anita; Falach, Reut; Mazor, Ohad; Alcalay, Ron; Gal, Yoav; Seliger, Nehama; Sabo, Tamar; Kronman, Chanoch

2015-01-01

Ricin, a plant-derived exotoxin, inhibits protein synthesis by ribosomal inactivation. Due to its wide availability and ease of preparation, ricin is considered a biothreat, foremost by respiratory exposure. We examined the in vivo interactions between ricin and cells of the lungs in mice intranasally exposed to the toxin and revealed multi-phasic cell-type-dependent binding profiles. While macrophages (MΦs) and dendritic cells (DCs) displayed biphasic binding to ricin, monophasic binding patterns were observed for other cell types; epithelial cells displayed early binding, while B cells and endothelial cells bound toxin late after intoxication. Neutrophils, which were massively recruited to the intoxicated lung, were refractive to toxin binding. Although epithelial cells bound ricin as early as MΦs and DCs, their rates of elimination differed considerably; a reduction in epithelial cell counts occurred late after intoxication and was restricted to alveolar type II cells only. The differential binding and cell-elimination patterns observed may stem from dissimilar accessibility of the toxin to different cells in the lung and may also reflect unequal interactions of the toxin with different cell-surface receptors. The multifaceted interactions observed in this study between ricin and the various cells of the target organ should be considered in the future development of efficient post-exposure countermeasures against ricin intoxication. PMID:26593946

Diverse profiles of ricin-cell interactions in the lung following intranasal exposure to ricin.

PubMed

Sapoznikov, Anita; Falach, Reut; Mazor, Ohad; Alcalay, Ron; Gal, Yoav; Seliger, Nehama; Sabo, Tamar; Kronman, Chanoch

2015-11-17

Ricin, a plant-derived exotoxin, inhibits protein synthesis by ribosomal inactivation. Due to its wide availability and ease of preparation, ricin is considered a biothreat, foremost by respiratory exposure. We examined the in vivo interactions between ricin and cells of the lungs in mice intranasally exposed to the toxin and revealed multi-phasic cell-type-dependent binding profiles. While macrophages (MΦs) and dendritic cells (DCs) displayed biphasic binding to ricin, monophasic binding patterns were observed for other cell types; epithelial cells displayed early binding, while B cells and endothelial cells bound toxin late after intoxication. Neutrophils, which were massively recruited to the intoxicated lung, were refractive to toxin binding. Although epithelial cells bound ricin as early as MΦs and DCs, their rates of elimination differed considerably; a reduction in epithelial cell counts occurred late after intoxication and was restricted to alveolar type II cells only. The differential binding and cell-elimination patterns observed may stem from dissimilar accessibility of the toxin to different cells in the lung and may also reflect unequal interactions of the toxin with different cell-surface receptors. The multifaceted interactions observed in this study between ricin and the various cells of the target organ should be considered in the future development of efficient post-exposure countermeasures against ricin intoxication.

Immunological and infectious risk factors for lung cancer in US veterans with HIV: a longitudinal cohort study.

PubMed

Sigel, Keith; Wisnivesky, Juan; Crothers, Kristina; Gordon, Kirsha; Brown, Sheldon T; Rimland, David; Rodriguez-Barradas, Maria C; Gibert, Cynthia; Goetz, Matthew Bidwell; Bedimo, Roger; Park, Lesley S; Dubrow, Robert

2017-02-01

HIV infection is independently associated with risk of lung cancer, but few data exist for the relation between longitudinal measurements of immune function and lung-cancer risk in people living with HIV. We followed up participants with HIV from the Veterans Aging Cohort Study for a minimum of 3 years between Jan 1, 1998, and Dec 31, 2012, and used cancer registry data to identify incident cases of lung cancer. The index date for each patient was the later of the date HIV care began or Jan 1, 1998. We excluded patients with less than 3 years' follow-up, prevalent diagnoses of lung cancer, or incomplete laboratory data. We used Cox regression models to investigate the relation between different time-updated lagged and cumulative exposures (CD4 cell count, CD8 cell count, CD4/CD8 ratio, HIV RNA, and bacterial pneumonia) and risk of lung cancer. Models were adjusted for age, race or ethnicity, smoking, hepatitis C virus infection, alcohol use disorders, drug use disorders, and history of chronic obstructive pulmonary disease and occupational lung disease. We identified 277 cases of incident lung cancer in 21 666 participants with HIV. In separate models for each time-updated 12 month lagged, 24 month simple moving average cumulative exposure, increased risk of lung cancer was associated with low CD4 cell count (p trend=0·001), low CD4/CD8 ratio (p trend=0·0001), high HIV RNA concentration (p=0·004), and more cumulative bacterial pneumonia episodes (12 month lag only; p trend=0·0004). In a mutually adjusted model including these factors, CD4/CD8 ratio and cumulative bacterial pneumonia episodes remained significant (p trends 0·003 and 0·004, respectively). In our large HIV cohort in the antiretroviral therapy era, we found evidence that dysfunctional immune activation and chronic inflammation contribute to the development of lung cancer in the setting of HIV infection. These findings could be used to target lung-cancer prevention measures to high-risk groups. US National Institutes of Health. Copyright © 2017 Elsevier Ltd. All rights reserved.

Excreta Sampling as an Alternative to In Vivo Measurements at the Hanford Site.

PubMed

Carbaugh, Eugene H; Antonio, Cheryl L; Lynch, Timothy P

2015-08-01

The capabilities of indirect radiobioassay by urine and fecal sample analysis were compared with the direct radiobioassay methods of whole body counting and lung counting for the most common radionuclides and inhalation exposure scenarios encountered by Hanford workers. Radionuclides addressed by in vivo measurement included 137Cs, 60Co, 154Eu, and 241Am as an indicator for plutonium mixtures. The same radionuclides were addressed using gamma energy analysis of urine samples, augmented by radiochemistry and alpha spectrometry methods for plutonium in urine and fecal samples. It was concluded that in vivo whole body counting and lung counting capability should be maintained at the Hanford Site for the foreseeable future, however, urine and fecal sample analysis could provide adequate, though degraded, monitoring capability for workers as a short-term alternative, should in vivo capability be lost due to planned or unplanned circumstances.

[Lung cancer in survivors of radiation exposure at the Chernobyl nuclear disaster].

PubMed

Zubovskiĭ, G A; Khrisanfov, S A

2003-01-01

Epidemiology, diagnostics and therapy of lung cancer in the aftermath of Chernobyl nuclear disaster are discussed on the basis of the data released by the Federal Expert Committee. Lung cancer appeared to be the main death-causing factor. The disease was far advanced (stage IIIb and IV) in 85% of cases. The effectiveness of diagnosis can be raised if such compulsory measures as annual bronchoscopic screenings and sputum counts are carried out. Atypical cell counts have to be run in the sputum samples from all the survivors who took part in the salvaging operations of 1986-1987 and are suffering acute and chronic respiratory diseases. Particular attention should be paid to those who were working under severe dust-pollution conditions in summer.

Risk factors for disseminated intravascular coagulation in patients with lung cancer.

PubMed

Nakano, Kentaro; Sugiyama, Kumiya; Satoh, Hideyuki; Shiromori, Sadaaki; Sugitate, Kei; Arifuku, Hajime; Yoshida, Naruo; Watanabe, Hiroyoshi; Tokita, Shingo; Wakayama, Tomoshige; Tatewaki, Masamitsu; Souma, Ryosuke; Koyama, Kenya; Hirata, Hirokuni; Fukushima, Yasutsugu

2018-05-31

The mortality rate from disseminated intravascular coagulation (DIC) is higher in patients with lung cancer than in non-lung cancer patients. Moreover, the prevalence of DIC varies among the pathologic types of lung cancer. This study analyzed the relationship between coagulation factors and the pathologic types of lung cancer. Twenty-six patients with progressive, inoperable stage IIB or higher lung cancer (20 men, 6 women; mean age 71 years; 11 Adeno, 10 squamous cell carcinoma, and 5 small cell carcinoma) and five healthy volunteers without respiratory disease (3 men, 2 women; mean age 72 years) were enrolled in the study. Blood samples were collected at lung cancer diagnosis, before treatment. White blood cell count, platelet count, serum C-reactive protein, fibrin/fibrinogen degradation products, fibrinogen, thrombin-antithrombin complex, and D-dimer levels differed significantly between lung cancer patients and the control group, but not among the pathologic types of lung cancer. Thrombomodulin levels were significantly higher in patients with Adeno and squamous cell carcinoma than in those with small cell carcinoma (P < 0.05 and P < 0.01, respectively). Antithrombin levels were significantly lower in patients with squamous cell carcinoma than in those with Adeno (P < 0.05). Coagulation disorders may develop secondary to chronic inflammation in patients with progressive lung cancer. DIC in lung cancer may be attributed to changes in anticoagulation factors, such as thrombomodulin and antithrombin, but not in other coagulation factors. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Quantitative computed tomography for the prediction of pulmonary function after lung cancer surgery: a simple method using simulation software.

PubMed

Ueda, Kazuhiro; Tanaka, Toshiki; Li, Tao-Sheng; Tanaka, Nobuyuki; Hamano, Kimikazu

2009-03-01

The prediction of pulmonary functional reserve is mandatory in therapeutic decision-making for patients with resectable lung cancer, especially those with underlying lung disease. Volumetric analysis in combination with densitometric analysis of the affected lung lobe or segment with quantitative computed tomography (CT) helps to identify residual pulmonary function, although the utility of this modality needs investigation. The subjects of this prospective study were 30 patients with resectable lung cancer. A three-dimensional CT lung model was created with voxels representing normal lung attenuation (-600 to -910 Hounsfield units). Residual pulmonary function was predicted by drawing a boundary line between the lung to be preserved and that to be resected, directly on the lung model. The predicted values were correlated with the postoperative measured values. The predicted and measured values corresponded well (r=0.89, p<0.001). Although the predicted values corresponded with values predicted by simple calculation using a segment-counting method (r=0.98), there were two outliers whose pulmonary functional reserves were predicted more accurately by CT than by segment counting. The measured pulmonary functional reserves were significantly higher than the predicted values in patients with extensive emphysematous areas (<-910 Hounsfield units), but not in patients with chronic obstructive pulmonary disease. Quantitative CT yielded accurate prediction of functional reserve after lung cancer surgery and helped to identify patients whose functional reserves are likely to be underestimated. Hence, this modality should be utilized for patients with marginal pulmonary function.

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

PubMed

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

2017-06-24

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

Twenty-four Years of Follow-Up for a Hanford Plutonium Wound Case

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

Carbaugh, Eugene H.; Lynch, Timothy P.; Antonio, Cheryl L.

2010-10-01

A 1985 plutonium puncture wound resulted in the initial deposition of 48 kBq of transuranic alpha activity, primarily 239Pu and 241Am, in a worker’s right index finger. Surgical excisions in the week following reduced the long-term residual wound activity to 5.4 kBq, and 164 DTPA chelation therapy administrations over a 17-month period resulted in urinary excretion of about 7 kBq. The case was published in 1988, but now 20 additional years of follow-up data are available. Annual bioassay measurements have included wound counts, skeleton counts, liver counts, lung counts, axillary lymph node counts, and urinalyses for plutonium and 241Am. Thesemore » measurements have shown relatively stable levels of 241Am at the wound site, with gradually increasing amounts of 241Am detected in the skeleton. Liver counts has shown erratic detection of 241Am, and lung counts indicate 241Am as shine from the axillary lymph nodes and skeleton. Urine excretion of 239Pu since termination of chelation therapy has typically ranged from 10 to 20 mBq d-1, with 241Am excretion being about 10% of that for 239Pu. In addition, the worker has undergone annual routine medical exams, which have not identified any adverse health effects associated with the intake.« less

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.

Mast cells in the human lung at high altitude

NASA Astrophysics Data System (ADS)

Heath, Donald

1992-12-01

Mast cell densities in the lung were measured in five native highlanders of La Paz (3600 m) and in one lowlander dying from high-altitude pulmonary oedema (HAPO) at 3440 m. Two of the highlanders were mestizos with normal pulmonary arteries and the others were Aymara Indians with muscular remodelling of their pulmonary vasculature. The aim of the investigation was to determine if accumulation of mast cells in the lung at high altitude (HA) is related to alveolar hypoxia alone, to a combination of hypoxia and muscularization of the pulmonary arterial tree, or to oedema of the lung. The lungs of four lowlanders were used as normoxic controls. The results showed that the mast cell density of the two Mestizos was in the normal range of lowlanders (0.6-8.8 cells/mm2). In the Aymara Indians the mast cell counts were raised (25.6-26.0 cells/mm2). In the lowlander dying from HAPO the mast cell count was greatly raised to 70.1 cells/mm2 lung tissue. The results show that in native highlanders an accumulation of mast cells in the lung is not related to hypoxia alone but to a combination of hypoxia and muscular remodelling of the pulmonary arteries. However, the most potent cause of increased mast cell density in the lung at high altitude appears to be high-altitude pulmonary oedema.

Prophylactic Effect of a Therapeutic Vaccine against TB Based on Fragments of Mycobacterium tuberculosis

PubMed Central

Cáceres, Neus; Pinto, Sergio; Díaz, Jorge; Cardona, Pere-Joan

2011-01-01

The prophylactic capacity of the RUTI® vaccine, based on fragmented cells of Mycobacterium tuberculosis, has been evaluated in respect to aerosol challenge with virulent bacilli. Subcutaneous vaccination significantly reduced viable bacterial counts in both lungs and spleens of C57Bl mice, when challenged 4 weeks after vaccination. RUTI® protected the spleen less than BCG. Following a 9 month vaccination-challenge interval, protection was observed for the lungs, but not for the spleen. Survival of infected guinea pigs was prolonged by vaccination given 5 weeks before challenge. Inoculations of RUTI® shortly after infection significantly reduced the viable bacterial counts in the lungs, when compared with infected control mice. Thus, vaccination by RUTI® has potential for both the prophylaxis and immunotherapy of tuberculosis. PMID:21647222

Prophylactic effect of a therapeutic vaccine against TB based on fragments of Mycobacterium tuberculosis.

PubMed

Vilaplana, Cristina; Gil, Olga; Cáceres, Neus; Pinto, Sergio; Díaz, Jorge; Cardona, Pere-Joan

2011-01-01

The prophylactic capacity of the RUTI® vaccine, based on fragmented cells of Mycobacterium tuberculosis, has been evaluated in respect to aerosol challenge with virulent bacilli. Subcutaneous vaccination significantly reduced viable bacterial counts in both lungs and spleens of C57Bl mice, when challenged 4 weeks after vaccination. RUTI® protected the spleen less than BCG. Following a 9 month vaccination-challenge interval, protection was observed for the lungs, but not for the spleen. Survival of infected guinea pigs was prolonged by vaccination given 5 weeks before challenge. Inoculations of RUTI® shortly after infection significantly reduced the viable bacterial counts in the lungs, when compared with infected control mice. Thus, vaccination by RUTI® has potential for both the prophylaxis and immunotherapy of tuberculosis.

A method for the in vivo measurement of americium-241 at long times post-exposure

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

Neton, J.W.

1988-01-01

This study investigated an improved method for the quantitative measurement, calibration and calculation of {sup 241}Am organ burdens in humans. The techniques developed correct for cross-talk or count-rate contributions from surrounding and adjacent organ burdens and assures for the proper assignment of activity to the lungs, liver and skeleton. In order to predict the net count-rates for the measurement geometries of the skull, liver and lung, a background prediction method was developed. This method utilizes data obtained from the measurement of a group of control subjects. Based on this data, a linear prediction equation was developed for each measurement geometry.more » In order to correct for the cross-contributions among the various deposition loci, a series of surrogate human phantom structures were measured. The results of measurements of {sup 241}Am depositions in six exposure cases have been evaluated using these new techniques and have indicated that lung burden estimates could be in error by as much as 100 percent when corrections are not made for contributions to the count-rate from other organs.« less

Pleural mesothelioma and lung cancer risks in relation to occupational history and asbestos lung burden

PubMed Central

Gilham, Clare; Rake, Christine; Burdett, Garry; Nicholson, Andrew G; Davison, Leslie; Franchini, Angelo; Carpenter, James; Hodgson, John; Darnton, Andrew; Peto, Julian

2016-01-01

Background We have conducted a population-based study of pleural mesothelioma patients with occupational histories and measured asbestos lung burdens in occupationally exposed workers and in the general population. The relationship between lung burden and risk, particularly at environmental exposure levels, will enable future mesothelioma rates in people born after 1965 who never installed asbestos to be predicted from their asbestos lung burdens. Methods Following personal interview asbestos fibres longer than 5 µm were counted by transmission electron microscopy in lung samples obtained from 133 patients with mesothelioma and 262 patients with lung cancer. ORs for mesothelioma were converted to lifetime risks. Results Lifetime mesothelioma risk is approximately 0.02% per 1000 amphibole fibres per gram of dry lung tissue over a more than 100-fold range, from 1 to 4 in the most heavily exposed building workers to less than 1 in 500 in most of the population. The asbestos fibres counted were amosite (75%), crocidolite (18%), other amphiboles (5%) and chrysotile (2%). Conclusions The approximate linearity of the dose–response together with lung burden measurements in younger people will provide reasonably reliable predictions of future mesothelioma rates in those born since 1965 whose risks cannot yet be seen in national rates. Burdens in those born more recently will indicate the continuing occupational and environmental hazards under current asbestos control regulations. Our results confirm the major contribution of amosite to UK mesothelioma incidence and the substantial contribution of non-occupational exposure, particularly in women. PMID:26715106

Effect of a syringe aspiration technique versus a mechanical suction technique and use of N-butylscopolammonium bromide on the quantity and quality of bronchoalveolar lavage fluid samples obtained from horses with the summer pasture endophenotype of equine asthma.

PubMed

Bowser, Jacquelyn E; Costa, Lais R R; Rodil, Alba U; Lopp, Christine T; Johnson, Melanie E; Wills, Robert W; Swiderski, Cyprianna E

2018-03-01

OBJECTIVE To evaluate the effect of 2 bronchoalveolar lavage (BAL) sampling techniques and the use of N-butylscopolammonium bromide (NBB) on the quantity and quality of BAL fluid (BALF) samples obtained from horses with the summer pasture endophenotype of equine asthma. ANIMALS 8 horses with the summer pasture endophenotype of equine asthma. PROCEDURES BAL was performed bilaterally (right and left lung sites) with a flexible videoendoscope passed through the left or right nasal passage. During lavage of the first lung site, a BALF sample was collected by means of either gentle syringe aspiration or mechanical suction with a pressure-regulated wall-mounted suction pump. The endoscope was then maneuvered into the contralateral lung site, and lavage was performed with the alternate fluid retrieval technique. For each horse, BAL was performed bilaterally once with and once without premedication with NBB (21-day interval). The BALF samples retrieved were evaluated for volume, total cell count, differential cell count, RBC count, and total protein concentration. RESULTS Use of syringe aspiration significantly increased total BALF volume (mean volume increase, 40 mL [approx 7.5% yield]) and decreased total RBC count (mean decrease, 142 cells/μL), compared with use of mechanical suction. The BALF nucleated cell count and differential cell count did not differ between BAL procedures. Use of NBB had no effect on BALF retrieval. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that retrieval of BALF by syringe aspiration may increase yield and reduce barotrauma in horses at increased risk of bronchoconstriction and bronchiolar collapse. Further studies to determine the usefulness of NBB and other bronchodilators during BAL procedures in horses are warranted.

Fluid biopsy for circulating tumor cell identification in patients with early-and late-stage non-small cell lung cancer: a glimpse into lung cancer biology

NASA Astrophysics Data System (ADS)

Wendel, Marco; Bazhenova, Lyudmila; Boshuizen, Rogier; Kolatkar, Anand; Honnatti, Meghana; Cho, Edward H.; Marrinucci, Dena; Sandhu, Ajay; Perricone, Anthony; Thistlethwaite, Patricia; Bethel, Kelly; Nieva, Jorge; van den Heuvel, Michel; Kuhn, Peter

2012-02-01

Circulating tumor cell (CTC) counts are an established prognostic marker in metastatic prostate, breast and colorectal cancer, and recent data suggest a similar role in late stage non-small cell lung cancer (NSCLC). However, due to sensitivity constraints in current enrichment-based CTC detection technologies, there are few published data about CTC prevalence rates and morphologic heterogeneity in early-stage NSCLC, or the correlation of CTCs with disease progression and their usability for clinical staging. We investigated CTC counts, morphology and aggregation in early stage, locally advanced and metastatic NSCLC patients by using a fluid-phase biopsy approach that identifies CTCs without relying on surface-receptor-based enrichment and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. HD-CTCs were analyzed in blood samples from 78 chemotherapy-naïve NSCLC patients. 73% of the total population had a positive HD-CTC count (>0 CTC in 1 mL of blood) with a median of 4.4 HD-CTCs mL-1 (range 0-515.6) and a mean of 44.7 (±95.2) HD-CTCs mL-1. No significant difference in the medians of HD-CTC counts was detected between stage IV (n = 31, range 0-178.2), stage III (n = 34, range 0-515.6) and stages I/II (n = 13, range 0-442.3). Furthermore, HD-CTCs exhibited a uniformity in terms of molecular and physical characteristics such as fluorescent cytokeratin intensity, nuclear size, frequency of apoptosis and aggregate formation across the spectrum of staging. Our results demonstrate that despite stringent morphologic inclusion criteria for the definition of HD-CTCs, the HD-CTC assay shows high sensitivity in the detection and characterization of both early- and late-stage lung cancer CTCs. Extensive studies are warranted to investigate the prognostic value of CTC profiling in early-stage lung cancer. This finding has implications for the design of extensive studies examining screening, therapy and surveillance in lung cancer patients.

Clearance of free silica in rat lungs by spraying with chinese herbal kombucha.

PubMed

Fu, Nai-Fang; Luo, Chang-Hui; Wu, Jun-Cai; Zheng, Yan-Yan; Gan, Yong-Jin; Ling, Jian-An; Liang, Heng-Qiu; Liang, Dan-Yu; Xie, Jing; Chen, Xiao-Qin; Li, Xian-Jun; Pan, Rui-Hui; Chen, Zuo-Xing; Jiang, Sheng-Jun

2013-01-01

The effects of spraying with kombucha and Chinese herbal kombucha were compared with treatments with tetrandrine in a rat silicosis model. Silica dust (50 mg) was injected into the lungs of rats, which were then treated with one of the experimental treatments for a month. The rats were then killed and the effects of the treatments were evaluated by examining the extent and severity of the histopathological lesions in the animals' lungs, measuring their organ coefficients and lung collagen contents, determining the dry and wet weights of their lungs, and measuring the free silica content of the dried lungs. In addition, lavage was performed on whole lungs taken from selected rats, and the numbers and types of cells in the lavage fluid were counted. The most effective treatment in terms of the ability to reduce lung collagen content and minimize the formation of pulmonary histopathological lesions was tetrandrine treatment, followed by Chinese herbal kombucha and non-Chinese herbal kombucha. However, the lavage fluid cell counts indicated that tetrandrine treatment had severe adverse effects on macrophage viability. This effect was much less pronounced for the kombucha and Chinese herbal kombucha treatments. Moreover, the free silica levels in the lungs of animals treated with Chinese herbal kombucha were significantly lower than those for any other silica-exposed group. These preliminary results indicate that spraying with Chinese herbal kombucha preparations can effectively promote the discharge of silica dust from lung tissues. Chinese herbal kombucha inhalation may thus be a useful new treatment for silicosis and other pneumoconiosis diseases.

Clearance of Free Silica in Rat Lungs by Spraying with Chinese Herbal Kombucha

PubMed Central

Fu, Nai-fang; Luo, Chang-hui; Wu, Jun-cai; Zheng, Yan-yan; Gan, Yong-jin; Ling, Jian-an; Liang, Heng-qiu; Liang, Dan-yu; Xie, Jing; Chen, Xiao-qin; Li, Xian-jun; Pan, Rui-hui; Chen, Zuo-Xing; Jiang, Sheng-jun

2013-01-01

The effects of spraying with kombucha and Chinese herbal kombucha were compared with treatments with tetrandrine in a rat silicosis model. Silica dust (50 mg) was injected into the lungs of rats, which were then treated with one of the experimental treatments for a month. The rats were then killed and the effects of the treatments were evaluated by examining the extent and severity of the histopathological lesions in the animals' lungs, measuring their organ coefficients and lung collagen contents, determining the dry and wet weights of their lungs, and measuring the free silica content of the dried lungs. In addition, lavage was performed on whole lungs taken from selected rats, and the numbers and types of cells in the lavage fluid were counted. The most effective treatment in terms of the ability to reduce lung collagen content and minimize the formation of pulmonary histopathological lesions was tetrandrine treatment, followed by Chinese herbal kombucha and non-Chinese herbal kombucha. However, the lavage fluid cell counts indicated that tetrandrine treatment had severe adverse effects on macrophage viability. This effect was much less pronounced for the kombucha and Chinese herbal kombucha treatments. Moreover, the free silica levels in the lungs of animals treated with Chinese herbal kombucha were significantly lower than those for any other silica-exposed group. These preliminary results indicate that spraying with Chinese herbal kombucha preparations can effectively promote the discharge of silica dust from lung tissues. Chinese herbal kombucha inhalation may thus be a useful new treatment for silicosis and other pneumoconiosis diseases. PMID:24023583

Complete Blood Count: MedlinePlus Lab Test Information

MedlinePlus

... your lungs and to the rest of your body Hematocrit , a measurement of how much of your blood is made ... Internet]. Bethesda (MD): U.S. Department of Health and Human Services; Your Guide to Anemia; [cited ... MedlinePlus Health Topics Bleeding Disorders Blood Count ...

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.

Lung inflammatory and oxidative alterations after exogenous surfactant therapy fortified with budesonide in rabbit model of meconium aspiration syndrome.

PubMed

Mikolka, P; Kopincová, J; Košútová, P; Čierny, D; Čalkovská, A; Mokrá, D

2016-12-22

Meconium aspiration syndrome (MAS) triggers inflammatory and oxidative pathways which can inactivate both pulmonary surfactant and therapeutically given exogenous surfactant. Glucocorticoid budesonide added to exogenous surfactant can inhibit inflammation and thereby enhance treatment efficacy. Neonatal meconium (25 mg/ml, 4 ml/kg) was administered intratracheally (i.t.) to rabbits. When the MAS model was prepared, animals were treated with budesonide i.t. (Pulmicort, 0.25 mg/kg, M+B); with surfactant lung lavage (Curosurf®, 10 ml/kg, 5 mg phospholipids/ml, M+S) followed by undiluted Curosurf® i.t. (100 mg phospholipids/kg); with combination of budesonide and surfactant (M+S+B); or were untreated (M); or served as controls with saline i.t. instead of meconium (C). Animals were oxygen-ventilated for additional 5 h. Cell counts in the blood and bronchoalveolar lavage fluid (BAL), lung edema formation (wet/dry weight ratio), oxidative damage of lipids/ proteins and inflammatory expression profiles (IL-2, IL-6, IL-13, TNF-alpha) in the lung homogenate and plasma were determined. Combined surfactant+budesonide therapy was the most effective in reduction of neutrophil counts in BAL, oxidative damage, levels and mRNA expression of cytokines in the lung, and lung edema formation compared to untreated animals. Curosurf fortified with budesonide mitigated lung inflammation and oxidative modifications what indicate the perspectives of this treatment combination for MAS therapy.

Cytological analysis of bronchoalveolar lavage fluid acquired by bronchoscopy in healthy ferrets: A pilot study

PubMed Central

Bercier, Marjorie; Langlois, Isabelle; Dunn, Marilyn; Hélie, Pierre; Burns, Patrick; Gara-Boivin, Carolyn

2016-01-01

The objective of this study was to investigate the normal cytological evaluation of bronchoalveolar lavage (BAL) fluid in healthy adult ferrets (N = 12). These ferrets underwent bronchoscopy and BAL using sterile saline [1.5 mL/kg body weight (BW)]. Percentage of fluid recovered, total leukocyte count, differential leukocyte count, and cell count of the epithelial lining fluid (ELF) were determined. The mean percentage of lavage volume recovered from the right lung and left lung were 67.8 ± 14.9% and 69.7 ± 20.0%, respectively. Gender (P = 0.12) and weight (P = 0.17) did not significantly affect the mean percentage of recovered volume. The mean percentage of recovered volume (P = 0.47) and the mean leukocyte count (P = 0.17) from the right and left lung were not significantly different. Macrophages were the main leukocyte component of the lavages, followed by neutrophils, lymphocytes, and eosinophils. The mean proportion of ELF in BAL fluid was 9.3 ± 3.7% v/v. Bronchoscopy is clinically useful for collecting good quality BAL samples for cytological analysis in ferrets. The leucocyte differential was established, which may help veterinarians to make better clinical decisions when treating respiratory disease. Further studies are required with a larger group in order to establish the healthy reference intervals for BAL values in ferrets. PMID:26733735

Cytological analysis of bronchoalveolar lavage fluid acquired by bronchoscopy in healthy ferrets: A pilot study.

PubMed

Bercier, Marjorie; Langlois, Isabelle; Dunn, Marilyn; Hélie, Pierre; Burns, Patrick; Gara-Boivin, Carolyn

2016-01-01

The objective of this study was to investigate the normal cytological evaluation of bronchoalveolar lavage (BAL) fluid in healthy adult ferrets (N = 12). These ferrets underwent bronchoscopy and BAL using sterile saline [1.5 mL/kg body weight (BW)]. Percentage of fluid recovered, total leukocyte count, differential leukocyte count, and cell count of the epithelial lining fluid (ELF) were determined. The mean percentage of lavage volume recovered from the right lung and left lung were 67.8 ± 14.9% and 69.7 ± 20.0%, respectively. Gender (P = 0.12) and weight (P = 0.17) did not significantly affect the mean percentage of recovered volume. The mean percentage of recovered volume (P = 0.47) and the mean leukocyte count (P = 0.17) from the right and left lung were not significantly different. Macrophages were the main leukocyte component of the lavages, followed by neutrophils, lymphocytes, and eosinophils. The mean proportion of ELF in BAL fluid was 9.3 ± 3.7% v/v. Bronchoscopy is clinically useful for collecting good quality BAL samples for cytological analysis in ferrets. The leucocyte differential was established, which may help veterinarians to make better clinical decisions when treating respiratory disease. Further studies are required with a larger group in order to establish the healthy reference intervals for BAL values in ferrets.

Characteristic features of tacrolimus-induced lung disease in rheumatoid arthritis patients.

PubMed

Sasaki, Takanori; Nakamura, Wataru; Inokuma, Shigeko; Matsubara, Erika

2016-02-01

This paper aims to study the background and clinical characteristics of tacrolimus (TAC)-induced lung disease. A case of a rheumatoid arthritis (RA) patient who developed TAC-induced interstitial lung disease (TAC-ILD) is reported. The Japanese Pharmaceuticals and Medical Devices Agency (PMDA) website was searched for cases of TAC-ILD and its prevalence among all cases of TAC-related adverse events. As for cases of TAC-ILD, its underlying disease, preexisting lung diseases, and fatal outcome were also searched. Literature review of TAC-ILD cases was added. A 65-year-old female RA patient with preexisting bronchiectasis developed near-fatal TAC-ILD. Amelioration of RA, ground-glass opacities in the upper, anterior, and central lung fields, and decrease in peripheral blood lymphocyte count were the major findings in this patient. A search of the PMDA website revealed the following: the prevalence of TAC-ILD was 3 % of all cases of TAC-related adverse events, 56 out of 85 RA cases (66 %), and one out of 15 other cases had a preexisting lung disease; the prevalences of fatal outcome in RA and other cases were 24 and 38 %, respectively. A few cases in the literature had preexisting ILD and developed diffuse alveolar damage. In our case, preexisting bronchiectasis, arthritis remission, newly developed ground-glass opacities (GGOs) in the upper, anterior, and central lung fields, and decrease in peripheral blood lymphocyte count were the major findings. From the search of the PMDA website, about one fourth of the cases with TAC-related lung injury had a fatal outcome, and among RA patients, two thirds had preexisting lung diseases.

Fast retrospective determination of radon exposure with a sensitive alpha scintillation probe.

PubMed

von Philipsborn, Henning; Just, Günther

2005-09-01

The background of a hand-held alpha ZnS scintillation probe of 44 cm(2) was reduced from the normal 50 counts per hour (cph) to 4 +/- 2 cph and the efficiency increased to 34%. The limit of detection for a 30 min measurement is now 5 Bq m(-2) Po-210 on glass surfaces, corresponding to about 200 Bq m(-3) indoor Rn-222 exposure for 20 years. The probe was successfully used for retrospective determination of radon exposure. The probe is simpler, faster and more convenient, and more economic than alpha spectrometry or nuclear track detectors currently used in the field of lung cancer epidemiology and long term radon exposure.

Systemic inflammation in 222.841 healthy employed smokers and nonsmokers: white blood cell count and relationship to spirometry

PubMed Central

2012-01-01

Background Smoking has been linked to low-grade systemic inflammation, a known risk factor for disease. This state is reflected in elevated white blood cell (WBC) count. Objective We analyzed the relationship between WBC count and smoking in healthy men and women across several age ranges who underwent preventive medical check-ups in the workplace. We also analysed the relationship between smoking and lung function. Methods Cross-sectional descriptive study in 163 459 men and 59 382 women aged between 16 and 70 years. Data analysed were smoking status, WBC count, and spirometry readings. Results Total WBC showed higher counts in both male and female smokers, around 1000 to 1300 cell/ml (t test, P < 0.001). Forced expiratory volume in 1 second (FEV1%) was higher in nonsmokers for both sexes between 25 to 54 years (t test, P < 0.001). Analysis of covariance showed a multiple variable effect of age, sex, smoking status, body mass index on WBC count. The relationship between WBC blood count and smoking status was confirmed after the sample was stratified for these variables. Smokers with airway obstruction measured by FEV1% were found to have higher WBC counts, in comparison to smokers with a normal FEV1% among similar age and BMI groups. Conclusions Smoking increases WBC count and affects lung function. The effects are evident across a wide age range, underlining the importance of initiating preventive measures as soon as an individual begins to smoke. PMID:22613769

Role of poly-(ADP-ribose) synthetase in lipopolysaccharide-induced vascular failure and acute lung injury in pigs.

PubMed

Albertini, M; Clement, M G; Lafortuna, C L; Caniatti, M; Magder, S; Abdulmalek, K; Hussain, S N

2000-06-01

To assess the contribution of poly (adenosine 5'-diphosphate ribose) synthetase (PARS) to the development of bacterial lipopolysaccharide (LPS)-induced acute lung injury and vascular failure in pigs. Four groups of anesthetized, paralyzed, and mechanically ventilated domestic white pigs. Group 1 served as control, whereas Escherichia coli LPS (20 microg/kg/h) was continuously infused in group 2. Group 3 received 20 mg/kg injection of 3-aminobenzamide (a selective inhibitor of PARS activity) 15 minutes before LPS infusion. Only 3-aminobenzamide and not LPS was injected in group 4. All animals were examined for 180 minutes. Systemic and pulmonary hemodynamics and lung mechanics were measured during the experimental period. Lung wet/dry ratio, bronchoalveolar lavage (BAL) protein levels and cell counts and lung nitrotyrosine (footprint of peroxynitrite) immunostaining were also measured in a few animals. LPS infusion evoked a progressive decline in systemic arterial pressure, a small increase in cardiac output, and biphasic elevation of pulmonary arterial pressure. Lung compliance declined progressively, whereas lung and total respiratory resistance rose significantly after LPS infusion. Prominent nitrotyrosine immunostaining was detected around small airways and pulmonary endothelium of LPS-infused animals. No significant changes in lung wet/dry ratio and BAL protein levels and cell counts were produced by LPS infusion. Pretreatment with 3-aminobenzamide did not alter the systemic and pulmonary hemodynamic responses to LPS infusion but eliminated the rise in pulmonary and total respiratory resistance. We concluded that PARS activation plays an important role in the changes of lung mechanics associated with LPS-induced acute lung injury but had no role in vascular failure.

Effects of trauma, hemorrhagic shock, and chronic stress on lung vascular endothelial growth factor.

PubMed

Loftus, Tyler J; Thomson, Andrew J; Kannan, Kolenkode B; Alamo, Ines G; Ramos, Harry N; Whitley, Elizabeth E; Efron, Philip A; Mohr, Alicia M

2017-04-01

Vascular endothelial growth factor (VEGF) and its receptors (VEGFR-1 and VEGFR-2) regulate vascular permeability and endothelial cell survival. We hypothesized that hemorrhagic shock (HS) and chronic stress (CS) would increase expression of lung VEGF and its receptors, potentiating pulmonary edema in lung tissue. Male Sprague-Dawley rats aged 8-9 wk were randomized: naïve control, lung contusion (LC), LC followed by HS (LCHS), and LCHS with CS in a restraint cylinder for 2 h/d (LCHS/CS). Animals were sacrificed on days 1 and 7. Expressions of lung VEGF, VEGFR-1, and VEGFR-2 were determined by polymerase chain reaction. Lung Injury Score (LIS) was graded on light microscopy by inflammatory cell counts, interstitial edema, pulmonary edema, and alveolar integrity (range: 0 = normal; 8 = severe injury). Seven days after LC, lung VEGF and VEGFR-1 were increased, and lung tissue healed (LIS: 0.8 ± 0.8). However, 7 d after LCHS and LCHS/CS, lung VEGF and VEGFR-1 expressions were decreased. VEGFR-2 was also decreased after LCHS/CS. LIS was elevated 7 d after LCHS and LCHS/CS (6.5 ± 1.0 and 8.2 ± 0.8). Increased LIS after LCHS and LCHS/CS was because of higher inflammatory cell counts, increased interstitial edema, and loss of alveolar integrity, whereas pulmonary edema was unchanged. Elevation of lung VEGF and VEGFR-1 expressions after LC alone was associated with healing of injured lung tissue. Expressions of VEGF, VEGFR-1, and VEGFR-2 were reduced after LCHS and LCHS/CS, and injured lung tissue did not heal. Persistent lung injury after severe trauma was because of inflammation rather than pulmonary edema. Copyright © 2016 Elsevier Inc. All rights reserved.

Intervention effect and dose-dependent response of tanreqing injection on airway inflammation in lipopolysaccharide-induced rats.

PubMed

Dong, Shoujin; Zhong, Yunqing; Yang, Kun; Xiong, Xiaoling; Mao, Bing

2013-08-01

To assess the effect of Tanreqing injection on airway inflammation in rats. A rat model of airway inflammation was generated with lipopolysaccharide (LPS). Tanreqing injection was given by intratracheal instillation, and bronchoalveolar lavage fluid (BALF) from the right lung was collected. BALF total cell and neutrophil counts were then determined. In addition, BALF levels of inflammatory cytokines interleukin-13, cytokine-induced neutrophil chemoat-tractant-1, and tumor necrosis factor-alpha were measured using enzyme linked immunosorbent assay. The middle lobe of the right lung was stained with hematoxylin-eosin and histological changes examined. LPS increased airway inflammation, decreased BALF inflammatory cell count, inflammatory cytokine levels, and suppressed leukocyte influx of the lung. The LPS-induced airway inflammation peaked at 24 h, decreased beginning at 48 h, and had decreased markedly by 96 h. Tanreqing injection contains anti-inflammatory properties, and inhibits airway inflammation in a dose-dependent manner.

Concordance of anaplastic lymphoma kinase (ALK) gene rearrangements between circulating tumor cells and tumor in non-small cell lung cancer

PubMed Central

Lim, Tony KH; Tan, Daniel Shao-Weng; Chua, Yong Wei; Ang, Mei Kim; Pang, Brendan; Lim, Chwee Teck; Takano, Angela; Lim, Alvin Soon-Tiong; Leong, Man Chun; Lim, Wan-Teck

2016-01-01

Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC) is routinely evaluated by fluorescent in-situ hybridization (FISH) testing on biopsy tissues. Testing can be challenging however, when suitable tissue samples are unavailable. We examined the relevance of circulating tumor cells (CTC) as a surrogate for biopsy-based FISH testing. We assessed paired tumor and CTC samples from patients with ALK rearranged lung cancer (n = 14), ALK-negative lung cancer (n = 12), and healthy controls (n = 5) to derive discriminant CTC counts, and to compare ALK rearrangement patterns. Blood samples were enriched for CTCs to be used for ALK FISH testing. ALK-positive CTCs counts were higher in ALK-positive NSCLC patients (3–15 cells/1.88 mL of blood) compared with ALK-negative NSCLC patients and healthy donors (0–2 cells/1.88 mL of blood). The latter range was validated as the ‘false positive’ cutoff for ALK FISH testing of CTCs. ALK FISH signal patterns observed on tumor biopsies were recapitulated in CTCs in all cases. Sequential CTC counts in an index case of lung cancer with no evaluable tumor tissue treated with crizotinib showed six, three and eleven ALK-positive CTCs per 1.88 mL blood at baseline, partial response and post-progression time points, respectively. Furthermore, ALK FISH rearrangement suggestive of gene copy number increase was observed in CTCs following progression. Recapitulation of ALK rearrangement patterns in the tumor on CTCs, suggested that CTCs might be used to complement tissue-based ALK testing in NSCLC to guide ALK-targeted therapy when suitable tissue biopsy samples are unavailable for testing. PMID:26993609

Concordance of anaplastic lymphoma kinase (ALK) gene rearrangements between circulating tumor cells and tumor in non-small cell lung cancer.

PubMed

Tan, Chye Ling; Lim, Tse Hui; Lim, Tony Kh; Tan, Daniel Shao-Weng; Chua, Yong Wei; Ang, Mei Kim; Pang, Brendan; Lim, Chwee Teck; Takano, Angela; Lim, Alvin Soon-Tiong; Leong, Man Chun; Lim, Wan-Teck

2016-04-26

Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC) is routinely evaluated by fluorescent in-situ hybridization (FISH) testing on biopsy tissues. Testing can be challenging however, when suitable tissue samples are unavailable. We examined the relevance of circulating tumor cells (CTC) as a surrogate for biopsy-based FISH testing. We assessed paired tumor and CTC samples from patients with ALK rearranged lung cancer (n = 14), ALK-negative lung cancer (n = 12), and healthy controls (n = 5) to derive discriminant CTC counts, and to compare ALK rearrangement patterns. Blood samples were enriched for CTCs to be used for ALK FISH testing. ALK-positive CTCs counts were higher in ALK-positive NSCLC patients (3-15 cells/1.88 mL of blood) compared with ALK-negative NSCLC patients and healthy donors (0-2 cells/1.88 mL of blood). The latter range was validated as the 'false positive' cutoff for ALK FISH testing of CTCs. ALK FISH signal patterns observed on tumor biopsies were recapitulated in CTCs in all cases. Sequential CTC counts in an index case of lung cancer with no evaluable tumor tissue treated with crizotinib showed six, three and eleven ALK-positive CTCs per 1.88 mL blood at baseline, partial response and post-progression time points, respectively. Furthermore, ALK FISH rearrangement suggestive of gene copy number increase was observed in CTCs following progression. Recapitulation of ALK rearrangement patterns in the tumor on CTCs, suggested that CTCs might be used to complement tissue-based ALK testing in NSCLC to guide ALK-targeted therapy when suitable tissue biopsy samples are unavailable for testing.

Aerobic Exercise Decreases Lung Inflammation by IgE Decrement in an OVA Mice Model.

PubMed

Camargo Hizume-Kunzler, Deborah; Greiffo, Flavia R; Fortkamp, Bárbara; Ribeiro Freitas, Gabriel; Keller Nascimento, Juliana; Regina Bruggemann, Thayse; Melo Avila, Leonardo; Perini, Adenir; Bobinski, Franciane; Duarte Silva, Morgana; Rocha Lapa, Fernanda; Paula Vieira, Rodolfo; Vargas Horewicz, Verônica; Soares Dos Santos, Adair Roberto; Cattelan Bonorino, Kelly

2017-06-01

Aerobic exercise (AE) reduces lung function decline and risk of exacerbations in asthmatic patients. However, the inflammatory lung response involved in exercise during the sensitization remains unclear. Therefore, we evaluated the effects of exercise for 2 weeks in an experimental model of sensitization and single ovalbumin-challenge. Mice were divided into 4 groups: mice non-sensitized and not submitted to exercise (Sedentary, n=10); mice non-sensitized and submitted to exercise (Exercise, n=10); mice sensitized and exposed to ovalbumin (OVA, n=10); and mice sensitized, submitted to exercise and exposed to OVA (OVA+Exercise, n=10). 24 h after the OVA/saline exposure, we counted inflammatory cells from bronchoalveolar fluid (BALF), lung levels of total IgE, IL-4, IL-5, IL-10 and IL-1ra, measurements of OVA-specific IgG1 and IgE, and VEGF and NOS-2 expression via western blotting. AE reduced cell counts from BALF in the OVA group (p<0.05), total IgE, IL-4 and IL-5 lung levels and OVA-specific IgE and IgG1 titers (p<0.05). There was an increase of NOS-2 expression, IL-10 and IL-1ra lung levels in the OVA groups (p<0.05). Our results showed that AE attenuated the acute lung inflammation, suggesting immunomodulatory properties on the sensitization process in the early phases of antigen presentation in asthma. © Georg Thieme Verlag KG Stuttgart · New York.

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

PubMed Central

Carvalho, Marcus V.H.; Marchi, Evaldo; Fruchi, Andre J.; Dias, Bruno V.B.; Pinto, Clovis L.; dos Santos, Geovane R.; Acencio, Milena M.P.

2017-01-01

OBJECTIVES: Tissue adhesives can be used to prevent pulmonary air leaks, which frequently occur after lung interventions. The objective of this study is to evaluate local and systemic effects of fibrin and cyanoacrylate tissue adhesives on lung lesions in rabbits. METHODS: Eighteen rabbits were submitted to videothoracoscopy + lung incision alone (control) or videothoracoscopy + lung incision + local application of fibrin or cyanoacrylate adhesive. Blood samples were collected and assessed for leukocyte, neutrophil and lymphocyte counts and interleukin-8 levels preoperatively and at 48 hours and 28 days post-operatively. After 28 days, the animals were euthanized for gross examination of the lung surface, and lung fragments were excised for histopathological analysis. RESULTS: Fibrin and cyanoacrylate produced similar adhesion scores of the lung to the parietal pleura. Microscopic analysis revealed uniform low-cellular tissue infiltration in the fibrin group and an intense tissue reaction characterized by dense inflammatory infiltration of granulocytes, giant cells and necrosis in the cyanoacrylate group. No changes were detected in the leukocyte, neutrophil or lymphocyte count at any time-point, while the interleukin-8 levels were increased in the fibrin and cyanoacrylate groups after 48 hours compared with the pre-operative control levels (p<0.01). CONCLUSION: Both adhesive agents promoted normal tissue healing, with a more pronounced local inflammatory reaction observed for cyanoacrylate. Among the serum markers of inflammation, only the interleukin-8 levels changed post-operatively, increasing after 48 hours and decreasing after 28 days to levels similar to those of the control group in both the fibrin and cyanoacrylate groups. PMID:29160425

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

PubMed

Carvalho, Marcus V H; Marchi, Evaldo; Fruchi, Andre J; Dias, Bruno V B; Pinto, Clovis L; Dos Santos, Geovane R; Acencio, Milena M P

2017-10-01

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

Fisetin, a bioactive flavonol, attenuates allergic airway inflammation through negative regulation of NF-κB.

PubMed

Goh, Fera Y; Upton, Nadine; Guan, Shouping; Cheng, Chang; Shanmugam, Muthu K; Sethi, Gautam; Leung, Bernard P; Wong, W S Fred

2012-03-15

Persistent activation of nuclear factor-κB (NF-κB) has been associated with the development of asthma. Fisetin (3,7,3',4'-tetrahydroxyflavone), a naturally occurring bioactive flavonol, has been shown to inhibit NF-κB activity. We hypothesized that fisetin may attenuate allergic asthma via negative regulation of the NF-κB activity. Female BALB/c mice sensitized and challenged with ovalbumin developed airway inflammation. Bronchoalveolar lavage fluid was assessed for total and differential cell counts, and cytokine and chemokine levels. Lung tissues were examined for cell infiltration and mucus hypersecretion, and the expression of inflammatory biomarkers. Airway hyperresponsiveness was monitored by direct airway resistance analysis. Fisetin dose-dependently inhibited ovalbumin-induced increases in total cell count, eosinophil count, and IL-4, IL-5 and IL-13 levels recovered in bronchoalveolar lavage fluid. It attenuated ovalbumin-induced lung tissue eosinophilia and airway mucus production, mRNA expression of adhesion molecules, chitinase, IL-17, IL-33, Muc5ac and inducible nitric oxide synthase in lung tissues, and airway hyperresponsiveness to methacholine. Fisetin blocked NF-κB subunit p65 nuclear translocation and DNA-binding activity in the nuclear extracts from lung tissues of ovalbumin-challenged mice. In normal human bronchial epithelial cells, fisetin repressed TNF-α-induced NF-κB-dependent reporter gene expression. Our findings implicate a potential therapeutic value of fisetin in the treatment of asthma through negative regulation of NF-κB pathway. Copyright © 2012 Elsevier B.V. All rights reserved.

Pleural mesothelioma and lung cancer risks in relation to occupational history and asbestos lung burden.

PubMed

Gilham, Clare; Rake, Christine; Burdett, Garry; Nicholson, Andrew G; Davison, Leslie; Franchini, Angelo; Carpenter, James; Hodgson, John; Darnton, Andrew; Peto, Julian

2016-05-01

We have conducted a population-based study of pleural mesothelioma patients with occupational histories and measured asbestos lung burdens in occupationally exposed workers and in the general population. The relationship between lung burden and risk, particularly at environmental exposure levels, will enable future mesothelioma rates in people born after 1965 who never installed asbestos to be predicted from their asbestos lung burdens. Following personal interview asbestos fibres longer than 5 µm were counted by transmission electron microscopy in lung samples obtained from 133 patients with mesothelioma and 262 patients with lung cancer. ORs for mesothelioma were converted to lifetime risks. Lifetime mesothelioma risk is approximately 0.02% per 1000 amphibole fibres per gram of dry lung tissue over a more than 100-fold range, from 1 to 4 in the most heavily exposed building workers to less than 1 in 500 in most of the population. The asbestos fibres counted were amosite (75%), crocidolite (18%), other amphiboles (5%) and chrysotile (2%). The approximate linearity of the dose-response together with lung burden measurements in younger people will provide reasonably reliable predictions of future mesothelioma rates in those born since 1965 whose risks cannot yet be seen in national rates. Burdens in those born more recently will indicate the continuing occupational and environmental hazards under current asbestos control regulations. Our results confirm the major contribution of amosite to UK mesothelioma incidence and the substantial contribution of non-occupational exposure, particularly in women. 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/

Technetium-fibrinogen lung scanning in canine lung contusion

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

Geller, E.; Khaw, B.A.; Strauss, H.W.

1984-07-01

To detect experimentally induced acute lung contusion in anesthetized dogs, serial radionuclide images of the lung were recorded following intravenous infusion of 99mTc-labelled human fibrinogen (Tc-HF). The accumulation of Tc-HF in canine lungs was serially quantitated for up to 20 hours after lung contusion. A contusion (number1) was produced in one lung, Tc-HF was injected IV after 15 minutes, and 75 minutes later a contralateral lung contusion (number2) was produced in a series of 14 dogs. At autopsy the excised lungs were scanned, sectioned, and counted for radioactivity. Radiolabelled fibrinogen accumulated within 2-4 minutes of contusion number2 and remained stablemore » over the next 20 hours in 14 dogs; contusion number1 was barely visible in four dogs. Lung Tc-HF activity in the central region of contusion number2 remained sixfold higher than in normal lung tissue. These data suggest that following lung contusion, fibrinogen deposition occurs rapidly and remains stable over a 20-hour interval of observation.« less

A high-resolution imaging technique using a whole-body, research photon counting detector CT system

NASA Astrophysics Data System (ADS)

Leng, S.; Yu, Z.; Halaweish, A.; Kappler, S.; Hahn, K.; Henning, A.; Li, Z.; Lane, J.; Levin, D. L.; Jorgensen, S.; Ritman, E.; McCollough, C.

2016-03-01

A high-resolution (HR) data collection mode has been introduced to a whole-body, research photon-counting-detector CT system installed in our laboratory. In this mode, 64 rows of 0.45 mm x 0.45 mm detector pixels were used, which corresponded to a pixel size of 0.25 mm x 0.25 mm at the iso-center. Spatial resolution of this HR mode was quantified by measuring the MTF from a scan of a 50 micron wire phantom. An anthropomorphic lung phantom, cadaveric swine lung, temporal bone and heart specimens were scanned using the HR mode, and image quality was subjectively assessed by two experienced radiologists. High spatial resolution of the HR mode was evidenced by the MTF measurement, with 15 lp/cm and 20 lp/cm at 10% and 2% modulation. Images from anthropomorphic phantom and cadaveric specimens showed clear delineation of small structures, such as lung vessels, lung nodules, temporal bone structures, and coronary arteries. Temporal bone images showed critical anatomy (i.e. stapes superstructure) that was clearly visible in the PCD system. These results demonstrated the potential application of this imaging mode in lung, temporal bone, and vascular imaging. Other clinical applications that require high spatial resolution, such as musculoskeletal imaging, may also benefit from this high resolution mode.

Measuring Transmission Efficiencies Of Mass Spectrometers

NASA Technical Reports Server (NTRS)

Srivastava, Santosh K.

1989-01-01

Coincidence counts yield absolute efficiencies. System measures mass-dependent transmission efficiencies of mass spectrometers, using coincidence-counting techniques reminiscent of those used for many years in calibration of detectors for subatomic particles. Coincidences between detected ions and electrons producing them counted during operation of mass spectrometer. Under certain assumptions regarding inelastic scattering of electrons, electron/ion-coincidence count is direct measure of transmission efficiency of spectrometer. When fully developed, system compact, portable, and used routinely to calibrate mass spectrometers.

Bacterial infection and acute lung injury in hamsters.

PubMed

Seidenfeld, J J; Mullins, R C; Fowler, S R; Johanson, W G

1986-07-01

Bacterial pneumonia is a common complication of lung injury that can be an important determinant of outcome. We studied experimental lung injury produced in hamsters by injecting 20 mg/kg paraquat (PQ) intraperitoneally; control animals received saline vehicle. Three days later, Pseudomonas aeruginosa (PAO1), 10(8) organisms in 0.25 ml, or saline, 0.25 ml, was inoculated intratracheally. Lung and systemic antibacterial defenses were studied at death 24 h later. Paraquat alone produced focal interstitial pneumonitis and neutrophilic alveolitis, and resulted in a 12% (3 of 26) mortality. PAO1 alone caused focal pneumonias and no deaths. Animals receiving both agents (PAO1/PQ) had extensive diffuse alveolar damage characterized by alveolar hemorrhage, edema, influx of neutrophils, and vasculitis; 50% (16 of 32) died within 96 h of PQ injection. Mean lung counts of PAO1 at death were 7.6 X 10(4) colony forming units/g in PAO1 and 2.8 X 10(7) in PAO1/PQ animals (p less than 0.05). PAO1 colony counts in liver were increased nearly 100-fold in PAO1/PQ animals (p less than 0.05). Half-time of clearance of P. aeruginosa from the blood was prolonged in PAO1 and in PAO1/PQ animals (p less than 0.05) but not in PQ animals. Phagocytosis of Staphylococcus aureus by leukocytes lavaged from the lung was not impaired in any group compared with that in control animals, but intracellular killing was impaired in PAO1 and PAO1/PQ but not in PQ animals. Paraquat injury impairs lung antibacterial defenses by uncertain mechanisms. Superinfection of PQ-injured lungs by PAO1 appears responsible for defects in intrapulmonary and systemic antibacterial defenses.

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.

Automated CT Scan Scores of Bronchiectasis and Air Trapping in Cystic Fibrosis

PubMed Central

Swiercz, Waldemar; Heltshe, Sonya L.; Anthony, Margaret M.; Szefler, Paul; Klein, Rebecca; Strain, John; Brody, Alan S.; Sagel, Scott D.

2014-01-01

Background: Computer analysis of high-resolution CT (HRCT) scans may improve the assessment of structural lung injury in children with cystic fibrosis (CF). The goal of this cross-sectional pilot study was to validate automated, observer-independent image analysis software to establish objective, simple criteria for bronchiectasis and air trapping. Methods: HRCT scans of the chest were performed in 35 children with CF and compared with scans from 12 disease control subjects. Automated image analysis software was developed to count visible airways on inspiratory images and to measure a low attenuation density (LAD) index on expiratory images. Among the children with CF, relationships among automated measures, Brody HRCT scanning scores, lung function, and sputum markers of inflammation were assessed. Results: The number of total, central, and peripheral airways on inspiratory images and LAD (%) on expiratory images were significantly higher in children with CF compared with control subjects. Among subjects with CF, peripheral airway counts correlated strongly with Brody bronchiectasis scores by two raters (r = 0.86, P < .0001; r = 0.91, P < .0001), correlated negatively with lung function, and were positively associated with sputum free neutrophil elastase activity. LAD (%) correlated with Brody air trapping scores (r = 0.83, P < .0001; r = 0.69, P < .0001) but did not correlate with lung function or sputum inflammatory markers. Conclusions: Quantitative airway counts and LAD (%) on HRCT scans appear to be useful surrogates for bronchiectasis and air trapping in children with CF. Our automated methodology provides objective quantitative measures of bronchiectasis and air trapping that may serve as end points in CF clinical trials. PMID:24114359

Effect of CPAP in a Mouse Model of Hyperoxic Neonatal Lung Injury

PubMed Central

Reyburn, Brent; Fiore, Juliann M. Di; Raffay, Thomas; Martin, Richard J.; Y.S., Prakash; Jafri, Anjum; MacFarlane, Peter M.

2015-01-01

Background Continuous positive airway pressure [CPAP] and supplemental oxygen have become the mainstay of neonatal respiratory support in preterm infants. Although oxygen therapy is associated with respiratory morbidities including bronchopulmonary dysplasia [BPD], the long-term effects of CPAP on lung function are largely unknown. We used a hyperoxia-induced mouse model of BPD to explore the effects of daily CPAP during the first week of life on later respiratory system mechanics. Objective To test the hypothesis that daily CPAP in a newborn mouse model of BPD improves longer term respiratory mechanics. Methods Mouse pups from C57BL/6 pregnant dams were exposed to room air [RA] or hyperoxia [50% O2, 24hrs/day] for the first postnatal week with or without exposure to daily CPAP [6cmH2O, 3hrs/day]. Respiratory system resistance [Rrs] and compliance [Crs] were measured following a subsequent 2 week period of room RA recovery. Additional measurements included radial alveolar counts and macrophage counts. Results Mice exposed to hyperoxia had significantly elevated Rrs, decreased Crs, reduced alveolarization, and increased macrophage counts at three weeks compared to RA treated mice. Daily CPAP treatment significantly improved Rrs, Crs and alveolarization, and decreased lung macrophage infiltration in hyperoxia-exposed pups. Conclusions We have demonstrated that daily CPAP had a longer term benefit on baseline respiratory system mechanics in a neonatal mouse model of BPD. We speculate that this beneficial effect of CPAP was the consequence of a decrease in the inflammatory response and resultant alveolar injury associated with hyperoxic newborn lung injury. PMID:26394387

Malondialdehyde-acetaldehyde (MAA) adducted surfactant protein induced lung inflammation is mediated through scavenger receptor a (SR-A1).

PubMed

Sapkota, Muna; DeVasure, Jane M; Kharbanda, Kusum K; Wyatt, Todd A

2017-02-13

Co-exposure to cigarette smoke and alcohol leads to the generation of high concentrations of acetaldehyde and malondialdehyde in the lung. These aldehydes being highly electrophilic in nature react with biologically relevant proteins such as surfactant protein D (SPD) through a Schiff base reaction to generate SPD adducted malondialdehyde-acetaldehyde adduct (SPD-MAA) in mouse lung. SPD-MAA results in an increase in lung pro-inflammatory chemokine, keratinocyte chemoattractant (KC), and the recruitment of lung lavage neutrophils. Previous in vitro studies in bronchial epithelial cells and macrophages show that scavenger receptor A (SR-A1/CD204) is a major receptor for SPD-MAA. No studies have yet examined the in vivo role of SR-A1 in MAA-mediated lung inflammation. Therefore, we hypothesize that in the absence of SR-A1, MAA-induced inflammation in the lung is reduced or diminished. To test this hypothesis, C57BL/6 WT and SR-A1 KO mice were nasally instilled with 50 μg/mL of SPD-MAA for 3 weeks (wks). After 3 weeks, bronchoalveolar lavage (BAL) fluid was collected and assayed for a total cell count, a differential cell count and CXCL1 (KC) chemokine. Lung tissue sections were stained with hematoxylin and eosin (H&E) and antibodies to MAA adduct. Results showed that BAL cellularity and influx of neutrophils were decreased in SR-A1 KO mice as compared to WT following repetitive SPD-MAA exposure. MAA adduct staining in the lung epithelium was decreased in SR-A1 KO mice. In comparison to WT, no increase in CXCL1 was observed in BAL fluid from SR-A1 KO mice over time. Overall, the data demonstrate that SR-A1/CD204 plays an important role in SPD-MAA induced inflammation in lung.

Nfib hemizygous mice are protected from hyperoxic lung injury and death.

PubMed

Kumar, Vasantha H S; Chaker El Khoury, Joseph; Gronostajski, Richard; Wang, Huamei; Nielsen, Lori; Ryan, Rita M

2017-08-01

Nuclear Factor I ( Nfi) genes encode transcription factors essential for the development of organ systems including the lung. Nfib null mice die at birth with immature lungs. Nfib hemizygous mice have reduced lung maturation with decreased survival. We therefore hypothesized that these mice would be more sensitive to lung injury and would have lower survival to hyperoxia. Adult Nfib hemizygous mice and their wild-type (Wt) littermates were exposed to 100% O 2 for 89, 80, 72 and 66 h for survival studies with lung outcome measurements at 66 h. Nfib hemizygous and Wt controls were also studied in RA at 66 h. Cell counts and cytokines were measured in bronchoalveolar lavage (BAL); lung sections examined by histopathology; lung angiogenic and oxidative stress gene expression assessed by real-time PCR Unexpectedly, Nfib hemizygous mice (0/14-0%) had significantly lower mortality compared to Wt mice (10/22-45%) at 80 h of hyperoxia ( P  < 0.003). LD 50 was 80 h in the Wt group versus 89 h in the hemizygous group. There were no differences in BAL cell counts between the groups. Among the cytokines studied, MIP-2 was significantly lower in hemizygous mice exposed to hyperoxia. New vessel formation, edema, congestion, and alveolar hemorrhage were noted on histopathology at 72 and 80 h in wild-type mice. Nfib hemizygous lungs had significant downregulation of genes involved in redox signaling and inflammatory pathways. Adult Nfib hemizygous mice are relatively resistant to hyperoxia compared to wild-type littermates. Mechanisms contributing to this resistance are not clear; however, transcription factors such as Nfib may regulate cell survival and play a role in modulating postnatal lung development. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Inhibition of acid-induced lung injury by hyperosmolar sucrose in rats.

PubMed

Safdar, Zeenat; Yiming, Maimiti; Grunig, Gabriele; Bhattacharya, Jahar

2005-10-15

Acid aspiration causes acute lung injury (ALI). Recently, we showed that a brief intravascular infusion of hyperosmolar sucrose, given concurrently with airway acid instillation, effectively blocks the ensuing ALI. The objective of the present study was to determine the extent to which intravascular infusion of hyperosmolar sucrose might protect against acid-induced ALI when given either before or after acid instillation. Our studies were conducted in anesthetized rats and in isolated, blood-perfused rat lungs. We instilled HCl through the airway, and we quantified lung injury in terms of the extravascular lung water (EVLW) content, filtration coefficient (Kfc), and cell counts and protein concentration in the bronchoalveolar lavage. We infused hyperosmolar sucrose via the femoral vein. In anesthetized rats, airway HCl instillation induced ALI as indicated by a 52% increase of EVLW and a threefold increase in Kfc. However, a 15-min intravenous infusion of hyperosmolar sucrose given up to 1 h before or 30 min after acid instillation markedly blunted the increases in EVLW, as well as the increases in cell count, and in protein concentration in the bronchoalveolar lavage. Hyperosmolar pretreatment also blocked the acid-induced increase of Kfc. Studies in isolated perfused lungs indicated that the protective effect of hyperosmolar sucrose was leukocyte independent. We conclude that a brief period of vascular hyperosmolarity protects against acid-induced ALI when the infusion is administered shortly before, or shortly after, acid instillation in the airway. The potential applicability of hyperosmolar sucrose in therapy for ALI requires consideration.

Effects of sodium salicylate on the determination of Lead-210/Bismuth-210 by Cerenkov counting.

PubMed

Wang, Yadong; Yang, Yonggang; Song, Lijuan; Ma, Yan; Luo, Maoyi; Dai, Xiongxin

2018-05-21

Due to the nature of Cerenkov radiation and instrumental limitations, detection efficiencies of 210 Bi by Cerenkov counting are generally quite low (~15%). Sodium salicylate, acting as a wavelength shifter, has been used to improve the detection efficiency of Cerenkov photons. In this study, we found that the addition of sodium salicylate could significantly increase the counting efficiencies of 210 Pb/ 210 Bi in aqueous samples. Meanwhile, a sharp increase of the counting efficiency for the alphas from 210 Po was also observed with the addition of high concentration of sodium salicylate, implying that scintillation light rather than Cerenkov photons from the alphas has been produced. Detailed studies about the effects of sodium salicylate on the counting of 210 Pb, 210 Bi and 210 Po were conducted. At low concentration (< 0.5 mg g -1 ) of sodium salicylate, only a small increase in Cerenkov counting efficiency for 210 Bi by the wavelength-shifting effect could be observed. Meanwhile, the counting efficiency for 210 Bi at high concentration (> 1 mg g -1 ) of sodium salicylate would significantly increase due to the scintillation effect. Copyright © 2018 Elsevier Ltd. All rights reserved.

Acute exposure to waterpipe tobacco smoke induces changes in the oxidative and inflammatory markers in mouse lung

PubMed Central

Khabour, Omar F.; Alzoubi, Karem H.; Bani-Ahmad, Mohammed; Dodin, Arwa; Eissenberg, Thomas; Shihadeh, Alan

2013-01-01

Context Tobacco smoking represents a global public health threat, claiming approximately 5 million lives a year. Waterpipe tobacco use has become popular particularly among youth in the past decade, buttressed by the perception that the waterpipe “filters” the smoke, rendering it less harmful than cigarette smoke. Objective In this study, we examined the acute exposure of waterpipe smoking on lung inflammation and oxidative stress in mice, and compared that to cigarette smoking. Materials and methods Mice were divided into three groups; fresh air control, cigarette and waterpipe. Animals were exposed to fresh air, cigarette, or waterpipe smoke using whole body exposure system one hour daily for 7 days. Results Both cigarette and waterpipe smoke exposure resulted in elevation of total white blood cell count, as well as absolute count of neutrophils, macrophages, and lymphocytes (P < 0.01). Both exposures also elevated proinflammatory markers such as TNF-α and IL-6 in BALF (P < 0.05), and oxidative stress markers including GPx activity in lungs (P < 0.05). Moreover, waterpipe smoke increased catalase activity in the lung (P < 0.05). However, none of the treatments altered IL-10 levels. Discussion and conclusion Results of cigarette smoking confirmed previous finding. Waterpipe results indicate that, similar to cigarettes, exposure to waterpipe tobacco smoke is harmful to the lungs. PMID:22906173

[Morphological characteristics of inflammation in HIV-associated pulmonary tuberculosis with regard to the expression of myeloperoxidase].

PubMed

Bykhalov, L S; Smirnov, A V

2015-01-01

to characterize the morphological features of inflammation and the degree of myeloperoxidase expression in the lung of patients who died from HIV-associated tuberculosis (TB). Autopsy lung tissue specimens from 229 patients with HIV-associated TB were examined. A comparison group consisted of dead TB mono-infected patients (n = 30). Dead HIV/TB co-infected patients were divided into subgroups: 1) 50 patients with Stage 4A-4B and a CD4(+)-lymphocyte count of more than 200 cells/µl; 2) 54 with Stage 4B-4C and a CD4(+)-lymphocyte count of 100 to 200 cells/µl; 3) 125 with Stage 4C-5 and a CD4(+)-lymphocyte count of less than 100 cells/µl. Histological and immunohistochemical examinations of lung slices were performed using antibodies to myeloperoxidase (MPO). The predominant types of an inflammatory response were revealed according to the level of CD4+ lymphocytes. The lungs in Subgroup 1 showed a predominant typical granulomatous response (82%). Subgroup 2 exhibited an exudative-productive inflammatory response (57.4%) while Subgroup 3 displayed an alterative necrotic type (92.8%). Subgroup 3 showed the most marked reduction in lymphocyte numbers in the areas of inflammation, which was accompanied by a significant increase in the relative density and other morphometric parameters of MPO-positive macrophages and granulocytes in the inflammatory infiltration zones and alveolar walls. The identified changes in the lungs suggest that there is a decline in the magnitude of a delayed type hypersensitivity reaction, a progression of alterative necrotic processes as CD4(+) lymphocytes decrease in the systemic blood flow, and an increase in the proportion of functionally immature macrophages in the areas of inflammation, which reflects a substantially impaired local immune response to the persistence of M. tuberculosis in HIV infection.

Mitogen-activated protein kinase phosphatase-1 modulates regional effects of injurious mechanical ventilation in rodent lungs.

PubMed

Park, Moo Suk; He, Qianbin; Edwards, Michael G; Sergew, Amen; Riches, David W H; Albert, Richard K; Douglas, Ivor S

2012-07-01

Mechanical ventilation induces heterogeneous lung injury by mitogen-activated protein kinase (MAPK) and nuclear factor-κB. Mechanisms regulating regional injury and protective effects of prone positioning are unclear. To determine the key regulators of the lung regional protective effects of prone positioning in rodent lungs exposed to injurious ventilation. Adult rats were ventilated with high (18 ml/kg, positive end-expiratory pressure [PEEP] 0) or low Vt (6 ml/kg; PEEP 3 cm H(2)O; 3 h) in supine or prone position. Dorsal-caudal lung mRNA was analyzed by microarray and MAPK phosphatases (MKP)-1 quantitative polymerase chain reaction. MKP-1(-/-) or wild-type mice were ventilated with very high (24 ml/kg; PEEP 0) or low Vt (6-7 ml/kg; PEEP 3 cm H(2)O). The MKP-1 regulator PG490-88 (MRx-108; 0.75 mg/kg) or phosphate-buffered saline was administered preventilation. Injury was assessed by lung mechanics, bronchioalveolar lavage cell counts, protein content, and lung injury scoring. Immunoblotting for MKP-1, and IκBα and cytokine ELISAs were performed on lung lysates. Prone positioning was protective against injurious ventilation in rats. Expression profiling demonstrated MKP-1 20-fold higher in rats ventilated prone rather than supine and regional reduction in p38 and c-jun N-terminal kinase activation. MKP-1(-/-) mice experienced amplified injury. PG490-88 improved static lung compliance and injury scores, reduced bronchioalveolar lavage cell counts and cytokine levels, and induced MKP-1 and IκBα. Injurious ventilation induces MAPK in an MKP-1-dependent fashion. Prone positioning is protective and induces MKP-1. PG490-88 induced MKP-1 and was protective against high Vt in a nuclear factor-κB-dependent manner. MKP-1 is a potential target for modulating regional effects of injurious ventilation.

TU-A-12A-02: Novel Lung Ventilation Imaging with Single Energy CT After Single Inhalation of Xenon: Comparison with SPECT Ventilation Images

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

Negahdar, M; Yamamoto, T; Shultz, D

Purpose: We propose a novel lung functional imaging method to determine the spatial distribution of xenon (Xe) gas in a single inhalation as a measure of regional ventilation. We compare Xe-CT ventilation to single-photon emission CT (SPECT) ventilation, which is the current clinical reference. Regional lung ventilation information may be useful for the diagnosis and monitoring of pulmonary diseases such as COPD, radiotherapy planning, and assessing the progression of toxicity after radiation therapy. Methods: In an IRB-approved clinical study, Xe-CT and SPECT ventilation scans were acquired for three patients including one patient with severe emphysema and two lung cancer patientsmore » treated with radiotherapy. For Xe- CT, we acquired two breath-hold single energy CT images of the entire lung with inspiration of 100% O2 and a mixture of 70% Xe and 30% O2, respectively. A video biofeedback system was used to achieve reproducible breath-holds. We used deformable image registration to align the breathhold images with each other to accurately subtract them, producing a map of the distribution of Xe as a surrogate of lung ventilation. We divided each lung into twelve parts and correlated the Hounsfield unit (HU) enhancement at each part with the SPECT ventilation count of the corresponding part of the lung. Results: The mean of the Pearson linear correlation coefficient values between the Xe-CT and ventilation SPECT count for all three patients were 0.62 (p<0.01). The Xe-CT image had a higher resolution than SPECT, and did not show central airway deposition artifacts that were present in the SPECT image. Conclusion: We developed a rapid, safe, clinically practical, and potentially widely accessible method for regional lung functional imaging. We demonstrated strong correlations between the Xe-CT ventilation image and SPECT ventilation image as the clinical reference. This ongoing study will investigate more patients to confirm this finding.« less

Adrenomedullin promotes lung angiogenesis, alveolar development, and repair.

PubMed

Vadivel, Arul; Abozaid, Sameh; van Haaften, Tim; Sawicka, Monika; Eaton, Farah; Chen, Ming; Thébaud, Bernard

2010-08-01

Bronchopulmonary dysplasia (BPD) and emphysema are significant global health problems at the extreme stages of life. Both are characterized by alveolar simplification and abnormal distal airspace enlargement due to arrested development or loss of alveoli, respectively. Both lack effective treatments. Mechanisms that inhibit distal lung growth are poorly understood. Adrenomedullin (AM), a recently discovered potent vasodilator, promotes angiogenesis and has protective effects on the cardiovascular and respiratory system. Its role in the developing lung is unknown. We hypothesized that AM promotes lung angiogenesis and alveolar development. Accordingly, we report that lung mRNA expression of AM increases during normal alveolar development. In vivo, intranasal administration of the AM antagonist, AM22-52 decreases lung capillary density (12.4 +/- 1.5 versus 18 +/- 1.5 in control animals; P < 0.05) and impairs alveolar development (mean linear intercept, 52.3 +/- 1.5 versus 43.8 +/- 1.8 [P < 0.05] and septal counts 62.0 +/- 2.7 versus 90.4 +/- 3.5 [P < 0.05]) in neonatal rats, resulting in larger and fewer alveoli, reminiscent of BPD. This was associated with decreased lung endothelial nitric oxide synthase and vascular endothelial growth factor-A mRNA expression. In experimental oxygen-induced BPD, a model of arrested lung vascular and alveolar growth, AM attenuates arrested lung angiogenesis (vessel density, 6.9 +/- 1.1 versus 16.2 +/- 1.3, P < 0.05) and alveolar development (mean linear intercept, 51.9 +/- 3.2 versus 44.4 +/- 0.7, septal counts 47.6 +/- 3.4 versus 67.7 +/- 4.0, P < 0.05), an effect in part mediated by inhibition of apoptosis. AM also prevents pulmonary hypertension in this model, as assessed by decreased right ventricular hypertrophy and pulmonary artery medial wall thickness. Our findings suggest a role for AM during normal alveolar development. AM may have therapeutic potential in diseases associated with alveolar injury.

Nano-Engineered Mesenchymal Stem Cells Increase Therapeutic Efficacy of Anticancer Drug Through True Active Tumor Targeting.

PubMed

Layek, Buddhadev; Sadhukha, Tanmoy; Panyam, Jayanth; Prabha, Swayam

2018-06-01

Tumor-targeted drug delivery has the potential to improve therapeutic efficacy and mitigate non-specific toxicity of anticancer drugs. However, current drug delivery approaches rely on inefficient passive accumulation of the drug carrier in the tumor. We have developed a unique, truly active tumor-targeting strategy that relies on engineering mesenchymal stem cells (MSC) with drug-loaded nanoparticles. Our studies using the A549 orthotopic lung tumor model show that nano-engineered MSCs carrying the anticancer drug paclitaxel (PTX) home to tumors and create cellular drug depots that release the drug payload over several days. Despite significantly lower doses of PTX, nano-engineered MSCs resulted in significant inhibition of tumor growth and superior survival. Anticancer efficacy of nano-engineered MSCs was confirmed in immunocompetent C57BL/6 albino female mice bearing orthotopic Lewis Lung Carcinoma (LL/2-luc) tumors. Furthermore, at doses that resulted in equivalent therapeutic efficacy, nano-engineered MSCs had no effect on white blood cell count, whereas PTX solution and PTX nanoparticle treatments caused leukopenia. Biodistribution studies showed that nano-engineered MSCs resulted in greater than 9-fold higher AUC lung of PTX (1.5 μg.day/g) than PTX solution and nanoparticles (0.2 and 0.1 μg.day/g tissue, respectively) in the target lung tumors. Furthermore, the lung-to-liver and the lung-to-spleen ratios of PTX were several folds higher for nano-engineered MSCs relative to those for PTX solution and nanoparticle groups, suggesting that nano-engineered MSCs demonstrate significantly less off-target deposition. In summary, our results demonstrate that nano-engineered MSCs can serve as an efficient carrier for tumor-specific drug delivery and significantly improved anti-cancer efficacy of conventional chemotherapeutic drugs. Mol Cancer Ther; 17(6); 1196-206. ©2018 AACR . ©2018 American Association for Cancer Research.

Hydroxysafflor yellow A of Carthamus tinctorius attenuates lung injury of aged rats exposed to gasoline engine exhaust by down-regulating platelet activation.

PubMed

Wang, Chaoyun; Wang, Chunhua; Ma, Chunlei; Huang, Qingxian; Sun, Hongliu; Zhang, Xiaomin; Bai, Xianyong

2014-02-15

Long-term inhalation of gasoline engine exhaust (GEE) increases the risk of respiratory disease. Studies have suggested involvement of platelets in the development of some lung diseases. Hydroxysafflor yellow A (HSYA), a flavonoid compound, prevents hemostasis. Therefore, we investigated its effects on GEE-induced lung injury, and role of platelets in injury. Sixty-week-old male Sprague-Dawley rats were exposed to GEE for 4h/day for 6 weeks, and then grouped as follows: control, GEE, GEE+HSYA, GEE+HSYA+GW9662, and GEE+GW9662. Arterial oxygen tension (PaO2), carbon dioxide tension (PaCO2), pH, and the PaO2/fraction of inspired oxygen ratio (PaO2/FiO2) in the blood were detected using a blood gas analyzer. Wet/dry lung weight ratio, total protein in bronchoalveolar lavage fluid (BALF), and cytokine concentrations in serum and BALF were determined. Furthermore, cyclic adenosine monophosphate (cAMP) level and expression levels of target proteins were analyzed. Platelets were counted and their state was evaluated. HSYA attenuated GEE-mediated decreases in PaO2, PaO2/FiO2, platelet cAMP level, protein kinase A (PKA) activity, and peroxisome proliferator-activated receptor γ (PPARγ) expression. HSYA also attenuated GEE-mediated increases in lung permeability, cytokine levels in serum and BALF, plasma platelet count, and ADP-mediated platelet aggregation. Moreover, it suppressed GEE-induced increases in the expression of adhesion molecules and proinflammatory cytokines in platelets and lung tissue. Therefore, HSYA is therapeutically effective for GEE-mediated lung injury and acts by enhancing PKA activity and inhibiting platelet activation. Copyright © 2013 Elsevier GmbH. All rights reserved.

Lung dendritic cells imprint T cell lung homing and promote lung immunity through the chemokine receptor CCR4

PubMed Central

Strassner, James P.

2013-01-01

T cell trafficking into the lung is critical for lung immunity, but the mechanisms that mediate T cell lung homing are not well understood. Here, we show that lung dendritic cells (DCs) imprint T cell lung homing, as lung DC–activated T cells traffic more efficiently into the lung in response to inhaled antigen and at homeostasis compared with T cells activated by DCs from other tissues. Consequently, lung DC–imprinted T cells protect against influenza more effectively than do gut and skin DC–imprinted T cells. Lung DCs imprint the expression of CCR4 on T cells, and CCR4 contributes to T cell lung imprinting. Lung DC–activated, CCR4-deficient T cells fail to traffic into the lung as efficiently and to protect against influenza as effectively as lung DC–activated, CCR4-sufficient T cells. Thus, lung DCs imprint T cell lung homing and promote lung immunity in part through CCR4. PMID:23960189

Milano summer particulate matter (PM10) triggers lung inflammation and extra pulmonary adverse events in mice.

PubMed

Farina, Francesca; Sancini, Giulio; Battaglia, Cristina; Tinaglia, Valentina; Mantecca, Paride; Camatini, Marina; Palestini, Paola

2013-01-01

Recent studies have suggested a link between particulate matter (PM) exposure and increased mortality and morbidity associated with pulmonary and cardiovascular diseases; accumulating evidences point to a new role for air pollution in CNS diseases. The purpose of our study is to investigate PM10sum effects on lungs and extra pulmonary tissues. Milano PM10sum has been intratracheally instilled into BALB/c mice. Broncho Alveolar Lavage fluid, lung parenchyma, heart and brain were screened for markers of inflammation (cell counts, cytokines, ET-1, HO-1, MPO, iNOS), cytotoxicity (LDH, ALP, Hsp70, Caspase8-p18, Caspase3-p17) for a putative pro-carcinogenic marker (Cyp1B1) and for TLR4 pathway activation. Brain was also investigated for CD68, TNF-α, GFAP. In blood, cell counts were performed while plasma was screened for endothelial activation (sP-selectin, ET-1) and for inflammation markers (TNF-α, MIP-2, IL-1β, MPO). Genes up-regulation (HMOX1, Cyp1B1, IL-1β, MIP-2, MPO) and miR-21 have been investigated in lungs and blood. Inflammation in the respiratory tract of PM10sum-treated mice has been confirmed in BALf and lung parenchyma by increased PMNs percentage, increased ET-1, MPO and cytokines levels. A systemic spreading of lung inflammation in PM10sum-treated mice has been related to the increased blood total cell count and neutrophils percentage, as well as to increased blood MPO. The blood-endothelium interface activation has been confirmed by significant increases of plasma ET-1 and sP-selectin. Furthermore PM10sum induced heart endothelial activation and PAHs metabolism, proved by increased ET-1 and Cyp1B1 levels. Moreover, PM10sum causes an increase in brain HO-1 and ET-1. These results state the translocation of inflammation mediators, ultrafine particles, LPS, metals associated to PM10sum, from lungs to bloodstream, thus triggering a systemic reaction, mainly involving heart and brain. Our results provided additional insight into the toxicity of PM10sum and could facilitate shedding light on mechanisms underlying the development of urban air pollution related diseases.

Health care resource utilization and characteristics of patients with eosinophilic asthma in secondary health care in Finland.

PubMed

Mäkelä, Mika J; Christensen, Helene Nordahl; Karlsson, Antti; Rastogi, Sarang; Kettunen, Kirsi

2018-01-01

Background : Eosinophilic airway inflammation is common in asthma patients and appears to be associated with severe exacerbations and loss of asthma control. Objective : To describe the resource utilization and clinical characteristics of patients with eosinophilic asthma. Design : Asthma patients ≥18 years with ≥1 blood eosinophil count in secondary care (South West Finland) during 2003‒2013 were included. Clinical characteristics (age, lung function, body mass index, and comorbidities) and asthma-related resource utilization (hospital admissions, outpatient visits, and emergency room [ER] visits) were retrieved. Resource utilization rates were compared for patients with blood eosinophil ≤ or >300 cells/μL, using adjusted negative binomial regression models. Results : Overall, 4,357 eligible patients were identified (mean age 60 years, females 68%), of which 1,927 (44%) had >300 eosinophil cells/μL blood. Patients with ≤300 and >300 eosinophil counts, exhibited similar clinical characteristics, including advanced age, poor lung function, and overweight. Comorbidities such as pneumonia, sinusitis, and nasal polyps, were more frequent among those with >300 eosinophil cells/μL blood compared with patients with lower counts. Eosinophil counts >300 cells/μL were associated with greater hospital admissions (rate ratio [RR] [95% confidence interval CI]: 1.13 [1.02;1.24]) and outpatient visits (RR [95% CI]: 1.11 [1.03;1.20]) compared with patients with lower eosinophil counts. Rates of ER visits were similar between the patient groups (RR [95% CI]: 0.99 [0.87;1.12]). Conclusions : Hospital admissions and outpatient visits occurred more often for patients with eosinophil counts >300 cells/µL, than for patients with lower eosinophil counts. Routine blood eosinophil screening might be useful to identify patients with an eosinophilic phenotype eligible for more targeted treatments.

Can mean platelet volume and neutrophil-to-lymphocyte ratio be biomarkers of acute exacerbation of bronchiectasis in children?

PubMed Central

Erdem, Semiha Bahceci; Karaman, Sait; Yazici, Selcuk; Can, Demet

2017-01-01

Introduction Bronchiectasis (BE) is a parenchymal lung disease evolving as a result of recurrent lung infections and chronic inflammation. Although it has been shown in adult studies that mean platelet volume (MPV) and neutrophil-to-lymphocyte ratio (NLR) can be used as biomarkers of airway inflammation, knowledge is limited in the paediatric age group. The aim of our study is to investigate the potential of MPV and NLR as biomarkers that may indicate acute exacerbations of non-cystic fibrosis BE in children. Material and methods Children with non-cystic fibrosis BE (n = 50), who were followed in the division of Paediatric Pulmonology of our hospital between June 2010 and July 2015, were involved in the present retrospective cross-sectional study. Haemogram values during acute exacerbations and non-exacerbation periods, and a control group were compared. Results In children with bronchiectasis, the average leukocyte count (p < 0.001), platelet count (p = 0.018), absolute neutrophil count (p < 0.001), and NLR (p < 0.001) were higher, as expected, when compared with the control group. NLR values, in the period of acute exacerbation were significantly higher than the values of both the non-exacerbation periods (p = 0.02) and the control group (p < 0.001). In contrast, MPV values in the period of acute exacerbation did not exhibit a significant difference from those of non-exacerbation periods (p = 0.530) and the control group (p = 0.103). Conclusions It was concluded that leukocyte count, platelet count, absolute neutrophil count, and NLR can be used to show chronic inflammation in BE, but only NLR and absolute neutrophil count can be used as biomarkers to show acute exacerbations. PMID:29472813

INTRACELLULAR LOCALIZATION AND QUANTITATION OF TRITIATED ANTIGENS IN RETICULOENDOTHELIAL TISSUES OF MICE DURING SECONDARY AND HYPERIMMUNE RESPONSES

PubMed Central

Roberts, Audrey N.; Haurowitz, Felix

1962-01-01

Autoradiography and quantitative radiochemical techniques have been used to determine intracellular localization of tritium and the quantity of tissue-bound tritium, respectively, following injections of H3-aniline azo PGG or H3-arsanilazo PGG to yield hyperimmune or secondary response stimulation in mice. Autoradiography revealed intracytoplasmic localization of grains in macrophages of spleen and lung sections, and in Kupffer cells of liver sections following intravenous and subcutaneous injections of H3-aniline azo PGG. Quantitation of tissue section surface radioactivities in the windowless flow counter and scintillation counter, and of dissolved tissue section activities in the scintillation counter, showed that greatest radioactivity was present in lung tissue, with less in spleen, liver, and mesenteric lymph nodes from these hyperimmunized mice. Autoradiographic studies on tissue sections from mice in secondary response stimulation after subcutaneous foot-pad injections of H3-arsanilazo PGG, showed intracellular and extracellular grains over regional popliteal node sections, with intracytoplasmic grain localization over macrophages and pyroninophilic plasmacytes. Scattered macrophages in spleen and lung sections also contained intracytoplasmic radioactivity. Clusters of antibody-synthesizing cells in the regional lymph nodes were demonstrated with fluorescence microscopy, and these cells were compared to similar cells possessing radioactivity as observed in the section autoradiographs. An occasional Russell body plasma cell containing specific antibody was observed in splenic impressions. Windowless flow counting showed that greatest radioactivity was in regional node sections, with less in spleen and lung, and none in contralateral lymph nodes. A quantitative comparison between windowless flow counting and autoradiography revealed that 20 counts were required to yield one silver grain. PMID:13974279

Inhaled nitric oxide pretreatment but not posttreatment attenuates ischemia-reperfusion-induced pulmonary microvascular leak.

PubMed

Chetham, P M; Sefton, W D; Bridges, J P; Stevens, T; McMurtry, I F

1997-04-01

Ischemia-reperfusion (I/R) pulmonary edema probably reflects a leukocyte-dependent, oxidant-mediated mechanism. Nitric oxide (NO) attenuates leukocyte-endothelial cell interactions and I/R-induced microvascular leak. Cyclic adenosine monophosphate (cAMP) agonists reverse and prevent I/R-induced microvascular leak, but reversal by inhaled NO (INO) has not been tested. In addition, the role of soluble guanylyl cyclase (sGC) activation in the NO protection effect is unknown. Rat lungs perfused with salt solution were grouped as either I/R, I/R with INO (10 or 50 ppm) on reperfusion, or time control. Capillary filtration coefficients (Kfc) were estimated 25 min before ischemia (baseline) and after 30 and 75 min of reperfusion. Perfusate cell counts and lung homogenate myeloperoxidase activity were determined in selected groups. Additional groups were treated with either INO (50 ppm) or isoproterenol (ISO-10 microM) after 30 min of reperfusion. Guanylyl cyclase was inhibited with 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ-15 microM), and Kfc was estimated at baseline and after 30 min of reperfusion. (1) Inhaled NO attenuated I/R-induced increases in Kfc. (2) Cell counts were similar at baseline. After 75 min of reperfusion, lung neutrophil retention (myeloperoxidase activity) and decreased perfusate neutrophil counts were similar in all groups. (3) In contrast to ISO, INO did not reverse microvascular leak. (4) 8-bromoguanosine 3',5'-cyclic monophosphate (8-br-cGMP) prevented I/R-induced microvascular leak in ODQ-treated lungs, but INO was no longer effective. Inhaled NO attenuates I/R-induced pulmonary microvascular leak, which requires sGC activation and may involve a mechanism independent of inhibition of leukocyte-endothelial cell interactions. In addition, INO is ineffective in reversing I/R-induced microvascular leak.

Quantitative basis for component factors of gas flow proportional counting efficiencies

NASA Astrophysics Data System (ADS)

Nichols, Michael C.

This dissertation investigates the counting efficiency calibration of a gas flow proportional counter with beta-particle emitters in order to (1) determine by measurements and simulation the values of the component factors of beta-particle counting efficiency for a proportional counter, (2) compare the simulation results and measured counting efficiencies, and (3) determine the uncertainty of the simulation and measurements. Monte Carlo simulation results by the MCNP5 code were compared with measured counting efficiencies as a function of sample thickness for 14C, 89Sr, 90Sr, and 90Y. The Monte Carlo model simulated strontium carbonate with areal thicknesses from 0.1 to 35 mg cm-2. The samples were precipitated as strontium carbonate with areal thicknesses from 3 to 33 mg cm-2 , mounted on membrane filters, and counted on a low background gas flow proportional counter. The estimated fractional standard deviation was 2--4% (except 6% for 14C) for efficiency measurements of the radionuclides. The Monte Carlo simulations have uncertainties estimated to be 5 to 6 percent for carbon-14 and 2.4 percent for strontium-89, strontium-90, and yttrium-90. The curves of simulated counting efficiency vs. sample areal thickness agreed within 3% of the curves of best fit drawn through the 25--49 measured points for each of the four radionuclides. Contributions from this research include development of uncertainty budgets for the analytical processes; evaluation of alternative methods for determining chemical yield critical to the measurement process; correcting a bias found in the MCNP normalization of beta spectra histogram; clarifying the interpretation of the commonly used ICRU beta-particle spectra for use by MCNP; and evaluation of instrument parameters as applied to the simulation model to obtain estimates of the counting efficiency from simulated pulse height tallies.

Inhibition of Acid-induced Lung Injury by Hyperosmolar Sucrose in Rats

PubMed Central

Safdar, Zeenat; Yiming, Maimiti; Grunig, Gabriele; Bhattacharya, Jahar

2005-01-01

Rationale: Acid aspiration causes acute lung injury (ALI). Recently, we showed that a brief intravascular infusion of hyperosmolar sucrose, given concurrently with airway acid instillation, effectively blocks the ensuing ALI. Objectives: The objective of the present study was to determine the extent to which intravascular infusion of hyperosmolar sucrose might protect against acid-induced ALI when given either before or after acid instillation. Methods: Our studies were conducted in anesthetized rats and in isolated, blood-perfused rat lungs. We instilled HCl through the airway, and we quantified lung injury in terms of the extravascular lung water (EVLW) content, filtration coefficient (Kfc), and cell counts and protein concentration in the bronchoalveolar lavage. We infused hyperosmolar sucrose via the femoral vein. Results: In anesthetized rats, airway HCl instillation induced ALI as indicated by a 52% increase of EVLW and a threefold increase in Kfc. However, a 15-min intravenous infusion of hyperosmolar sucrose given up to 1 h before or 30 min after acid instillation markedly blunted the increases in EVLW, as well as the increases in cell count, and in protein concentration in the bronchoalveolar lavage. Hyperosmolar pretreatment also blocked the acid-induced increase of Kfc. Studies in isolated perfused lungs indicated that the protective effect of hyperosmolar sucrose was leukocyte independent. Conclusions: We conclude that a brief period of vascular hyperosmolarity protects against acid-induced ALI when the infusion is administered shortly before, or shortly after, acid instillation in the airway. The potential applicability of hyperosmolar sucrose in therapy for ALI requires consideration. PMID:16109982

Dosimetric assessment from 212Pb inhalation at a thorium purification plant.

PubMed

Campos, M P; Pecequilo, B R S

2004-01-01

At the Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, Brazil, there is a facility (thorium purification plant) where materials with high thorium concentrations are manipulated. In order to estimate afterwards the lung cancer risk for the workers, the thoron daughter (212Pb) levels were assessed and the committed effective and lung committed equivalent doses for workers in place. A total of 28 air filter samples were measured by total alpha counting through the modified Kusnetz method, to determine the 212Pb concentraion. The committed effective dose and lung committed equivalent dose due to 212Pb inhalation were derived from compartmental analysis following the ICRP 66 lung compartmental model, and ICRP 67 lead metabolic model.

Ventilation/perfusion SPECT or SPECT/CT for lung function imaging in patients with pulmonary emphysema?

PubMed

Froeling, Vera; Heimann, Uwe; Huebner, Ralf-Harto; Kroencke, Thomas J; Maurer, Martin H; Doellinger, Felix; Geisel, Dominik; Hamm, Bernd; Brenner, Winfried; Schreiter, Nils F

2015-07-01

To evaluate the utility of attenuation correction (AC) of V/P SPECT images for patients with pulmonary emphysema. Twenty-one patients (mean age 67.6 years) with pulmonary emphysema who underwent V/P SPECT/CT were included. AC/non-AC V/P SPECT images were compared visually and semiquantitatively. Visual comparison of AC/non-AC images was based on a 5-point likert scale. Semiquantitative comparison assessed absolute counts per lung (aCpLu) and lung lobe (aCpLo) for AC/non-AC images using software-based analysis; percentage counts (PC = (aCpLo/aCpLu) × 100) were calculated. Correlation between AC/non-AC V/P SPECT images was analyzed using Spearman's rho correlation coefficient; differences were tested for significance with the Wilcoxon rank sum test. Visual analysis revealed high conformity for AC and non-AC V/P SPECT images. Semiquantitative analysis of PC in AC/non-AC images had an excellent correlation and showed no significant differences in perfusion (ρ = 0.986) or ventilation (ρ = 0.979, p = 0.809) SPECT/CT images. AC of V/P SPECT images for lung lobe-based function imaging in patients with pulmonary emphysema do not improve visual or semiquantitative image analysis.

In vitro gallium-67 lung index for the evaluation of sarcoidosis

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

Braude, A.C.; Cohen, R.; Rahmani, R.

1984-11-01

In the evaluation of the active alveolitis of pulmonary sarcoidosis, both the proportional lymphocyte count obtained by bronchoalveolar lavage and state of activation of the alveolar macrophage by gallium scanning are required. We injected 6 mCi (200 MBq) of /sup 67/Ga intravenously on 24 occasions in 13 patients with biopsy-proved sarcoidosis. Forty-eight hours later, patients were scanned with a rectilinear scanner and the generated scintigrams were evaluated using the NIH index. Seventy-two hours after injection, bronchoalveolar lavage was performed, and venous blood was sampled. The harvested lavage fluid was analyzed for absolute and proportional cell counts, and radioactivity was measuredmore » in blood and BAL fluid. An in vitro /sup 67/Ga index was generated and expressed as counts/100,000 alveolar macrophages/ml blood (mean, 0.0146 +/- 0.0087 SD). There was a significant relationship between the in vitro index and proportional lymphocyte BAL counts (r . 0.79; p less than 0.002) that was comparable to that obtained using the NIH index (r . 0.74; p less than 0.005). These data suggest that the in vitro index might offer a more objective assessment of /sup 67/Ga uptake by the lung, but this would require validation against clinical parameters in a prospective study.« less

Methods to improve routine bioassay monitoring for freshly separated, poorly transported plutonium

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

Bihl, D.E.; Lynch, T.P.; Carbaugh, E.H.

1988-09-01

Several human cases involving inhalation of plutonium oxide at Hanford have shown clearance half-times from the lung that are much longer than the 500-day half-time recommended for class Y plutonium in Publication 30 of the International Commission on Radiological Protection(ICRP). The more tenaciously retained material is referred to as super class Y plutonium. The ability to detect super class Y plutonium by current routine bioassay measurements is shown to be poor. Pacific Northwest Laboratory staff involved in the Hanford Internal Dosimetry Program investigated four methods to se if improvements in routine monitoring of workers for fresh super class Y plutoniummore » are feasible. The methods were lung counting, urine sampling, fecal sampling, and use of diethylenetriaminepentaacetate (DTPA) to enhance urinary excretion. Use of DTPA was determined to be not feasible. Routine fecal sampling was found to be feasible but not recommended. Recommendations were made to improve the detection level for routine annual urinalysis and routine annual lung counting. 12 refs., 9 figs., 7 tabs.« less

Calibration of phoswich-based lung counting system using realistic chest phantom.

PubMed

Manohari, M; Mathiyarasu, R; Rajagopal, V; Meenakshisundaram, V; Indira, R

2011-03-01

A phoswich detector, housed inside a low background steel room, coupled with a state-of-art pulse shape discrimination (PSD) electronics is recently established at Radiological Safety Division of IGCAR for in vivo monitoring of actinides. The various parameters of PSD electronics were optimised to achieve efficient background reduction in low-energy regions. The PSD with optimised parameters has reduced steel room background from 9.5 to 0.28 cps in the 17 keV region and 5.8 to 0.3 cps in the 60 keV region. The Figure of Merit for the timing spectrum of the system is 3.0. The true signal loss due to PSD was found to be less than 2 %. The phoswich system was calibrated with Lawrence Livermore National Laboratory realistic chest phantom loaded with (241)Am activity tagged lung set. Calibration factors for varying chest wall composition and chest wall thickness in terms of muscle equivalent chest wall thickness were established. (241)Am activity in the JAERI phantom which was received as a part of IAEA inter-comparison exercise was estimated. This paper presents the optimisation of PSD electronics and the salient results of the calibration.

[Establishment and evaluation of extracorporeal circulation model in rats].

PubMed

Xie, Xiao-Jun; Tao, Kai-Yu; Tang, Meng-Lin; Du, Lei; An, Qi; Lin, Ke; Gan, Chang-Ping; Chen, You-Wen; Luo, Shu-Hua

2012-09-01

To establish an extracorporeal circulation (ECC) rat model, and evaluate the inflammatory response and organ injury induced in the model. SD rats were anesthetized and cannulated from right common carotid artery to left femoral vein to establish the bypass of extracorporeal circulation. Then the rats were randomly divided into ECC group and sham group. The rats in ECC group were subjected to extracorporeal circulation for 2 hours and then rest for 2 hours, while the rats in sham group were only observed for 4 hours without extracorporeal circulation. After that, blood routine examination, blood gas analysis, the measurement of pro-inflammatory factors in bronchoalveolar lavage fluid and lung tissue were performed to evaluate the lung injury induced by ECC. Circulating endothelial cells were also calculated by flow cytometry to assess the vascular endothelial injury. At 2 hours after ECC, red blood cell counts in both groups kept normal, while leukocyte and neutrophil counts, plasmatic tumor necrosis factor-a level and neutrophil elastase level, circulating endothelial cells in the rats of ECC group were significantly higher than those in sham group. Tumor necrosis factor-alpha in bronchoalveolar lavage fluid and water content in lung of the ECC rats were also significantly higher, while the oxygenation index was significantly lower. Neutrophil infiltration was also observed in lung tissues with increased thickness of alveolar membrane in ECC group. The ECC model established from right common carotid artery to left femoral vein in our study can successfully induce systemic inflammatory response, and acute lung injury associated with inflammation.

Inhibition of insulin-like growth factor receptor-1 reduces necroptosis-related markers and attenuates LPS-induced lung injury in mice.

PubMed

Lee, Su Hwan; Shin, Ju Hye; Song, Joo Han; Leem, Ah Young; Park, Moo Suk; Kim, Young Sam; Chang, Joon; Chung, Kyung Soo

2018-04-15

Insulin-like growth factor-1 (IGF-1) levels are known to increase in the bronchoalveolar lavage fluid (BALF) of patients with acute respiratory distress syndrome. Herein, we investigated the role of IGF-1 in lipopolysaccharide (LPS)-induced lung injury. In LPS-treated cells, expressions of receptor-interacting protein 3 (RIP3) and phosphorylated mixed lineage kinase domain-like protein (MLKL) were decreased in IGF-1 receptor small interfering RNA (siRNA)-treated cells compared to control cells. The levels of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-10, tumour necrosis factor-α, and macrophage inflammatory protein 2/C-X-C motif chemokine ligand 2 in the supernatant were significantly reduced in IGF-1 receptor siRNA-treated cells compared to control cells. In LPS-induced murine lung injury model, total cell counts, polymorphonuclear leukocytes counts, and pro-inflammatory cytokine levels in the BALF were significantly lower and histologically detected lung injury was less common in the group treated with IGF-1 receptor monoclonal antibody compared to the non-treated group. On western blotting, RIP3 and phosphorylated MLKL expressions were relatively decreased in the IGF-1 receptor monoclonal antibody group compared to the non-treated group. IGF-1 may be associated with RIP3-mediated necroptosis in vitro, while blocking of the IGF-1 pathway may reduce LPS-induced lung injuries in vivo. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of surfactant/budesonide therapy on oxidative modifications in the lung in experimental meconium-induced lung injury.

PubMed

Mikolka, P; Kopincova, J; Tomcikova Mikusiakova, L; Kosutova, P; Antosova, M; Calkovska, A; Mokra, D

2016-02-01

Meconium aspiration syndrome (MAS) is a serious condition, which can be treated with exogenous surfactant and mechanical ventilation. However, meconium-induced inflammation, lung edema and oxidative damage may inactivate delivered surfactant and thereby reduce effectiveness of the therapy. As we presumed that addition of anti-inflammatory agent into the surfactant may alleviate inflammation and enhance efficiency of the therapy, this study was performed to evaluate effects of surfactant therapy enriched with budesonide versus surfactant-only therapy on markers of oxidative stress in experimental model of MAS. Meconium suspension (25 mg/ml, 4 ml/kg) was instilled into the trachea of young rabbits, whereas one group of animals received saline instead of meconium (C group, n = 6). In meconium-instilled animals, respiratory failure developed within 30 min. Then, meconium-instilled animals were divided into 3 groups according to therapy (n = 6 each): with surfactant therapy (M + S group), with surfactant + budesonide therapy (M + S + B), and without therapy (M group). Surfactant therapy consisted of two bronchoalveolar lavages (BAL) with diluted surfactant (Curosurf, 5 mg phospholipids/ml, 10 ml/kg) followed by undiluted surfactant (100 mg phospholipids/kg), which was in M + S + B group enriched with budesonide (Pulmicort, 0.5 mg/ml). Animals were oxygen-ventilated for additional 5 hours. At the end of experiment, blood sample was taken for differential white blood cell (WBC) count. After euthanizing animals, left lung was saline-lavaged and cell differential in BAL was determined. Oxidative damage, i.e. oxidation of lipids (thiobarbituric acid reactive substance (TBARS) and conjugated dienes) and proteins (dityrosine and lysine-lipoperoxidation products) was estimated in lung homogenate and isolated mitochondria. Total antioxidant capacity was evaluated in lung homogenate and plasma. Meconium instillation increased transmigration of neutrophils and production of free radicals compared to controls (P < 0.05). Surfactant therapy, but particularly combined surfactant + budesonide therapy reduced markers of oxidative stress versus untreated animals (P < 0.05). In conclusion, budesonide added into surfactant enhanced effect of therapy on oxidative damage of the lung.

Exercise-Induced Asthma

MedlinePlus

... as triggers include: Cold air Dry air Air pollution High pollen counts Chlorine in swimming pools Chemicals used with ice rink resurfacing equipment Respiratory infections or other lung disease Activities with extended periods of deep breathing, such ...

Evaluation of the preventive effect of dexpanthenol in radiation injury by lung perfusion scintigraphy: a preclinical experimental model of radiation injury.

PubMed

Koç, Zehra P; İn, Erdal; Karslioğlu, İhsan; Üçer, Özlem; Canpolat, Sinan

2015-12-01

The aim of this study was to show the preventative effects of dexpanthenol in radiation injuries caused by radiotherapy (RT) through the use of lung perfusion scintigraphy in the pre-RT and post-RT periods. Six male New Zealand rabbits (5-6 months of age and ∼2.5-3 kg in weight) were the used in this study. The animals were subjected to Tc-macroaggregated albumin lung perfusion scintigraphy in the pre-RT and post-RT (i.e. 2 weeks after treatment) periods. The scintigraphies were performed with the same dose by the same staff and the methodology used the same acquisition parameters. The rabbits were divided into two groups: group I (administered RT only) and group II (also administered intramuscular 500 mg dexpanthenol injections for 14 consecutive days after RT). Quantification was performed to compare the groups and the quantification variables were compared using a paired samples t-test, with P value less than 0.05 considered to be statistically significant. Histopathological analysis was also carried out. The post-RT scintigraphies indicated a decrease in the counts in both lungs, suggesting early post-RT injury. The difference between the counts obtained from both lungs in groups I and II was significantly different and favoured group II. Histopathological results confirmed the scintigraphy results. It is possible to estimate post-RT changes in the early period (in contrast to previous data) by lung perfusion scintigraphy. Dexpanthenol may also reduce the effects of RT to a degree. Although this is the first study to report the preventive effects of dexpanthenol on RT injuries, further studies are warranted in this area.

Ameliorating effect of an interferon inducer polyinosinic-polycytidylic acid on bleomycin-induced lung fibrosis in hamsters. Morphologic and biochemical evidence.

PubMed Central

Giri, S. N.; Hyde, D. M.

1988-01-01

The effects of polyinosinic-polycytidylic acid (Poly I:C), an inducer of interferons, on bleomycin (Bleo)-induced lung fibrosis was studied in hamsters. Poly I:C (10 mg/kg intraperitoneally) was administered for two days and immediately before intratracheal instillation of bleomycin (7.5 U/kg) or an equivalent volume of saline and thereafter daily for 13 days. The lung hydroxyproline in control, Poly I:C, Bleo, and Bleo + Poly I:C groups averaged 791, 752, 1177, and 766 micrograms/lung. As compared to control, the prolyl hydroxylase activity in the Bleo group was increased by 83% whereas in Bleo + Poly I:C group, the activity was increased by 42%. Protein in the bronchoalveolar lavage supernatant in Poly I:C, Bleo and Bleo + Poly I:C groups were 72, 286, and 206% of the control, respectively. There was no difference in total leukocyte counts between Bleo + Poly I:C and Bleo groups, but the differential cell counts were changed. The numbers of neutrophils, monocytes, lymphocytes, and eosinophils were 50, 84, 91, and 10% of Bleo group, respectively. Morphometric estimates of the volume of parenchymal lesion within the lung showed that hamsters in Bleo + Poly I:C group had significantly less volume of lesion (1.0 cucm) than the Bleo group (1.6 cucm). In addition, the fibrotic lesions in Bleo + Poly I:C group were multifocal and primarily proximal acinar in location, had fewer extracellular fibers, neutrophils and monocytes. Poly I:C treatment ameliorated bleomycin-induced lung collagen accumulation. Images Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 PMID:2462354

Effects of Phosphodiesterase 4 Inhibition on Alveolarization and Hyperoxia Toxicity in Newborn Rats

PubMed Central

Méhats, Céline; Franco-Montoya, Marie-Laure; Boucherat, Olivier; Lopez, Emmanuel; Schmitz, Thomas; Zana, Elodie; Evain-Brion, Danièle; Bourbon, Jacques; Delacourt, Christophe; Jarreau, Pierre-Henri

2008-01-01

Background Prolonged neonatal exposure to hyperoxia is associated with high mortality, leukocyte influx in airspaces, and impaired alveolarization. Inhibitors of type 4 phosphodiesterases are potent anti-inflammatory drugs now proposed for lung disorders. The current study was undertaken to determine the effects of the prototypal phosphodiesterase-4 inhibitor rolipram on alveolar development and on hyperoxia-induced lung injury. Methodology/Findings Rat pups were placed under hyperoxia (FiO2>95%) or room air from birth, and received rolipram or its diluent daily until sacrifice. Mortality rate, weight gain and parameters of lung morphometry were recorded on day 10. Differential cell count and cytokine levels in bronchoalveolar lavage and cytokine mRNA levels in whole lung were recorded on day 6. Rolipram diminished weight gain either under air or hyperoxia. Hyperoxia induced huge mortality rate reaching 70% at day 10, which was prevented by rolipram. Leukocyte influx in bronchoalveolar lavage under hyperoxia was significantly diminished by rolipram. Hyperoxia increased transcript and protein levels of IL-6, MCP1, and osteopontin; rolipram inhibited the increase of these proteins. Alveolarization was impaired by hyperoxia and was not restored by rolipram. Under room air, rolipram-treated pups had significant decrease of Radial Alveolar Count. Conclusions Although inhibition of phosphodiesterases 4 prevented mortality and lung inflammation induced by hyperoxia, it had no effect on alveolarization impairment, which might be accounted for by the aggressiveness of the model. The less complex structure of immature lungs of rolipram-treated pups as compared with diluent-treated pups under room air may be explained by the profound effect of PDE4 inhibition on weight gain that interfered with normal alveolarization. PMID:18941502

Open lung approach versus standard protective strategies: Effects on driving pressure and ventilatory efficiency during anesthesia - A pilot, randomized controlled trial.

PubMed

Ferrando, Carlos; Suarez-Sipmann, Fernando; Tusman, Gerardo; León, Irene; Romero, Esther; Gracia, Estefania; Mugarra, Ana; Arocas, Blanca; Pozo, Natividad; Soro, Marina; Belda, Francisco J

2017-01-01

Low tidal volume (VT) during anesthesia minimizes lung injury but may be associated to a decrease in functional lung volume impairing lung mechanics and efficiency. Lung recruitment (RM) can restore lung volume but this may critically depend on the post-RM selected PEEP. This study was a randomized, two parallel arm, open study whose primary outcome was to compare the effects on driving pressure of adding a RM to low-VT ventilation, with or without an individualized post-RM PEEP in patients without known previous lung disease during anesthesia. Consecutive patients scheduled for major abdominal surgery were submitted to low-VT ventilation (6 ml·kg-1) and standard PEEP of 5 cmH2O (pre-RM, n = 36). After 30 min estabilization all patients received a RM and were randomly allocated to either continue with the same PEEP (RM-5 group, n = 18) or to an individualized open-lung PEEP (OL-PEEP) (Open Lung Approach, OLA group, n = 18) defined as the level resulting in maximal Cdyn during a decremental PEEP trial. We compared the effects on driving pressure and lung efficiency measured by volumetric capnography. OL-PEEP was found at 8±2 cmH2O. 36 patients were included in the final analysis. When compared with pre-RM, OLA resulted in a 22% increase in compliance and a 28% decrease in driving pressure when compared to pre-RM. These parameters did not improve in the RM-5. The trend of the DP was significantly different between the OLA and RM-5 groups (p = 0.002). VDalv/VTalv was significantly lower in the OLA group after the RM (p = 0.035). Lung recruitment applied during low-VT ventilation improves driving pressure and lung efficiency only when applied as an open-lung strategy with an individualized PEEP in patients without lung diseases undergoing major abdominal surgery. ClinicalTrials.gov NCT02798133.

Comparison of 133 xenon ventilation equilibrium scan (XV) and 99m technetium transmission (TT) scan for use in regional lung analysis by 2D gamma scintigraphy in healthy and cystic fibrosis lungs.

PubMed

Zeman, Kirby L; Wu, Jihong; Donaldson, Scott H; Bennett, William D

2013-04-01

Quantification of particle deposition in the lung by gamma scintigraphy requires a reference image for location of regions of interest (ROIs) and normalization to lung thickness. In various laboratories, the reference image is made by a transmission scan ((57)Co or (99m)Tc) or gas ventilation scan ((133)Xe or (81)Kr). There has not been a direct comparison of measures from the two methods. We compared (99m)Tc transmission scans to (133)Xe equilibrium ventilation scans as reference images for 38 healthy subjects and 14 cystic fibrosis (CF) patients for their effects on measures of regional particle deposition: the central-to-peripheral ratio of lung counts (C/P); and ROI area versus forced vital capacity. Whole right lung ROI was based on either an isocontour threshold of three times the soft tissue transmission (TT) or a threshold of 20% of peak xenon ventilation counts (XV). We used a central ROI drawn to 50% of height and of width of the whole right lung ROI and placed along the left lung margin and centered vertically. In general, the correlation of normalized C/P (nC/P) between the two methods was strong. However, the value of nC/P was significantly smaller for the XV method than the TT method. Regression equations for the relationship of nC/P between the two methods were, for healthy subjects, y=0.75x+0.61, R(2)=0.64 using rectangular ROIs and y=0.76x+0.45, R(2)=0.66 using isocontour ROIs; and for CF patients, y=0.94x+0.46, R(2)=0.43 and y=0.85x+0.42, R(2)=0.41, respectively. (1) A transmission scan with an isocontour outline in combination with a rectangular central region to define the lung borders may be more useful than a ventilation scan. (2) Close correlation of nC/Ps measured by transmission or gas ventilation should allow confident comparison of values determined by the two methods.

Effect of peritoneal cavity lavage with 0.9% and 3.0% saline solution in the lung and spleen of gerbils with induced peritonitis.

PubMed

Nunes, Vinícius Rodrigues Taranto; Barbuto, Rafael Calvão; Vidigal, Paula Vieira Teixeira; Pena, Guilherme Nogueira; Rocha, Silvia Lunardi; de Siqueira, Lucas Tourinho; Caliari, Marcelo Vidigal; de Araujo, Ivana Duval

2014-04-01

Peritoneal cavity lavage is used widely in the treatment of peritonitis. Nonetheless, some studies question its rationale and prove it to be deleterious to the mesothelium. The present study aims to determine whether 0.9% and 3.0% saline lavage of the peritoneal cavity have an effect on the early systemic inflammatory response, namely, in the lung injury and splenic cellularity of gerbils with induced peritonitis. Thirty-four male gerbils were divided into four groups: Control (n=9), submitted to laparotomy at time zero, re-laparotomy after 2 h, and sacrificed after a total of 6 h from start; untreated (n=8), submitted to peritonitis induction through cecal ligation and puncture (CLP) at time zero, re-laparotomy intended for drying of abdominal cavity and resection of the ischemic cecum after 2 h, and sacrifice after a total of 6 h from start; saline (n=8), submitted to peritonitis induction through CLP at time zero, re-laparotomy intended for warm 0.9% saline lavage of the abdominal cavity and resection of the ischemic cecum after 2 h, and sacrificed after a total of 6 h from start; and hypertonic (n=9), submitted to peritonitis induction through CLP at time zero, re-laparotomy intended for warm hypertonic saline (3.0%) lavage of the abdominal cavity and resection of the ischemic cecum after 2 h, and sacrificed after a total of 6 h from start. After sacrifice, we collected the left lung and the spleen for morphometric analysis. In the both the saline and hypertonic groups, there was significant decrease in the mean nuclei count in the lungs, compared with the untreated group (p<0.01). There was no difference in terms of nuclei count in the spleen among groups (p>0.05). The present study demonstrated that the peritoneal lavage with large volumes of warm 0.9% and 3.0% saline has a beneficial effect on the early systemic inflammatory response in infected animals, modulating and reducing the lung injury but having no effect on splenic cell count.

An analysis of dependency of counting efficiency on worker anatomy for in vivo measurements: whole-body counting

NASA Astrophysics Data System (ADS)

Zhang, Binquan; Mille, Matthew; Xu, X. George

2008-07-01

In vivo radiobioassay is integral to many health physics and radiological protection programs dealing with internal exposures. The Bottle Manikin Absorber (BOMAB) physical phantom has been widely used for whole-body counting calibrations. However, the shape of BOMAB phantoms—a collection of plastic, cylindrical shells which contain no bones or internal organs—does not represent realistic human anatomy. Furthermore, workers who come in contact with radioactive materials have rather different body shape and size. To date, there is a lack of understanding about how the counting efficiency would change when the calibrated counter is applied to a worker with complicated internal organs or tissues. This paper presents a study on various in vivo counting efficiencies obtained from Monte Carlo simulations of two BOMAB phantoms and three tomographic image-based models (VIP-Man, NORMAN and CNMAN) for a scenario involving homogeneous whole-body radioactivity contamination. The results reveal that a phantom's counting efficiency is strongly dependent on the shape and size of a phantom. Contrary to what was expected, it was found that only small differences in efficiency were observed when the density and material composition of all internal organs and tissues of the tomographic phantoms were changed to water. The results of this study indicate that BOMAB phantoms with appropriately adjusted size and shape can be sufficient for whole-body counting calibrations when the internal contamination is homogeneous.

Hepatic Warm Ischemia-Reperfusion-Induced Increase in Pulmonary Capillary Filtration Is Ameliorated by Administration of a Multidrug Resistance-Associated Protein 1 Inhibitor and Leukotriene D4 Antagonist (MK-571) Through Reducing Neutrophil Infiltration and Pulmonary Inflammation and Oxidative Stress in Rats.

PubMed

Yeh, D Y-W; Yang, Y-C; Wang, J-J

2015-05-01

Hepatopulmonary syndrome (HPS) is the major complication subsequent to liver ischemia and reperfusion (I/R) injury after resection or transplantation of liver. Hallmarks of HPS include increases in pulmonary leukotrienes and neutrophil recruitment and infiltrating across capillaries. We aimed to investigate the protective efficacy of MK-571, a multidrug resistance-associated protein 1 inhibitor and leukotriene D4 agonist, against hepatic I/R injury-associated change in capillary filtration. Eighteen Sprague-Dawley male rats were evenly divided into a sham-operated group, a hepatic I/R group, and an MK-571-treated I/R group. MK-571 was administered intraperitoneally 15 min before hepatic ischemia and every 12 hours during reperfusion. Ischemia was conducted by occluding the hepatic artery and portal vein for 30 min, followed by removing the clamps and closing the incision. Forty-eight hours after hepatic ischemia, we assessed the pulmonary capillary filtration coefficient (Kfc) through the use of in vitro-isolated, perfused rat lung preparation. We also measured the lung wet-to-dry weight ratio (W/D) and protein concentration in broncho-alveolar lavage fluid (PCBAL). Lung inflammation and oxidative stress were evaluated by use of tissue tumor necrosis factor (TNF)-α and malondialdehyde levels and lavage differential macrophage and neutrophil cell count. Hepatic I/R injury markedly increased Kfc, W/D, PCBAL, tissue TNF-α level, and differential neutrophil cell count (P < .05). MK-571 treatment reduced neutrophil infiltration and lung inflammation and improved pulmonary capillary filtration, collectively suggesting lung protection. Treatment with MK-571 before and during hepatic ischemia and reperfusion protects lung against pulmonary capillary barrier function impairment through decreasing pulmonary lung inflammation and lavage neutrophils. Copyright © 2015 Elsevier Inc. All rights reserved.

Rapamycin reverses paraquat-induced acute lung injury in a rat model through inhibition of NFκB activation

PubMed Central

Chen, Da; Ma, Tao; Liu, Xiao-Wei; Yang, Chen; Liu, Zhi

2015-01-01

Objective: To evaluate the role of rapamycin (RAPA) in paraquat (PQ)-induced acute lung injury. Methods: Lung tissues were stained with HE and lung histology was observed. Mortality rate, and neutrophil and leukocyte count in blood and bronchoalveolar lavage fluid (BALF) were recorded. Protein content in BALF was determined by Coomassie blue staining. Malondialdehyde (MDA) content, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activity in blood were determined by thiobarbituric acid (TBA) assay, pyrogallol autoxidation method, and modified Haefman method, respectively. The NF-κB activity was measured by gel electrophoretic mobility shift assay (EMSA). Carbon dioxide partial pressure (PaCO2), partial pressure of oxygen (PaO2) and pH values were measured by automated blood gas analyzer. Results: HE staining results demonstrated RAPA alleviated pathological changes of acute alveolitis in SD rats. Trend of protein content in BALF was PQ group > RAPA treatment group > control group (P < 0.05). Neutrophil and leukocyte count in RAPA treatment group was significantly lower than PQ group at 3, 5, and 7 days after injection (P < 0.05). Trend of MDA content was RAPA treatment group > PQ group > control group (P < 0.05). Trend of GSH-Px and SOD activity was control group > RAPA treatment group > PQ group (P < 0.05). Compared with PQ group, PaO2 in RAPA treatment group was markedly higher and PaCO2 was lower (P < 0.05). Conclusion: PQ-induced acute lung injury was effectively reversed with RAPA, through inhibition of NF-κB activation. PMID:26191153

Efficiency of synaptic transmission of single-photon events from rod photoreceptor to rod bipolar dendrite.

PubMed

Schein, Stan; Ahmad, Kareem M

2006-11-01

A rod transmits absorption of a single photon by what appears to be a small reduction in the small number of quanta of neurotransmitter (Q(count)) that it releases within the integration period ( approximately 0.1 s) of a rod bipolar dendrite. Due to the quantal and stochastic nature of release, discrete distributions of Q(count) for darkness versus one isomerization of rhodopsin (R*) overlap. We suggested that release must be regular to narrow these distributions, reduce overlap, reduce the rate of false positives, and increase transmission efficiency (the fraction of R* events that are identified as light). Unsurprisingly, higher quantal release rates (Q(rates)) yield higher efficiencies. Focusing here on the effect of small changes in Q(rate), we find that a slightly higher Q(rate) yields greatly reduced efficiency, due to a necessarily fixed quantal-count threshold. To stabilize efficiency in the face of drift in Q(rate), the dendrite needs to regulate the biochemical realization of its quantal-count threshold with respect to its Q(count). These considerations reveal the mathematical role of calcium-based negative feedback and suggest a helpful role for spontaneous R*. In addition, to stabilize efficiency in the face of drift in degree of regularity, efficiency should be approximately 50%, similar to measurements.

Waiting Narratives of Lung Transplant Candidates

PubMed Central

Yelle, Maria T.; Stevens, Patricia E.; Lanuza, Dorothy M.

2013-01-01

Before 2005, time accrued on the lung transplant waiting list counted towards who was next in line for a donor lung. Then in 2005 the lung allocation scoring system was implemented, which meant the higher the illness severity scores, the higher the priority on the transplant list. Little is known of the lung transplant candidates who were listed before 2005 and were caught in the transition when the lung allocation scoring system was implemented. A narrative analysis was conducted to explore the illness narratives of seven lung transplant candidates between 2006 and 2007. Arthur Kleinman's concept of illness narratives was used as a conceptual framework for this study to give voice to the illness narratives of lung transplant candidates. Results of this study illustrate that lung transplant candidates expressed a need to tell their personal story of waiting and to be heard. Recommendation from this study calls for healthcare providers to create the time to enable illness narratives of the suffering of waiting to be told. Narrative skills of listening to stories of emotional suffering would enhance how healthcare providers could attend to patients' stories and hear what is most meaningful in their lives. PMID:23476760

Waiting narratives of lung transplant candidates.

PubMed

Yelle, Maria T; Stevens, Patricia E; Lanuza, Dorothy M

2013-01-01

Before 2005, time accrued on the lung transplant waiting list counted towards who was next in line for a donor lung. Then in 2005 the lung allocation scoring system was implemented, which meant the higher the illness severity scores, the higher the priority on the transplant list. Little is known of the lung transplant candidates who were listed before 2005 and were caught in the transition when the lung allocation scoring system was implemented. A narrative analysis was conducted to explore the illness narratives of seven lung transplant candidates between 2006 and 2007. Arthur Kleinman's concept of illness narratives was used as a conceptual framework for this study to give voice to the illness narratives of lung transplant candidates. Results of this study illustrate that lung transplant candidates expressed a need to tell their personal story of waiting and to be heard. Recommendation from this study calls for healthcare providers to create the time to enable illness narratives of the suffering of waiting to be told. Narrative skills of listening to stories of emotional suffering would enhance how healthcare providers could attend to patients' stories and hear what is most meaningful in their lives.

Pulmonary actinomycosis

MedlinePlus

The health care provider will perform a physical exam, and ask about your medical history and symptoms. Tests that may be done include: Bronchoscopy with culture Complete blood count (CBC) Chest x-ray Chest CT scan Lung biopsy Modified AFB smear of sputum ...

Protective effects of edaravone combined puerarin on inhalation lung injury induced by black gunpowder smog.

PubMed

Wang, Zhengguan; Li, Ruibing; Liu, Yifan; Liu, Xiaoting; Chen, Wenyan; Xu, Shumin; Guo, Yuni; Duan, Jinyang; Chen, Yihong; Wang, Chengbin

2015-05-01

The present study aimed to investigate the combined effects of puerarin with edaravone on inhalation lung injury induced by black gunpowder smog. Male Wistar rats were divided into five groups (control group, edaravone group, puerarin group, edaravone combined with puerarin group and inhalation group). The severity of pulmonary injuries was evaluated after inducing acute lung injury. Arterial blood gas, inflammatory cytokines, biochemical, parameters, cell counting, W/D weight ratio and histopathology were analyzed. Results in lung tissues, either edaravone or puerarin treatment alone showed significant protective effects against neutrophil infiltration and tissue injury, as demonstrated by myeloperoxidase activity and histopathological analysis (all p<0.05). In addition, combined treatment with both edaravone and puerarin demonstrated additive protective effects on smog-induced lung injury, compared with single treatment. Combination of edaravone and puerarin shows promise as a new treatment option for acute lung injury/acute respiratory distress syndrome patients. Copyright © 2015 Elsevier B.V. All rights reserved.

STEFFY-software to calculate nuclide-specific total counting efficiency in well-type γ-ray detectors.

PubMed

Pommé, S

2012-09-01

A software package is presented to calculate the total counting efficiency for the decay of radionuclides in a well-type γ-ray detector. It is specifically applied to primary standardisation of activity by means of 4πγ-counting with a NaI(Tl) well-type scintillation detector. As an alternative to Monte Carlo simulations, the software combines good accuracy with superior speed and ease-of-use. It is also well suited to investigate uncertainties associated with the 4πγ-counting method for a variety of radionuclides and detector dimensions. In this paper, the underlying analytical models for the radioactive decay and subsequent counting efficiency of the emitted radiation in the detector are summarised. Copyright © 2012 Elsevier Ltd. All rights reserved.

Validity of mini-dose gallium for objective quantification of alveolitis in pulmonary sarcoidosis

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

Vitti, R.; Maurer, A.H.; Siegel, J.A.

1985-05-01

Patents (pts) with pulmonary sarcoidosis will often have frequent gallium (Ga) studies to assess the response of alveolitis to corticosteroid therapy. Since many pts are young and the cumulative radiation burden significant the authors have evaluated the ability of computer based Ga lung imaging to reliably quantify Ga activity using a 0.5 mCi dose of Ga. Twelve pts with biopsy proven pulmonary sarcoidosis received 0.5 mCi of Ga-67 citrate intravenously and had a posterior view of the chest including a portion of the liver obtained at 24 hrs post injection. At 24 hrs the pts received an additional 2.5 mCimore » and were then imaged at 48 and 72 hrs. A gallium score (GS) was computer generated as follows: regions of interest (ROI's) were manually created for the lungs, liver and background. Following a 9 point spatial smooth and background subtraction, the images were scaled so that the liver activity was assigned an arbitrary value of 400 counts per pixel. The resulting average counts per pixel for the lungs were then summed for the GS. Using a paired T-test there was only a borderline significant difference (0.05« less

Kinetics of leukocyte sequestration in the lungs of acutely septic primates: A study using sup 111 In-labeled autologous leukocytes

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

Hangen, D.H.; Segall, G.M.; Harney, E.W.

1990-03-01

To further clarify the role of leukocytes in the pathogenesis of ARDS, we studied the localization and kinetics of leukocyte migration using 111In-labeled autologous white cell scans ({sup 111}In wbc scans) in four primates made acutely septic with infusions of Escherichia coli. Whole body images were obtained with a gamma camera and were acquired on computer every 15 min beginning immediately after the E. coli infusion. Simultaneous measurements of C5a and peripheral blood leukocyte count were also obtained. Within 5 min of initiating sepsis, three major events occurred: complement activation as measured by the production of C5a, a profound fallmore » in peripheral leukocyte count, and a significant increase in the sequestration of leukocytes in the lungs. The pulmonary sequestration reached a peak at 15 min with a mean of 152% of baseline activity. This sequestration consisted of a population that was predominantly neutrophils. Damage to the pulmonary capillary endothelium was demonstrated by an increase in extravascular lung water. The results support a role for neutrophils and complement as mediators in the pathogenesis of ARDS.« less

The effect of patient position during trauma surgery on fat embolism syndrome: An experimental study.

PubMed

Syed, Khalid A; Blankstein, Michael; Bhandari, Mohit; Nakane, Masaki; Zdero, Radovan; Schemitsch, Emil H

2014-03-01

The aim of this study was to compare the effect of supine versus lateral position on clinical signs of fat embolism during orthopedic trauma surgery. Dogs served as the current study model, which could be extended and/or serve as a basis for future in vivo studies on humans. It was hypothesized that there would be an effect of position on clinical signs of fat embolism syndrome in a dog model. 12 dogs were assigned to supine (n = 6) and lateral (n = 6) position groups. Airway pressures, heart rate, blood pressure, cardiac output, pulmonary artery pressure, pulmonary artery wedge pressure, right atrial pressure, arterial and venous blood gases, white blood count, platelet count and neutrophil count were obtained. Dogs were then subjected to pulmonary contusion in three areas of one lung. Fat embolism was generated by reaming one femur and tibia, followed by pressurization of the canal. No difference was found in any parameters measured between supine and lateral positions at any time (0.126 < P < 0.856). The position of trauma patients undergoing reamed intramedullary nailing did not alter the presentation of the features of the lung secondary to fat embolism.

A pilot study to monitor changes in spirometry and lung volume, following an exacerbation of Chronic Obstructive Pulmonary Disease (COPD), as part of a supported discharge program.

PubMed

Cushen, Breda; McCormack, Niamh; Hennigan, Kerrie; Sulaiman, Imran; Costello, Richard W; Deering, Brenda

2016-10-01

One-third of patients with an exacerbation of Chronic Obstructive Pulmonary Disease(COPD) are re-hospitalised at 90 days. Exacerbation recovery is associated with reductions in lung hyperinflation and improvements in symptoms and physical activity. We assessed the feasibility of monitoring these clinical parameters in the home. We hypothesised that the degree of change in spirometry and lung volumes differs between those who had an uneventful recovery and those who experienced a further exacerbation. Hospitalised patients with an acute exacerbation of COPD referred for a supported discharge program participated in the study. Spirometry and Inspiratory Vital Capacity(IVC) were measured in the home at Days 1, 14 and 42 post-discharge. Patients also completed Medical Research Council(MRC), Borg and COPD Assessment Test(CAT) scores and were provided with a tri-axial accelerometer. Any new exacerbation events were recorded. Sixty-five patients with 72 exacerbation episodes were recruited. Fifty percent experienced a second exacerbation. Adequate IVC measurements were achieved by 90%, while only 70% completed spirometry. Uneventful recovery was accompanied by significant improvements in physiological measurements at day14, improved symptom scores and step count, p < 0.05. Failure of MRC to improve was predictive of re-exacerbation(Area Under Receiver Operating Curve(AUROC) 0.6713) with improvements in FEV 1 ≥100 ml(AUROC 0.6613) and mean daily step count ≥396 steps(AUROC 0.6381) predictive of recovery. Monitoring the pattern of improvement in spirometry, lung volumes, symptoms and step count following a COPD exacerbation may help to identify patients at risk of re-exacerbation. It is feasible to carry out these assessments in the home as part of a supported discharge programme. Copyright © 2016 Elsevier Ltd. All rights reserved.

SU-E-I-79: Source Geometry Dependence of Gamma Well-Counter Measurements

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

Park, M; Belanger, A; Kijewski, M

Purpose: To determine the effect of liquid sample volume and geometry on counting efficiency in a gamma well-counter, and to assess the relative contributions of sample geometry and self-attenuation. Gamma wellcounters are standard equipment in clinical and preclinical studies, for measuring patient blood radioactivity and quantifying animal tissue uptake for tracer development and other purposes. Accurate measurements are crucial. Methods: Count rates were measured for aqueous solutions of 99m- Tc at four liquid volume values in a 1-cm-diam tube and at six volume values in a 2.2-cm-diam vial. Total activity was constant for all volumes, and data were corrected formore » decay. Count rates from a point source in air, supported by a filter paper, were measured at seven heights between 1.3 and 5.7 cm from the bottom of a tube. Results: Sample volume effects were larger for the tube than for the vial. For the tube, count efficiency relative to a 1-cc volume ranged from 1.05 at 0.05 cc to 0.84 at 3 cc. For the vial, relative count efficiency ranged from 1.02 at 0.05 cc to 0.87 at 15 cc. For the point source, count efficiency relative to 1.3 cm from the tube bottom ranged from 0.98 at 1.8 cm to 0.34 at 5.7 cm. The relative efficiency of a 3-cc liquid sample in a tube compared to a 1-cc sample is 0.84; the average relative efficiency for the solid sample in air between heights in the tube corresponding to the surfaces of those volumes (1.3 and 4.8 cm) is 0.81, implying that the major contribution to efficiency loss is geometry, rather than attenuation. Conclusion: Volume-dependent correction factors should be used for accurate quantitation radioactive of liquid samples. Solid samples should be positioned at the bottom of the tube for maximum count efficiency.« less

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

Morais, J.; Carrier, L.; Gariepy, G.

Eosinophilic pneumonia is usually diagnosed based on the findings on chest x-ray, white blood count, and transbronchial biopsy. After reporting a case of Ga-67 lung uptake in eosinophilic pneumonia, its histopathology is discussed and the mechanisms of Ga-67 uptake by inflammatory lesions are reviewed.

Particle and Photon Detection: Counting and Energy Measurement

PubMed Central

Janesick, James; Tower, John

2016-01-01

Fundamental limits for photon counting and photon energy measurement are reviewed for CCD and CMOS imagers. The challenges to extend photon counting into the visible/nIR wavelengths and achieve energy measurement in the UV with specific read noise requirements are discussed. Pixel flicker and random telegraph noise sources are highlighted along with various methods used in reducing their contribution on the sensor’s read noise floor. Practical requirements for quantum efficiency, charge collection efficiency, and charge transfer efficiency that interfere with photon counting performance are discussed. Lastly we will review current efforts in reducing flicker noise head-on, in hopes to drive read noise substantially below 1 carrier rms. PMID:27187398

Early bronchopulmonary involvement in Crohn disease: a case report

PubMed Central

Valletta, Enrico; Bertini, Marina; Sette, Luciano; Braggion, Cesare; Pradal, Ugo; Zannoni, Marina

2001-01-01

Background Bronchopulmonary manifestations of Crohn disease have been rarely described in children, including both subclinical pulmonary involvement and severe lung disease. Case presentation A 6.5-year-old girl is described with early recurrent bronchopulmonary symptoms both at presentation and in the quiescent phase of Crohn disease. Pulmonary function tests (lung volumes and flows, bronchial reactivity and carbon monoxide diffusing capacity) were normal. Bronchoalveolar cytology showed increased (30%) lymphocyte counts and bronchial biopsy revealed thickening of basal membrane and active chronic inflammation. Conclusions Clinical and histological findings in our young patient suggest involvement of both distal and central airways in an early phase of lung disease. The pathogenesis of Crohn disease-associated lung disorders is discussed with reference to the available literature. A low threshold for pulmonary evaluation seems to be advisable in all children with CD. PMID:11734067

Pembrolizumab combined with stereotactic body radiotherapy in a patient with human immunodeficiency virus and advanced non-small cell lung cancer: a case report.

PubMed

Li, Dongqi; He, Chuanchun; Xia, Yaoxiong; Du, Yaxi; Zhang, Jing

2018-04-23

Pembrolizumab has significantly improved outcomes in patients with advanced non-small cell lung cancer. Combining programmed death-1 inhibitor with stereotactic body radiotherapy showed a slight toxicity and good benefits in recent clinical trials. However, patients infected with human immunodeficiency virus were excluded from most trials because it was assumed that their anti-tumor immunity was compromised compared with immunocompetent patients. In June 2016, a 52-year-old Chinese man presented with human immunodeficiency virus and lung adenocarcinoma (T1bN3M1b). From November 2016 to December 2016, systemic chemotherapy and palliative radiotherapy for bone metastasis of femoral neck were carried out, but the tumor progressed. In January 2017, after immunochemistry detection of programmed death-1 and programmed death-ligand 1 expression (both > 50%), pembrolizumab was started. Three weeks after pembrolizumab, we combined stereotactic body radiotherapy for the primary lung tumor. He received no comfort and his CD4 lymphocyte count was stable. Human immunodeficiency virus-ribonucleic acid remained below the limits of detection. In March 2017, after three cycles of pembrolizumab and 5 weeks of stereotactic body radiotherapy therapy, he suddenly presented with palpitations. Emergency computed tomography scanning showed massive pericardial effusion and interstitial pneumonia. So we interrupted the pembrolizumab use and initiated treatment with prednisolone 1 mg/kg; however, the tumor progressed. Then, his CD4 lymphocyte count declined. Finally he died in June 2017 due to dyscrasia. Pembrolizumab combined with SBRT therapy for patients with human immunodeficiency virus infection and non-small cell lung cancer may lead to serious immune-related adverse events and more clinical trials are needed.

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

Grading the neuroendocrine tumors of the lung: an evidence-based proposal.

PubMed

Rindi, G; Klersy, C; Inzani, F; Fellegara, G; Ampollini, L; Ardizzoni, A; Campanini, N; Carbognani, P; De Pas, T M; Galetta, D; Granone, P L; Righi, L; Rusca, M; Spaggiari, L; Tiseo, M; Viale, G; Volante, M; Papotti, M; Pelosi, G

2014-02-01

Lung neuroendocrine tumors are catalogued in four categories by the World Health Organization (WHO 2004) classification. Its reproducibility and prognostic efficacy was disputed. The WHO 2010 classification of digestive neuroendocrine neoplasms is based on Ki67 proliferation assessment and proved prognostically effective. This study aims at comparing these two classifications and at defining a prognostic grading system for lung neuroendocrine tumors. The study included 399 patients who underwent surgery and with at least 1 year follow-up between 1989 and 2011. Data on 21 variables were collected, and performance of grading systems and their components was compared by Cox regression and multivariable analyses. All statistical tests were two-sided. At Cox analysis, WHO 2004 stratified patients into three major groups with statistically significant survival difference (typical carcinoid vs atypical carcinoid (AC), P=0.021; AC vs large-cell/small-cell lung neuroendocrine carcinomas, P<0.001). Optimal discrimination in three groups was observed by Ki67% (Ki67% cutoffs: G1 <4, G2 4-<25, G3 ≥25; G1 vs G2, P=0.021; and G2 vs G3, P≤0.001), mitotic count (G1 ≤2, G2 >2-47, G3 >47; G1 vs G2, P≤0.001; and G2 vs G3, P≤0.001), and presence of necrosis (G1 absent, G2 <10% of sample, G3 >10% of sample; G1 vs G2, P≤0.001; and G2 vs G3, P≤0.001) at uni and multivariable analyses. The combination of these three variables resulted in a simple and effective grading system. A three-tiers grading system based on Ki67 index, mitotic count, and necrosis with cutoffs specifically generated for lung neuroendocrine tumors is prognostically effective and accurate.

Influence of propofol and volatile anaesthetics on the inflammatory response in the ventilated lung.

PubMed

Kalimeris, K; Christodoulaki, K; Karakitsos, P; Batistatou, A; Lekka, M; Bai, M; Kitsiouli, E; Nakos, G; Kostopanagiotou, G

2011-07-01

The immunomodulatory effects of volatile anaesthetics in vitro and the protective effect of propofol in lung injury spurred us to study the effects of volatile anaesthetics and propofol on lung tissue in vivo. Twenty-seven pigs were randomized to 4-h general anaesthesia with propofol (8 mg/kg/h, group P, n=9), sevoflurane [minimum alveolar concentration (MAC)=1.0, group S, n=9) or desflurane (MAC=1.0, group D, n=9). Four healthy animals served as the no-ventilation group. Bronchoalveolar lavage fluid (BALF) was obtained to measure the cell counts, platelet-activating factor acetylhydrolase (PAF-AcH), phospholipase A(2) (PLA(2)) and superoxide dismutase (SOD) activity. Lung tissues were evaluated histologically and for caspase-3 expression. Volatile anaesthetics reduced PAF-AcH levels without affecting PLA(2) activity and resulted in decreased alveolar macrophage and increased lymphocyte counts in BALF (sevoflurane: 29 ± 23%; desflurane: 26 ± 6%, both P<0.05 compared with 4 ± 2% in the no-ventilation group). These findings were accompanied by atelectasis and inflammatory cells' infiltration in the inhalational anaesthetics groups. Also, sevoflurane reduced SOD activity and both sevoflurane and desflurane induced significant caspase-3 expression. In contrast, propofol resulted in a minor degree of inflammation and preserved BALF cells' composition without triggering apoptosis. Halogenated anaesthetics seem to trigger an immune lymphocytic response in the lung, inducing significant apoptosis and impairment of PAF-AcH. In contrast, propofol preserves anti-inflammatory and anti-oxidant defences during mechanical ventilation, thus preventing the emergence of apoptosis. © 2011 The Authors. Acta Anaesthesiologica Scandinavica © 2011 The Acta Anaesthesiologica Scandinavica Foundation.

Incentive spirometry does not enhance recovery after thoracic surgery.

PubMed

Gosselink, R; Schrever, K; Cops, P; Witvrouwen, H; De Leyn, P; Troosters, T; Lerut, A; Deneffe, G; Decramer, M

2000-03-01

To investigate the additional effect of incentive spirometry to chest physiotherapy to prevent postoperative pulmonary complications after thoracic surgery for lung and esophageal resections. Randomized controlled trial. University hospital, intensive care unit, and surgical department. Sixty-seven patients (age, 59 +/- 13 yrs; forced expiratory volume in 1 sec, 93% +/- 22% predicted) undergoing elective thoracic surgery for lung (n = 40) or esophagus (n = 27) resection. Physiotherapy (breathing exercises, huffing, and coughing) (PT) plus incentive spirometry (IS) was compared with PT alone. Lung function, body temperature, chest radiograph, white blood cell count, and number of hospital and intensive care unit days were all measured. Pulmonary function was significantly reduced after surgery (55% of the initial value) and improved significantly in the postoperative period in both groups. However, no differences were observed in the recovery of pulmonary function between the groups. The overall score of the chest radiograph, based on the presence of atelectasis, was similar in both treatment groups. Eight patients (12%) (three patients with lobectomy and five with esophagus resection) developed a pulmonary complication (abnormal chest radiograph, elevated body temperature and white blood cell count), four in each treatment group. Adding IS to regular PT did not reduce hospital or intensive care unit stay. Pulmonary complications after lung and esophagus surgery were relatively low. The addition of IS to PT did not further reduce pulmonary complications or hospital stay. Although we cannot rule out beneficial effects in a subgroup of high-risk patients, routine use of IS after thoracic surgery seems to be ineffective.

Antiinflammatory Effect of N-Acetylcysteine Combined with Exogenous Surfactant in Meconium-Induced Lung Injury.

PubMed

Mikolka, P; Kopincova, J; Mikusiakova, L Tomcikova; Kosutova, P; Calkovska, A; Mokra, D

2016-01-01

Neonatal meconium aspiration syndrome (MAS) can be treated by exogenous surfactant (S). However, aspirated meconium initiates local inflammation and oxidation which may inactivate surfactant and reduce its action. This experimental study estimated whether combined use of surfactant and the antioxidant N-acetylcysteine (NAC) can enhance effectiveness of therapy. Meconium-instilled rabbits were non-treated (M), treated with monotherapies (M + S, M + NAC), combined therapy (M + S + NAC), or received saline instead of meconium (controls, C). Surfactant therapy consisted of two lung lavages (BAL) with diluted Curosurf (5 mg phospholipids/ml, 10 ml/kg) followed by undiluted Curosurf (100 mg phospholipids/kg). N-acetylcysteine (Acc Injekt, 10 mg/kg) was given intravenously in M + S + NAC group 10 min after surfactant therapy. Animals were oxygen-ventilated for additional 5 h. Then, differential white cell count in the blood (WBC) was determined. Left lung was saline-lavaged and differential cell count in BAL was determined. In right lung tissue, wet/dry weight ratio, oxidation markers (TBARS, 3NT) and interleukines (IL-2, IL-6, IL-13, and TNFα) using ELISA and RT-PCR were estimated. Combined S + NAC therapy significantly decreased W/D ratio, TBARS, 3NT, and IL, whereas the effect of monotherapies (either S or NAC) was less obvious. In conclusion, addition of NAC to surfactant treatment may enhance the therapeutic outcome in MAS.

Etoposide; colchicine; mitomycin C and cyclophosphamide tested in the in vitro mammalian cell micronucleus test (MNvit) in Chinese hamster lung (CHL) cells at Covance laboratories; Harrogate UK in support of OECD draft Test Guideline 487.

PubMed

Fowler, Paul; Whitwell, James; Jeffrey, Laura; Young, Jamie; Smith, Katie; Kirkland, David

2010-10-29

The following genotoxic chemicals were tested in the in vitro micronucleus assay, at Covance Laboratories, Harrogate, UK in the Chinese hamster lung cell line CHL. Etoposide (a topoisomerase inhibitor), colchicine (an aneugen), mitomycin C (a DNA cross linking agent) and cyclophosphamide (an alkylating agent requiring metabolic activation) were treated with and without cytokinesis block (by addition of cytochalasin B). This work formed part of a collaborative evaluation of the toxicity measures recommended in the draft OECD Test Guideline 487 for the in vitro micronucleus test. The toxicity measures used, detecting both cytostasis and cell death, were relative population doubling, relative increase in cell counts and relative cell counts for treatments in the absence of cytokinesis block, and replication index or cytokinesis blocked proliferation index in the presence of cytokinesis block. All of the chemicals tested gave significant increases in the percentage of micronucleated cells with and without cytokinesis block at concentrations giving approximately 60% toxicity (cytostasis and cell death) or less by all of the toxicity measures used. The outcomes from this series of tests support the use of relative increase in cell counts and relative population doubling, as well as relative cell counts, as appropriate measures of cytotoxicity for the non-cytokinesis blocked in vitro micronucleus assay. Copyright © 2010 Elsevier B.V. All rights reserved.

Hematologic variables associated with brain failure in patients with small-cell lung cancer.

PubMed

Suzuki, Ryoko; Wei, Xiong; Allen, Pamela K; Welsh, James W; Komaki, Ritsuko; Lin, Steven H

2018-06-12

We sought factors associated with the development of brain metastases after treatment of small cell lung cancer (SCLC) in patients without brain involvement at diagnosis. We analyzed 293 patients with SCLC without brain metastases who received chemotherapy, thoracic radiation therapy (TRT), or both in 2001-2015. Pretreatment hematologic markers (platelet count, neutrophil count, lymphocyte count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lactate dehydrogenase) and other clinical characteristics were evaluated for correlation with brain metastases-free survival (BMFS). Cutoffs were established with receiver operating characteristics curves. Factors significant in univariate analysis were used to build a multivariate Cox model for BMFS. Median follow-up time was 14.3 months. Brain metastases developed in 115 patients (39%)-32% of those with low pretreatment platelet counts (PPC) (≤270 × 10 9 /L) and 46% of those with high PPC (>270 × 10 9 /L). Median BMFS time for all patients was 27.9 months. Two-year BMFS rates were worse for patients with high PPC (14.6% vs. 22.1% low, P = 0.009). High PPC was independently associated with inferior BMFS (P = 0.038), as were receipt of TRT <45 Gy and no prophylactic cranial irradiation (both P < 0.001). High PPC was associated with increased rates of brain metastasis in patients with SCLC with no evidence of brain disease at diagnosis. Copyright © 2018. Published by Elsevier B.V.

Continuous Activity Monitoring During Concurrent Chemoradiotherapy

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

Ohri, Nitin, E-mail: ohri.nitin@gmail.com; Kabarriti, Rafi; Bodner, William R.

Purpose: To perform a prospective trial testing the feasibility and utility of acquiring activity data as a measure of health status during concurrent chemoradiotherapy. Methods and Materials: Ambulatory patients who were planned for treatment with concurrent chemoradiotherapy with curative intent for cancers of the head and neck, lung, or gastrointestinal tract were provided with activity monitors before treatment initiation. Patients were asked to wear the devices continuously throughout the radiation therapy course. Step count data were downloaded weekly during radiation therapy and 2 and 4 weeks after radiation therapy completion. The primary objective was to demonstrate feasibility, defined as collection ofmore » step counts for 80% of the days during study subjects' radiation therapy courses. Secondary objectives included establishing step count as a dynamic predictor of unplanned hospitalization risk. Results: Thirty-eight enrolled patients were treated with concurrent chemoradiotherapy. Primary diagnoses included head and neck cancer (n=11), lung cancer (n=13), and a variety of gastrointestinal cancers (n=14). Step data were collected for 1524 of 1613 days (94%) during patients' radiation therapy courses. Fourteen patients were hospitalized during radiation therapy or within 4 weeks of radiation therapy completion. Cox regression modeling demonstrated a significant association between recent step counts (3-day average) and hospitalization risk, with a 38% reduction in the risk of hospitalization for every 1000 steps taken each day (hazard ratio 0.62, 95% confidence interval 0.46-0.83, P=.002). Inferior quality of life scores and impaired performance status were not associated with increased hospitalization risk. Conclusion: Continuous activity monitoring during concurrent chemoradiotherapy is feasible and well-tolerated. Step counts may serve as powerful, objective, and dynamic indicators of hospitalization risk.« less

Design Study of an Incinerator Ash Conveyor Counting System - 13323

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

Jaederstroem, Henrik; Bronson, Frazier

A design study has been performed for a system that should measure the Cs-137 activity in ash from an incinerator. Radioactive ash, expected to consist of both Cs-134 and Cs-137, will be transported on a conveyor belt at 0.1 m/s. The objective of the counting system is to determine the Cs-137 activity and direct the ash to the correct stream after a diverter. The decision levels are ranging from 8000 to 400000 Bq/kg and the decision error should be as low as possible. The decision error depends on the total measurement uncertainty which depends on the counting statistics and themore » uncertainty in the efficiency of the geometry. For the low activity decision it is necessary to know the efficiency to be able to determine if the signal from the Cs-137 is above the minimum detectable activity and that it generates enough counts to reach the desired precision. For the higher activity decision the uncertainty of the efficiency needs to be understood to minimize decision errors. The total efficiency of the detector is needed to be able to determine if the detector will be able operate at the count rate at the highest expected activity. The design study that is presented in this paper describes how the objectives of the monitoring systems were obtained, the choice of detector was made and how ISOCS (In Situ Object Counting System) mathematical modeling was used to calculate the efficiency. The ISOCS uncertainty estimator (IUE) was used to determine which parameters of the ash was important to know accurately in order to minimize the uncertainty of the efficiency. The examined parameters include the height of the ash on the conveyor belt, the matrix composition and density and relative efficiency of the detector. (authors)« less

Diet-induced obesity reprograms the inflammatory response of the murine lung to inhaled endotoxin

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

Tilton, Susan C., E-mail: susan.tilton@pnnl.gov; Waters, Katrina M.; Karin, Norman J.

The co-occurrence of environmental factors is common in complex human diseases and, as such, understanding the molecular responses involved is essential to determine risk and susceptibility to disease. We have investigated the key biological pathways that define susceptibility for pulmonary infection during obesity in diet-induced obese (DIO) and regular weight (RW) C57BL/6 mice exposed to inhaled lipopolysaccharide (LPS). LPS induced a strong inflammatory response in all mice as indicated by elevated cell counts of macrophages and neutrophils and levels of proinflammatory cytokines (MDC, MIP-1γ, IL-12, RANTES) in the bronchoalveolar lavage fluid. Additionally, DIO mice exhibited 50% greater macrophage cell counts,more » but decreased levels of the cytokines, IL-6, TARC, TNF-α, and VEGF relative to RW mice. Microarray analysis of lung tissue showed over half of the LPS-induced expression in DIO mice consisted of genes unique for obese mice, suggesting that obesity reprograms how the lung responds to subsequent insult. In particular, we found that obese animals exposed to LPS have gene signatures showing increased inflammatory and oxidative stress response and decreased antioxidant capacity compared with RW. Because signaling pathways for these responses can be common to various sources of environmentally induced lung damage, we further identified biomarkers that are indicative of specific toxicant exposure by comparing gene signatures after LPS exposure to those from a parallel study with cigarette smoke. These data show obesity may increase sensitivity to further insult and that co-occurrence of environmental stressors result in complex biosignatures that are not predicted from analysis of individual exposures. - Highlights: ► Obesity modulates inflammatory markers in BAL fluid after LPS exposure. ► Obese animals have a unique transcriptional signature in lung after LPS exposure. ► Obesity elevates inflammatory stress and reduces antioxidant capacity in the lung. ► Toxicant-specific biomarkers predict exposure independent of systemic inflammation.« less

Enhanced perfusion defect clarity and inhomogeneity in smokers' lungs with deep-inspiratory breath-hold perfusion SPECT images.

PubMed

Suga, Kazuyoshi; Yasuhiko, Kawakami; Iwanaga, Hideyuki; Hayashi, Norio; Yamashita, Tomio; Matsunaga, Naofumi

2005-09-01

Deep-inspiratory breath-hold (DIBrH) Tc-99m-macroaggregated albumin (MAA) SPECT images were developed to accurately evaluate perfusion impairment in smokers' lungs. DIBrH SPECT was performed in 28 smokers with or without low attenuation areas (LAA) on CT images, using a triple-headed SPECT system and a laser light respiratory tracking device. DIBrH SPECT images were reconstructed from every 4 degrees projection of five adequate 360 degrees projection data sets with almost the same respiratory dimension at 20 sec DIBrH. Perfusion defect clarity was assessed by the lesion (defect)-to-contralateral normal lung count ratios (L/N ratios). Perfusion inhomogeneity was assessed by the coefficient of variation (CV) values of pixel counts and correlated with the diffusing capacity of the lungs for carbon monoxide/alveolar volume (DLCO/VA) ratios. The results were compared with those on conventional images. Five DIBrH projection data sets with minimal dimension differences of 2.9+/-0.6 mm were obtained in all subjects. DIBrH images enhanced perfusion defects compared with conventional images, with significantly higher L/N ratios (P<0.0001), and detected a total of 109 (26.9%) additional detects (513 vs. 404), with excellent inter-observer agreement (kappa value of 0.816). CV values in the smokers' lungs on DIBrH images were also significantly higher compared with those on conventional images (0.31+/-0.10 vs. 0.19+/-0.06, P<0.0001). CV values in smokers on DIBrH images showed a significantly closer correlation with DLCO/VA ratios compared with conventional images (R = 0.872, P<0.0001 vs. R=0.499, P<0.01). By reducing adverse effect of respiratory motion, DIBrH SPECT images enhance perfusion defect clarity and inhomogeneity, and provide more accurate assessment of impaired perfusion in smokers' lungs compared with conventional images.

Surgery for lung adenocarcinoma with smokers' polycythemia: a case report.

PubMed

Sugiura, Yasoo; Nemoto, Etsuo; Shinoda, Hiromi; Nakamura, Naoya; Kaseda, Shizuka

2013-02-01

Smoking is a cause of cancer and polycythemia. Therefore, surgeons who treat patients with cancer may also encounter patients with polycythemia. However, few cases of surgical patients with polycythemia have been reported; in particular, a surgical case involving smokers' polycythemia has never been reported. We herein report a patient with lung cancer and smokers' polycythemia who successfully underwent lobectomy with control of hematocrit based on a modified formula in the perioperative period. A 67-year-old man underwent abdominoperineal resection for rectal carcinoma in June 2008. A ground glass opacity had been identified in the upper lobe of the right lung and was gradually enlarging. In March 2012, bronchoscopic cytology for investigation of the mass revealed non-small cell lung cancer, suggesting primary lung non-small cell carcinoma (T1bN0M0, Stage IA). When he was referred to our hospital for surgery, his complete blood count showed a red blood cell level of 6.50×106/μL, hemoglobin of 21.0 g/dL, and hematocrit of 60.1%. The hematologists' diagnosis was secondary polycythemia due to heavy smoking (smokers' polycythemia) because the white blood cell and platelet counts were within normal limits and the erythropoietin was not increased. We calculated the appropriate phlebotomy and infusion volumes based on a formula that we modified. After 550 g of blood was phlebotomized to reduce the hematocrit to approximately 55%, video-assisted right lung upper lobectomy with lymph node dissection was performed in April 2012. The hematocrit was maintained at <50% postoperatively, and the patient was uneventfully discharged on postoperative day 7. The predictive hematocrit and measured hematocrit were very closely approximated in this case. We experienced a patient with smokers' polycythemia who underwent right upper lobectomy for adenocarcinoma. The findings in this case report are meaningful for surgeons treating cancer patients because there are few reports discussing the perioperative care of surgical patients with polycythemia.

Surgery for lung adenocarcinoma with smokers’ polycythemia: a case report

PubMed Central

2013-01-01

Background Smoking is a cause of cancer and polycythemia. Therefore, surgeons who treat patients with cancer may also encounter patients with polycythemia. However, few cases of surgical patients with polycythemia have been reported; in particular, a surgical case involving smokers’ polycythemia has never been reported. We herein report a patient with lung cancer and smokers’ polycythemia who successfully underwent lobectomy with control of hematocrit based on a modified formula in the perioperative period. Case presentation A 67-year-old man underwent abdominoperineal resection for rectal carcinoma in June 2008. A ground glass opacity had been identified in the upper lobe of the right lung and was gradually enlarging. In March 2012, bronchoscopic cytology for investigation of the mass revealed non-small cell lung cancer, suggesting primary lung non-small cell carcinoma (T1bN0M0, Stage IA). When he was referred to our hospital for surgery, his complete blood count showed a red blood cell level of 6.50×106/μL, hemoglobin of 21.0 g/dL, and hematocrit of 60.1%. The hematologists’ diagnosis was secondary polycythemia due to heavy smoking (smokers’ polycythemia) because the white blood cell and platelet counts were within normal limits and the erythropoietin was not increased. We calculated the appropriate phlebotomy and infusion volumes based on a formula that we modified. After 550 g of blood was phlebotomized to reduce the hematocrit to approximately 55%, video-assisted right lung upper lobectomy with lymph node dissection was performed in April 2012. The hematocrit was maintained at <50% postoperatively, and the patient was uneventfully discharged on postoperative day 7. The predictive hematocrit and measured hematocrit were very closely approximated in this case. Conclusion We experienced a patient with smokers’ polycythemia who underwent right upper lobectomy for adenocarcinoma. The findings in this case report are meaningful for surgeons treating cancer patients because there are few reports discussing the perioperative care of surgical patients with polycythemia. PMID:23374961

PPO-ethanol system as wavelength shifter for the Cherenkov counting technique using a liquid scintillation counter

NASA Astrophysics Data System (ADS)

Takiue, Makoto; Fujii, Haruo; Ishikawa, Hiroaki

1984-12-01

2, 5-diphenyloxazole (PPO) has been proposed as a wavelength shifter for Cherenkov counting. Since PPO is not incorporated with water, we have introduced the fluor into water in the form of micelle using a PPO-ethanol system. This technique makes it possible to obtain a high Cherenkov counting efficiency under stable sample conditions, attributed to the proper spectrometric features of the PPO. The 32P Cherenkov counting efficiency (68.4%) obtained from this technique is large as that measured with a conventional Cherenkov technique.

Performance characteristics of high-conductivity channel electron multipliers. [as UV and x ray detector

NASA Technical Reports Server (NTRS)

Timothy, J. G.; Bybee, R. L.

1978-01-01

The paper describes a new type of continuous channel multiplier (CEM) fabricated from a low-resistance glass to produce a high-conductivity channel section and thereby obtain a high count-rate capability. The flat-cone cathode configuration of the CEM is specifically designed for the detection of astigmatic exit images from grazing-incidence spectrometers at the optimum angle of illumination for high detection efficiencies at XUV wavelengths. Typical operating voltages are in the range of 2500-2900 V with stable counting plateau slopes in the range 3-6% per 100-V increment. The modal gain at 2800 V was typically in the range (50-80) million. The modal gain falls off at count rates in excess of about 20,000 per sec. The detection efficiency remains essentially constant to count rates in excess of 2 million per sec. Higher detection efficiencies (better than 20%) are obtained by coating the CEM with MgF2. In life tests of coated CEMs, no measurable change in detection efficiency was measured to a total accumulated signal of 2 times 10 to the 11th power counts.

Characterization of the seven-day course of pulmonary response following unilateral lung acid injury in rats.

PubMed

Setzer, Florian; Schmidt, Barbara; Hueter, Lars; Schwarzkopf, Konrad; Sänger, Jörg; Schreiber, Torsten

2018-01-01

Aspiration of gastric acid is an important cause of acute lung injury. The time course of the pulmonary response to such an insult beyond the initial 48 hours is incompletely characterized. The purpose of this study was to comprehensively describe the pulmonary effects of focal lung acid injury over a seven day period in both directly injured and not directly injured lung tissue. Male Wistar rats underwent left-endobronchial instillation with hydrochloric acid and were sacrificed at 4, 24, 48, 96 or 168 h after the insult. Healthy non-injured animals served as controls. We assessed inflammatory cell counts and cytokine levels in right and left lung lavage fluid and blood, arterial oxygen tension, alterations in lung histology, lung wet-to-dry weight ratio and differential lung perfusion. Lung acid instillation induced an early strong inflammatory response in the directly affected lung, peaking at 4-24 hours, with only partial resolution after 7 days. A less severe response with complete resolution after 4 days was seen in the opposite lung. Alveolar cytokine levels, with exception of IL-6, only partially reflected the localization of lung injury and the time course of the functional and histologic alterations. Alveolar leucocyte subpopulations exhibited different time courses in the acid injured lung with persistent elevation of alveolar lymphocytes and macrophages. After acid instillation there was an early transient decrease in arterial oxygen tension and lung perfusion was preferentially distributed to the non-injured lung. These findings provide a basis for further research in the field of lung acid injury and for studies exploring effects of mechanical ventilation on injured lungs. Incomplete recovery in the directly injured lung 7 days after acid instillation suggests that increased vulnerability and susceptibility to further noxious stimuli are still present at that time.

Environmental asbestos exposure in rural Turkey and risk of lung cancer.

PubMed

Metintas, Selma; Metintas, Muzaffer; Ak, Guntulu; Kalyoncu, Cemalettin

2012-01-01

The aim of this study was to determine the risk of lung cancer in a cohort of villagers with environmental asbestos exposure. The study was carried out as a field-based epidemiological study. Information from 3143 individuals in 15 asbestos exposed villages and 2175 individuals in 12 control villages was obtained. Asbestos fiber type to which villagers were exposed mainly was tremolite or tremolite, actinolite, chrysotile mixtures. The cumulative fiber count of the villagers during their lifespan ranged from 0.19 to 4.61 fiber-years/ml. The annual average incidence ratio of lung cancer was 135.21/100,000 persons/year in men and 47.28 in women in the asbestos exposed villages. For the control villages, this ratio was 60.15/100,000 person/year in men and 15.06 in women. Being a male, advanced age, smoking and asbestos exposure were established to increase the risk of lung cancer. Environmental asbestos exposure in rural area is a risk factor for lung cancer independent of smoking.

Interstitial Lung Diseases in the U.S. Mining Industry: Using MSHA Data to Examine Trends and the Prevention Effects of Compliance with Health Regulations, 1996-2015.

PubMed

Yorio, Patrick L; Laney, A Scott; Halldin, Cara N; Blackley, David J; Moore, Susan M; Wizner, Kerri; Radonovich, Lewis J; Greenawald, Lee A

2018-04-12

Given the recent increase in dust-induced lung disease among U.S. coal miners and the respiratory hazards encountered across the U.S. mining industry, it is important to enhance an understanding of lung disease trends and the organizational contexts that precede these events. In addition to exploring overall trends reported to the Mine Safety and Health Administration (MSHA), the current study uses MSHA's enforcement database to examine whether or not compliance with health regulations resulted in fewer mine-level counts of these diseases over time. The findings suggest that interstitial lung diseases were more prevalent in coal mines compared to other mining commodities, in Appalachian coal mines compared to the rest of the United States, and in underground compared to surface coal mines. Mines that followed a relevant subset of MSHA's health regulations were less likely to report a lung disease over time. The findings are discussed from a lung disease prevention strategy perspective. © 2018 Society for Risk Analysis.

Tracking of Mesenchymal Stem Cells with Fluorescence Endomicroscopy Imaging in Radiotherapy-Induced Lung Injury

NASA Astrophysics Data System (ADS)

Perez, Jessica R.; Ybarra, Norma; Chagnon, Frederic; Serban, Monica; Lee, Sangkyu; Seuntjens, Jan; Lesur, Olivier; El Naqa, Issam

2017-01-01

Mesenchymal stem cells (MSCs) have potential for reducing inflammation and promoting organ repair. However, limitations in available techniques to track them and assess this potential for lung repair have hindered their applicability. In this work, we proposed, implemented and evaluated the use of fluorescence endomicroscopy as a novel imaging tool to track MSCs in vivo. MSCs were fluorescently labeled and injected into a rat model of radiation-induced lung injury via endotracheal (ET) or intravascular (IV) administration. Our results show that MSCs were visible in the lungs with fluorescence endomicroscopy. Moreover, we developed an automatic cell counting algorithm to quantify the number of detected cells in each condition. We observed a significantly higher number of detected cells in ET injection compared to IV and a slight increase in the mean number of detected cells in irradiated lungs compared to control, although the latter did not reach statistical significance. Fluorescence endomicroscopy imaging is a powerful new minimally invasive and translatable tool that can be used to track and quantify MSCs in the lungs and help assess their potential in organ repair.

AMD3100 ameliorates cigarette smoke-induced emphysema-like manifestations in mice.

PubMed

Barwinska, Daria; Oueini, Houssam; Poirier, Christophe; Albrecht, Marjorie E; Bogatcheva, Natalia V; Justice, Matthew J; Saliba, Jacob; Schweitzer, Kelly S; Broxmeyer, Hal E; March, Keith L; Petrache, Irina

2018-05-10

We have shown that cigarette smoke (CS)-induced pulmonary emphysema-like manifestations are preceded by marked suppression of the number and function of bone marrow hematopoietic progenitor cells (HPC). To investigate if a limited availability of HPC may contribute to CS-induced lung injury, we used an FDA-approved antagonist of the interactions of SDF-1 with its receptor CXCR4 to promote intermittent HPC mobilization and tested its ability to limit emphysema-like injury following chronic CS. We administered AMD3100 (5mg/kg) to mice during a chronic CS exposure protocol of up to 24 weeks. AMD3100 treatment did not affect either lung SDF-1 levels, which were reduced by CS, or lung inflammatory cell counts. However, AMD3100 markedly improved CS-induced bone marrow HPC suppression and significantly ameliorated emphysema-like endpoints such as alveolar airspace size, lung volumes, and lung static compliance. These results suggest that antagonism of SDF-1 binding to CXCR4 is associated with protection of both bone marrow and lungs during chronic CS exposure, thus encouraging future studies of potential therapeutic benefit of AMD3100 in emphysema.

Acute respiratory toxicity following inhalation exposure to soman in guinea pigs.

PubMed

Perkins, Michael W; Pierre, Zdenka; Rezk, Peter; Sabnekar, Praveena; Kabra, Kareem; Chanda, Soma; Oguntayo, Samuel; Sciuto, Alfred M; Doctor, Bhupendra P; Nambiar, Madhusoodana P

2010-06-01

Respiratory toxicity and lung injury following inhalation exposure to chemical warfare nerve agent soman was examined in guinea pigs without therapeutics to improve survival. A microinstillation inhalation exposure technique that aerosolizes the agent in the trachea was used to administer soman to anesthetized age and weight matched male guinea pigs. Animals were exposed to 280, 561, 841, and 1121 mg/m(3) concentrations of soman for 4 min. Survival data showed that all saline controls and animals exposed to 280 and 561 mg/m(3) soman survived, while animals exposed to 841, and 1121 mg/m(3) resulted in 38% and 13% survival, respectively. The microinstillation inhalation exposure LCt(50) for soman determined by probit analysis was 827.2mg/m(3). A majority of the animals that died at 1121 mg/m(3) developed seizures and died within 15-30 min post-exposure. There was a dose-dependent decrease in pulse rate and blood oxygen saturation of animals exposed to soman at 5-6.5 min post-exposure. Body weight loss increased with the dose of soman exposure. Bronchoalveolar lavage (BAL) fluid and blood acetylcholinesterase and butyrylcholinesterase activity was inhibited dose-dependently in soman treated groups at 24h. BAL cells showed a dose-dependent increase in cell death and total cell counts following soman exposure. Edema by wet/dry weight ratio of the accessory lung lobe and trachea was increased slightly in soman exposed animals. An increase in total bronchoalveolar lavage fluid protein was observed in soman exposed animals at all doses. Differential cell counts of BAL and blood showed an increase in total lymphocyte counts and percentage of neutrophils. These results indicate that microinstillation inhalation exposure to soman causes respiratory toxicity and acute lung injury in guinea pigs. (c) 2010 Elsevier Inc. All rights reserved.

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

Perkins, Michael W.; Pierre, Zdenka; Rezk, Peter

Respiratory toxicity and lung injury following inhalation exposure to chemical warfare nerve agent soman was examined in guinea pigs without therapeutics to improve survival. A microinstillation inhalation exposure technique that aerosolizes the agent in the trachea was used to administer soman to anesthetized age and weight matched male guinea pigs. Animals were exposed to 280, 561, 841, and 1121 mg/m{sup 3} concentrations of soman for 4 min. Survival data showed that all saline controls and animals exposed to 280 and 561 mg/m{sup 3} soman survived, while animals exposed to 841, and 1121 mg/m{sup 3} resulted in 38% and 13% survival,more » respectively. The microinstillation inhalation exposure LCt{sub 50} for soman determined by probit analysis was 827.2 mg/m{sup 3}. A majority of the animals that died at 1121 mg/m{sup 3} developed seizures and died within 15-30 min post-exposure. There was a dose-dependent decrease in pulse rate and blood oxygen saturation of animals exposed to soman at 5-6.5 min post-exposure. Body weight loss increased with the dose of soman exposure. Bronchoalveolar lavage (BAL) fluid and blood acetylcholinesterase and butyrylcholinesterase activity was inhibited dose-dependently in soman treated groups at 24 h. BAL cells showed a dose-dependent increase in cell death and total cell counts following soman exposure. Edema by wet/dry weight ratio of the accessory lung lobe and trachea was increased slightly in soman exposed animals. An increase in total bronchoalveolar lavage fluid protein was observed in soman exposed animals at all doses. Differential cell counts of BAL and blood showed an increase in total lymphocyte counts and percentage of neutrophils. These results indicate that microinstillation inhalation exposure to soman causes respiratory toxicity and acute lung injury in guinea pigs.« less

[Safety and effectiveness of pemetrexed in patients with non-small cell lung cancer in Japan - analysis of post-marketing surveillance].

PubMed

Okubo, Sumiko; Kobayashi, Noriko; Taketsuna, Masanori; Kaneko, Naoya; Enatsu, Sotaro; Nishiuma, Shinichi

2014-04-01

The safety and effectiveness of pemetrexed(PEM)in patients with non-small cell lung cancer(NSCLC)were reviewed using data from post-marketing surveillance. Among 699 patients registered from June 2009 to May 2010, 683 patients were analyzed(343, first-line therapy: 340, second-line therapy or beyond). Patient backgrounds were as follows: median age=65 years(16.1%B75 years old); 64.7% male; 91.9% performance status 0-1; 83.2% Stage IV; 99.0% non-squamous cell cancer. Also, 86% of the first-line and 20% of the second-line cohort were receiving a concomitant anti-cancer drug(mostly platinum agents). The incidence rate of adverse drug reactions(ADR)was 76.7%, including serious cases(18.0%). The most common ADRs were decreased white blood cell count(26.8%), decreased neutrophil count(25.3%), anemia(19.2%), decreased platelet count(17.0%), and nausea(23.0%). The incidence of interstitial lung disease, which is a concern during chemotherapy, was 2.6%. Peripheral neuropathy and alopecia, events influencing a patient's quality of life, were less than 1%. The estimated median survival time was 23.2 months[95%CI: 19.8 months-not calculable]in the first-line cohort, and 11.8 months[95% CI: 10.5-13.7 months]in the B second-line cohort. The surveillance results showed no apparent difference in total ADRs in this current study compared to the safety profile established in clinical trials previously conducted in Japan and overseas. These results demonstrate the safety and effectiveness of PEM treatment for NSCLC patients in daily clinical settings.

Prior publication productivity, grant percentile ranking, and topic-normalized citation impact of NHLBI cardiovascular R01 grants.

PubMed

Kaltman, Jonathan R; Evans, Frank J; Danthi, Narasimhan S; Wu, Colin O; DiMichele, Donna M; Lauer, Michael S

2014-09-12

We previously demonstrated absence of association between peer-review-derived percentile ranking and raw citation impact in a large cohort of National Heart, Lung, and Blood Institute cardiovascular R01 grants, but we did not consider pregrant investigator publication productivity. We also did not normalize citation counts for scientific field, type of article, and year of publication. To determine whether measures of investigator prior productivity predict a grant's subsequent scientific impact as measured by normalized citation metrics. We identified 1492 investigator-initiated de novo National Heart, Lung, and Blood Institute R01 grant applications funded between 2001 and 2008 and linked the publications from these grants to their InCites (Thompson Reuters) citation record. InCites provides a normalized citation count for each publication stratifying by year of publication, type of publication, and field of science. The coprimary end points for this analysis were the normalized citation impact per million dollars allocated and the number of publications per grant that has normalized citation rate in the top decile per million dollars allocated (top 10% articles). Prior productivity measures included the number of National Heart, Lung, and Blood Institute-supported publications each principal investigator published in the 5 years before grant review and the corresponding prior normalized citation impact score. After accounting for potential confounders, there was no association between peer-review percentile ranking and bibliometric end points (all adjusted P>0.5). However, prior productivity was predictive (P<0.0001). Even after normalizing citation counts, we confirmed a lack of association between peer-review grant percentile ranking and grant citation impact. However, prior investigator publication productivity was predictive of grant-specific citation impact. © 2014 American Heart Association, Inc.

Long-term treatment with royal jelly improves bleomycin-induced pulmonary fibrosis in rats.

PubMed

Zargar, Hamid Reza; Hemmati, Ali Asghar; Ghafourian, Mehri; Arzi, Ardeshir; Rezaie, Anahita; Javad-Moosavi, Seyed Ali

2017-01-01

This study investigated the anti-fibrotic potential of royal jelly (RJ) powder against bleomycin-induced pulmonary fibrosis in rats. The rats were given RJ orally (25, 50, and 100 mg/kg per day) for 7 consecutive days before the administration of single intratracheal instillation of bleomycin (BLM) at 7.5 IU/kg. RJ doses were continued for 21 days after BLM exposure. Fibrotic changes in the lungs were studied by cell count and analysis of cytokine levels in the bronchoalveolar lavage fluid (BALF), histopathological examination, and assaying oxidative stress biomarkers in lung tissue. The results showed that BLM administration significantly increased the fibrotic changes, collagen content, and levels of malondialdehyde and decreased total thiol and glutathione peroxidase antioxidant contents in the rats' lung tissue. An increase in the level of cell counts and pro-inflammatory and pro-fibrotic cytokines such as TNF-α and TGF-β in BALF was observed. Also, it significantly decreased IFN-γ, an anti-fibrotic cytokine, in BALF. However, RJ (50 and 100 mg/kg) reversed all of these biochemical indices as well as histopathological alterations induced by BLM. The present study demonstrates that RJ, by its antioxidant and anti-inflammatory properties, attenuates oxidative damage and fibrosis induced by BLM.

Aerosol Drug Delivery During Noninvasive Positive Pressure Ventilation: Effects of Intersubject Variability and Excipient Enhanced Growth

PubMed Central

Walenga, Ross L.; Kaviratna, Anubhav; Hindle, Michael

2017-01-01

Abstract Background: Nebulized aerosol drug delivery during the administration of noninvasive positive pressure ventilation (NPPV) is commonly implemented. While studies have shown improved patient outcomes for this therapeutic approach, aerosol delivery efficiency is reported to be low with high variability in lung-deposited dose. Excipient enhanced growth (EEG) aerosol delivery is a newly proposed technique that may improve drug delivery efficiency and reduce intersubject aerosol delivery variability when coupled with NPPV. Materials and Methods: A combined approach using in vitro experiments and computational fluid dynamics (CFD) was used to characterize aerosol delivery efficiency during NPPV in two new nasal cavity models that include face mask interfaces. Mesh nebulizer and in-line dry powder inhaler (DPI) sources of conventional and EEG aerosols were both considered. Results: Based on validated steady-state CFD predictions, EEG aerosol delivery improved lung penetration fraction (PF) values by factors ranging from 1.3 to 6.4 compared with conventional-sized aerosols. Furthermore, intersubject variability in lung PF was very high for conventional aerosol sizes (relative differences between subjects in the range of 54.5%–134.3%) and was reduced by an order of magnitude with the EEG approach (relative differences between subjects in the range of 5.5%–17.4%). Realistic in vitro experiments of cyclic NPPV demonstrated similar trends in lung delivery to those observed with the steady-state simulations, but with lower lung delivery efficiencies. Reaching the lung delivery efficiencies reported with the steady-state simulations of 80%–90% will require synchronization of aerosol administration during inspiration and reducing the size of the EEG aerosol delivery unit. Conclusions: The EEG approach enabled high-efficiency lung delivery of aerosols administered during NPPV and reduced intersubject aerosol delivery variability by an order of magnitude. Use of an in-line DPI device that connects to the NPPV mask appears to be a convenient method to rapidly administer an EEG aerosol and synchronize the delivery with inspiration. PMID:28075194

Composition of tobaccos from countries with high and low incidences of lung cancer. I. Selenium, polonium-210, Alternaria, tar, and nicotine.

PubMed

Bogden, J D; Kemp, F W; Buse, M; Thind, I S; Louria, D B; Forgacs, J; Llanos, G; Moncoya Terrones, I

1981-01-01

Tobaccos from countries with high and low incidences of lung cancer were analyzed. Tobacco concentrations of polonium-210 were similar in cigarettes from high- and low-incidence countries, as were levels of cigarette smoke tar and nicotine. Tobaccos from low-incidence countries had significantly lower Alternaria spore counts. Mean selenium concentrations of tobaccos from the high-incidence countries (0.16 +/- 0.05 micrograms/g) were significantly lower than those of tobaccos from the low-incidence countries (0.49 +/- 0.22 micrograms/g).

Effects of HIFU induced cavitation on flooded lung parenchyma.

PubMed

Wolfram, Frank; Dietrich, Georg; Boltze, Carsten; Jenderka, Klaus Vitold; Lesser, Thomas Günther

2017-01-01

High intensity focused ultrasound (HIFU) has gained clinical interest as a non-invasive local tumour therapy in many organs. In addition, it has been shown that lung cancer can be targeted by HIFU using One-Lung Flooding (OLF). OLF generates a gas free saline-lung compound in one lung wing and therefore acoustic access to central lung tumours. It can be assumed that lung parenchyma is exposed to ultrasound intensities in the pre-focal path and in cases of misguiding. If so, cavitation might be induced in the saline fraction of flooded lung and cause tissue damage. Therefore this study was aimed to determine the thresholds of HIFU induced cavitation and tissue erosion in flooded lung. Resected human lung lobes were flooded ex-vivo. HIFU (1,1 MHz) was targeted under sonographic guidance into flooded lung parenchyma. Cavitation events were counted using subharmonic passive cavitation detection (PCD). B-Mode imaging was used to detect cavitation and erosion sonographically. Tissue samples out of the focal zone were analysed histologically. In flooded lung, a PCD and a sonographic cavitation detection threshold of 625  Wcm - 2 ( p r  = 4, 3  MPa ) and 3.600  Wcm - 2 ( p r  = 8, 3  MPa ) was found. Cavitation in flooded lung appears as blurred hyperechoic focal region, which enhances echogenity with insonation time. Lung parenchyma erosion was detected at intensities above 7.200  Wcm - 2 ( p r  = 10, 9  MPa ). Cavitation occurs in flooded lung parenchyma, which can be detected passively and by B-Mode imaging. Focal intensities required for lung tumour ablation are below levels where erosive events occur. Therefore focal cavitation events can be monitored and potential risk from tissue erosion in flooded lung avoided.

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.

Skull counting in late stages after internal contamination by actinides.

PubMed

Tani, Kotaro; Shutt, Arron; Kurihara, Osamu; Kosako, Toshiso

2015-02-01

Monitoring preparation for internal contamination with actinides (e.g. Pu and Am) is required to assess internal doses at nuclear fuel cycle-related facilities. In this paper, the authors focus on skull counting in case of single-incident inhalation of (241)Am and propose an effective procedure for skull counting with an existing system, taking into account the biokinetic behaviour of (241)Am in the human body. The predicted response of the system to skull counting under a certain counting geometry was found to be only ∼1.0 × 10(-5) cps Bq(-1) 1y after intake. However, this disadvantage could be remedied by repeated measurements of the skull during the late stage of the intake due to the predicted response reaching a plateau at about the 1000th day after exposure and exceeding that in the lung counting. Further studies are needed for the development of a new detection system with higher sensitivity to perform reliable internal dose estimations based on direct measurements. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

WE-FG-207B-07: Feasibility of Low Dose Lung Cancer Screening with a Whole-Body Photon Counting CT: First Human Results

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

Symons, R; Cork, T; Folio, L

2016-06-15

Purpose: To evaluate the feasibility of using a whole-body photon counting detector (PCD) CT scanner for low dose lung cancer screening compared to a conventional energy integrating detector (EID) system. Methods: Radiation dose-matched EID and PCD scans of the COPDGene 2 phantom and 2 human volunteers were acquired. Phantom images were acquired at different radiation dose levels (CTDIvol: 3.0, 1.5, and 0.75 mGy) and different tube voltages (120, 100, and 80 kVp), while human images were acquired at vendor recommended low-dose lung cancer screening settings. EID and PCD images were compared for quantitative Hounsfield unit accuracy, noise levels, and contrast-to-noisemore » ratios (CNR) for detection of ground-glass nodules (GGNs) and emphysema. Results: The PCD Hounsfield unit accuracy was better for water at all scan parameters, and for lung, GGN and emphysema equivalent regions of interest (ROIs) at 1.5 and 0.75 mGy. PCD attenuation accuracy was more consistent for all scan parameters (all P<0.01), while Hounsfield units for lung, GGN and emphysema ROIs changed significantly for EID with decreasing dose (all P<0.001). PCD showed lower noise levels at the lowest dose setting at 120, 100 and 80 kVp (15.2±0.3 vs 15.8±0.2, P=0.03; 16.1±0.3 vs 18.0±0.4, P=0.003; and 16.1±0.3 vs 17.9±0.3, P=0.001, respectively), resulting in superior CNR for the detection of GGNs and emphysema at 100 and 80 kVp. Significantly lower PCD noise levels were confirmed in volunteer images. Conclusion: PCD provided better Hounsfield unit accuracy for lung, ground-glass, and emphysema-equivalent foams at 1.5 and 0.75 mGy with less variability than EID. Additionally, PCD showed less noise, and higher CNR at 0.75 mGy for both 100 and 80 kVp. PCD technology may help reduce radiation exposure in lung cancer screening while maintaining diagnostic quality.« less

Pathway focused protein profiling indicates differential function for IL-1B, -18 and VEGF during initiation and resolution of lung inflammation evoked by carbon nanoparticle exposure in mice

PubMed Central

2009-01-01

Background Carbonaceous nanoparticles possess an emerging source of human exposure due to the massive release of combustion products and the ongoing revolution in nanotechnology. Pulmonary inflammation caused by deposited nanoparticles is central for their adverse health effects. Epidemiological studies suggest that individuals with favourable lung physiology are at lower risk for particulate matter associated respiratory diseases probably due to efficient control of inflammation and repair process. Therefore we selected a mouse strain C3H/HeJ (C3) with robust lung physiology and exposed it to moderately toxic carbon nanoparticles (CNP) to study the elicited pulmonary inflammation and its resolution. Methods 5 μg, 20 μg and 50 μg CNP were intratracheally (i.t.) instilled in C3 mice to identify the optimal dose for subsequent time course studies. Pulmonary inflammation was assessed using histology, bronchoalveolar lavage (BAL) analysis and by a panel of 62 protein markers. Results 1 day after instillation of CNP, C3 mice exhibited a typical dose response, with the lowest dose (5 μg) representing the 'no effect level' as reflected by polymorphonuclear leucocyte (PMN), and BAL/lung concentrations of pro-inflammatory proteins. Histological analysis and BAL-protein concentration did not reveal any evidence of tissue injury in 20 μg CNP instilled animals. Accordingly time course assessment of the inflammatory response was performed after 3 and 7 days with this dose (20 μg). Compared to day 1, BAL PMN counts were significantly decreased at day 3 and completely returned to normal by day 7. We have identified protein markers related to the acute response and also to the time dependent response in lung and BAL. After complete resolution of PMN influx on day 7, we detected elevated concentrations of 20 markers that included IL1B, IL18, FGF2, EDN1, and VEGF in lung and/or BAL. Biological pathway analysis revealed these factors to be involved in a closely regulated molecular cascade with IL1B/IL18 as upstream and FGF2/EDN1/VEGF as downstream molecules. Conclusion Considering the role of VEGF, FGF2 and EDN1 in lung development and morphogenesis together with the lack of any evident tissue damage we suggest a protective/homeostatic machinery to be associated in lungs of stable organisms to counter the CNP challenge as a precautionary measure. PMID:19954533

[Study on the anti-NTHi infection of Hap recombinant protein in vivo].

PubMed

Li, Wan-yi; Wang, Bao-ning; Zuo, Feng-qiong; Zeng, Wei; Feng, Feng; Kuang, Yu; Jiang, Zhong-hua; Li, Ming-yuan

2010-07-01

To observe the immune effect of Hap recombinant protein on murine model of bronchopneumonia infected with NTHi, and explore the mechanism about the anti-NTHi infection. The C57BL/6 mice intranasally immunized with purified Hap recombinant protein and CT-B were challenged by NTHi encased in agar beads. The immunifaction of anti-infection was observed through encocyte counting of BALF, bacteria detection of lung and the pathologyical change of lung tissue. In the challenge with NTHi experiment, the inflammatory exudation of the infected murine and pathological change of lung tissue was relieved by combined immunization of Hap recombinant protein and CT-B, and quantity of NTHi in lung of the infected murine was reduced obviously. The Hap recombinant protein also had good ability of anti-NTHi infection in the murine model of NTHi bronchopneumonia. This study could offer the oretical and experimental basis for development of new vaccine against NTHi.

[The expression and significance of chemokines eotaxin and RANTES in the rat model of allergic rhinitis].

PubMed

Tian, Cuiling; Lei, Xiaoping; Shui, Minhong; Zhang, Yanhong; Jia, Qianwei; Tu, Jing; Lian, Gang; Tang, Siquan

2014-07-01

To explore the expression and significance of Eotaxin and RANTES in the rat model of allergic rhinitis (AR). 20 female SD rats in 6-7 weeks were randomly divided into control group and AR group (n = 10, respectively). AR rat model was made with ovalbumin stimulation. To detect pathological changes in mucosa and chemokine Eotaxin, RANTES in their nasal and lung tissues after execution. Compared with the control group, Lung EOS cell counted higher in AR group and the difference was significant (P < 0.01); the AR rats nasal mucosa and lung tissue of Eotaxin, RANTES expression was significantly increased (P < 0.01). There exist high expression of Eotaxin, RANTES, infiltration of eosinophils in nasal and lung tissue of model rats with allergic rhinitis, inferring that the upper and lower respiratory tract inflammatory response has obvious consistency.

Extrapulmonary transport of MWCNT following inhalation exposure.

PubMed

Mercer, Robert R; Scabilloni, James F; Hubbs, Ann F; Wang, Liying; Battelli, Lori A; McKinney, Walter; Castranova, Vincent; Porter, Dale W

2013-08-09

Inhalation exposure studies of mice were conducted to determine if multi-walled carbon nanotubes (MWCNT) distribute to the tracheobronchial lymphatics, parietal pleura, respiratory musculature and/or extrapulmonary organs. Male C57BL/6 J mice were exposed in a whole-body inhalation system to a 5 mg/m3 MWCNT aerosol for 5 hours/day for 12 days (4 times/week for 3 weeks, lung burden 28.1 ug/lung). At 1 day and 336 days after the 12 day exposure period, mice were anesthetized and lungs, lymph nodes and extrapulmonary tissues were preserved by whole body vascular perfusion of paraformaldehyde while the lungs were inflated with air. Separate, clean-air control groups were studied at 1 day and 336 days post-exposure. Sirius Red stained sections from lung, tracheobronchial lymph nodes, diaphragm, chest wall, heart, brain, kidney and liver were analyzed. Enhanced darkfield microscopy and morphometric methods were used to detect and count MWCNT in tissue sections. Counts in tissue sections were expressed as number of MWCNT per g of tissue and as a percentage of total lung burden (Mean ± S.E., N = 8 mice per group). MWCNT burden in tracheobronchial lymph nodes was determined separately based on the volume density in the lymph nodes relative to the volume density in the lungs. Field emission scanning electron microscopy (FESEM) was used to examine MWCNT structure in the various tissues. Tracheobronchial lymph nodes were found to contain 1.08 and 7.34 percent of the lung burden at 1 day and 336 days post-exposure, respectively. Although agglomerates account for approximately 54% of lung burden, only singlet MWCNT were observed in the diaphragm, chest wall, liver, kidney, heart and brain. At one day post exposure, the average length of singlet MWCNT in liver and kidney, was comparable to that of singlet MWCNT in the lungs 8.2 ± 0.3 versus 7.5 ± 0.4 um, respectively. On average, there were 15,371 and 109,885 fibers per gram in liver, kidney, heart and brain at 1 day and 336 days post-exposure, respectively. The burden of singlet MWCNT in the lymph nodes, diaphragm, chest wall and extrapulmonary organs at 336 days post-exposure was significantly higher than at 1 day post-exposure. Inhaled MWCNT, which deposit in the lungs, are transported to the parietal pleura, the respiratory musculature, liver, kidney, heart and brain in a singlet form and accumulate with time following exposure. The tracheobronchial lymph nodes contain high levels of MWCNT following exposure and further accumulate over nearly a year to levels that are a significant fraction of the lung burden 1 day post-exposure.

Sampling characteristics and calibration of snorkel counts to estimate stream fish populations

USGS Publications Warehouse

Weaver, D.; Kwak, Thomas J.; Pollock, Kenneth

2014-01-01

Snorkeling is a versatile technique for estimating lotic fish population characteristics; however, few investigators have evaluated its accuracy at population or assemblage levels. We evaluated the accuracy of snorkeling using prepositioned areal electrofishing (PAE) for estimating fish populations in a medium-sized Appalachian Mountain river during fall 2008 and summer 2009. Strip-transect snorkel counts were calibrated with PAE counts in identical locations among macrohabitats, fish species or taxa, and seasons. Mean snorkeling efficiency (i.e., the proportion of individuals counted from the true population) among all taxa and seasons was 14.7% (SE, 2.5%), and the highest efficiencies were for River Chub Nocomis micropogon at 21.1% (SE, 5.9%), Central Stoneroller Campostoma anomalum at 20.3% (SE, 9.6%), and darters (Percidae) at 17.1% (SE, 3.7%), whereas efficiencies were lower for shiners (Notropis spp., Cyprinella spp., Luxilus spp.) at 8.2% (SE, 2.2%) and suckers (Catostomidae) at 6.6% (SE, 3.2%). Macrohabitat type, fish taxon, or sampling season did not significantly explain variance in snorkeling efficiency. Mean snorkeling detection probability (i.e., probability of detecting at least one individual of a taxon) among fish taxa and seasons was 58.4% (SE, 6.1%). We applied the efficiencies from our calibration study to adjust snorkel counts from an intensive snorkeling survey conducted in a nearby reach. Total fish density estimates from strip-transect counts adjusted for snorkeling efficiency were 7,288 fish/ha (SE, 1,564) during summer and 15,805 fish/ha (SE, 4,947) during fall. Precision of fish density estimates is influenced by variation in snorkeling efficiency and sample size and may be increased with additional sampling effort. These results demonstrate the sampling properties and utility of snorkeling to characterize lotic fish assemblages with acceptable efficiency and detection probability, less effort, and no mortality, compared with traditional sampling methods.

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

Risk Profiling May Improve Lung Cancer Screening

Cancer.gov

A new modeling study suggests that individualized, risk-based selection of ever-smokers for lung cancer screening may prevent more lung cancer deaths and improve the effectiveness and efficiency of screening compared with current screening recommendations

A novel algorithm for solving the true coincident counting issues in Monte Carlo simulations for radiation spectroscopy.

PubMed

Guan, Fada; Johns, Jesse M; Vasudevan, Latha; Zhang, Guoqing; Tang, Xiaobin; Poston, John W; Braby, Leslie A

2015-06-01

Coincident counts can be observed in experimental radiation spectroscopy. Accurate quantification of the radiation source requires the detection efficiency of the spectrometer, which is often experimentally determined. However, Monte Carlo analysis can be used to supplement experimental approaches to determine the detection efficiency a priori. The traditional Monte Carlo method overestimates the detection efficiency as a result of omitting coincident counts caused mainly by multiple cascade source particles. In this study, a novel "multi-primary coincident counting" algorithm was developed using the Geant4 Monte Carlo simulation toolkit. A high-purity Germanium detector for ⁶⁰Co gamma-ray spectroscopy problems was accurately modeled to validate the developed algorithm. The simulated pulse height spectrum agreed well qualitatively with the measured spectrum obtained using the high-purity Germanium detector. The developed algorithm can be extended to other applications, with a particular emphasis on challenging radiation fields, such as counting multiple types of coincident radiations released from nuclear fission or used nuclear fuel.

Exaggerated Acute Lung Injury and Impaired Antibacterial Defenses During Staphylococcus aureus Infection in Rats with the Metabolic Syndrome

PubMed Central

Feng, Xiaomei; Maze, Mervyn; Koch, Lauren G.; Britton, Steven L.; Hellman, Judith

2015-01-01

Rats with Metabolic Syndrome (MetaS) have a dysregulated immune response to the aseptic trauma of surgery. We hypothesized that rats with MetaS would have dysregulated inflammation, increased lung injury, and less effective antibacterial defenses during Staphylococcus (S.) aureus sepsis as compared to rats without MetaS. Low capacity runner (LCR; a model of MetaS) and high capacity runner (HCR) rats were challenged intravenously with S. aureus bacteria. After 48 h, inflammatory mediators and bacteria were quantified in the blood, bronchoalveolar lavage fluid (BALF), and lung homogenates. Lungs were analyzed histologically. BALF protein and lung wet-dry ratios were quantified to assess for vascular leak. Endpoints were compared in infected LCR vs HCR rats. LCR rats had higher blood and lung S. aureus counts, as well as higher levels of IL-6 in plasma, lungs and BALF, MIP-2 in plasma and lung, and IL-17A in lungs. Conversely, LCR rats had lower levels of IL-10 in plasma and lungs. Although lactate levels, and liver and renal function tests were similar between groups, LCR rats had higher BALF protein and lung wet-dry ratios, and more pronounced acute lung injury histologically. During S. aureus bacteremia, as compared with HCR rats, LCR (MetaS) rats have heightened pro-inflammatory responses, accompanied by increased acute lung injury and vascular leak. Notably, despite an augmented pro-inflammatory phenotype, LCR rats have higher bacterial levels in their blood and lungs. The MetaS state may exacerbate lung injury and vascular leak by attenuating the inflammation-resolving response, and by weakening antimicrobial defenses. PMID:25978669

Lung Cancer Risk Associated with Regulated and Unregulated Chrysotile Asbestos Fibers.

PubMed

Hamra, Ghassan B; Richardson, David B; Dement, John; Loomis, Dana

2017-03-01

Regulation of asbestos fibers in the workplace is partly determined by which fibers can be visually counted. However, a majority of fibers are too short and thin to count this way and are, consequently, not subject to regulation. We estimate lung cancer risk associated with asbestos fibers of varying length and width. We apply an order-constrained prior both to leverage external information from toxicological studies of asbestos health effects. This prior assumes that risk from asbestos fibers increases with increasing length and decreases with increasing width. When we apply a shared mean for the effect of all asbestos fiber exposure groups, the rate ratios for each fiber group per unit exposure appear mostly equal. Rate ratio estimates for fibers of diameter <0.25 μm and length <1.5 and 1.5-5.0 μm are the most precise. When applying an order-constrained prior, we find that estimates of lung cancer rate ratio per unit of exposure to unregulated fibers 20-40 and >40 μm in the thinnest fiber group are similar in magnitude to estimates of risk associated with long fibers in the regulated fraction of airborne asbestos fibers. Rate ratio estimates for longer fibers are larger than those for shorter fibers, but thicker and thinner fibers do not differ as the toxicologically derived prior had expected. Credible intervals for fiber size-specific risk estimates overlap; thus, we cannot conclude that there are substantial differences in effect by fiber size. Nonetheless, our results suggest that some unregulated asbestos fibers may be associated with increased incidence of lung cancer.

The natural history of fetal cells in postpartum murine maternal lung and bone marrow: a two-stage phenomenon.

PubMed

Pritchard, Stephanie; Peter, Inga; Johnson, Kirby L; Bianchi, Diana W

2012-01-01

During pregnancy, fetal cells cross into the maternal organs where they reside postpartum. Evidence from multiple laboratories suggests that these microchimeric fetal cells contribute to maternal tissue repair after injury. In mouse models, most injury experiments are performed during pregnancy; however, in a clinical setting most injuries or diseases occur postpartum. Therefore, experiments using animal models should be designed to address questions in the time period following delivery. In order to provide a baseline for such experiments, we analyzed the natural history of fetal cells in the postpartum maternal organs. Female C57BL/6J mice were mated to males homozygous for the enhanced green fluorescent protein gene. Fetal cells in the maternal lungs and bone marrow were identified by their green fluorescence using in a high-speed flow cytometer and their counts were compared between the lung and bone marrow. Spearman correlation analysis was used to identify relationships between the duration of time postpartum and the cell counts and ratio of live and dead cells. Our results show that fetal cells persist in these organs until at least three months postpartum in healthy female mice. We show a two-stage decline, with an initial two and a half-week rapid clearance followed by a trend of gradual decrease. Additionally, an increase in the ratio of live to dead cells within the lung over time suggests that these cells may replicate in vivo. The results presented here will inform the design of future experiments and may have implications for women's health.

Development of the brain's structural network efficiency in early adolescence: A longitudinal DTI twin study.

PubMed

Koenis, Marinka M G; Brouwer, Rachel M; van den Heuvel, Martijn P; Mandl, René C W; van Soelen, Inge L C; Kahn, René S; Boomsma, Dorret I; Hulshoff Pol, Hilleke E

2015-12-01

The brain is a network and our intelligence depends in part on the efficiency of this network. The network of adolescents differs from that of adults suggesting developmental changes. However, whether the network changes over time at the individual level and, if so, how this relates to intelligence, is unresolved in adolescence. In addition, the influence of genetic factors in the developing network is not known. Therefore, in a longitudinal study of 162 healthy adolescent twins and their siblings (mean age at baseline 9.9 [range 9.0-15.0] years), we mapped local and global structural network efficiency of cerebral fiber pathways (weighted with mean FA and streamline count) and assessed intelligence over a three-year interval. We find that the efficiency of the brain's structural network is highly heritable (locally up to 74%). FA-based local and global efficiency increases during early adolescence. Streamline count based local efficiency both increases and decreases, and global efficiency reorganizes to a net decrease. Local FA-based efficiency was correlated to IQ. Moreover, increases in FA-based network efficiency (global and local) and decreases in streamline count based local efficiency are related to increases in intellectual functioning. Individual changes in intelligence and local FA-based efficiency appear to go hand in hand in frontal and temporal areas. More widespread local decreases in streamline count based efficiency (frontal cingulate and occipital) are correlated with increases in intelligence. We conclude that the teenage brain is a network in progress in which individual differences in maturation relate to level of intellectual functioning. © 2015 Wiley Periodicals, Inc.

Partial liquid ventilation with perfluorocarbon improves gas exchange and decreases inflammatory response in oleic acid-induced lung injury in beagles.

PubMed

Suh, G Y; Chung, M P; Park, S J; Park, J W; Kim, H C; Kim, H; Han, J; Rhee, C H; Kwon, O J

1999-12-01

The aim of this study was to determine the effect of partial liquid ventilation (PLV) using a perfluorocarbon (PFC) on gas exchange and lung inflammatory response in a canine acute lung injury model. After inducing severe lung injury by oleic acid infusion, beagle dogs were randomized to receive either gas ventilation only (control group, n = 6) or PLV (PLV group, n = 7) by sequential instillation of 10 mL/kg of perfluorodecalin (PFC) at 30 min intervals till functional residual capacity was attained. Measurements were made every 30 min till 210 min. Then the lungs were removed and bronchoalveolar lavage (BAL) (35 mL/kg) was performed on the right lung and the left lung was submitted for histologic analysis. There was significant improvement in PaO2 and PaCO2 in the PLV group compared to the control group (p < 0.05) which was associated with a significant decrease in shunt (p < 0.05). There was no significant difference in parameters of lung mechanics and hemodynamics. There was a significant decrease in cell count and neutrophil percentage in BAL fluid and significantly less inflammation and exudate scores in histology in the PLV group (p < 0.05). We conclude that PLV with perfluorodecalin improves gas exchange and decreases inflammatory response in the acutely-injured lung.

Dual hit lipopolysaccharide & oleic acid combination induced rat model of acute lung injury/acute respiratory distress syndrome.

PubMed

Hagawane, T N; Gaikwad, R V; Kshirsagar, N A

2016-05-01

Despite advances in therapy and overall medical care, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) management remains a problem. Hence the objective of this study was to develop a rat model that mimics human ALI/ARDS. Four groups of Wistar rats, 48 per group were treated with (i) intratracheal (IT) lipopolysaccharide (LPS) (5 mg/kg) dissolved in normal saline (NS), (ii) intravenous (iv) oleic acid (OA) (250 μl/kg) suspension in bovine serum albumin (BSA), (iii) dual hit: IT LPS (2 mg/kg) dissolved in NS and iv OA (100 μl/kg) and (iv) control group: IT NS and iv BSA. From each group at set periods of time various investigations like chest x-rays, respiratory rate (RR), tidal volume (TV), total cell count, differential cell count, total protein count and cytokine levels in bronchoalveolar lavage fluid (BALF), lung wet/dry weight ratio and histopathological examination were done. It was noted that the respiratory rate, and tumour necrosis factor-α (TNF-α) levels were significantly higher at 4 h in the dual hit group as compared to LPS, OA and control groups. Interleukin-6 (IL-6) levels were significantly higher in the dual hit group as compared to LPS at 8 and 24 h, OA at 8 h and control (at all time intervals) group. IL-1β levels were significantly higher in LPS and dual hit groups at all time intervals, but not in OA and control groups. The injury induced in dual hit group was earlier and more sustained as compared to LPS and OA alone. The lung pathology and changes in respiration functions produced by the dual hit model were closer to the diagnostic criteria of ALI/ARDS in terms of clinical manifestations and pulmonary injury and the injury persisted longer as compared to LPS and OA single hit model. Therefore, the ARDS model produced by the dual hit method was closer to the diagnostic criteria of ARDS in terms of clinical manifestations and pulmonary injury.

[A case of radiation pneumonitis with eosinophilia in bronchoalveolar lavage fluid].

PubMed

Kawai, Seiko; Baba, Kenji; Tanaka, Hiroyuki; Takahashi, Daisuke; Yagi, Takeo; Hattori, Tsutomu; Etsuro, Yamaguchi

2008-01-01

A 78-year-old man was admitted to our hospital for irradiation therapy of non-resectable primary lung squamous cell carcinoma of the right middle lobe (T3N2M0). The Linac irradiation through opposing 2 gates (2Gy per day and 60Gy in total) was performed to the affected area including the metastatic right hilar and mediastinal lymphadenopathy. One week after completing the irradiation therapy, fever developed with infiltrates in the area from the right middle lobe to the right lower lobe, which did not necessarily coincide with the irradiated area. Antibiotic therapies were not effective. Both the serum LDH level and eosinophil count in the peripheral blood increased. Bronchoalveolar lavage was performed at the right B8, and differential cell counts of the lavage fluid were: macrophages, 17%; lymphocytes, 60%; neutrophils, 5%; and eosinophils, 18%. No significant organisms were obtained by culture of the lavage fluid. The %VC and DLCO/VA became lower than before the irradiation therapy. Thus, the patient was given a diagnosis of radiation pneumonitis. Treatment with 40mg/day oral prednisolone was commenced with a stepwise dose-reduction (5mg every two weeks) until reaching the maintenance dose of 15mg/day. The serum LDH level and blood eosinophil count recovered promptly to the normal range. The pulmonary infiltrates and the lung functions substantially improved. There have been few reports of radiation pneumonitis in which eosinophil counts increased in peripheral blood and bronchoalveolar lavage fluid after irradiation therapy. In the present case report, the possible mechanisms for the irradiation-induced eosinophilia were also reviewed.

Efficient statistical mapping of avian count data

USGS Publications Warehouse

Royle, J. Andrew; Wikle, C.K.

2005-01-01

We develop a spatial modeling framework for count data that is efficient to implement in high-dimensional prediction problems. We consider spectral parameterizations for the spatially varying mean of a Poisson model. The spectral parameterization of the spatial process is very computationally efficient, enabling effective estimation and prediction in large problems using Markov chain Monte Carlo techniques. We apply this model to creating avian relative abundance maps from North American Breeding Bird Survey (BBS) data. Variation in the ability of observers to count birds is modeled as spatially independent noise, resulting in over-dispersion relative to the Poisson assumption. This approach represents an improvement over existing approaches used for spatial modeling of BBS data which are either inefficient for continental scale modeling and prediction or fail to accommodate important distributional features of count data thus leading to inaccurate accounting of prediction uncertainty.

Photon Counting Detectors for the 1.0 - 2.0 Micron Wavelength Range

NASA Technical Reports Server (NTRS)

Krainak, Michael A.

2004-01-01

We describe results on the development of greater than 200 micron diameter, single-element photon-counting detectors for the 1-2 micron wavelength range. The technical goals include quantum efficiency in the range 10-70%; detector diameter greater than 200 microns; dark count rate below 100 kilo counts-per-second (cps), and maximum count rate above 10 Mcps.

Corticosteroids and fetal intervention interact to alter lung maturation in preterm lambs.

PubMed

Tabor, B L; Lewis, J F; Ikegami, M; Polk, D; Jobe, A H

1994-04-01

The relationship between cortisol infusion and time of fetal catheterization on postnatal lung function of prematurely delivered lambs was investigated with the hypothesis that the intervention of catheterization would alter fetal responsiveness to the maturational effects of corticosteroids. Fetal catheterization was performed on d 117 or on d 122 of gestation. Cortisol or saline control infusions were begun on d 126, with delivery 60 h later on d 128. The animals were ventilated for 1.25 h after delivery, and compliance, the ventilation efficiency index, labeled albumin leak into and out of the lungs, alveolar and lung saturated phosphatidylcholine and surfactant protein A were measured to evaluate lung performance and biochemical indicators of maturation. Cortisol improved compliance and ventilation efficiency and decreased labeled albumin recovery without changing alveolar saturated phosphatidylcholine or surfactant protein A in the animals catheterized at 122 d relative to 122-d saline-infused animals. However, the animals catheterized at 117 d and infused with saline were as mature as assessed by compliance and ventilation efficiency as the 122-d cortisol-treated animals. The 117-d cortisol-infused animals had significantly augmented lung function relative to either 117-d saline-infused or 122-d cortisol-treated lambs and were the only group that had increased alveolar surfactant protein A and lung saturated phosphatidylcholine pool sizes. This study demonstrates that the response of the fetal lung to a maturational agent such as cortisol is dependent on the history of previous fetal interventions.

Effect of the lung allocation score on lung transplantation in the United States.

PubMed

Egan, Thomas M; Edwards, Leah B

2016-04-01

On May 4, 2005, the system for allocation of deceased donor lungs for transplant in the United States changed from allocation based on waiting time to allocation based on the lung allocation score (LAS). We sought to determine the effect of the LAS on lung transplantation in the United States. Organ Procurement and Transplantation Network data on listed and transplanted patients were analyzed for 5 calendar years before implementation of the LAS (2000-2004), and compared with data from 6 calendar years after implementation (2006-2011). Counts were compared between eras using the Wilcoxon rank sum test. The rates of transplant increase within each era were compared using an F-test. Survival rates computed using the Kaplan-Meier method were compared using the log-rank test. After introduction of the LAS, waitlist deaths decreased significantly, from 500/year to 300/year; the number of lung transplants increased, with double the annual increase in rate of lung transplants, despite no increase in donors; the distribution of recipient diagnoses changed dramatically, with significantly more patients with fibrotic lung disease receiving transplants; age of recipients increased significantly; and 1-year survival had a small but significant increase. Allocating lungs for transplant based on urgency and benefit instead of waiting time was associated with fewer waitlist deaths, more transplants performed, and a change in distribution of recipient diagnoses to patients more likely to die on the waiting list. Copyright © 2016 International Society for Heart and Lung Transplantation. All rights reserved.

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

42 CFR 486.328 - Condition: Reporting of data.

Code of Federal Regulations, 2013 CFR

2013-10-01

... double lung transplant will be counted as three organs transplanted. A kidney/pancreas transplant will... Registry of Transplant Beneficiaries, and DHHS, as requested by the Secretary. The data may include, but... recovered, by type of organ; and (9) Number of organs transplanted, by type of organ. (b) An OPO must...

42 CFR 486.328 - Condition: Reporting of data.

Code of Federal Regulations, 2014 CFR

2014-10-01

... double lung transplant will be counted as three organs transplanted. A kidney/pancreas transplant will... Registry of Transplant Beneficiaries, and DHHS, as requested by the Secretary. The data may include, but... recovered, by type of organ; and (9) Number of organs transplanted, by type of organ. (b) An OPO must...

42 CFR 486.328 - Condition: Reporting of data.

Code of Federal Regulations, 2012 CFR

2012-10-01

... double lung transplant will be counted as three organs transplanted. A kidney/pancreas transplant will... Registry of Transplant Beneficiaries, and DHHS, as requested by the Secretary. The data may include, but... recovered, by type of organ; and (9) Number of organs transplanted, by type of organ. (b) An OPO must...

Nanostructured Lipid Carriers as Multifunctional Nanomedicine Platform for Pulmonary Co-Delivery of Anticancer Drugs and siRNA

PubMed Central

Taratula, Oleh; Kuzmov, Andriy; Shah, Milin; Garbuzenko, Olga B.; Minko, Tamara

2013-01-01

We developed, synthesized, and tested a multifunctional nanostructured lipid nanocarrier-based system (NLCS) for efficient delivery of an anticancer drug and siRNA directly into the lungs by inhalation. The system contains: (1) nanostructured lipid carriers (NLC); (2) anticancer drug (doxorubicin or paclitaxel); (3) siRNA targeted to MRP1 mRNA as a suppressor of pump drug resistance; (4) siRNA targeted to BCL2 mRNA as a suppressor of nonpump cellular resistance and (5) a modified synthetic analog of luteinizing hormone-releasing hormone (LHRH) as a targeting moiety specific to the receptors that are overexpressed in the plasma membrane of lung cancer cells. The NLCS was tested in vitro using human lung cancer cells and in vivo utilizing mouse orthotopic model of human lung cancer. After inhalation, the proposed NLCS effectively delivered its payload into lung cancer cells leaving healthy lung tissues intact and also significantly decreasing the exposure of healthy organs when compared with intravenous injection. The NLCS showed enhanced antitumor activity when compared with intravenous treatment. The data obtained demonstrated high efficiency of proposed NLCS for tumor-targeted local delivery by inhalation of anticancer drugs and mixture of siRNAs specifically to lung cancer cells and, as a result, efficient suppression of tumor growth and prevention of adverse side effects on healthy organs. PMID:23648833

Automated Image Analysis of Lung Branching Morphogenesis from Microscopic Images of Fetal Rat Explants

PubMed Central

Rodrigues, Pedro L.; Rodrigues, Nuno F.; Duque, Duarte; Granja, Sara; Correia-Pinto, Jorge; Vilaça, João L.

2014-01-01

Background. Regulating mechanisms of branching morphogenesis of fetal lung rat explants have been an essential tool for molecular research. This work presents a new methodology to accurately quantify the epithelial, outer contour, and peripheral airway buds of lung explants during cellular development from microscopic images. Methods. The outer contour was defined using an adaptive and multiscale threshold algorithm whose level was automatically calculated based on an entropy maximization criterion. The inner lung epithelium was defined by a clustering procedure that groups small image regions according to the minimum description length principle and local statistical properties. Finally, the number of peripheral buds was counted as the skeleton branched ends from a skeletonized image of the lung inner epithelia. Results. The time for lung branching morphometric analysis was reduced in 98% in contrast to the manual method. Best results were obtained in the first two days of cellular development, with lesser standard deviations. Nonsignificant differences were found between the automatic and manual results in all culture days. Conclusions. The proposed method introduces a series of advantages related to its intuitive use and accuracy, making the technique suitable to images with different lighting characteristics and allowing a reliable comparison between different researchers. PMID:25250057

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.

Total body calcium analysis. [neutron irradiation

NASA Technical Reports Server (NTRS)

Lewellen, T. K.; Nelp, W. B.

1974-01-01

A technique to quantitate total body calcium in humans is developed. Total body neutron irradiation is utilized to produce argon 37. The radio argon, which diffuses into the blood stream and is excreted through the lungs, is recovered from the exhaled breath and counted inside a proportional detector. Emphasis is placed on: (1) measurement of the rate of excretion of radio argon following total body neutron irradiation; (2) the development of the radio argon collection, purification, and counting systems; and (3) development of a patient irradiation facility using a 14 MeV neutron generator. Results and applications are discussed in detail.

The protective effect of dopamine on ventilator-induced lung injury via the inhibition of NLRP3 inflammasome.

PubMed

Yang, Xiaomei; Sun, Xiaotong; Chen, Hongli; Xi, Guangmin; Hou, Yonghao; Wu, Jianbo; Liu, Dejie; Wang, Huanliang; Hou, Yuedong; Yu, Jingui

2017-04-01

Dopamine (DA), a neurotransmitter, was previously shown to have anti-inflammatory effects. However, its role in ventilator-induced lung injury (VILI) has not been explicitly demonstrated. This study aimed to investigate the therapeutic efficacy and molecular mechanisms of dopamine in VILI. Rats were treated with dopamine during mechanical ventilation. Afterwards, the influence of dopamine on histological changes, pulmonary edema, the lung wet/dry (W/D) ratio, myeloperoxidase (MPO) activity, polymorphonuclear(PMN)counts, inflammatory cytokine levels, and NLRP3 inflammasome protein expression were examined. Our results showed that dopamine significantly attenuated lung tissue injury, the lung W/D ratio, MPO activity and neutrophil infiltration. Moreover, it inhibited inflammatory cytokine levels in the Bronchoalveolar lavage fluid (BAL). In addition, dopamine significantly inhibited ventilation-induced NLRP3 activation. Our experimental findings demonstrate that dopamine exerted protective effects in VILI by alleviating the inflammatory response through inhibition of NLRP3 signaling pathways. The present study indicated that dopamine could be a potential effective therapeutic strategy for the treatment of VILI. Copyright © 2017 Elsevier B.V. All rights reserved.

HIV infection is associated with an increased risk for lung cancer, independent of smoking.

PubMed

Kirk, Gregory D; Merlo, Christian; O' Driscoll, Peter; Mehta, Shruti H; Galai, Noya; Vlahov, David; Samet, Jonathan; Engels, Eric A

2007-07-01

Human immunodeficiency virus (HIV)-infected persons have an elevated risk for lung cancer, but whether the increase reflects solely their heavy tobacco use remains an open question. The Acquired Immunodeficiency Syndrome (AIDS) Link to the Intravenous Experience Study has prospectively observed a cohort of injection drug users in Baltimore, Maryland, since 1988, using biannual collection of clinical, laboratory, and behavioral data. Lung cancer deaths were identified through linkage with the National Death Index. Cox proportional hazards regression was used to examine the effect of HIV infection on lung cancer risk, controlling for smoking status, drug use, and clinical variables. Among 2086 AIDS Link to the Intravenous Experience Study participants observed for 19,835 person-years, 27 lung cancer deaths were identified; 14 of the deaths were among HIV-infected persons. All but 1 (96%) of the patients with lung cancer were smokers, smoking a mean of 1.2 packs per day. Lung cancer mortality increased during the highly active antiretroviral therapy era, compared with the pre-highly active antiretroviral therapy period (mortality rate ratio, 4.7; 95% confidence interval, 1.7-16). After adjusting for age, sex, smoking status, and calendar period, HIV infection was associated with increased lung cancer risk (hazard ratio, 3.6; 95% confidence interval, 1.6-7.9). Preexisting lung disease, particularly noninfectious diseases and asthma, displayed trends for increased lung cancer risk. Illicit drug use was not associated with increased lung cancer risk. Among HIV-infected persons, smoking remained the major risk factor; CD4 cell count and HIV load were not strongly associated with increased lung cancer risk, and trends for increased risk with use of highly active antiretroviral therapy were not significant. HIV infection is associated with significantly increased risk for developing lung cancer, independent of smoking status.

Tutorial on X-ray photon counting detector characterization.

PubMed

Ren, Liqiang; Zheng, Bin; Liu, Hong

2018-01-01

Recent advances in photon counting detection technology have led to significant research interest in X-ray imaging. As a tutorial level review, this paper covers a wide range of aspects related to X-ray photon counting detector characterization. The tutorial begins with a detailed description of the working principle and operating modes of a pixelated X-ray photon counting detector with basic architecture and detection mechanism. Currently available methods and techniques for charactering major aspects including energy response, noise floor, energy resolution, count rate performance (detector efficiency), and charge sharing effect of photon counting detectors are comprehensively reviewed. Other characterization aspects such as point spread function (PSF), line spread function (LSF), contrast transfer function (CTF), modulation transfer function (MTF), noise power spectrum (NPS), detective quantum efficiency (DQE), bias voltage, radiation damage, and polarization effect are also remarked. A cadmium telluride (CdTe) pixelated photon counting detector is employed for part of the characterization demonstration and the results are presented. This review can serve as a tutorial for X-ray imaging researchers and investigators to understand, operate, characterize, and optimize photon counting detectors for a variety of applications.

Total pollen counts do not influence active surface measurements

NASA Astrophysics Data System (ADS)

Moshammer, Hanns; Schinko, Herwig; Neuberger, Manfred

We investigated the temporal association of various aerosol parameters with pollen counts in the pollen season (April 2001) in Linz, Austria. We were especially interested in the relationship between active surface (or Fuchs' surface) because we had shown previously (Atmos. Environ. 37 (2003) 1737-1744) that this parameter during the same observation period was a better predictor for acute respiratory symptoms in school children (like wheezing, shortness of breath, and cough) and reduced lung function on the same day than particle mass (PM 10). While active surface is most sensitive for fine particles with a diameter of less than 100 nm it has no strict upper cut-off regarding particle size and so could eventually be influenced also by larger particles if their numbers were high. All particle mass parameters tested (TSP, PM 10, PM 1) were weakly ( r approximately 0.2) though significantly correlated with pollen counts but neither was active surface nor total particle counts (CPC). The weak association of particle mass and pollen counts was due mainly to similar diurnal variations and a linear trend over time. Only the mass of the coarse fraction (TSP minus PM 10) remained associated with pollen counts significantly after controlling for these general temporal patterns.

[A case of both cryptococcal pneumonia and meningitis with idiopathic CD4+T-lymphocytopenia followed up over a long time].

PubMed

Anzai, Fumio; Yamamoto, Akito; Tannai, Noriyuki; Abe, Hideki; Tsuchiya, Kayoko; Kusajima, Kenji; Shimoide, Hisao; Nunomura, Maki

2009-07-01

A 62-year-old man had felt cold-like symptoms for 2 months. He visited a clinic for a health check in late July 1998 and chest X-ray film showed an infiltrative shadow in the left middle and lower lung fields. Next day he had a fever of 38.3 degrees C and felt breathless. Six days thereafter he had a cough, thick head and felt fatigue. Chest X-ray films showed other infiltrative shadows in the bilateral upper lung fields. He worked in a race track and was exposed to pigeons and seabirds at that time. Culture of sputum grew Cryptococcus neoformans. He was admitted and was treated with intravenous antifungal drugs. Cerebrospinal fluid examination revealed positive Indian ink stain for C. neoformans. The CD4 + T-lymphocyte count and CD8 + T-lymphocyte count were 143.4 cells/mm3 and 1288.8 cells/mm3 respectively, but without HIV infection. Cryptococcal pneumonia and meningitis with Idiopathic CD4 + T-lymphocytopenia was diagnosed. After induction therapy, the symptoms improved but abnormal shadows remained on chest X-ray films. Maintenance therapy has been continued at doses of 200 mg/day of fluconazole for 10 years. He has had no symptoms, but the abnormal X-ray shadow has persisted and the CD4 count has remained low during the same period.

The influence of the structural orientation of amide linkers on the serum compatibility and lung transfection properties of cationic amphiphiles.

PubMed

Srujan, Marepally; Chandrashekhar, Voshavar; Reddy, Rakesh C; Prabhakar, Rairala; Sreedhar, Bojja; Chaudhuri, Arabinda

2011-08-01

Understanding the structural parameters of cationic amphiphiles which can influence gene transfer efficiencies of cationic amphiphiles continues to remain important for designing efficient liposomal gene delivery reagents. Previously we demonstrated the influence of structural orientation of the ester linker (widely used in covalently tethering the polar head and the non-polar tails) in modulating in vitro gene transfer efficiencies of cationic amphiphiles. However, our previously described cationic amphiphiles with ester linkers failed to deliver genes under in vivo conditions. Herein we report on the development of a highly serum compatible cationic amphiphile with circulation stable amide linker which shows remarkable selectivity in transfecting mouse lung. We also demonstrate that reversing structural orientation of the amide linker adversely affects both serum compatibility and the lung selective gene transfer property. Dynamic laser light scattering and atomic force microscopic studies revealed smaller average hydrodynamic sizes of the liposomes of transfection efficient lipid than those for the liposomes of transfection incompetent analog (148 ± 1 nm vs 214 ± 4 nm). Average surface potential of the liposomes of transfection competent amphiphiles were found to be significantly higher than that for the liposomes of transfection incompetent analog (10.7 ± 5.4 mV vs 2.8 ± 1.3 mV, respectively). Findings in fluorescence resonance energy transfer and dye entrapment experiments support lower rigidity and higher biomembrane fusogenicity of the liposomes of the transfection efficient amphiphiles. Importantly, cationic lipoplexes of the novel amide-linker based amphiphile exhibited higher mouse lung selective gene transfer properties than DOTAP, one of the widely used commercially available liposomal lung transfection kits. In summary, the present findings demonstrate for the first time that amide linker structural orientation profoundly influences the serum compatibility and lung transfection efficiencies of cationic amphiphiles. Copyright © 2011 Elsevier Ltd. All rights reserved.

Prognostic significance of blood coagulation tests in carcinoma of the lung and colon.

PubMed

Wojtukiewicz, M Z; Zacharski, L R; Moritz, T E; Hur, K; Edwards, R L; Rickles, F R

1992-08-01

Blood coagulation test results were collected prospectively in patients with previously untreated, advanced lung or colon cancer who entered into a clinical trial. In patients with colon cancer, reduced survival was associated (in univariate analysis) with higher values obtained at entry to the study for fibrinogen, fibrin(ogen) split products, antiplasmin, and fibrinopeptide A and accelerated euglobulin lysis times. In patients with non-small cell lung cancer, reduced survival was associated (in univariate analysis) with higher fibrinogen and fibrin(ogen) split products, platelet counts and activated partial thromboplastin times. In patients with small cell carcinoma of the lung, only higher activated partial thromboplastin times were associated (in univariate analysis) with reduced survival in patients with disseminated disease. In multivariate analysis, higher activated partial thromboplastin times were a significant independent predictor of survival for patients with non-small cell lung cancer limited to one hemithorax and with disseminated small cell carcinoma of the lung. Fibrin(ogen) split product levels were an independent predictor of survival for patients with disseminated non-small cell lung cancer as were both the fibrinogen and fibrinopeptide A levels for patients with disseminated colon cancer. These results suggest that certain tests of blood coagulation may be indicative of prognosis in lung and colon cancer. The heterogeneity of these results suggests that the mechanism(s), intensity, and pathophysiological significance of coagulation activation in cancer may differ between tumour types.

Budesonide ameliorates lung function of the cigarette smoke-exposed rats through reducing matrix metalloproteinase-1 content

PubMed Central

Sun, Jiawei; Zhang, Ping; Zhang, Bin; Li, Kang; Li, Zhu; Li, Junhong; Zhang, Yongjian; Sun, Wuzhuang

2015-01-01

Objectives: This study was conducted to investigate an effect of inhaled budesonide on cigarette smoke-exposed lungs with a possible mechanism involved in the event. Methods: Rats were exposed to air (control) and cigarette smoke (smoking) in presence and absence of budesonide. Inflammatory cell count in bronchoalveolar lavage fluid (BALF), lung function testing, mean liner intercept (MLI) in lung tissue, mean alveolar number (MAN) and a ratio of bronchial wall thickness and external diameter (BWT/D) were determined in the grouped rats, respectively. Contents of matrix metalloproteinase (MMP)-1, MMP-2 and tissue inhibitor of metalloproteinase (TIMP)-2 productions in BALF were examined as well. Results: There were significant changes in the above assessments in the smoking rats as compared to those in the control rats (all P < 0.01 and 0.05). Budesonide inhalation significantly decreased the numbers of the BALF cells and partly reversed lung function decline in the challenged rats (P < 0.01 and 0.05). However, this corticosteroid did not influence pathological changes in fine structures of the tobacco smoke-exposed lungs. Treatment with budesonide resulted in an obvious decrease in the MMP-1 but not MMP-2 and TIMP-2 productions (P < 0.05). Conclusion: Inhaled budesonide mitigates the ongoing inflammatory process in the smoked lungs and ameliorates declining lung function through reducing MMP-1 content. PMID:26191209

Budesonide ameliorates lung function of the cigarette smoke-exposed rats through reducing matrix metalloproteinase-1 content.

PubMed

Sun, Jiawei; Zhang, Ping; Zhang, Bin; Li, Kang; Li, Zhu; Li, Junhong; Zhang, Yongjian; Sun, Wuzhuang

2015-01-01

This study was conducted to investigate an effect of inhaled budesonide on cigarette smoke-exposed lungs with a possible mechanism involved in the event. Rats were exposed to air (control) and cigarette smoke (smoking) in presence and absence of budesonide. Inflammatory cell count in bronchoalveolar lavage fluid (BALF), lung function testing, mean liner intercept (MLI) in lung tissue, mean alveolar number (MAN) and a ratio of bronchial wall thickness and external diameter (BWT/D) were determined in the grouped rats, respectively. Contents of matrix metalloproteinase (MMP)-1, MMP-2 and tissue inhibitor of metalloproteinase (TIMP)-2 productions in BALF were examined as well. There were significant changes in the above assessments in the smoking rats as compared to those in the control rats (all P<0.01 and 0.05). Budesonide inhalation significantly decreased the numbers of the BALF cells and partly reversed lung function decline in the challenged rats (P<0.01 and 0.05). However, this corticosteroid did not influence pathological changes in fine structures of the tobacco smoke-exposed lungs. Treatment with budesonide resulted in an obvious decrease in the MMP-1 but not MMP-2 and TIMP-2 productions (P<0.05). Inhaled budesonide mitigates the ongoing inflammatory process in the smoked lungs and ameliorates declining lung function through reducing MMP-1 content.

Low-dose lung cancer screening with photon-counting CT: a feasibility study

NASA Astrophysics Data System (ADS)

Symons, Rolf; Cork, Tyler E.; Sahbaee, Pooyan; Fuld, Matthew K.; Kappler, Steffen; Folio, Les R.; Bluemke, David A.; Pourmorteza, Amir

2017-01-01

To evaluate the feasibility of using a whole-body photon-counting detector (PCD) CT scanner for low-dose lung cancer screening compared to a conventional energy integrating detector (EID) system. Radiation dose-matched EID and PCD scans of the COPDGene 2 phantom were acquired at different radiation dose levels (CTDIvol: 3.0, 1.5, and 0.75 mGy) and different tube voltages (120, 100, and 80 kVp). EID and PCD images were compared for quantitative Hounsfield unit (HU) accuracy, noise levels, and contrast-to-noise ratios (CNR) for detection of ground-glass nodules (GGN) and emphysema. The PCD HU accuracy was better than EID for water at all scan parameters. PCD HU stability for lung, GGN and emphysema regions were superior to EID and PCD attenuation values were more reproducible than EID for all scan parameters (all P  <  0.01), while HUs for lung, GGN and emphysema ROIs changed significantly for EID with decreasing dose (all P  <  0.001). PCD showed lower noise levels at the lowest dose setting at 120, 100 and 80 kVp (15.2  ±  0.3 HU versus 15.8  ±  0.2 HU, P  =  0.03 16.1  ±  0.3 HU versus 18.0  ±  0.4 HU, P  =  0.003 and 16.1  ±  0.3 HU versus 17.9  ±  0.3 HU, P  =  0.001, respectively), resulting in superior CNR for evaluation of GGNs and emphysema at 100 and 80 kVp. PCD provided better HU stability for lung, ground-glass, and emphysema-equivalent foams at lower radiation dose settings with better reproducibility than EID. Additionally, PCD showed up to 10% less noise, and 11% higher CNR at 0.75 mGy for both 100 and 80 kVp. PCD technology may help reduce radiation exposure in lung cancer screening while maintaining diagnostic quality.

Toward efficient biomechanical-based deformable image registration of lungs for image-guided radiotherapy

NASA Astrophysics Data System (ADS)

Al-Mayah, Adil; Moseley, Joanne; Velec, Mike; Brock, Kristy

2011-08-01

Both accuracy and efficiency are critical for the implementation of biomechanical model-based deformable registration in clinical practice. The focus of this investigation is to evaluate the potential of improving the efficiency of the deformable image registration of the human lungs without loss of accuracy. Three-dimensional finite element models have been developed using image data of 14 lung cancer patients. Each model consists of two lungs, tumor and external body. Sliding of the lungs inside the chest cavity is modeled using a frictionless surface-based contact model. The effect of the type of element, finite deformation and elasticity on the accuracy and computing time is investigated. Linear and quadrilateral tetrahedral elements are used with linear and nonlinear geometric analysis. Two types of material properties are applied namely: elastic and hyperelastic. The accuracy of each of the four models is examined using a number of anatomical landmarks representing the vessels bifurcation points distributed across the lungs. The registration error is not significantly affected by the element type or linearity of analysis, with an average vector error of around 2.8 mm. The displacement differences between linear and nonlinear analysis methods are calculated for all lungs nodes and a maximum value of 3.6 mm is found in one of the nodes near the entrance of the bronchial tree into the lungs. The 95 percentile of displacement difference ranges between 0.4 and 0.8 mm. However, the time required for the analysis is reduced from 95 min in the quadratic elements nonlinear geometry model to 3.4 min in the linear element linear geometry model. Therefore using linear tetrahedral elements with linear elastic materials and linear geometry is preferable for modeling the breathing motion of lungs for image-guided radiotherapy applications.

UV superconducting nanowire single-photon detectors with high efficiency, low noise, and 4 K operating temperature

NASA Astrophysics Data System (ADS)

Wollman, E. E.; Verma, V. B.; Beyer, A. D.; Briggs, R. M.; Korzh, B.; Allmaras, J. P.; Marsili, F.; Lita, A. E.; Mirin, R. P.; Nam, S. W.; Shaw, M. D.

2017-10-01

For photon-counting applications at ultraviolet wavelengths, there are currently no detectors that combine high efficiency (> 50%), sub-nanosecond timing resolution, and sub-Hz dark count rates. Superconducting nanowire single-photon detectors (SNSPDs) have seen success over the past decade for photon-counting applications in the near-infrared, but little work has been done to optimize SNSPDs for wavelengths below 400 nm. Here, we describe the design, fabrication, and characterization of UV SNSPDs operating at wavelengths between 250 and 370 nm. The detectors have active areas up to 56 ${\\mu}$m in diameter, 70 - 80% efficiency, timing resolution down to 60 ps FWHM, blindness to visible and infrared photons, and dark count rates of ~ 0.25 counts/hr for a 56 ${\\mu}$m diameter pixel. By using the amorphous superconductor MoSi, these UV SNSPDs are also able to operate at temperatures up to 4.2 K. These performance metrics make UV SNSPDs ideal for applications in trapped-ion quantum information processing, lidar studies of the upper atmosphere, UV fluorescent-lifetime imaging microscopy, and photon-starved UV astronomy.

Logistic regression for dichotomized counts.

PubMed

Preisser, John S; Das, Kalyan; Benecha, Habtamu; Stamm, John W

2016-12-01

Sometimes there is interest in a dichotomized outcome indicating whether a count variable is positive or zero. Under this scenario, the application of ordinary logistic regression may result in efficiency loss, which is quantifiable under an assumed model for the counts. In such situations, a shared-parameter hurdle model is investigated for more efficient estimation of regression parameters relating to overall effects of covariates on the dichotomous outcome, while handling count data with many zeroes. One model part provides a logistic regression containing marginal log odds ratio effects of primary interest, while an ancillary model part describes the mean count of a Poisson or negative binomial process in terms of nuisance regression parameters. Asymptotic efficiency of the logistic model parameter estimators of the two-part models is evaluated with respect to ordinary logistic regression. Simulations are used to assess the properties of the models with respect to power and Type I error, the latter investigated under both misspecified and correctly specified models. The methods are applied to data from a randomized clinical trial of three toothpaste formulations to prevent incident dental caries in a large population of Scottish schoolchildren. © The Author(s) 2014.

CD16-positive circulating monocytes and fibrotic manifestations of systemic sclerosis.

PubMed

Lescoat, Alain; Lecureur, Valérie; Roussel, Mikael; Sunnaram, Béatrice Ly; Ballerie, Alice; Coiffier, Guillaume; Jouneau, Stéphane; Fardel, Olivier; Fest, Thierry; Jégo, Patrick

2017-07-01

The objective of this study is to assess the association of clinical manifestations of systemic sclerosis (SSc) with the absolute count of circulating blood monocyte subpopulations according to their membrane expression of CD16. Forty-eight consecutive patients fulfilling the 2013 ACR/EULAR classification criteria for SSc were included in this cross-sectional study. CD16+ monocyte absolute count was defined by flow cytometry and confronted to the clinical characteristics of SSc patients. Twenty-three healthy donors (HD) were randomly selected for comparison. SSc patients had an increased number of total circulating blood monocytes compared to HD (p < 0.001). The CD16- subpopulation absolute count was increased in SSc patients compared to HD (p < 0.001) but was similar in limited SSc (lSSc) and diffuse SSc (dSSc). On the contrary, the CD16+ population absolute count was increased in dSSc compared to both HD and lSSc patients (dSSc 0.071 Giga/L (±0.034) vs HD 0.039 Giga/L (±0.030), p < 0.01, and dSSc 0.071 Giga/L (±0.034) vs lSSc 0.048 Giga/L (±0.024), p < 0.05). The CD16+ monocyte subpopulation absolute count was significantly correlated with the severity of skin fibrosis evaluated by the modified Rodnan skin score (p < 0.001). The CD16+ monocyte subpopulation was also associated with pulmonary fibrosis (p < 0.05), with the severity of the restrictive ventilatory defect evaluated by total lung capacity (p < 0.05) and with the pulmonary function impairment reflected by diffusing capacity of the lungs for carbon monoxyde measures (p < 0.01). These results suggest that CD16+ monocytes are associated with the main fibrotic manifestations of SSc and their role in the pathogenesis of fibrosis in this autoimmune disorder should therefore be further considered.

Coagulation activation by MC28 fibrosarcoma cells facilitates lung tumor formation.

PubMed

Amirkhosravi, M; Francis, J L

1995-01-01

Tumor cells interact with the hemostatic system in various ways and may thus influence malignant growth and spread. MC28 fibrosarcoma cells possess a potent procoagulant activity (PCA) and form lung tumors following intravenous injection. The aim of this work was to study the relationship between PCA, intravascular coagulation and lung seeding in the MC28 model. MC28 cells were injected into control, warfarinized and heparinized hooded Lister rats. Coagulation changes were monitored by thromboelastography (TEG) and Sonoclot analysis (SA), lung fibrin formation by light and electron microscopy, tumor seeding by macroscopic counting and tumor cell and platelet deposition in the lungs by radiolabelling. PCA was measured by chromogenic assay. MC28 PCA was characterized as a tissue factor-factor VIIa complex that probably arose during cell culture or disaggregation of solid tumors. Injection of tumor cells caused marked coagulopathy and was rapidly (within 30 min) followed by fibrin deposition in the lungs and accumulation of radiolabelled platelets. Heparin and warfarin significantly reduced lung seeding (p < 0.001) and reduced retention of radiolabelled tumor cells in the pulmonary circulation (p < 0.01). Inhibition of cellular PCA by prior treatment with concanavalin A markedly reduced intravascular coagulation and lung seeding. We conclude that MC28 cells cause intravascular coagulation as a direct result of their procoagulant activity. The data suggest that tumor cells form complexes with platelets and fibrin which are retained in the lungs long enough for extravasation and seeding to occur.(ABSTRACT TRUNCATED AT 250 WORDS)

An integrated nanotechnology-enabled transbronchial image-guided intervention strategy for peripheral lung cancer

PubMed Central

Jin, Cheng S.; Wada, Hironobu; Anayama, Takashi; McVeigh, Patrick Z; Hu, Hsin Pei; Hirohashi, Kentaro; Nakajima, Takahiro; Kato, Tatsuya; Keshavjee, Shaf; Hwang, David; Wilson, Brian C.; Zheng, Gang; Yasufuku, Kazuhiro

2016-01-01

Early detection and efficient treatment modality of early-stage peripheral lung cancer is essential. Current non-surgical treatments for peripheral lung cancer show critical limitations associated with various complications, requiring alternative minimally invasive therapeutics. Porphysome nanoparticle-enabled fluorescence-guided transbronchial photothermal therapy (PTT) of peripheral lung cancer was developed and demonstrated in preclinical animal models. Systemically-administered porphysomes accumulated in lung tumors with significantly enhanced disease-to-normal tissue contrast, as confirmed in three subtypes of orthotopic human lung cancer xenografts (A549, H460 and H520) in mice and in an orthotopic VX2 tumor in rabbits. An in-house prototype fluorescence bronchoscope demonstrated the capability of porphysomes for in vivo imaging of lung tumors in the mucosal/submucosal layers, providing real-time fluorescence guidance for transbronchial PTT. Porphysomes also enhanced the efficacy of transbronchial PTT significantly and resulted in selective and efficient tumor tissue ablation in the rabbit model. A clinically used cylindrical diffuser fiber successfully achieved tumor-specific thermal ablation, showing promising evidence for the clinical translation of this novel platform to impact upon non-surgical treatment of early-stage peripheral lung cancer. PMID:27543602

Utility of Bronchoalveolar Lavage for the Diagnosis of Asbestos-Related Diseases.

PubMed

Cruz, María Jesús; Curull, Victor; Pijuan, Lara; Álvarez-Simón, Daniel; Sánchez-Font, Albert; de Gracia, Javier; Culebras, Mario; Ferrer, Jaume

2017-06-01

Bronchoalveolar lavage (BAL) analysis has been proposed as an objective technique for confirming asbestos exposure. However, the reliability and diagnostic yield of this procedure has not been studied in Spain. The aim of this study was to assess the usefulness of the analysis of asbestos bodies (AB) in bronchoalveolar lavage (BAL) for the diagnosis of asbestos-related diseases (ARD). BAL samples from 72 patients (66 male, mean age 66 years) undergoing bronchoscopy were analyzed. Lung tissue from 23 of these patients was also analyzed. Asbestos exposure was assessed by anamnesis and a review of the patient's medical records. BAL and lung samples were processed and AB count was determined by light microscopy. The accepted threshold value to diagnose asbestos-related diseases was 1 AB/ml BAL or 1000 AB/gr dry tissue. Thirty-nine patients reported exposure to asbestos. Of these, 13 (33%) presented AB values above 1 AB/ml BAL. In the 33 non-exposed patients, 5 (15%) presented AB values above 1 AB/ml BAL. There was a significant difference between the AB levels of exposed and non-exposed patients (P=.006). The ROC curve showed that a value of 0.5 AB/ml BAL achieved the most satisfactory sensitivity, 46%, and a specificity of 83%. The correlation between AB levels in BAL and lung was 0.633 (P=.002). BAL study provides objective evidence of exposure to asbestos. The good correlation between the AB counts in BAL and lung tissue indicates that both techniques are valid for the analysis of asbestos content. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Comparison of two methods for recovering migrating Ascaris suum larvae from the liver and lungs of pigs.

PubMed

Slotved, H C; Roepstorff, A; Barnes, E H; Eriksen, L; Nansen, P

1996-08-01

Nine groups of 5 pigs were inoculated with Ascaris suum eggs on day 0. Groups 1, 2, and 3 were inoculated with 100 eggs, groups 4, 5, and 6 with 1,000 eggs, and groups 7, 8, and 9 with 10,000 eggs. On day 3, groups 1, 4, and 7 were slaughtered, on day 7 groups 2, 5, and 8, and on day 10 groups 3, 6, and 9. The liver (days 3 and 7) and lungs (days 3, 7, and 10) were removed and 2, 25% samples of both organs were collected. Larvae were recovered from 1 sample by the Baermann method and from the other by an agar-gel method. Overall there were no significant differences in the liver larval recovery between the 2 methods. The use of the agar-gel method resulted in a very clean suspension of larvae and thereby reduced the sample counting time by a factor of 5-10 compared to the Baermann method. With both methods larval recovery from the lungs resulted in a clean larval suspension that was easy to count, and there were overall no significant differences between the 2 methods, although there was a tendency toward the Baermann method recovering more larvae from the lungs than the agar-gel method. The tissue sample dry weight did not significantly influence larval recovery by the agar-gel method, and the time interval from slaughtering to start of incubation on day 3 (interval 51-92 min), day 7 (interval 37-114 min), and day 10 (interval 50-129 min) had no significant effect on recovery by either method.

Diet-Induced Obesity Reprograms the Inflammatory Response of the Murine Lung to Inhaled Endotoxin

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

Tilton, Susan C.; Waters, Katrina M.; Karin, Norman J.

The co-occurrence of environmental factors is common in complex human diseases and, as such, understanding the molecular responses involved is essential to determine risk and susceptibility to disease. We have investigated the key biological pathways that define susceptibility for pulmonary infection during obesity in diet-induced obese (DIO) and regular weight (RW) C57BL/6 mice exposed to inhaled lipopolysaccharide (LPS). LPS induced a strong inflammatory response in all mice as indicated by elevated cell counts of macrophages and neutrophils and levels of proinflammatory cytokines (MDC, MIP-1γ, IL-12, RANTES) in the bronchoalveolar lavage fluid. Additionally, DIO mice exhibited 50% greater macrophage cell counts,more » but decreased levels of the cytokines, IL-6, TARC, TNF-α, and VEGF relative to RW mice. Microarray analysis of lung tissue showed over half of the LPS-induced expression in DIO mice consisted of genes unique for obese mice, suggesting that obesity reprograms how the lung responds to subsequent insult. In particular, we found that obese animals exposed to LPS have gene signatures showing increased inflammatory and oxidative stress response and decreased antioxidant capacity compared with RW. Because signaling pathways for these responses can be common to various sources of environmentally induced lung damage, we further identified biomarkers that are indicative of specific toxicant exposure by comparing gene signatures after LPS exposure to those from a parallel study with cigarette smoke. These data show obesity may increase sensitivity to further insult and that co-occurrence of environmental stressors result in complex biosignatures that are not predicted from analysis of individual exposures.« less

Bacterial extract (OM-85) with human-equivalent doses does not inhibit the development of asthma in a murine model.

PubMed

Rodrigues, A; Gualdi, L P; de Souza, R G; Vargas, M H M; Nuñez, N K; da Cunha, A A; Jones, M H; Pinto, L A; Stein, R T; Pitrez, P M

OM-85 is an immunostimulant bacterial lysate, which has been proven effective in reducing the number of lower airways infections. We investigated the efficacy of the bacterial lysate OM-85 in the primary prevention of a murine model of asthma. In the first phase of our study the animals received doses of 0.5μg, 5μg and 50μg of OM-85 through gavage for five days (days -10 to -6 of the protocol), 10 days prior to starting the sensitisation with ovalbumin (OVA), in order to evaluate the results of dose-response protocols. A single dose (5μg) was then chosen in order to verify in detail the effect of OM-85 on the pulmonary allergic response. Total/differential cells count and cytokine levels (IL-4, IL-5, IL-13 and IFN-γ) from bronchoalveolar lavage fluid (BALF), OVA-specific IgE levels from serum, lung function and lung histopathological analysis were evaluated. OM-85 did not reduce pulmonary eosinophilic response, regardless of the dose used. In the phase protocol using 5μg/animal of OM-85, no difference was shown among the groups studied, including total cell and eosinophil counts in BALF, serum OVA-specific IgE, lung histopathologic findings and lung resistance. However, OM-85 decreased IL-5 and IL-13 levels in BALF. OM-85, administered in early life in mice in human-equivalent doses, does not inhibit the development of allergic pulmonary response in mice. Copyright © 2016 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

Potentiated Interaction between Ineffective Doses of Budesonide and Formoterol to Control the Inhaled Cadmium-Induced Up-Regulation of Metalloproteinases and Acute Pulmonary Inflammation in Rats

PubMed Central

Zhang, Wenhui; Zhi, Jianming; Cui, Yongyao; Zhang, Fan; Habyarimana, Adélite; Cambier, Carole; Gustin, Pascal

2014-01-01

The anti-inflammatory properties of glucocorticoids are well known but their protective effects exerted with a low potency against heavy metals-induced pulmonary inflammation remain unclear. In this study, a model of acute pulmonary inflammation induced by a single inhalation of cadmium in male Sprague-Dawley rats was used to investigate whether formoterol can improve the anti-inflammatory effects of budesonide. The cadmium-related inflammatory responses, including matrix metalloproteinase-9 (MMP-9) activity, were evaluated. Compared to the values obtained in rats exposed to cadmium, pretreatment of inhaled budesonide (0.5 mg/15 ml) elicited a significant decrease in total cell and neutrophil counts in bronchoalveolar lavage fluid (BALF) associated with a significant reduction of MMP-9 activity which was highly correlated with the number of inflammatory cells in BALF. Additionally, cadmium-induced lung injuries characterized by inflammatory cell infiltration within alveoli and the interstitium were attenuated by the pre-treatment of budesonide. Though the low concentration of budesonide (0.25 mg/15 ml) exerted a very limited inhibitory effects in the present rat model, its combination with an inefficient concentration of formoterol (0.5 mg/30 ml) showed an enhanced inhibitory effect on neutrophil and total cell counts as well as on the histological lung injuries associated with a potentiation of inhibition on the MMP-9 activity. In conclusion, high concentration of budesonide alone could partially protect the lungs against cadmium exposure induced-acute neutrophilic pulmonary inflammation via the inhibition of MMP-9 activity. The combination with formoterol could enhance the protective effects of both drugs, suggesting a new therapeutic strategy for the treatment of heavy metals-induced lung diseases. PMID:25313925

Bioaccumulation of selected heavy metals and histopathological and hematobiochemical alterations in backyard chickens reared in an industrial area, India.

PubMed

Kar, Indrajit; Mukhopadhayay, Sunit Kumar; Patra, Amlan Kumar; Pradhan, Saktipada

2018-02-01

This study was carried out to determine the concentrations of four heavy metals, cadmium (Cd), lead (Pb), copper (Cu), and cobalt (Co), and histopathological lesions in tissues of chickens reared in an industrial area of West Bengal, India. In particular, Mejhia Block was selected as a heavy metal-exposed area and Vatar Block (120 km away from industrially polluted areas) as a reference site. Samples were collected from the backyard chickens in these areas. Concentrations of heavy metals in soil, water, feedstuffs, tissues (liver, kidney, spleen, lung, and muscle), and droppings were greater (p < 0.05) in the polluted site than in the reference site. The greatest tissue concentrations of Cd and Pb were noted in the kidney, followed by the liver, lung, spleen, and muscle, whereas Cu and Co concentrations accumulated in these tissues resulted in the following: liver > kidney > lung > spleen > muscle. Heavy metal concentrations were greater in older chickens (> 1 year) than in young chickens (< 1 year). Packed cell volume, total erythrocyte counts, hemoglobin, total protein, and total leucocyte counts were significantly (p < 0.01) lower in the blood picture of chickens in the exposed area. Different serum enzymes and biochemical profiles were altered due to heavy metal exposure. Histological changes revealed necrotic lesions and tubulitis in the kidney, degeneration and necrosis in liver parenchyma, and periarteriolitis, peribronchiolitis, and presence of hemosiderin pigment in the lung of chickens in the exposed site. Results indicated that backyard chickens in heavy metal-exposed site may show pathological lesions in different tissues due to accumulation of heavy metals, and thus, the consumption of chicken meat from the industrially exposed site may pose a potential health risk to local residents of polluted sites.

Pulmonary uptake in indium-111-antimyosin fab fragment imaging following human cardia transplantation

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

Folke, M.; Hesse, B.; Mortensen, S.A.

1994-02-01

Recent studies suggest that cardiac uptake of {sup 111}In-labeled antimyosin monoclonal antibody may be estimated semiquantitatively by calculating a heart-to-lung activity ratio, with pulmonary uptake serving as a reference region. The authors obtained 96 {sup 111}In-antimyosin scintigraphs to monitor rejection occurrence after heart transplantation in 26 patients. On five scintigraphs, the count rate density in ROIs over the lungs was markedly higher (mean 53% higher) than that in the immediately preceding and following scintigraphs, whereas the activity in the heart was essentially unchanged. Four of these scintigraphs coincided with ongoing pulmonary infection and the fifth with an occurrence of amore » high anti-CMV titer. The mechanism of apparent nonspecific antimyosin accumulation in the lungs is uncertain, although increased capillary permeability may be one possibility. Attention should be given to activity in the lungs if this activity is used as a reference in studies of {sup 111}In-antimyosin uptake in the heart. 15 refs., 3 figs., 1 tab.« less

Effects of peroxisome proliferator-activated receptor-β/δ on sepsis induced acute lung injury.

PubMed

Wang, Cairui; Zhou, Guopeng; Zeng, Zeng

2014-01-01

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the first steps in the development of multiple organ failure induced by sepsis. A systemic excessive inflammatory reaction is currently the accepted mechanism of the pathogenesis of sepsis. Several studies have suggested a protective role of the peroxisome proliferator activated receptor-β/δ (PPAR-β/δ) in related inflammatory diseases. But the role of PPARβ/δ in ALI remains uncertain. The aim of this study was to investigate the role and possible mechanism of PPARβ/δ in ALI induced by sepsis. Cecal ligation and puncture (CLP) was used as a sepsis model. Rats were randomly divided into four groups, the control group (CON, n = 6), sham-operation group (SHAM, n = 12), cecal ligation and puncture group (CLP, n = 30), GW501516 group (CLP+GW, n = 25), which underwent CLP and were subcutaneously injected with the PPAR-β/δ agonist GW501516 (0.05 mg/100 g body weight). Survival was monitored to 24 hours after operation. Blood pressure, serum creatinine, blood urea nitrogen, aspartate aminotrasferase and alanine aminotrasferase were measured after CLP. Concentrations of tumor necrosis factor α (TNF-α) and interleukin (IL)-1β in serum were detected by enzyme linked immunosorbent assay (ELISA) kits. Lung tissue samples were stained with H&E and scored according to the degree of inflammation. Bacterial colonies were counted in the peritoneal fluid. Alveolar macrophages were cultured and incubated with GW501516 (0.15 µmol/L) and PPARβ/δ adenovirus and then treated with Lipopolysaccharide (2 µg/ml) for 2 hours. The TNF-α, IL-1β and IL-6 RNA in lung and alveolar macrophages were determined by real-time PCR. Phosphorylation of signal transducer and activator of transcription 3 (STAT3) in lung and alveolar macrophages was detected by Western blotting. GW501516 significantly increased the survival of septic rats, decreased histological damage of the lungs, reduced inflammatory cytokines in serum and lung tissues of septic rats and did not increase counts of peritoneal bacteria. In vitro, GW501516 and over-expression of PPARβ/δ attenuated gene expression of TNF-α, IL-1β and IL-6 in alveolar macrophages. Both in vivo and in vitro, PPARβ/δ inhibited the phosphorylation of STAT3. PPARβ/δ plays a protective role in sepsis induced ALI via suppressing excessive inflammation.

Mechanical ventilation drives pneumococcal pneumonia into lung injury and sepsis in mice: protection by adrenomedullin.

PubMed

Müller-Redetzky, Holger C; Will, Daniel; Hellwig, Katharina; Kummer, Wolfgang; Tschernig, Thomas; Pfeil, Uwe; Paddenberg, Renate; Menger, Michael D; Kershaw, Olivia; Gruber, Achim D; Weissmann, Norbert; Hippenstiel, Stefan; Suttorp, Norbert; Witzenrath, Martin

2014-04-14

Ventilator-induced lung injury (VILI) contributes to morbidity and mortality in acute respiratory distress syndrome (ARDS). Particularly pre-injured lungs are susceptible to VILI despite protective ventilation. In a previous study, the endogenous peptide adrenomedullin (AM) protected murine lungs from VILI. We hypothesized that mechanical ventilation (MV) contributes to lung injury and sepsis in pneumonia, and that AM may reduce lung injury and multiple organ failure in ventilated mice with pneumococcal pneumonia. We analyzed in mice the impact of MV in established pneumonia on lung injury, inflammation, bacterial burden, hemodynamics and extrapulmonary organ injury, and assessed the therapeutic potential of AM by starting treatment at intubation. In pneumococcal pneumonia, MV increased lung permeability, and worsened lung mechanics and oxygenation failure. MV dramatically increased lung and blood cytokines but not lung leukocyte counts in pneumonia. MV induced systemic leukocytopenia and liver, gut and kidney injury in mice with pneumonia. Lung and blood bacterial burden was not affected by MV pneumonia and MV increased lung AM expression, whereas receptor activity modifying protein (RAMP) 1-3 expression was increased in pneumonia and reduced by MV. Infusion of AM protected against MV-induced lung injury (66% reduction of pulmonary permeability p < 0.01; prevention of pulmonary restriction) and against VILI-induced liver and gut injury in pneumonia (91% reduction of AST levels p < 0.05, 96% reduction of alanine aminotransaminase (ALT) levels p < 0.05, abrogation of histopathological changes and parenchymal apoptosis in liver and gut). MV paved the way for the progression of pneumonia towards ARDS and sepsis by aggravating lung injury and systemic hyperinflammation leading to liver, kidney and gut injury. AM may be a promising therapeutic option to protect against development of lung injury, sepsis and extrapulmonary organ injury in mechanically ventilated individuals with severe pneumonia.

[Heparin-induced thrombocytopenia developed during the acute phase after left upper lobectomy for lung cancer].

PubMed

Mitomo, Hideki; Miyamoto, Akira; Tabata, Toshiharu; Sugawara, Takafumi; Yabuki, Hiroshi; Fujimura, Shigefumi

2014-12-01

Heparin-induced thrombocytopenia (HIT) is a serious adverse effect of heparin administration. This must not be rarely encountered but is not often reported in Japan compared to Western countries. A 68-year-old woman underwent left upper lobectomy for lung cancer. Low-dose unfractionated heparin was administrated to prevent thromboembolism after the operation. Two days later, sudden dyspnea appeared and ultracardiosonography showing an extensive thromboembolus from the main trunk to both main branches of pulmonary artery indicated pulmonary embolization. After the establishment of percutaneous cardiopulmonary support (PCPS) support, the embolus was removed by emergent open heart surgery. However, despite further unfractionated heparin administration following embolization surgery, other thrombus was identified in both the bi-lateral internal jagular veins and inferior vena cava by ultrasonography and contrast computed tomography( CT). Her platelet count was decreased gradually despite platelet transfusion. Plate factor 4( PF4) antibody against heparin in her blood examination was found, and HIT II was diagnosed. Discontinuation of unfractionated heparin and administration of antithrombin agent improved platelet count, and no additional embolization was identified.

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.

Lung asbestos burden in shipyard and construction workers with mesothelioma: Comparison with burdens in subjects with asbestosis of lung cancer

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

Warnock, M.L.

1989-10-01

Although mesothelioma is generally considered to be caused by asbestos, epidemiologic studies indicate that some cases have another cause. In order to determine whether pulmonary asbestos burden can be used to define asbestos-related mesotheliomas, asbestos burden was quantified in 27 shipyard or construction workers with diffuse malignant mesothelioma of the pleura or peritoneum and a history of asbestos exposure. Their burden was significantly greater than the burden found in 19 unexposed men. The burdens were also compared to those of previously reported subjects with asbestosis or lung cancer. The median concentration for total amphibole fibers (2.7 million/g dry lung) inmore » subjects with mesothelioma did not differ significantly from our previously reported median values for 14 subjects with asbestosis (1.3 million/g dry lung) or for 60 asbestos workers with lung cancer (1.3 million/g dry lung). Fiber size distribution for amosite, the most prevalent fiber type, was similar in all three subject groups. Fifteen of 25 (60%) subjects with mesothelioma had mild asbestosis. Asbestos body (AB) concentrations were {ge} 1900/g dry lung, and total amphibole fiber concentrations were {ge}390,000/g dry lung. Counts of ABs{ge}0.5/cm{sup 2} in histologic sections always signified both of these concentrations in extracts. Thus, histologic sections showing {ge}0.5 ABs/cm{sup 2} or extracts containing asbestos body or amphibole fiber concentrations of at least 1900 or 390,000/g dry lung, respectively, will confirm an asbestos related mesothelioma.« less

Late-occurring pulmonary pathologies following inhalation of mixed oxide (uranium + plutonium oxide) aerosol in the rat.

PubMed

Griffiths, N M; Van der Meeren, A; Fritsch, P; Abram, M-C; Bernaudin, J-F; Poncy, J L

2010-09-01

Accidental exposure by inhalation to alpha-emitting particles from mixed oxide (MOX: uranium and plutonium oxide) fuels is a potential long-term health risk to workers in nuclear fuel fabrication plants. For MOX fuels, the risk of lung cancer development may be different from that assigned to individual components (plutonium, uranium) given different physico-chemical characteristics. The objective of this study was to investigate late effects in rat lungs following inhalation of MOX aerosols of similar particle size containing 2.5 or 7.1% plutonium. Conscious rats were exposed to MOX aerosols and kept for their entire lifespan. Different initial lung burdens (ILBs) were obtained using different amounts of MOX. Lung total alpha activity was determined by external counting and at autopsy for total lung dose calculation. Fixed lung tissue was used for anatomopathological, autoradiographical, and immunohistochemical analyses. Inhalation of MOX at ILBs ranging from 1-20 kBq resulted in lung pathologies (90% of rats) including fibrosis (70%) and malignant lung tumors (45%). High ILBs (4-20 kBq) resulted in reduced survival time (N = 102; p < 0.05) frequently associated with lung fibrosis. Malignant tumor incidence increased linearly with dose (up to 60 Gy) with a risk of 1-1.6% Gy for MOX, similar to results for industrial plutonium oxide alone (1.9% Gy). Staining with antibodies against Surfactant Protein-C, Thyroid Transcription Factor-1, or Oct-4 showed differential labeling of tumor types. In conclusion, late effects following MOX inhalation result in similar risk for development of lung tumors as compared with industrial plutonium oxide.

Classification algorithm of lung lobe for lung disease cases based on multislice CT images

NASA Astrophysics Data System (ADS)

Matsuhiro, M.; Kawata, Y.; Niki, N.; Nakano, Y.; Mishima, M.; Ohmatsu, H.; Tsuchida, T.; Eguchi, K.; Kaneko, M.; Moriyama, N.

2011-03-01

With the development of multi-slice CT technology, to obtain an accurate 3D image of lung field in a short time is possible. To support that, a lot of image processing methods need to be developed. In clinical setting for diagnosis of lung cancer, it is important to study and analyse lung structure. Therefore, classification of lung lobe provides useful information for lung cancer analysis. In this report, we describe algorithm which classify lungs into lung lobes for lung disease cases from multi-slice CT images. The classification algorithm of lung lobes is efficiently carried out using information of lung blood vessel, bronchus, and interlobar fissure. Applying the classification algorithms to multi-slice CT images of 20 normal cases and 5 lung disease cases, we demonstrate the usefulness of the proposed algorithms.

Granulocyte colony-stimulating factor improves host defense to resuscitated shock and polymicrobial sepsis without provoking generalized neutrophil-mediated damage.

PubMed

Patton, J H; Lyden, S P; Ragsdale, D N; Croce, M A; Fabian, T C; Proctor, K G

1998-05-01

Granulocyte colony-stimulating factor (G-CSF) increases production and release of neutrophil precursors and activates multiple functions of circulating polymorphonuclear neutrophils (PMNs). G-CSF has therapeutic effects in many experimental models of sepsis; its actions with superimposed reperfusion insults are unknown. In traumatic conditions, G-CSF could exacerbate unregulated, PMN-dependent injury to otherwise normal host tissue or, it could partially reverse trauma-induced immune suppression, which may improve long-term outcome. This study tested whether stimulating PMN proliferation and function with G-CSF during recovery from trauma+sepsis potentiated reperfusion injury or whether it improved host defense. Anesthetized swine were subjected to cecal ligation and incision, 35% hemorrhage, and 1 hr of hypotension. Resuscitation consisted of intravenous G-CSF (5 microg/kg) or placebo followed by shed blood and 40 mL/kg of lactated Ringer's solution. The control group received laparotomy only. G-CSF or placebo was given daily. Animals were killed at 4 days. Observers, blind to the protocol, graded autopsy samples for localization of infection and quality of abscess wall formation. Data included complete blood count, granulocyte oxidative burst after phorbol myristate acetate stimulation in vitro (GO2B), bronchoalveolar lavage (BAL) cell count, BAL noncellular protein, lipopolysaccharide-stimulated tumor necrosis factor production in whole blood in vitro (lipopolysaccharide-tumor necrosis factor), and lung tissue myeloperoxidase (MPO). Neutrophilia and localization of infection, were significantly improved by G-CSF. Variables altered by G-CSF, though not significantly, showed GO2B potential increased by 50%, lipopolysaccharide-tumor necrosis factor decreased by 50%, and improved survival versus placebo (100% vs. 70%). G-CSF did not increase lung MPO, BAL cell count, or BAL protein. Both arterial and venous O2 saturations were unaltered. Our data show that G-CSF initiated at the time of resuscitation reduced the sequelae of posttrauma sepsis by increasing PMN proliferation and function without potentiating PMN-mediated lung reperfusion injury.

Avalanche photodiode photon counting receivers for space-borne lidars

NASA Technical Reports Server (NTRS)

Sun, Xiaoli; Davidson, Frederic M.

1991-01-01

Avalanche photodiodes (APD) are studied for uses as photon counting detectors in spaceborne lidars. Non-breakdown APD photon counters, in which the APD's are biased below the breakdown point, are shown to outperform: (1) conventional APD photon counters biased above the breakdown point; (2) conventional APD photon counters biased above the breakdown point; and (3) APD's in analog mode when the received optical signal is extremely weak. Non-breakdown APD photon counters were shown experimentally to achieve an effective photon counting quantum efficiency of 5.0 percent at lambda = 820 nm with a dead time of 15 ns and a dark count rate of 7000/s which agreed with the theoretically predicted values. The interarrival times of the counts followed an exponential distribution and the counting statistics appeared to follow a Poisson distribution with no after pulsing. It is predicted that the effective photon counting quantum efficiency can be improved to 18.7 percent at lambda = 820 nm and 1.46 percent at lambda = 1060 nm with a dead time of a few nanoseconds by using more advanced commercially available electronic components.

[Lung auscultation--an overview].

PubMed

Bürgi, Urs; Huber, Lars Christian

2015-07-01

The auscultation of the lungs is - among anamnesis - the most important part in the assessment of patients presenting with pulmonary symptoms. The lung auscultation is reproducible, cost efficient and very helpful to distinguish between differential diagnoses, in particular in emergency situations. Detection and description of lung sounds requires experience and should be performed by strict adherence to the internationally accepted terminology. © Georg Thieme Verlag KG Stuttgart · New York.

Lung flooding enables efficient lung sonography and tumour imaging in human ex vivo and porcine in vivo lung cancer model

PubMed Central

2013-01-01

Background Sonography has become the imaging technique of choice for guiding intraoperative interventions in abdominal surgery. Due to artefacts from residual air content, however, videothoracoscopic and open intraoperative ultrasound-guided thermoablation of lung malignancies are impossible. Lung flooding is a new method that allows complete ultrasound imaging of lungs and their tumours. Methods Fourteen resected tumourous human lung lobes were examined transpleurally with B-mode ultrasound before (in atelectasis) and after lung flooding with isotonic saline solution. In two swine, the left lung was filled with 15 ml/kg isotonic saline solution through the left side of a double-lumen tube. Lung tumours were simulated by transthoracic ultrasound-guided injection of 5 ml of purified bovine serum albumin in glutaraldehyde, centrally into the left lower lung lobe. The rate of tumour detection, the severity of disability caused by residual gas, and sonomorphology of the lungs and tumours were assessed. Results The ex vivo tumour detection rate was 100% in flooded human lung lobes and 43% (6/14) in atelectatic lungs. In all cases of atelectasis, sonographic tumour imaging was impaired by residual gas. Tumours and atelectatic tissue were isoechoic. In 28% of flooded lungs, a little residual gas was observed that did not impair sonographic tumour imaging. In contrast to tumours, flooded lung tissue was hyperechoic, homogeneous, and of fine-grained structure. Because of the bronchial wall three-laminar structure, sonographic differentiation of vessels and bronchi was possible. In all cases, malignant tumours in the flooded lung appeared well-demarcated from the lung parenchyma. Adenocarcinoma, squamous, and large cell carcinomas were hypoechoic. Bronchioloalveolar cell carcinoma was slightly hyperechoic. Transpleural sonography identifies endobronchial tumour growth and bronchial wall destruction. With transthoracic sonography, the flooded animal lung can be completely examined in vivo. There is no residual gas, which interferes with ultrasound. Pulmonary vessels and bronchi are clearly differentiated. Simulated lung lesions can easily be detected inside the lung lobe. Conclusions Lung flooding enables complete lung sonography and tumour detection. We have developed a novel method that efficiently uses ultrasound for guiding intraoperative interventions in open and endoscopic lung surgery. PMID:23841910

Curcumin protects the developing lung against long-term hyperoxic injury

PubMed Central

Sakurai, R.; Villarreal, P.; Husain, S.; Liu, Jie; Sakurai, T.; Tou, E.; Torday, J. S.

2013-01-01

Curcumin, a potent anti-inflammatory and antioxidant agent, modulates peroxisome proliferator-activated receptor-γ signaling, a key molecule in the etiology of bronchopulmonary dysplasia (BPD). We have previously shown curcumin's acute protection against neonatal hyperoxia-induced lung injury. However, its longer-term protection against BPD is not known. Hypothesizing that concurrent treatment with curcumin protects the developing lung against hyperoxia-induced lung injury long-term, we determined if curcumin protects against hyperoxic neonatal rat lung injury for the first 5 days of life, as determined at postnatal day (PND) 21. One-day-old rat pups were exposed to either 21 or 95% O2 for 5 days with or without curcumin treatment (5 mg/kg) administered intraperitoneally one time daily, following which the pups grew up to PND21 in room air. At PND21 lung development was determined, including gross and cellular structural and functional effects, and molecular mediators of inflammatory injury. To gain mechanistic insights, embryonic day 19 fetal rat lung fibroblasts were examined for markers of apoptosis and MAP kinase activation following in vitro exposure to hyperoxia for 24 h in the presence or absence of curcumin (5 μM). Curcumin effectively blocked hyperoxia-induced lung injury based on systematic analysis of markers for lung injury (apoptosis, Bcl-2/Bax, collagen III, fibronectin, vimentin, calponin, and elastin-related genes) and lung morphology (radial alveolar count and alveolar septal thickness). Mechanistically, curcumin prevented the hyperoxia-induced increases in cleaved caspase-3 and the phosphorylation of Erk1/2. Molecular effects of curcumin, both structural and cytoprotective, suggest that its actions against hyperoxia-induced lung injury are mediated via Erk1/2 activation and that it is a potential intervention against BPD. PMID:23812632

Jaagsiekte Sheep Retrovirus Envelope Efficiently Pseudotypes Human Immunodeficiency Virus Type 1-Based Lentiviral Vectors

PubMed Central

Liu, Shan-Lu; Halbert, Christine L.; Miller, A. Dusty

2004-01-01

Jaagsiekte sheep retrovirus (JSRV) infects lung epithelial cells in sheep, and oncoretroviral vectors bearing JSRV Env can mediate transduction of human cells, suggesting that such vectors might be useful for lung-directed gene therapy. Here we show that JSRV Env can also efficiently pseudotype a human immunodeficiency virus type 1-based lentiviral vector, a more suitable vector for transduction of slowly dividing lung epithelial cells. We created several chimeric Env proteins that, unlike the parental Env, do not transform rodent fibroblasts but are still capable of pseudotyping lentiviral and oncoretroviral vectors. PMID:14963173

Assessment of Erythroid and Granulocytic Hematopoietic Lineages in Patients with Non-Small-Cell Lung Carcinoma.

PubMed

Goldberg, V E; Polyakova, T Yu; Popova, N O; Vysotskaya, V V; Simolina, E I; Belevich, Yu V; Tuzikova, T P; Goldberg, A V; Zhdanov, V V; Miroshnichenko, L A; Udut, E V; Simanina, E V; Dygai, A M; Zyuz'kov, G N

2017-08-01

The toxic effects of combined cisplatin/docetaxel therapy cycles on erythroid and granulocytic hematopoietic lineages as well as their intercycle recovery were examined in patients with stage III-IV non-small-cell lung carcinoma. Responsiveness of the blood system to this therapy remained at a high level. Combined therapy pronouncedly activated the key elements of the erythroid and granulocytic hematopoietic lineages leading to accumulation of immature and mature myelokaryocytes in the bone marrow, enlargement of the medullary pool of mature neutrophils, and increase in the count of medullary erythroid and granulocytic precursor cells under conditions of their accelerated maturation.

Why change. A look at the current system of disability determination and workers' compensation for occupational lung disease

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

Richman, S.I.

1982-12-01

Under the current system of disability determination and workers' compensation for occupational lung disease, disabled workers or their survivors can reasonably count on being compensated. However, by rejecting established scientific truth in order to pay workers' compensation in circumstances where disability or death had not been due to occupation, the system has operated unfairly and has undermined public confidence and respect. To gain more scientific integrity and fairness, the system should be changed to provide for adjudication by scientifically informed disability boards. The adversary system sould be retained, however, as needed protection against bias, quackery, and mendacity.

Waveguide integrated superconducting single-photon detectors with high internal quantum efficiency at telecom wavelengths

PubMed Central

Kahl, Oliver; Ferrari, Simone; Kovalyuk, Vadim; Goltsman, Gregory N.; Korneev, Alexander; Pernice, Wolfram H. P.

2015-01-01

Superconducting nanowire single-photon detectors (SNSPDs) provide high efficiency for detecting individual photons while keeping dark counts and timing jitter minimal. Besides superior detection performance over a broad optical bandwidth, compatibility with an integrated optical platform is a crucial requirement for applications in emerging quantum photonic technologies. Here we present SNSPDs embedded in nanophotonic integrated circuits which achieve internal quantum efficiencies close to unity at 1550 nm wavelength. This allows for the SNSPDs to be operated at bias currents far below the critical current where unwanted dark count events reach milli-Hz levels while on-chip detection efficiencies above 70% are maintained. The measured dark count rates correspond to noise-equivalent powers in the 10−19 W/Hz−1/2 range and the timing jitter is as low as 35 ps. Our detectors are fully scalable and interface directly with waveguide-based optical platforms. PMID:26061283

Waveguide integrated superconducting single-photon detectors with high internal quantum efficiency at telecom wavelengths.

PubMed

Kahl, Oliver; Ferrari, Simone; Kovalyuk, Vadim; Goltsman, Gregory N; Korneev, Alexander; Pernice, Wolfram H P

2015-06-10

Superconducting nanowire single-photon detectors (SNSPDs) provide high efficiency for detecting individual photons while keeping dark counts and timing jitter minimal. Besides superior detection performance over a broad optical bandwidth, compatibility with an integrated optical platform is a crucial requirement for applications in emerging quantum photonic technologies. Here we present SNSPDs embedded in nanophotonic integrated circuits which achieve internal quantum efficiencies close to unity at 1550 nm wavelength. This allows for the SNSPDs to be operated at bias currents far below the critical current where unwanted dark count events reach milli-Hz levels while on-chip detection efficiencies above 70% are maintained. The measured dark count rates correspond to noise-equivalent powers in the 10(-19) W/Hz(-1/2) range and the timing jitter is as low as 35 ps. Our detectors are fully scalable and interface directly with waveguide-based optical platforms.

Home energy efficiency and radon related risk of lung cancer: modelling study

PubMed Central

Milner, James; Shrubsole, Clive; Das, Payel; Jones, Benjamin; Ridley, Ian; Chalabi, Zaid; Hamilton, Ian; Armstrong, Ben; Davies, Michael

2014-01-01

Objective To investigate the effect of reducing home ventilation as part of household energy efficiency measures on deaths from radon related lung cancer. Design Modelling study. Setting England. Intervention Home energy efficiency interventions, motivated in part by targets for reducing greenhouse gases, which entail reduction in uncontrolled ventilation in keeping with good practice guidance. Main outcome measures Modelled current and future distributions of indoor radon levels for the English housing stock and associated changes in life years due to lung cancer mortality, estimated using life tables. Results Increasing the air tightness of dwellings (without compensatory purpose-provided ventilation) increased mean indoor radon concentrations by an estimated 56.6%, from 21.2 becquerels per cubic metre (Bq/m3) to 33.2 Bq/m3. After the lag in lung cancer onset, this would result in an additional annual burden of 4700 life years lost and (at peak) 278 deaths. The increases in radon levels for the millions of homes that would contribute most of the additional burden are below the threshold at which radon remediation measures are cost effective. Fitting extraction fans and trickle ventilators to restore ventilation will help offset the additional burden but only if the ventilation related energy efficiency gains are lost. Mechanical ventilation systems with heat recovery may lower radon levels and the risk of cancer while maintaining the advantage of energy efficiency for the most airtight dwellings but there is potential for a major adverse impact on health if such systems fail. Conclusion Unless specific remediation is used, reducing the ventilation of dwellings will improve energy efficiency only at the expense of population wide adverse impact on indoor exposure to radon and risk of lung cancer. The implications of this and other consequences of changes to ventilation need to be carefully evaluated to ensure that the desirable health and environmental benefits of home energy efficiency are not compromised by avoidable negative impacts on indoor air quality. PMID:24415631

d-limonene exhibits antitumor activity by inducing autophagy and apoptosis in lung cancer.

PubMed

Yu, Xiao; Lin, Hongyan; Wang, Yu; Lv, Wenwen; Zhang, Shuo; Qian, Ying; Deng, Xiaobei; Feng, Nannan; Yu, Herbert; Qian, Biyun

2018-01-01

d-limonene is a plant extract with widespread application, and it has been recently reported to have antiproliferative and proapoptotic effects on cancer cells. However, the mechanisms by which d-limonene achieves these effects, especially in lung cancer, are not entirely clear. Therefore, the goal of this study was to examine the effects of d-limonene on lung cancer and explore its mechanisms of action. We examined the therapeutic effects of d-limonene on lung cancer cells and in a xenograft animal model by characterizing its effects on the pathways of apoptosis and autophagy. Cell proliferation was measured using the Cell Counting Kit-8, and apoptosis was determined by flow cytometric analysis. Levels of LC3 puncta, an autophagy marker, were analyzed by laser scanning confocal microscopy. Autophagy and apoptosis-related gene expression were assessed by real-time quantitative polymerase chain reaction and Western blot. d-limonene inhibited the growth of lung cancer cells and suppressed the growth of transplanted tumors in nude mice. Expression of apoptosis and autophagy-related genes were increased in tumors after treatment with d-limonene. Furthermore, the use of chloroquine, an autophagy inhibitor, and knockdown of the atg5 gene, suppressed the apoptosis induced by d-limonene. d-limonene may have a therapeutic effect on lung cancer as it can induce apoptosis of lung cancer cells by promoting autophagy.

Effects of Diet-Induced Mild Obesity on Airway Hyperreactivity and Lung Inflammation in Mice

PubMed Central

Jung, Sun Hee; Kwon, Jang-Mi; Shim, Jae Won; Kim, Deok Soo; Jung, Hye Lim; Park, Moon Soo; Park, Soo-Hee; Lee, Jinmi; Lee, Won-Young

2013-01-01

Purpose Obesity has been suggested to be linked to asthma. However, it is not yet known whether obesity directly leads to airway hyperreactivity (AHR) or obesity-induced airway inflammation associated with asthma. We investigated obesity-related changes in adipokines, AHR, and lung inflammation in a murine model of asthma and obesity. Materials and Methods We developed mouse models of chronic asthma via ovalbumin (OVA)-challenge and of obesity by feeding a high-fat diet, and then performed the methacholine bronchial provocation test, and real-time PCR for leptin, leptin receptor, adiponectin, adiponectin receptor (adipor1 and 2), vascular endothelial growth factor (VEGF), transforming growth factor (TGF) β, and tumor necrosis factor (TNF) α in lung tissue. We also measured cell counts in bronchoalveolar lavage fluid. Results Both obese and lean mice chronically exposed to OVA developed eosinophilic lung inflammation and AHR to methacholine. However, obese mice without OVA challenge did not develop AHR or eosinophilic inflammation in lung tissue. In obese mice, lung mRNA expressions of leptin, leptin receptor, VEGF, TGF, and TNF were enhanced, and adipor1 and 2 expressions were decreased compared to mice in the control group. On the other hand, there were no differences between obese mice with or without OVA challenge. Conclusion Diet-induced mild obesity may not augment AHR or eosinophilic lung inflammation in asthma. PMID:24142648

Hyperoxia exacerbates postnatal inflammation-induced lung injury in neonatal BRP-39 null mutant mice promoting the M1 macrophage phenotype.

PubMed

Syed, Mansoor A; Bhandari, Vineet

2013-01-01

Hyperoxia exposure to developing lungs-critical in the pathogenesis of bronchopulmonary dysplasia-may augment lung inflammation by inhibiting anti-inflammatory mediators in alveolar macrophages. We sought to determine the O2-induced effects on the polarization of macrophages and the role of anti-inflammatory BRP-39 in macrophage phenotype and neonatal lung injury. We used RAW264.7, peritoneal, and bone marrow derived macrophages for polarization (M1/M2) studies. For in vivo studies, wild-type (WT) and BRP-39(-/-) mice received continuous exposure to 21% O2 (control mice) or 100% O2 from postnatal (PN) 1 to PN7 days, along with intranasal lipopolysaccharide (LPS) administered on alternate days (PN2, -4, and -6). Lung histology, bronchoalveolar lavage (BAL) cell counts, BAL protein, and cytokines measurements were performed. Hyperoxia differentially contributed to macrophage polarization by enhancing LPS induced M1 and inhibiting interleukin-4 induced M2 phenotype. BRP-39 absence led to further enhancement of the hyperoxia and LPS induced M1 phenotype. In addition, BRP-39(-/-) mice were significantly more sensitive to LPS plus hyperoxia induced lung injury and mortality compared to WT mice. These findings collectively indicate that BRP-39 is involved in repressing the M1 proinflammatory phenotype in hyperoxia, thereby deactivating inflammatory responses in macrophages and preventing neonatal lung injury.

Ultrafast time measurements by time-correlated single photon counting coupled with superconducting single photon detector

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

Shcheslavskiy, V., E-mail: vis@becker-hickl.de; Becker, W.; Morozov, P.

Time resolution is one of the main characteristics of the single photon detectors besides quantum efficiency and dark count rate. We demonstrate here an ultrafast time-correlated single photon counting (TCSPC) setup consisting of a newly developed single photon counting board SPC-150NX and a superconducting NbN single photon detector with a sensitive area of 7 × 7 μm. The combination delivers a record instrument response function with a full width at half maximum of 17.8 ps and system quantum efficiency ∼15% at wavelength of 1560 nm. A calculation of the root mean square value of the timing jitter for channels withmore » counts more than 1% of the peak value yielded about 7.6 ps. The setup has also good timing stability of the detector–TCSPC board.« less

Pulmonary infections and risk of lung cancer among persons with AIDS.

PubMed

Shebl, Fatma M; Engels, Eric A; Goedert, James J; Chaturvedi, Anil K

2010-11-01

Lung cancer risk is significantly increased among persons with AIDS (PWA), and increased smoking may not explain all of the elevated risk, suggesting a role for additional cofactors. We investigated whether AIDS-defining pulmonary infections (recurrent pneumonia, Pneumocystis jirovecii pneumonia, and pulmonary tuberculosis) affected the risk of subsequent lung cancer over 10 years after AIDS onset among 322,675 PWA, whose records were linked with cancer registries in 11 US regions. We assessed lung cancer hazard ratios (HRs) using Cox regression and indirectly adjusted HRs for confounding by smoking. Individuals with recurrent pneumonia (n = 5317) were at significantly higher lung cancer risk than those without [HR = 1.63, 95% confidence interval (CI) = 1.08 to 2.46, adjusted for age, race, sex, HIV acquisition mode, CD4 count, and AIDS diagnosis year]. This association was especially strong among young PWA (<50 years HR = 1.99 vs. ≥50 years HR = 1.10) and was significantly elevated during 5-10 years after recurrent pneumonia diagnosis (HR = 2.41; 95% CI = 1.07 to 5.47). Although attenuated, HRs for recurrent pneumonia remained nonsignificantly elevated after indirect adjustment for smoking. Lung cancer risk was unrelated to tuberculosis [(n = 13,878) HR = 1.12, 95% CI = 0.82 to 1.53] or Pneumocystis jirovecii pneumonia [(n = 69,771) HR = 0.97, 95% CI = 0.80 to 1.18]. The increased lung cancer risk associated with recurrent pneumonia supports the hypothesis that chronic pulmonary inflammation arising from infections contributes to lung carcinogenesis.

Experimental study of “Tong Xia” purgative method in ameliorating lung injury in acute necrotizing pancreatitis

PubMed Central

Xia, Qing; Jiang, Jun-Ming; Gong, Xu; Chen, Guang-Yuan; Li, Lei; Huang, Zong-Wen

2000-01-01

AIM: To investigate the role of tumor necrosis factor (TNF) in lung injury during acute necrotizing pancreatitis (ANP), and the therapeutic ef fect of “Tong Xia” purgative method in minimizing the severity of lung injury. METHODS: Fourteen canines were randomly divided into 3 groups: the “Tong Xia” treatment group (n = 5) using Dachengqitang; saline control group (n = 5), and the sham operation group (n = 4). TNF activity in serum and in bronchoalveolar lavage fluid (BALF), the serum endotoxin levels were meas ured, and the severity of lung injury evaluated. RESULTS: Elevation of TNF activity was more prominent in BALF than in serum. TNF activity in serum at 6 and 12 h and in BALF was significantly decreased in the “Tong Xia” treatment group than in the saline control one (q = 21.11, q = 12.07, q = 9.03, respectively, P < 0.01) and the lung injury was significantly alleviated at 12 h as compared with that in the saline group, manifested as amelioration of the lung wet/dry weight ratio, decrease in protein concentration and neutrophils count in BALF, and improvement of pulmonary inflammatory changes. A positive correlation was demonstrated between serum TNF activity and endotoxin level. CONCLUSION: Hypersecretion of TNF is shown to be one of the majo r causes of lung injury during ANP; “Tong Xia” purgative method could allevia te the degree of lung injury mediated by TNF. PMID:11819536

Evaluating point count efficiency relative to territory mapping in cropland birds

Treesearch

Andre Cyr; Denis Lepage; Kathryn Freemark

1995-01-01

Species richness, composition, and abundance of farmland birds were compared between point counts (50-m, 100-m, and 150-m radius half circles) and territory mapping on three 40-ha plots in Québec, Canada. Point counts of smaller radii tended to have larger density estimates than counts of larger radii. Territory mapping detected 10 species more than 150-m...

High quantum efficiency and low dark count rate in multi-layer superconducting nanowire single-photon detectors

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

Jafari Salim, A., E-mail: ajafaris@uwaterloo.ca; Eftekharian, A.; University of Waterloo, Waterloo, Ontario N2L 3G1

In this paper, we theoretically show that a multi-layer superconducting nanowire single-photon detector (SNSPD) is capable of approaching characteristics of an ideal SNSPD in terms of the quantum efficiency, dark count, and band-width. A multi-layer structure improves the performance in two ways. First, the potential barrier for thermally activated vortex crossing, which is the major source of dark counts and the reduction of the critical current in SNSPDs is elevated. In a multi-layer SNSPD, a vortex is made of 2D-pancake vortices that form a stack. It will be shown that the stack of pancake vortices effectively experiences a larger potentialmore » barrier compared to a vortex in a single-layer SNSPD. This leads to an increase in the experimental critical current as well as significant decrease in the dark count rate. In consequence, an increase in the quantum efficiency for photons of the same energy or an increase in the sensitivity to photons of lower energy is achieved. Second, a multi-layer structure improves the efficiency of single-photon absorption by increasing the effective optical thickness without compromising the single-photon sensitivity.« less

Age-related differences in pulmonary inflammatory responses to JP-8 jet fuel aerosol inhalation.

PubMed

Wang, S; Young, R S; Witten, M L

2001-02-01

Our previous studies have demonstrated that JP-8 jet fuel aerosol inhalation induced lung injury and dysfunction. To further examine JP-8 jet fuel-induced inflammatory mechanisms, a total of 40 male C57BL/6 mice (young, 3.5 months; adult, 12 months; half in each age group) were randomly assigned to the exposure or control groups. Mice were nose-only exposed to room air or atmospheres of 1000 mg/m3 JP-8 jet fuel for 1 h/day for 7 days. Lung injury was assessed by pulmonary mechanics, respiratory permeability, lavaged cell profile, and chemical mediators in bronchoalveolar lavage fluid (BALF). The young and adult mice exposed to JP-8 jet fuel had similar values with regards to increased lung dynamic compliance, lung permeability, BALF cell count, and decreased PGE2. However, there were several different responses between the young-versus-adult mice with respect to BALF cell differential, TNF-alpha, and 8-iso-PGF2,, levels after exposure to JP-8 jet fuel. These data suggest that JP-8 jet fuel may have different inflammatory mechanisms leading to lung injury and dysfunction in the younger-versus-adult mice.

The Effect of Different Doses of Cigarette Smoke in a Mouse Lung Tumor Model

PubMed Central

Santiago, Ludmilla Nadir; de Camargo Fenley, Juliana; Braga, Lúcia Campanario; Cordeiro, José Antônio; Cury, Patrícia M.

2009-01-01

Few studies have used Balb/c mice as an animal model for lung carcinogenesis. In this study, we investigated the effect of different doses of cigarette smoking in the urethane-induced Balb/c mouse lung cancer model. After injection of 3mg/kg urethane intraperitoneally, the mice were then exposed to tobacco smoke once or twice a day, five times a week, in a closed chamber. The animals were randomly divided into four groups. The control group (G0) received urethane only. The experimental groups (G1, G2 and G3) received urethane and exposure to the smoke of 3 cigarettes for 10 minutes once a day, 3 cigarettes for 10 minutes twice a day, and 6 cigarettes for 10 minutes twice a day, respectively. The mice were sacrificed after 16 weeks of exposure, and the number of nodules and hyperplasia in the lungs was counted. The results showed no statistically significant difference in the mean number of nodules and hyperplasia among the different groups, suggesting that the Balb/c mice are not suitable to study the pathogenesis of tobacco smoking-induced tumor progression in the lungs. PMID:19079653

Formononetin inhibited the inflammation of LPS-induced acute lung injury in mice associated with induction of PPAR gamma expression.

PubMed

Ma, Zhanqiang; Ji, Weiwei; Fu, Qiang; Ma, Shiping

2013-12-01

Formononetin has shown a variety of pharmacologic properties including anti-inflammatory effect. In the present study, we analyzed the role of formononetin in acute lung injury induced by lipopolysaccharide (LPS) in mice. The cell counting in the bronchoalveolar lavage fluid (BALF) was measured. The animal lung edema degree was evaluated by wet/dry weight ratio. The superoxidase dismutase (SOD) activity and myeloperoxidase (MPO) activity was assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators, tumor necrosis factor-α (TNF-α) and IL-6,were assayed by enzyme-linked immunosorbent assay method. Pathological changes of hung tissues were observed by HE staining. Peroxisome proliferator-activated receptor (PPAR)-γ gene expression was measured by real-time PCR. The data showed that treatment with the formononetin group markedly attenuated inflammatory cell numbers in the BALF, increased PPAR-γ gene expression and improved SOD activity and inhibited MPO activity. The histological changes of the lungs were also significantly improved by formononetin compared to LPS group. The results indicated that formononetin has a protective effect on LPS-induced acute lung injury in mice.

Screening for Chronic Obstructive Pulmonary Disease (COPD) in an Urban HIV Clinic: A Pilot Study

PubMed Central

Kaner, Robert J.; Glesby, Marshall J.

2015-01-01

Abstract Increased smoking and a detrimental response to tobacco smoke in the lungs of HIV/AIDS patients result in an increased risk for COPD. We aimed to determine the predictive value of a COPD screening strategy validated in the general population and to identify HIV-related factors associated with decreased lung function. Subjects at least 35 years of age at an HIV clinic in New York City completed a COPD screening questionnaire and peak flow measurement. Those with abnormal results and a random one-third of normal screens had spirometry. 235 individuals were included and 89 completed spirometry. Eleven (12%) had undiagnosed airway obstruction and 5 had COPD. A combination of a positive questionnaire and abnormal peak flow yielded a sensitivity of 20% (specificity 93%) for detection of COPD. Peak flow alone had a sensitivity of 80% (specificity 80%). Abnormal peak flow was associated with an AIDS diagnosis (p=0.04), lower nadir (p=0.001), and current CD4 counts (p=0.001). Nadir CD4 remained associated in multivariate analysis (p=0.05). Decreased FEV1 (<80% predicted) was associated with lower CD4 count nadir (p=0.04) and detectable current HIV viral load (p=0.01) in multivariate analysis. Questionnaire and peak flow together had low sensitivity, but abnormal peak flow shows potential as a screening tool for COPD in HIV/AIDS. These data suggest that lung function may be influenced by HIV-related factors. PMID:25723842

Expression of nitric oxide synthase-2 in the lungs decreases airway resistance and responsiveness.

PubMed

Hjoberg, Josephine; Shore, Stephanie; Kobzik, Lester; Okinaga, Shoji; Hallock, Arlene; Vallone, Joseph; Subramaniam, Venkat; De Sanctis, George T; Elias, Jack A; Drazen, Jeffrey M; Silverman, Eric S

2004-07-01

Individuals with asthma have increased levels of nitric oxide in their exhaled air. To explore its role, we have developed a regulatable transgenic mouse capable of overexpressing inducible nitric oxide synthase in a lung-specific fashion. The CC10-rtTA-NOS-2 mouse contains two transgenes, a reverse tetracycline transactivator under the control of the Clara cell protein promoter and the mouse nitric oxide synthase-2 (NOS-2) coding region under control of a tetracycline operator. Addition of doxycycline to the drinking water of CC10-rtTA-NOS-2 mice causes an increase in nitric oxide synthase-2 that is largely confined to the airway epithelium. The fraction of expired nitric oxide increases over the first 24 h from approximately 10 parts per billion to a plateau of approximately 20 parts per billion. There were no obvious differences between CC10-rtTA-NOS-2 mice, with or without doxycycline, and wild-type mice in lung histology, bronchoalveolar protein, total cell count, or count differentials. However, airway resistance was lower in CC10-rtTA-NOS-2 mice with doxycycline than in CC10-rtTA-NOS-2 mice without doxycycline or wild-type mice with doxycycline. Moreover, doxycycline-treated CC10-rtTA-NOS-2 mice were hyporesponsive to methacholine compared with other groups. These data suggest that increased nitric oxide in the airways has no proinflammatory effects per se and may have beneficial effects on pulmonary function.

LINKING LUNG AIRWAY STRUCTURE TO PULMONARY FUNCTION VIA COMPOSITE BRIDGE REGRESSION

PubMed Central

Chen, Kun; Hoffman, Eric A.; Seetharaman, Indu; Jiao, Feiran; Lin, Ching-Long; Chan, Kung-Sik

2017-01-01

The human lung airway is a complex inverted tree-like structure. Detailed airway measurements can be extracted from MDCT-scanned lung images, such as segmental wall thickness, airway diameter, parent-child branch angles, etc. The wealth of lung airway data provides a unique opportunity for advancing our understanding of the fundamental structure-function relationships within the lung. An important problem is to construct and identify important lung airway features in normal subjects and connect these to standardized pulmonary function test results such as FEV1%. Among other things, the problem is complicated by the fact that a particular airway feature may be an important (relevant) predictor only when it pertains to segments of certain generations. Thus, the key is an efficient, consistent method for simultaneously conducting group selection (lung airway feature types) and within-group variable selection (airway generations), i.e., bi-level selection. Here we streamline a comprehensive procedure to process the lung airway data via imputation, normalization, transformation and groupwise principal component analysis, and then adopt a new composite penalized regression approach for conducting bi-level feature selection. As a prototype of composite penalization, the proposed composite bridge regression method is shown to admit an efficient algorithm, enjoy bi-level oracle properties, and outperform several existing methods. We analyze the MDCT lung image data from a cohort of 132 subjects with normal lung function. Our results show that, lung function in terms of FEV1% is promoted by having a less dense and more homogeneous lung comprising an airway whose segments enjoy more heterogeneity in wall thicknesses, larger mean diameters, lumen areas and branch angles. These data hold the potential of defining more accurately the “normal” subject population with borderline atypical lung functions that are clearly influenced by many genetic and environmental factors. PMID:28280520

Photon-counting image sensors for the ultraviolet

NASA Technical Reports Server (NTRS)

Jenkins, E. B.

1985-01-01

An investigation on specific performance details of photon counting, ultraviolet image sensors having 2-dimensional formats is reviewed. In one study, controlled experiments were performed which compare the quantum efficiencies, in pulse counting mode, of CsI photocathodes deposited on: (1) the front surface of a microchannel plate (MCP), (2) a solid surface in front of an MCP, and (3) an intensified CCD image sensor (ICCD) where a CCD is directly bombarded by accelerated photoelectrons. Tests indicated that the detection efficiency of the CsI-coated MCP at 1026 A is lower by a factor of 2.5 than that of the MCP with a separate, opaque CsI photocathode, and the detection efficiency ratio increases substantially at longer wavelengths (ratio is 5 at 1216 A and 20 at 1608 A).

99mTc-Hexamethylpropyleneamine Oxime Imaging for Early Detection of Acute Lung Injury in Rats Exposed to Hyperoxia or Lipopolysaccharide Treatment

PubMed Central

Audi, Said H.; Clough, Anne V.; Haworth, Steven T.; Medhora, Meetha; Ranji, Mahsa; Densmore, John C.; Jacobs, Elizabeth R.

2016-01-01

99mTc-Hexamethylpropyleneamine oxime (HMPAO) is a clinical single-photon emission computed tomography biomarker of tissue oxidoreductive state. Our objective was to investigate whether HMPAO lung uptake can serve as a pre-clinical marker of lung injury in two well-established rat models of human acute lung injury (ALI). Rats were exposed to >95% O2 (hyperoxia) or treated with intratracheal lipopolysaccharide (LPS), with first endpoints obtained 24 hours later. HMPAO was administered intravenously before and after treatment with the glutathione-depleting agent diethyl maleate (DEM), scintigraphy images were acquired, and HMPAO lung uptake was quantified from the images. We also measured breathing rates, heart rates, oxygen saturation, bronchoalveolar lavage (BAL) cell counts and protein, lung homogenate glutathione (GSH) content, and pulmonary vascular endothelial filtration coefficient (Kf). For hyperoxia rats, HMPAO lung uptake increased after 24 hours (134%) and 48 hours (172%) of exposure. For LPS-treated rats, HMPAO lung uptake increased (188%) 24 hours after injury and fell with resolution of injury. DEM reduced HMPAO uptake in hyperoxia and LPS rats by a greater fraction than in normoxia rats. Both hyperoxia exposure (18%) and LPS treatment (26%) increased lung homogenate GSH content, which correlated strongly with HMPAO uptake. Neither of the treatments had an effect on Kf at 24 hours. LPS-treated rats appeared healthy but exhibited mild tachypnea, BAL and histological evidence of inflammation, and increased wet and dry lung weights. These results suggest the potential utility of HMPAO as a tool for detecting ALI at a phase likely to exhibit minimal clinical evidence of injury. PMID:26974426

99MTc-Hexamethylpropyleneamine Oxime Imaging for Early Detection of Acute Lung Injury in Rats Exposed to Hyperoxia or Lipopolysaccharide Treatment.

PubMed

Audi, Said H; Clough, Anne V; Haworth, Steven T; Medhora, Meetha; Ranji, Mahsa; Densmore, John C; Jacobs, Elizabeth R

2016-10-01

Tc-Hexamethylpropyleneamine oxime (HMPAO) is a clinical single-photon emission computed tomography biomarker of tissue oxidoreductive state. Our objective was to investigate whether HMPAO lung uptake can serve as a preclinical marker of lung injury in two well-established rat models of human acute lung injury (ALI).Rats were exposed to >95% O2 (hyperoxia) or treated with intratracheal lipopolysaccharide (LPS), with first endpoints obtained 24 h later. HMPAO was administered intravenously before and after treatment with the glutathione-depleting agent diethyl maleate (DEM), scintigraphy images were acquired, and HMPAO lung uptake was quantified from the images. We also measured breathing rates, heart rates, oxygen saturation, bronchoalveolar lavage (BAL) cell counts and protein, lung homogenate glutathione (GSH) content, and pulmonary vascular endothelial filtration coefficient (Kf).For hyperoxia rats, HMPAO lung uptake increased after 24 h (134%) and 48 h (172%) of exposure. For LPS-treated rats, HMPAO lung uptake increased (188%) 24 h after injury and fell with resolution of injury. DEM reduced HMPAO uptake in hyperoxia and LPS rats by a greater fraction than in normoxia rats. Both hyperoxia exposure (18%) and LPS treatment (26%) increased lung homogenate GSH content, which correlated strongly with HMPAO uptake. Neither of the treatments had an effect on Kf at 24 h. LPS-treated rats appeared healthy but exhibited mild tachypnea, BAL, and histological evidence of inflammation, and increased wet and dry lung weights. These results suggest the potential utility of HMPAO as a tool for detecting ALI at a phase likely to exhibit minimal clinical evidence of injury.

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

PubMed

Fujii, T; Tanaka, M; Yazaki, Y; Kitabayashi, H; Koizumi, T; Kubo, K; Sekiguchi, M; Yano, K

1999-06-01

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

Vasculature surrounding a nodule: A novel lung cancer biomarker.

PubMed

Wang, Xiaohua; Leader, Joseph K; Wang, Renwei; Wilson, David; Herman, James; Yuan, Jian-Min; Pu, Jiantao

2017-12-01

To investigate whether the vessels surrounding a nodule depicted on non-contrast, low-dose computed tomography (LDCT) can discriminate benign and malignant screen detected nodules. We collected a dataset consisting of LDCT scans acquired on 100 subjects from the Pittsburgh Lung Screening study (PLuSS). Fifty subjects were diagnosed with lung cancer and 50 subjects had suspicious nodules later proven benign. For the lung cancer cases, the location of the malignant nodule in the LDCT scans was known; while for the benign cases, the largest nodule in the LDCT scan was used in the analysis. A computer algorithm was developed to identify surrounding vessels and quantify the number and volume of vessels that were connected or near the nodule. A nonparametric receiver operating characteristic (ROC) analysis was performed based on a single nodule per subject to assess the discriminability of the surrounding vessels to provide a lung cancer diagnosis. Odds ratio (OR) were computed to determine the probability of a nodule being lung cancer based on the vessel features. The areas under the ROC curves (AUCs) for vessel count and vessel volume were 0.722 (95% CI=0.616-0.811, p<0.01) and 0.676 (95% CI=0.565-0.772), respectively. The number of vessels attached to a nodule was significantly higher in the lung cancer group 9.7 (±9.6) compared to the non-lung cancer group 4.0 (±4.3) CONCLUSION: Our preliminary results showed that malignant nodules are often surrounded by more vessels compared to benign nodules, suggesting that the surrounding vessel characteristics could serve as lung cancer biomarker for indeterminate nodules detected during LDCT lung cancer screening using only the information collected during the initial visit. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of counting methods for oceanic radium-228

NASA Astrophysics Data System (ADS)

Orr, James C.

1988-07-01

Measurement of open ocean 228Ra is difficult, typically requiring at least 200 L of seawater. The burden of collecting and processing these large-volume samples severely limits the widespread use of this promising tracer. To use smaller-volume samples, a more sensitive means of analysis is required. To seek out new and improved counting method(s), conventional 228Ra counting methods have been compared with some promising techniques which are currently used for other radionuclides. Of the conventional methods, α spectrometry possesses the highest efficiency (3-9%) and lowest background (0.0015 cpm), but it suffers from the need for complex chemical processing after sampling and the need to allow about 1 year for adequate ingrowth of 228Th granddaughter. The other two conventional counting methods measure the short-lived 228Ac daughter while it remains supported by 228Ra, thereby avoiding the complex sample processing and the long delay before counting. The first of these, high-resolution γ spectrometry, offers the simplest processing and an efficiency (4.8%) comparable to α spectrometry; yet its high background (0.16 cpm) and substantial equipment cost (˜30,000) limit its widespread use. The second no-wait method, β-γ coincidence spectrometry, also offers comparable efficiency (5.3%), but it possesses both lower background (0.0054 cpm) and lower initial cost (˜12,000). Three new (i.e., untried for 228Ra) techniques all seem to promise about a fivefold increase in efficiency over conventional methods. By employing liquid scintillation methods, both α spectrometry and β-γ coincidence spectrometry can improve their counter efficiency while retaining low background. The third new 228Ra counting method could be adapted from a technique which measures 224Ra by 220Rn emanation. After allowing for ingrowth and then counting for the 224Ra great-granddaughter, 228Ra could be back calculated, thereby yielding a method with high efficiency, where no sample processing is required. The efficiency and background of each of the three new methods have been estimated and are compared with those of the three methods currently employed to measure oceanic 228Ra. From efficiency and background, the relative figure of merit and the detection limit have been determined for each of the six counters. These data suggest that the new counting methods have the potential to measure most 228Ra samples with just 30 L of seawater, to better than 5% precision. Not only would this reduce the time, effort, and expense involved in sample collection, but 228Ra could then be measured on many small-volume samples (20-30 L) previously collected with only 226Ra in mind. By measuring 228Ra quantitatively on such small-volume samples, three analyses (large-volume 228Ra, large-volume 226Ra, and small-volume 226Ra) could be reduced to one, thereby dramatically improving analytical precision.

Study of inflammatory responses to crocidolite and basalt wool in the rat lung.

PubMed

Adamis, Z; Kerényi, T; Honma, K; Jäckel, M; Tátrai, E; Ungváry, G

2001-03-09

The subacute effects of crocidolite and basalt wool dusts were studied by nmeans of biochemical, morphological. and histological methods 1 and .3 mo after intrabronchial instillation. The cell count, protein and phospholipid contents, and lactate dehydrogenase (LDH) activity were determined in the bronchoalveolar lavage (BAL). Both types of fibers induced a prolonged inflammatory reaction in the lung. All the parameters studied in the experimental groups were more markedly elevated after 3 mo. Relative to the control, the protein and LDH values were increased three- to fivefold, the phospholipid content twofold, and the number of free cells in the BAL exceeded the control level up to ninefold. The inflammatory responses to crocidolite and basalt wool in the lung did not differ significantly. In spite of this, basalt wool is recoinmended as an asbestos substitute, as the use of this man-nade fiber may result in a significantly lower release of dust than that from crocidolite.

Estimated Costs for Delivery of HIV Antiretroviral Therapy to Individuals with CD4+ T-Cell Counts >350 cells/uL in Rural Uganda

PubMed Central

Jain, Vivek; Chang, Wei; Byonanebye, Dathan M.; Owaraganise, Asiphas; Twinomuhwezi, Ellon; Amanyire, Gideon; Black, Douglas; Marseille, Elliot; Kamya, Moses R.; Havlir, Diane V.; Kahn, James G.

2015-01-01

Background Evidence favoring earlier HIV ART initiation at high CD4+ T-cell counts (CD4>350/uL) has grown, and guidelines now recommend earlier HIV treatment. However, the cost of providing ART to individuals with CD4>350 in Sub-Saharan Africa has not been well estimated. This remains a major barrier to optimal global cost projections for accelerating the scale-up of ART. Our objective was to compute costs of ART delivery to high CD4+count individuals in a typical rural Ugandan health center-based HIV clinic, and use these data to construct scenarios of efficient ART scale-up. Methods Within a clinical study evaluating streamlined ART delivery to 197 individuals with CD4+ cell counts >350 cells/uL (EARLI Study: NCT01479634) in Mbarara, Uganda, we performed a micro-costing analysis of administrative records, ART prices, and time-and-motion analysis of staff work patterns. We computed observed per-person-per-year (ppy) costs, and constructed models estimating costs under several increasingly efficient ART scale-up scenarios using local salaries, lowest drug prices, optimized patient loads, and inclusion of viral load (VL) testing. Findings Among 197 individuals enrolled in the EARLI Study, median pre-ART CD4+ cell count was 569/uL (IQR 451–716). Observed ART delivery cost was $628 ppy at steady state. Models using local salaries and only core laboratory tests estimated costs of $529/$445 ppy (+/-VL testing, respectively). Models with lower salaries, lowest ART prices, and optimized healthcare worker schedules reduced costs by $100–200 ppy. Costs in a maximally efficient scale-up model were $320/$236 ppy (+/- VL testing). This included $39 for personnel, $106 for ART, $130/$46 for laboratory tests, and $46 for administrative/other costs. A key limitation of this study is its derivation and extrapolation of costs from one large rural treatment program of high CD4+ count individuals. Conclusions In a Ugandan HIV clinic, ART delivery costs—including VL testing—for individuals with CD4>350 were similar to estimates from high-efficiency programs. In higher efficiency scale-up models, costs were substantially lower. These favorable costs may be achieved because high CD4+ count patients are often asymptomatic, facilitating more efficient streamlined ART delivery. Our work provides a framework for calculating costs of efficient ART scale-up models using accessible data from specific programs and regions. PMID:26632823

Estimated Costs for Delivery of HIV Antiretroviral Therapy to Individuals with CD4+ T-Cell Counts >350 cells/uL in Rural Uganda.

PubMed

Jain, Vivek; Chang, Wei; Byonanebye, Dathan M; Owaraganise, Asiphas; Twinomuhwezi, Ellon; Amanyire, Gideon; Black, Douglas; Marseille, Elliot; Kamya, Moses R; Havlir, Diane V; Kahn, James G

2015-01-01

Evidence favoring earlier HIV ART initiation at high CD4+ T-cell counts (CD4>350/uL) has grown, and guidelines now recommend earlier HIV treatment. However, the cost of providing ART to individuals with CD4>350 in Sub-Saharan Africa has not been well estimated. This remains a major barrier to optimal global cost projections for accelerating the scale-up of ART. Our objective was to compute costs of ART delivery to high CD4+count individuals in a typical rural Ugandan health center-based HIV clinic, and use these data to construct scenarios of efficient ART scale-up. Within a clinical study evaluating streamlined ART delivery to 197 individuals with CD4+ cell counts >350 cells/uL (EARLI Study: NCT01479634) in Mbarara, Uganda, we performed a micro-costing analysis of administrative records, ART prices, and time-and-motion analysis of staff work patterns. We computed observed per-person-per-year (ppy) costs, and constructed models estimating costs under several increasingly efficient ART scale-up scenarios using local salaries, lowest drug prices, optimized patient loads, and inclusion of viral load (VL) testing. Among 197 individuals enrolled in the EARLI Study, median pre-ART CD4+ cell count was 569/uL (IQR 451-716). Observed ART delivery cost was $628 ppy at steady state. Models using local salaries and only core laboratory tests estimated costs of $529/$445 ppy (+/-VL testing, respectively). Models with lower salaries, lowest ART prices, and optimized healthcare worker schedules reduced costs by $100-200 ppy. Costs in a maximally efficient scale-up model were $320/$236 ppy (+/- VL testing). This included $39 for personnel, $106 for ART, $130/$46 for laboratory tests, and $46 for administrative/other costs. A key limitation of this study is its derivation and extrapolation of costs from one large rural treatment program of high CD4+ count individuals. In a Ugandan HIV clinic, ART delivery costs--including VL testing--for individuals with CD4>350 were similar to estimates from high-efficiency programs. In higher efficiency scale-up models, costs were substantially lower. These favorable costs may be achieved because high CD4+ count patients are often asymptomatic, facilitating more efficient streamlined ART delivery. Our work provides a framework for calculating costs of efficient ART scale-up models using accessible data from specific programs and regions.

Rapid enumeration of viable bacteria by image analysis

NASA Technical Reports Server (NTRS)

Singh, A.; Pyle, B. H.; McFeters, G. A.

1989-01-01

A direct viable counting method for enumerating viable bacteria was modified and made compatible with image analysis. A comparison was made between viable cell counts determined by the spread plate method and direct viable counts obtained using epifluorescence microscopy either manually or by automatic image analysis. Cultures of Escherichia coli, Salmonella typhimurium, Vibrio cholerae, Yersinia enterocolitica and Pseudomonas aeruginosa were incubated at 35 degrees C in a dilute nutrient medium containing nalidixic acid. Filtered samples were stained for epifluorescence microscopy and analysed manually as well as by image analysis. Cells enlarged after incubation were considered viable. The viable cell counts determined using image analysis were higher than those obtained by either the direct manual count of viable cells or spread plate methods. The volume of sample filtered or the number of cells in the original sample did not influence the efficiency of the method. However, the optimal concentration of nalidixic acid (2.5-20 micrograms ml-1) and length of incubation (4-8 h) varied with the culture tested. The results of this study showed that under optimal conditions, the modification of the direct viable count method in combination with image analysis microscopy provided an efficient and quantitative technique for counting viable bacteria in a short time.

Pulmonary drug delivery. Part II: The role of inhalant delivery devices and drug formulations in therapeutic effectiveness of aerosolized medications

PubMed Central

Labiris, N R; Dolovich, M B

2003-01-01

Research in the area of pulmonary drug delivery has gathered momentum in the last several years, with increased interest in using the lung as a means of delivering drugs systemically. Advances in device technology have led to the development of more efficient delivery systems capable of delivering larger doses and finer particles into the lung. As more efficient pulmonary delivery devices and sophisticated formulations become available, physicians and health professionals will have a choice of a wide variety of device and formulation combinations that will target specific cells or regions of the lung, avoid the lung's clearance mechanisms and be retained within the lung for longer periods. It is now recognized that it is not enough just to have inhalation therapy available for prescribing; physicians and other healthcare providers need a basic understanding of aerosol science, inhaled formulations, delivery devices, and bioequivalence of products to prescribe these therapies optimally. PMID:14616419

[Regulation of airway stem cell proliferation in idiopathic pulmonary fibrosis].

PubMed

Yang, S X; Wu, Q; Sun, X; Li, X; Li, K; Xu, L; Li, Y; Zhang, Q Y; Zhang, Y C; Chen, H Y

2016-09-01

To investigate the effect of fibroblasts on regulating airway stem cell proliferation in idiopathic pulmonary fibrosis. Lung cell suspension was prepared from β-actin-GFP mice. Airway stem cells were obtained by fluorescence activated cell sorting and co-cultured with lung fibroblasts. The fibroblasts were treated with TGF-β inhibitor SB43142. The expression of growth factors FGF1/2 and the effect of FGF1/2 on stem cell proliferation were observed. The cloning efficiency of airway stem cells, when co-cultured with normal lung fibroblast cells for 8 days, was (3.5±1.1)%, while the cloning efficiency was reduced to (0.04±0.04)% when co-cultured with lung fibroblasts from idiopathic pulmonary fibrosis patients. The difference between the 2 groups was statistically significant(P=0.002 5). TGF-β receptor inhibitor SB431542 increased lung fibroblast growth factors FGF1/2 expression.FGF1 mRNA expression was increased to the experimental group 0.005 5 from 0.000 2 in the control group.FGF2 mRNA expression of the amount raised to the experimental group 0.000 15 from 0.000 8 in the control group.FGF1/2 promoted the growth of airway stem cells. After FGF1/2 was co-cultured with normal lung fibroblast cells for 8 days, the cloning efficiency of airway stem cells was (0.3±0.1)%. During the development of idiopathic pulmonary fibrosis, fibroblast secreted FGF1/2 regulate airway stem cell proliferation.

ESTIMATION OF RADIOACTIVE CALCIUM-45 BY LIQUID SCINTILLATION COUNTING

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

Lutwak, L.

1959-03-01

A liquid sclntillation counting method is developed for determining radioactive calcium-45 in biological materials. The calcium-45 is extracted, concentrated, and dissolved in absolute ethyl alcohol to which is added 0.4% diphenyloxazol in toluene. Counting efficiency is about 65 percent with standard deviation of the J-57 engin 7.36 percent. (auth)

Increasing point-count duration increases standard error

USGS Publications Warehouse

Smith, W.P.; Twedt, D.J.; Hamel, P.B.; Ford, R.P.; Wiedenfeld, D.A.; Cooper, R.J.

1998-01-01

We examined data from point counts of varying duration in bottomland forests of west Tennessee and the Mississippi Alluvial Valley to determine if counting interval influenced sampling efficiency. Estimates of standard error increased as point count duration increased both for cumulative number of individuals and species in both locations. Although point counts appear to yield data with standard errors proportional to means, a square root transformation of the data may stabilize the variance. Using long (>10 min) point counts may reduce sample size and increase sampling error, both of which diminish statistical power and thereby the ability to detect meaningful changes in avian populations.

Peculiarities of the Inflammatory Process in the Reproductive Organs of C57Bl/6 Female Mice with Experimental Tuberculosis.

PubMed

Sukhikh, G T; Kayukova, S I; Bocharova, I V; Donnikov, A E; Lepekha, L N; Demikhova, O V; Uvarova, E V; Berezovskii, Yu S; Smirnova, T G

2016-04-01

Intravenous infection of C57Bl/6 female mice with M. tuberculosis H37Rv led to involvement of the lungs and dissemination of the tuberculous infection to the abdominal and pelvic organs. M. tuberculosis were detected in the lungs and spleen in 14, 35, and 90 days and in the uterine horns in 90 days after infection. Morphological analysis of organs showed successive development of exudative necrotic tuberculosis of the lungs, acute and chronic nonspecific inflammation in the reproductive organs (vagina, uterus, and uterine horns). The inflammatory process in the reproductive organs was associated with the development of anaerobic dysbiosis, that was most pronounced in 35 days after infection. Antituberculous therapy was followed by reduction of M. tuberculosis count in the lungs and spleen in 60 and 90 days after infection, eliminatation of M. tuberculosis in the uterine horns, arrest of nonspecific inflammation in female reproductive organs, recovery of the balance between aerobic and anaerobic microflora, and development of candidiasis of the urogenital mucosa.

Optimization of the Agar-gel Method for Isolation of Migrating Ascaris suum Larvae From the Liver and Lungs of Pigs

PubMed Central

Saeed, I; Roepstorff, A; Rasmussen, T; Høg, M; Jungersen, G

2001-01-01

Experiments on use of an agar-gel method for recovery of migrating Ascaris suum larvae from the liver and lungs of pigs were conducted to obtain fast standardized methods. Subsamples of blended tissues of pig liver and lungs were mixed with agar to a final concentration of 1% agar and the larvae allowed to migrate out of the agar-gel into 0.9% NaCl at 38°C. The results showed that within 3 h more than 88% of the recoverable larvae migrated out of the liver agar-gel and more than 83% of the obtained larvae migrated out of the lung agar-gel. The larvae were subsequently available in a very clean suspension which reduced the sample counting time. Blending the liver for 60 sec in a commercial blender showed significantly higher larvae recovery than blending for 30 sec. Addition of gentamycin to reduce bacterial growth during incubation, glucose to increase larval motility during migration or ice to increase sedimentation of migrated larvae did not influence larvae recovery significantly. PMID:11503373

Incidental Transient Cortical Blindness after Lung Resection.

PubMed

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

2016-03-01

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

[A case of loxoprofen sodium-induced bronchiolitis obliterans organizing pneumonia (BOOP)].

PubMed

Fujita, Kazue; Sakamoto, Osamu; Matsumoto, Mitsuhiro; Kohrogi, Hirotsugu; Suga, Moritaka

2003-12-01

A 78-year-old man was referred to our department because of an abnormal shadow on the chest radiograph and liver dysfunction after lung resection for lung cancer. Following the operation, loxoprofen sodium was administered to control his chest pain. A chest radiograph on admission showed airspace consolidation in the right lower lung field. In addition, leukocytosis and elevation of CRP were observed. Although piperacillin sodium was given to him, airspace consolidation on a chest radiograph was increased. A bronchoalveolar lavage fluid study showed that total cell counts and proportion of lymphocytes were increased, and the CD4/CD8 ratio was 1.77. A transbronchial lung biopsy specimen revealed organizing pneumonia with Masson bodies. Furthermore, a lymphocyte stimulation test for loxoprofen sodium was positive. From the clinical course, laboratory data and pathologic findings, we considered this case to be loxoprofen sodium-induced BOOP. Withdrawal of loxoprofen sodium and treatment with corticosteroid resulted in marked improvement of the clinical findings. Although a rare occurrence, it is important to recognize that BOOP can be caused by loxoprofen sodium.

Design, synthesis, and structure-activity relationships of 2-benzylidene-1-indanone derivatives as anti-inflammatory agents for treatment of acute lung injury.

PubMed

Xiao, Siyang; Zhang, Wenxin; Chen, Hongjin; Fang, Bo; Qiu, Yinda; Chen, Xianxin; Chen, Lingfeng; Shu, Sheng; Zhang, Yali; Zhao, Yunjie; Liu, Zhiguo; Liang, Guang

2018-01-01

The purpose of this study was to design and synthesize novel 2-benzylidene-1-indanone derivatives for treatment of acute lung injury. A series of 39 novel 2-benzylidene-indanone structural derivatives were synthesized and evaluated for anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated murine primary macrophages. Most of the obtained compounds effectively inhibited the LPS-induced expression of IL-6 and TNF-α. The most active compound, 8f , was found to significantly reduce LPS-induced pulmonary inflammation, as reflected by reductions in the concentration of total protein, inflammatory cell count, as well as the lung wet/dry ratio in bronchoalveolar lavage (BAL) fluid. Furthermore, 8f effectively inhibited mRNA expression of several inflammatory cytokines after LPS challenge in vitro and in vivo. Administration of 8f also blocked LPS-induced activation of the proinflammatory NF-κB/MAPK signaling pathway. The simple synthetic preparation and biological properties of these derivatives make these 2-benzylidene-indanone scaffolds promising new entities for the development of anti-inflammatory therapeutics for the treatment of acute lung injury.

Intranasal IFNγ extends passive IgA antibody protection of mice against Mycobacterium tuberculosis lung infection

PubMed Central

Reljic, R; Clark, S O; Williams, A; Falero-Diaz, G; Singh, M; Challacombe, S; Marsh, P D; Ivanyi, J

2006-01-01

Intranasal inoculation of mice with monoclonal IgA against the α-crystallin (acr1) antigen can diminish the tuberculous infection in the lungs. As this effect has been observed only over a short-term, we investigated if it could be extended by inoculation of IFNγ 3 days before infection, and further coinoculations with IgA, at 2 h before and 2 and 7 days after aerosol infection with Mycobacterium tuberculosis H37Rv. This treatment reduced the lung infection at 4 weeks more than either IgA or IFNγ alone (i.e. 17-fold, from 4·2 × 107 to 2·5 × 106 CFU, P = 0·006), accompanied also by lower granulomatous infiltration of the lungs. IFNγ added prior to infection of mouse peritoneal macrophages with IgA-opsonized bacilli resulted in a synergistic increase of nitric oxide and TNFα production and a 2–3 fold decrease in bacterial counts. Our improved results suggest, that combined treatment with IFNγ and IgA could be developed towards prophylactic treatment of AIDS patients, or as an adjunct to chemotherapy. PMID:16487246

Construction of Chinese adult male phantom library and its application in the virtual calibration of in vivo measurement.

PubMed

Chen, Yizheng; Qiu, Rui; Li, Chunyan; Wu, Zhen; Li, Junli

2016-03-07

In vivo measurement is a main method of internal contamination evaluation, particularly for large numbers of people after a nuclear accident. Before the practical application, it is necessary to obtain the counting efficiency of the detector by calibration. The virtual calibration based on Monte Carlo simulation usually uses the reference human computational phantom, and the morphological difference between the monitored personnel with the calibrated phantom may lead to the deviation of the counting efficiency. Therefore, a phantom library containing a wide range of heights and total body masses is needed. In this study, a Chinese reference adult male polygon surface (CRAM_S) phantom was constructed based on the CRAM voxel phantom, with the organ models adjusted to match the Chinese reference data. CRAM_S phantom was then transformed to sitting posture for convenience in practical monitoring. Referring to the mass and height distribution of the Chinese adult male, a phantom library containing 84 phantoms was constructed by deforming the reference surface phantom. Phantoms in the library have 7 different heights ranging from 155 cm to 185 cm, and there are 12 phantoms with different total body masses in each height. As an example of application, organ specific and total counting efficiencies of Ba-133 were calculated using the MCNPX code, with two series of phantoms selected from the library. The influence of morphological variation on the counting efficiency was analyzed. The results show only using the reference phantom in virtual calibration may lead to an error of 68.9% for total counting efficiency. Thus the influence of morphological difference on virtual calibration can be greatly reduced using the phantom library with a wide range of masses and heights instead of a single reference phantom.

Construction of Chinese adult male phantom library and its application in the virtual calibration of in vivo measurement

NASA Astrophysics Data System (ADS)

Chen, Yizheng; Qiu, Rui; Li, Chunyan; Wu, Zhen; Li, Junli

2016-03-01

In vivo measurement is a main method of internal contamination evaluation, particularly for large numbers of people after a nuclear accident. Before the practical application, it is necessary to obtain the counting efficiency of the detector by calibration. The virtual calibration based on Monte Carlo simulation usually uses the reference human computational phantom, and the morphological difference between the monitored personnel with the calibrated phantom may lead to the deviation of the counting efficiency. Therefore, a phantom library containing a wide range of heights and total body masses is needed. In this study, a Chinese reference adult male polygon surface (CRAM_S) phantom was constructed based on the CRAM voxel phantom, with the organ models adjusted to match the Chinese reference data. CRAMS phantom was then transformed to sitting posture for convenience in practical monitoring. Referring to the mass and height distribution of the Chinese adult male, a phantom library containing 84 phantoms was constructed by deforming the reference surface phantom. Phantoms in the library have 7 different heights ranging from 155 cm to 185 cm, and there are 12 phantoms with different total body masses in each height. As an example of application, organ specific and total counting efficiencies of Ba-133 were calculated using the MCNPX code, with two series of phantoms selected from the library. The influence of morphological variation on the counting efficiency was analyzed. The results show only using the reference phantom in virtual calibration may lead to an error of 68.9% for total counting efficiency. Thus the influence of morphological difference on virtual calibration can be greatly reduced using the phantom library with a wide range of masses and heights instead of a single reference phantom.

Matrix Metalloproteinase-8 Inactivates Macrophage Inflammatory Protein-1α to Reduce Acute Lung Inflammation and Injury in Mice

PubMed Central

Quintero, Pablo A.; Knolle, Martin D.; Cala, Luisa F.; Zhuang, Yuehong; Owen, Caroline A.

2010-01-01

To determine the role of matrix metalloproteinase-8 (MMP-8) in acute lung injury (ALI), we delivered LPS or bleomycin by the intratracheal route to MMP-8−/− mice versus WT mice or subjected the mice to hyperoxia (95% O2) and measured lung inflammation and injury at intervals. MMP-8−/− mice with ALI had greater increases in lung PMN and macrophage counts, measures of alveolar capillary barrier injury, lung elastance, and mortality than WT mice with ALI. Bronchoalveolar lavage fluid (BALF) from LPS-treated MMP-8−/− mice had more macrophage inflammatory protein-1α (MIP-1α) than BALF from LPS-treated WT mice, but similar levels of other pro- and anti-inflammatory mediators. MIP-1α−/− mice with ALI had less acute lung inflammation and injury than WT mice with ALI, confirming that MIP-1α promotes acute lung inflammation and injury in mice. Genetically deleting MIP-1α in MMP-8−/− mice abrogated the increased lung inflammation and injury and mortality in MMP-8−/− mice with ALI. Soluble MMP-8 cleaved and inactivated MIP-1α in vitro, but membrane-bound MMP-8 on activated PMNs had greater MIP-1α-degrading activity than soluble MMP-8. High levels of membrane-bound MMP-8 were detected on lung PMNs from LPS-treated WT mice, but soluble, active MMP-8 was not detected in BALF samples. Thus, MMP-8 has novel roles in restraining lung inflammation and in limiting alveolar capillary barrier injury during ALI in mice by inactivating MIP-1α. In addition, membrane-bound MMP-8 on activated lung PMNs is likely to be the key bioactive form of the enzyme that limits lung inflammation and alveolar capillary barrier injury during ALI. PMID:20042585

The Cost-Effectiveness of High-Risk Lung Cancer Screening and Drivers of Program Efficiency.

PubMed

Cressman, Sonya; Peacock, Stuart J; Tammemägi, Martin C; Evans, William K; Leighl, Natasha B; Goffin, John R; Tremblay, Alain; Liu, Geoffrey; Manos, Daria; MacEachern, Paul; Bhatia, Rick; Puksa, Serge; Nicholas, Garth; McWilliams, Annette; Mayo, John R; Yee, John; English, John C; Pataky, Reka; McPherson, Emily; Atkar-Khattra, Sukhinder; Johnston, Michael R; Schmidt, Heidi; Shepherd, Frances A; Soghrati, Kam; Amjadi, Kayvan; Burrowes, Paul; Couture, Christian; Sekhon, Harmanjatinder S; Yasufuku, Kazuhiro; Goss, Glenwood; Ionescu, Diana N; Hwang, David M; Martel, Simon; Sin, Don D; Tan, Wan C; Urbanski, Stefan; Xu, Zhaolin; Tsao, Ming-Sound; Lam, Stephen

2017-08-01

Lung cancer risk prediction models have the potential to make programs more affordable; however, the economic evidence is limited. Participants in the National Lung Cancer Screening Trial (NLST) were retrospectively identified with the risk prediction tool developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. The high-risk subgroup was assessed for lung cancer incidence and demographic characteristics compared with those in the low-risk subgroup and the Pan-Canadian Early Detection of Lung Cancer Study (PanCan), which is an observational study that was high-risk-selected in Canada. A comparison of high-risk screening versus standard care was made with a decision-analytic model using data from the NLST with Canadian cost data from screening and treatment in the PanCan study. Probabilistic and deterministic sensitivity analyses were undertaken to assess uncertainty and identify drivers of program efficiency. Use of the risk prediction tool developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial with a threshold set at 2% over 6 years would have reduced the number of individuals who needed to be screened in the NLST by 81%. High-risk screening participants in the NLST had more adverse demographic characteristics than their counterparts in the PanCan study. High-risk screening would cost $20,724 (in 2015 Canadian dollars) per quality-adjusted life-year gained and would be considered cost-effective at a willingness-to-pay threshold of $100,000 in Canadian dollars per quality-adjusted life-year gained with a probability of 0.62. Cost-effectiveness was driven primarily by non-lung cancer outcomes. Higher noncurative drug costs or current costs for immunotherapy and targeted therapies in the United States would render lung cancer screening a cost-saving intervention. Non-lung cancer outcomes drive screening efficiency in diverse, tobacco-exposed populations. Use of risk selection can reduce the budget impact, and screening may even offer cost savings if noncurative treatment costs continue to rise. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

The lung in space.

PubMed

Prisk, G Kim

2005-09-01

The lung is exquisitely sensitive to gravity, which induces gradients in ventilation, blood flow, and gas exchange. Studies of lungs in microgravity provide a means of elucidating the effects of gravity. They suggest a mechanism by which gravity serves to match ventilation to perfusion, making for a more efficient lung than anticipated. Despite predictions, lungs do not become edematous, and there is no disruption to, gas exchange in microgravity. Sleep disturbances in microgravity are not a result of respiratory-related events; obstructive sleep apnea is caused principally by the gravitational effects on the upper airways. In microgravity, lungs may be at greater risk to the effects of inhaled aerosols.

The lung in space

NASA Technical Reports Server (NTRS)

Prisk, G. Kim

2005-01-01

The lung is exquisitely sensitive to gravity, which induces gradients in ventilation, blood flow, and gas exchange. Studies of lungs in microgravity provide a means of elucidating the effects of gravity. They suggest a mechanism by which gravity serves to match ventilation to perfusion, making for a more efficient lung than anticipated. Despite predictions, lungs do not become edematous, and there is no disruption to, gas exchange in microgravity. Sleep disturbances in microgravity are not a result of respiratory-related events; obstructive sleep apnea is caused principally by the gravitational effects on the upper airways. In microgravity, lungs may be at greater risk to the effects of inhaled aerosols.

Characterization of Libby, MT amphibole (LA) elongated particles for toxicology studies: Field Collection, sample preparation, dose characterization, and particle counting methods using SEM/EDS

EPA Science Inventory

Since 1999, the US EPA and USGS have been studying the chemistry, mineralogy, and morphology of the amphiboles from the Rainy Creek Complex of Libby, MT (LA), following an increased incidence of lung and pleural diseases. LA material collected in 2000 (LA2000) was described in M...

Total Airway Count on Computed Tomography and the Risk of Chronic Obstructive Pulmonary Disease Progression. Findings from a Population-based Study.

PubMed

Kirby, Miranda; Tanabe, Naoya; Tan, Wan C; Zhou, Guohai; Obeidat, Ma'en; Hague, Cameron J; Leipsic, Jonathon; Bourbeau, Jean; Sin, Don D; Hogg, James C; Coxson, Harvey O

2018-01-01

Studies of excised lungs show that significant airway attrition in the "quiet" zone occurs early in chronic obstructive pulmonary disease (COPD). To determine if the total number of airways quantified in vivo using computed tomography (CT) reflects early airway-related disease changes and is associated with lung function decline independent of emphysema in COPD. Participants in the multicenter, population-based, longitudinal CanCOLD (Canadian Chronic Obstructive Lung Disease) study underwent inspiratory/expiratory CT at visit 1; spirometry was performed at four visits over 6 years. Emphysema was quantified as the CT inspiratory low-attenuation areas below -950 Hounsfield units. CT total airway count (TAC) was measured as well as airway inner diameter and wall area using anatomically equivalent airways. Participants included never-smokers (n = 286), smokers with normal spirometry at risk for COPD (n = 298), Global Initiative for Chronic Obstructive Lung Disease (GOLD) I COPD (n = 361), and GOLD II COPD (n = 239). TAC was significantly reduced by 19% in both GOLD I and GOLD II compared with never-smokers (P < 0.0001) and by 17% in both GOLD I and GOLD II compared with at-risk participants (P < 0.0001) after adjusting for low-attenuation areas below -950 Hounsfield units. Further analysis revealed parent airways with missing daughter branches had reduced inner diameters (P < 0.0001) and thinner walls (P < 0.0001) compared with those without missing daughter branches. Among all CT measures, TAC had the greatest influence on FEV 1 (P < 0.0001), FEV 1 /FVC (P < 0.0001), and bronchodilator responsiveness (P < 0.0001). TAC was independently associated with lung function decline (FEV 1 , P = 0.02; FEV 1 /FVC, P = 0.01). TAC may reflect the airway-related disease changes that accumulate in the "quiet" zone in early/mild COPD, indicating that TAC acquired with commercially available software across various CT platforms may be a biomarker to predict accelerated COPD progression.

Mortality among people living with HIV/AIDS with non-small-cell lung cancer in the modern HAART Era.

PubMed

Smith, Danielle M; Salters, Kate A; Eyawo, Oghenowede; Franco-Villalobos, Conrado; Jabbari, Shahab; Wiseman, Sam M; Press, Natasha; Montaner, Julio S G; Man, S F Paul; Hull, Mark; Hogg, Robert S

2018-02-07

People living with HIV (PLWHA) with adequate access to modern combination antiretroviral therapy (cART) are living longer and experiencing reduced AIDS-related morbidity and mortality. However, increases in non-AIDS related conditions, such as certain cancers, have accompanied these therapeutic advances over time. As such, our study objective was to determine the impact of HIV on all-cause and lung cancer-specific mortality amongst PLWHA with diagnoses of non-small-cell lung cancer (NSCLC) and HIV-negative individuals with NSCLC. This analysis was inclusive of PLWHA on and off cART over the age of 19 years and a 10% comparison sample from the BC population ≥19 years, over a 13-year period (2000-2013). Kaplan-Meier estimates, Cox PH models, and competing risk analysis for all-cause and cause-specific mortality (respectively) compared PLWHA to HIV-negative individuals, controlling for age, gender, cancer stage, co-morbidities; and nadir CD4 count, viral load, and injection drug use for a HIV-positive specific analysis. We identified 71 PLWHA and 2463 HIV-negative individuals diagnosed with NSCLC between 2000 and 2013. PLWHA with NSCLC were diagnosed at a significantly younger age than HIV-negative individuals (median age 57 vs 71 years, p < 0.01). We found no significant difference in lung cancer-specific mortality. However, in multivariate analysis, HIV was associated with greater all-cause mortality (adjusted hazard ratio [aHR]:1.44; 95% confidence interval [CI]: 1.08-1.90), with median survival of 4 months for PLWHA, and 10 months for HIV-negative. Higher nadir CD4 count was protective against mortality (aHR: 0.33, 95% CI: 0.17-0.64) amongst PLWHA in multivariate analysis. Our analysis suggests that PLWHA in the modern cART era experience similar lung cancer survival outcomes compared to the general BC population with NSCLC. However, we also observed significantly higher all-cause mortality among PLWHA with NSCLC, which may warrant further inquiry into the role of HIV in exacerbating mortality among PLWHA with comorbidities and cancer.

Glutathione S-transferase M1 (GSTM1) polymorphisms and lung cancer: a literature-based systematic HuGE review and meta-analysis.

PubMed

Carlsten, C; Sagoo, G S; Frodsham, A J; Burke, W; Higgins, J P T

2008-04-01

Multiple genes have been studied for potential associations with lung cancer. The gene most frequently associated with increased risk has been glutathione S-transferase M1 (GSTM1). The glutathione S-transferase enzyme family is known to catalyze detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. In this review, the authors summarize the available evidence associating lung cancer with the GSTM1 gene. They describe results from an updated meta-analysis of 98 published genetic association studies investigating the relation between the GSTM1 null variant and lung cancer risk including 19,638 lung cancer cases and 25,266 controls (counting cases and controls in each study only once). All studies considered, the GSTM1 null variant was associated with an increased risk of lung cancer (odds ratio (OR) = 1.22, 95% confidence interval (CI): 1.14, 1.30), but no increase in risk was seen (OR = 1.01, 95% CI: 0.91, 1.12) when only the five largest studies (>500 cases each) were considered. Furthermore, while GSTM1 null status conferred a significantly increased risk of lung cancer to East Asians (OR = 1.38, 95% CI: 1.24, 1.55), such a genotype did not confer increased risk to Caucasians. More data regarding the predictive value of GSTM1 genetic testing are needed before population-based testing may be reasonably considered.

Decreased lung function with mediation of blood parameters linked to e-waste lead and cadmium exposure in preschool children.

PubMed

Zeng, Xiang; Xu, Xijin; Boezen, H Marike; Vonk, Judith M; Wu, Weidong; Huo, Xia

2017-11-01

Blood lead (Pb) and cadmium (Cd) levels have been associated with lower lung function in adults and smokers, but whether this also holds for children from electronic waste (e-waste) recycling areas is still unknown. To investigate the contribution of blood heavy metals and lung function levels, and the relationship among living area, the blood parameter levels, and the lung function levels, a total of 206 preschool children from Guiyu (exposed area), and Haojiang and Xiashan (reference areas) were recruited and required to undergo blood tests and lung function tests during the study period. Preschool children living in e-waste exposed areas were found to have a 1.37 μg/dL increase in blood Pb, 1.18 μg/L increase in blood Cd, and a 41.00 × 10 9 /L increase in platelet counts, while having a 2.82 g/L decrease in hemoglobin, 92 mL decrease in FVC and 86 mL decrease in FEV 1 . Each unit of hemoglobin (1 g/L) decline was associated with 5 mL decrease in FVC and 4 mL decrease in FEV 1 . We conclude that children living in e-waste exposed area have higher levels of blood Pb, Cd and platelets, and lower levels of hemoglobin and lung function. Hemoglobin can be a good predictor for lung function levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

EGF receptor tyrosine kinase inhibitors diminish transforming growth factor-alpha-induced pulmonary fibrosis.

PubMed

Hardie, William D; Davidson, Cynthia; Ikegami, Machiko; Leikauf, George D; Le Cras, Timothy D; Prestridge, Adrienne; Whitsett, Jeffrey A; Korfhagen, Thomas R

2008-06-01

Transforming growth factor-alpha (TGF-alpha) is a ligand for the EGF receptor (EGFR). EGFR activation is associated with fibroproliferative processes in human lung disease and animal models of pulmonary fibrosis. We determined the effects of EGFR tyrosine kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva) on the development and progression of TGF-alpha-induced pulmonary fibrosis. Using a doxycycline-regulatable transgenic mouse model of lung-specific TGF-alpha expression, we determined effects of treatment with gefitinib and erlotinib on changes in lung histology, total lung collagen, pulmonary mechanics, pulmonary hypertension, and expression of genes associated with synthesis of ECM and vascular remodeling. Induction in the lung of TGF-alpha caused progressive pulmonary fibrosis over an 8-wk period. Daily administration of gefitinib or erlotinib prevented development of fibrosis, reduced accumulation of total lung collagen, prevented weight loss, and prevented changes in pulmonary mechanics. Treatment of mice with gefitinib 4 wk after the induction of TGF-alpha prevented further increases in and partially reversed total collagen levels and changes in pulmonary mechanics and pulmonary hypertension. Increases in expression of genes associated with synthesis of ECM as well as decreases of genes associated with vascular remodeling were also prevented or partially reversed. Administration of gefitinib or erlotinib did not cause interstitial fibrosis or increases in lavage cell counts. Administration of small molecule EGFR tyrosine kinase inhibitors prevented further increases in and partially reversed pulmonary fibrosis induced directly by EGFR activation without inducing inflammatory cell influx or additional lung injury.

Sex differences in the expression of lung inflammatory mediators in response to ozone

PubMed Central

Cabello, Noe; Mishra, Vikas; Sinha, Utkarshna; DiAngelo, Susan L.; Chroneos, Zissis C.; Ekpa, Ndifreke A.; Cooper, Timothy K.; Caruso, Carla R.

2015-01-01

Sex differences in the incidence of respiratory diseases have been reported. Women are more susceptible to inflammatory lung disease induced by air pollution and show worse adverse pulmonary health outcomes than men. However, the mechanisms underlying these differences remain unknown. In the present study, we hypothesized that sex differences in the expression of lung inflammatory mediators affect sex-specific immune responses to environmental toxicants. We focused on the effects of ground-level ozone, a major air pollutant, in the expression and regulation of lung immunity genes. We exposed adult male and female mice to 2 ppm of ozone or filtered air (control) for 3 h. We compared mRNA levels of 84 inflammatory genes in lungs harvested 4 h postexposure using a PCR array. We also evaluated changes in lung histology and bronchoalveolar lavage fluid cell counts and protein content at 24 and 72 h postexposure. Our results revealed sex differences in lung inflammation triggered by ozone exposure and in the expression of genes involved in acute phase and inflammatory responses. Major sex differences were found in the expression of neutrophil-attracting chemokines (Ccl20, Cxcl5, and Cxcl2), the proinflammatory cytokine interleukin-6, and oxidative stress-related enzymes (Ptgs2, Nos2). In addition, the phosphorylation of STAT3, known to mediate IL-6-related immune responses, was significantly higher in ozone-exposed mice. Together, our observations suggest that a differential regulation of the lung immune response could be implicated in the observed increased susceptibility to adverse health effects from ozone observed in women vs. men. PMID:26342085

Effect of Advanced HIV Infection on the Respiratory Microbiome.

PubMed

Twigg, Homer L; Knox, Kenneth S; Zhou, Jin; Crothers, Kristina A; Nelson, David E; Toh, Evelyn; Day, Richard B; Lin, Huaiying; Gao, Xiang; Dong, Qunfeng; Mi, Deming; Katz, Barry P; Sodergren, Erica; Weinstock, George M

2016-07-15

Previous work found the lung microbiome in healthy subjects infected with HIV was similar to that in uninfected subjects. We hypothesized the lung microbiome from subjects infected with HIV with more advanced disease would differ from that of an uninfected control population. To measure the lung microbiome in an HIV-infected population with advanced disease. 16s RNA gene sequencing was performed on acellular bronchoalveolar lavage (BAL) fluid from 30 subjects infected with HIV with advanced disease (baseline mean CD4 count, 262 cells/mm(3)) before and up to 3 years after starting highly active antiretroviral therapy (HAART) and compared with 22 uninfected control subjects. The lung microbiome in subjects infected with HIV with advanced disease demonstrated decreased alpha diversity (richness and diversity) and greater beta diversity compared with uninfected BAL. Differences improved with HAART, but still persisted up to 3 years after starting therapy. Population dispersion in the group infected with HIV was significantly greater than in the uninfected cohort and declined after treatment. There were differences in the relative abundance of some bacteria between the two groups at baseline and after 1 year of therapy. After 1 year on HAART, HIV BAL contained an increased abundance of Prevotella and Veillonella, bacteria previously associated with lung inflammation. The lung microbiome in subjects infected with HIV with advanced disease is altered compared with an uninfected population both in diversity and bacterial composition. Differences remain up to 3 years after starting HAART. We speculate an altered lung microbiome in HIV infection may contribute to chronic inflammation and lung complications seen in the HAART era.

The effect of in vitro tracheal occlusion on branching morphogenesis in fetal lung explants from the rat nitrofen model of congenital diaphragmatic hernia.

PubMed

Grushka, Jeremy R; Al-Abbad, Saleh; Baird, Robert; Puligandla, Pramod; Kaplan, Feige; Laberge, Jean-Martin

2010-05-01

Fetal tracheal occlusion (TO) has been investigated as a treatment option for lung hypoplasia secondary to congenital diaphragmatic hernia. Tracheal occlusion has been shown to accelerate lung growth, but its effect on bronchial branching is unknown. In this study, we characterize the effects of in vitro TO on bronchial branch development in fetal lung explants derived from the nitrofen rat model of congenital diaphragmatic hernia. Rat dams were gavaged nitrofen on gestational day 9.5, and fetal lungs were harvested for explant culture on gestational day 14 (term, 22 days). Four experimental groups were investigated, with TO performed ex vivo using cautery: control, control + TO, nitrofen, and nitrofen + TO. Explants were incubated for 72 hours. Representative photographs were taken at 0, 24, 48, and 72 hours from the time of culture, and the number of distal branches was counted for each explant. The Student t test was used to compare distal branch measurements. A minimum of 12 fetal lung explants were cultured for each group. By 24 hours, all explants undergoing TO had more branch iterations than explants that did not. Moreover, TO in nitrofen-exposed explants increased bronchial branching to control levels by 24 hours in culture. Our results suggest that TO at day 14 increases branching in normal and nitrofen-exposed lung explants. In addition, TO increases airway branching in nitrofen-exposed explants to control levels suggesting that early TO reverses the lung hypoplasia seen in this model. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Lung cancer incidence and survival among HIV-infected and uninfected women and men.

PubMed

Hessol, Nancy A; Martínez-Maza, Otoniel; Levine, Alexandra M; Morris, Alison; Margolick, Joseph B; Cohen, Mardge H; Jacobson, Lisa P; Seaberg, Eric C

2015-06-19

To determine the lung cancer incidence and survival time among HIV-infected and uninfected women and men. Two longitudinal studies of HIV infection in the United States. Data from 2549 women in the Women's Interagency HIV Study (WIHS) and 4274 men in the Multicenter AIDS Cohort Study (MACS), all with a history of cigarette smoking, were analyzed. Lung cancer incidence rates and incidence rate ratios were calculated using Poisson regression analyses. Survival time was assessed using Kaplan-Meier and Cox proportional-hazard analyses. Thirty-seven women and 23 men developed lung cancer (46 HIV-infected and 14 HIV-uninfected) during study follow-up. In multivariable analyses, the factors that were found to be independently associated with a higher lung cancer incidence rate ratios were older age, less education, 10 or more pack-years of smoking, and a prior diagnosis of AIDS pneumonia (vs. HIV-uninfected women). In an adjusted Cox model that allowed different hazard functions for each cohort, a history of injection drug use was associated with shorter survival, and a lung cancer diagnosis after 2001 was associated with longer survival. In an adjusted Cox model restricted to HIV-infected participants, nadir CD4 lymphocyte cell count less than 200 was associated with shorter survival time. Our data suggest that pulmonary damage and inflammation associated with HIV infection may be causative for the increased risk of lung cancer. Encouraging and assisting younger HIV-infected smokers to quit and to sustain cessation of smoking is imperative to reduce the lung cancer burden in this population.

Lung disease at diagnosis in infants with cystic fibrosis detected by newborn screening.

PubMed

Sly, Peter D; Brennan, Siobhain; Gangell, Catherine; de Klerk, Nicholas; Murray, Conor; Mott, Lauren; Stick, Stephen M; Robinson, Philip J; Robertson, Colin F; Ranganathan, Sarath C

2009-07-15

The promise of newborn screening (NBS) for cystic fibrosis (CF) has not been fully realized, and the extent of improvement in respiratory outcomes is unclear. We hypothesized that significant lung disease was present at diagnosis. To determine the extent of lung disease in a geographically defined population of infants with CF diagnosed after detection by NBS. Fifty-seven infants (median age, 3.6 mo) with CF underwent bronchoalveolar lavage and chest computed tomography (CT) using a three-slice inspiratory and expiratory protocol. Despite the absence of respiratory symptoms in 48 (84.2%) of infants, a substantial proportion had lung disease with bacterial infection detected in 12 (21.1%), including Staphylococcus aureus (n = 4) and Pseudomonas aeruginosa (n = 3); neutrophilic inflammation (41. 4 x 10(3) cells/ml representing 18.7% of total cell count); proinflammatory cytokines, with 44 (77.2%) having detectable IL-8; and 17 (29.8%) having detectable free neutrophil elastase activity. Inflammation was increased in those with infection and respiratory symptoms; however, the majority of those infected were asymptomatic. Radiologic evidence of structural lung disease was common, with 46 (80.7%) having an abnormal CT; 11 (18.6%) had bronchial dilatation, 27 (45.0%) had bronchial wall thickening, and 40 (66.7%) had gas trapping. On multivariate analysis, free neutrophil elastase activity was associated with structural lung disease. Most children with structural lung disease had no clinically apparent lung disease. These data support the need for full evaluation in infancy and argue for new treatment strategies, especially those targeting neutrophilic inflammation, if the promise of NBS for CF is to be realized.

Does the covariance structure matter in longitudinal modelling for the prediction of future CD4 counts?

PubMed

Taylor, J M; Law, N

1998-10-30

We investigate the importance of the assumed covariance structure for longitudinal modelling of CD4 counts. We examine how individual predictions of future CD4 counts are affected by the covariance structure. We consider four covariance structures: one based on an integrated Ornstein-Uhlenbeck stochastic process; one based on Brownian motion, and two derived from standard linear and quadratic random-effects models. Using data from the Multicenter AIDS Cohort Study and from a simulation study, we show that there is a noticeable deterioration in the coverage rate of confidence intervals if we assume the wrong covariance. There is also a loss in efficiency. The quadratic random-effects model is found to be the best in terms of correctly calibrated prediction intervals, but is substantially less efficient than the others. Incorrectly specifying the covariance structure as linear random effects gives too narrow prediction intervals with poor coverage rates. Fitting using the model based on the integrated Ornstein-Uhlenbeck stochastic process is the preferred one of the four considered because of its efficiency and robustness properties. We also use the difference between the future predicted and observed CD4 counts to assess an appropriate transformation of CD4 counts; a fourth root, cube root and square root all appear reasonable choices.

Influence of Survey Length and Radius Size on Grassland Bird Surveys by Point Counts at Williams Lake, British Columbia

Treesearch

Jean-Pierre L. Savard; Tracey D. Hooper

1995-01-01

We examine the effect of survey length and radius on the results of point count surveys for grassland birds at Williams Lake, British Columbia. Four- and 8-minute counts detected on average 68 percent and 85 percent of the number of birds detected during 12-minute counts. The most efficient sampling duration was 4 minutes, as long as travel time between points was...

Evaluation of serum and pleural levels of endostatin and vascular epithelial growth factor in lung cancer patients with pleural effusion.

PubMed

Zhang, Yu; Yu, Li-Ke; Xia, Ning

2012-03-01

To evaluate the diagnostic value of endostatin (ES), vascular endothelial growth factor (VEGF) and carcinoembryonic antigen (CEA) in both serum and pleural effusion of lung cancer patients. Levels of ES, VEGF and CEA in 52 malignant pleural effusion due to lung cancer and 50 patients with non-malignant disease were measured by using sandwich enzyme-linked immunosorbent assay and microparticle enzyme immunoassay. The ES, VEGF and CEA levels in pleural effusion and serum, and their ratio (F/S) were higher in lung cancer group than that in benign group, and the differences were statistically significant (P<0.05). The diagnostic efficiency of ES+VEGF for lung cancer was superior to either single detection. The diagnostic efficiency of ES+VEGF+CEA was superior to either ES+VEGF or ES+CEA. The results suggest that ES, VEGF and CEA might be useful in the differentiation between benign and malignant pleural effusion due to lung cancer. In comparison with either single determination of concentration in serum or pleural fluid, the combined detection of two or three markers is of important clinical significance in the diagnosis of lung cancer. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Positive correlation between postoperative tumor recurrence and changes in circulating tumor cell counts in pulmonary venous blood (pvCTC) during surgical manipulation in non-small cell lung cancer.

PubMed

Hashimoto, Masaki; Tanaka, Fumihiro; Yoneda, Kazue; Takuwa, Teruhisa; Matsumoto, Seiji; Okumura, Yoshitomo; Kondo, Nobuyuki; Tsujimura, Tohru; Nakano, Takashi; Hasegawa, Seiki

2018-01-01

In non-small cell lung cancer (NSCLC), circulating tumor cells (CTC) are shed and circulate to the peripheral blood through the pulmonary vein. Previously, CTC count in pulmonary venous blood (pvCTC) was shown to significantly increase after surgical manipulation. Therefore, we assessed the correlation between the changes in the pvCTC count (ΔpvCTC) and clinical outcomes. Consecutive patients with peripheral-type, NSCLC, who underwent lobectomy or bi-lobectomy through open thoracotomy, were enrolled prospectively. Before and after lobectomy, 2.5 mL of blood was drawn from the associated lobar pulmonary vein (PV), and was served for the quantitative evaluation of CTC using the CellSearch ® system. The cut-off point of ΔpvCTC was determined according to clinical outcomes and ΔpvCTC using receiver operation characteristic (ROC) curve. Then the correlation between ΔpvCTC and clinical outcomes was evaluated by Kaplan-Meier analyses and log-rank test. In addition, the correlation between ΔpvCTC and perioperative variables was assessed. A total of 30 patients were enrolled, tumor recurrence occurred in 11 patients over a median follow-up of 64.4 months. Of these, 7 patients had distant metastasis and 4 had local recurrence. The median ΔpvCTC was 49 cells/2.5 mL, and pvCTC-count was increased during surgical manipulation in 24 patients (80%). We divided patients into two groups based on ΔpvCTC with the cut-off value as 119 cells/2.5 mL according to ROC curve. Significant shorter time to distant metastasis (TDM) (P=0.0123) was observed in high ΔpvCTC group (ΔpvCTC ≥119 cells/2.5 mL) than low ΔpvCTC group (ΔpvCTC <119 cells/ 2.5mL). Neither disease-free survival (DFS) nor overall survival (OS) was significantly correlated with ΔpvCTC. Increasing pvCTC count during surgical manipulation was significantly correlated with postoperative distant metastasis in completely resected NSCLC patients. Significant shorter TDM was observed in patient with high ΔpvCTC group.

Feasibility of using single photon counting X-ray for lung tumor position estimation based on 4D-CT.

PubMed

Aschenbrenner, Katharina P; Guthier, Christian V; Lyatskaya, Yulia; Boda-Heggemann, Judit; Wenz, Frederik; Hesser, Jürgen W

2017-09-01

In stereotactic body radiation therapy of lung tumors, reliable position estimation of the tumor is necessary in order to minimize normal tissue complication rate. While kV X-ray imaging is frequently used, continuous application during radiotherapy sessions is often not possible due to concerns about the additional dose. Thus, ultra low-dose (ULD) kV X-ray imaging based on a single photon counting detector is suggested. This paper addresses the lower limit of photons to locate the tumor reliably with an accuracy in the range of state-of-the-art methods, i.e. a few millimeters. 18 patient cases with four dimensional CT (4D-CT), which serves as a-priori information, are included in the study. ULD cone beam projections are simulated from the 4D-CTs including Poisson noise. The projections from the breathing phases which correspond to different tumor positions are compared to the ULD projection by means of Poisson log-likelihood (PML) and correlation coefficient (CC), and template matching under these metrics. The results indicate that in full thorax imaging five photons per pixel suffice for a standard deviation in tumor positions of less than half a breathing phase. Around 50 photons per pixel are needed to achieve this accuracy with the field of view restricted to the tumor region. Compared to CC, PML tends to perform better for low photon counts and shifts in patient setup. Template matching only improves the position estimation in high photon counts. The quality of the reconstruction is independent of the projection angle. The accuracy of the proposed ULD single photon counting system is in the range of a few millimeters and therefore comparable to state-of-the-art tumor tracking methods. At the same time, a reduction in photons per pixel by three to four orders of magnitude relative to commercial systems with flatpanel detectors can be achieved. This enables continuous kV image-based position estimation during all fractions since the additional dose to the patient is negligible. Copyright © 2017. Published by Elsevier GmbH.

Protective effects of aerobic exercise on acute lung injury induced by LPS in mice

PubMed Central

2012-01-01

Introduction The regular practice of physical exercise has been associated with beneficial effects on various pulmonary conditions. We investigated the mechanisms involved in the protective effect of exercise in a model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Methods Mice were divided into four groups: Control (CTR), Exercise (Exe), LPS, and Exercise + LPS (Exe + LPS). Exercised mice were trained using low intensity daily exercise for five weeks. LPS and Exe + LPS mice received 200 µg of LPS intratracheally 48 hours after the last physical test. We measured exhaled nitric oxide (eNO); respiratory mechanics; neutrophil density in lung tissue; protein leakage; bronchoalveolar lavage fluid (BALF) cell counts; cytokine levels in BALF, plasma and lung tissue; antioxidant activity in lung tissue; and tissue expression of glucocorticoid receptors (Gre). Results LPS instillation resulted in increased eNO, neutrophils in BALF and tissue, pulmonary resistance and elastance, protein leakage, TNF-alpha in lung tissue, plasma levels of IL-6 and IL-10, and IL-1beta, IL-6 and KC levels in BALF compared to CTR (P ≤0.02). Aerobic exercise resulted in decreases in eNO levels, neutrophil density and TNF-alpha expression in lung tissue, pulmonary resistance and elastance, and increased the levels of IL-6, IL-10, superoxide dismutase (SOD-2) and Gre in lung tissue and IL-1beta in BALF compared to the LPS group (P ≤0.04). Conclusions Aerobic exercise plays important roles in protecting the lungs from the inflammatory effects of LPS-induced ALI. The effects of exercise are mainly mediated by the expression of anti-inflammatory cytokines and antioxidants, suggesting that exercise can modulate the inflammatory-anti-inflammatory and the oxidative-antioxidative balance in the early phase of ALI. PMID:23078757

The pattern of early lung parenchymal and air space injury following acute blood loss.

PubMed

Younger, J G; Taqi, A S; Jost, P F; Till, G O; Johnson, K J; Stern, S A; Hirschl, R B

1998-07-01

Acute lung injury is a frequent clinical occurrence following blood loss and trauma. The nature of this injury remains poorly understood. To examine the relative parenchymal and intra-alveolar distribution of inflammation in a rat model of hemorrhage and resuscitation. Rats were anesthetized and subjected to hemorrhage followed by resuscitation with shed blood and saline. Myeloperoxidase activity of lung homogenates and cytology of bronchoalveolar lavage fluid were used to measure total lung and intra-alveolar neutrophil invasion. Extravasation of i.v.-administered [125I]-albumin was used to determine total lung and alveolar permeability. Permeability results were analyzed using their base-10 logarithmic transformations. 86 animals were studied. Whole-lung myeloperoxidase activity was increased (control = 0.34 +/- 0.16 units, injured = 0.84 +/- 0.43 units, p < 0.01), while there was no difference in intra-alveolar leukocyte counts (injured = 1.85 +/- 1.30 x 10(5)/mL, control = 2.44 +/- 1.75 x 10(5)/mL, p = 0.40), suggesting that the cellular component of the injury was more severe in the intravascular and interstitial spaces. There was a strong trend toward increased permeability in the interstitial compartment, and a significant increase in permeability in the intra-alveolar compartment (whole-lung permeability: control = -0.27 +/- 0.19 units, injured = 0.10 +/- 0.55 units, p = 0.06; alveolar permeability: control = -2.00 +/- 0.47 units, injured = -1.32 +/- 0.49 units, p < 0.01), suggesting that the loss of integrity to macromolecules was not limited to the interstitium. Hemorrhage and resuscitation resulted in an acute lung injury characterized by extravasation of intravascular protein into both the interstitium and the intra-alveolar space. Neutrophil invasion of the lung was demonstrable only in the interstitial compartment.

B cells in chronic obstructive pulmonary disease: moving to center stage

PubMed Central

Polverino, Francesca; Seys, Leen J. M.; Bracke, Ken R.

2016-01-01

Chronic inflammatory responses in the lungs contribute to the development and progression of chronic obstructive pulmonary disease (COPD). Although research studies focused initially on the contributions of the innate immune system to the pathogenesis of COPD, more recent studies have implicated adaptive immune responses in COPD. In particular, studies have demonstrated increases in B cell counts and increases in the number and size of B cell-rich lymphoid follicles in COPD lungs that correlate directly with COPD severity. There are also increases in lung levels of mediators that promote B cell maturation, activation, and survival in COPD patients. B cell products such as autoantibodies directed against lung cells, components of cells, and extracellular matrix proteins are also present in COPD lungs. These autoantibodies may contribute to lung inflammation and injury in COPD patients, in part, by forming immune complexes that activate complement components. Studies of B cell-deficient mice and human COPD patients have linked B cells most strongly to the emphysema phenotype. However, B cells have protective activities during acute exacerbations of COPD by promoting adaptive immune responses that contribute to host defense against pathogens. This review outlines the evidence that links B cells and B cell-rich lymphoid follicles to the pathogenesis of COPD and the mechanisms involved. It also reviews the potential and limitations of B cells as therapeutic targets to slow the progression of human COPD. PMID:27542809

Transumbilical Thoracoscopy Versus Conventional Thoracoscopy for Lung Wedge Resection: Safety and Efficacy in a Live Canine Model.

PubMed

Chen, Tzu-Ping; Yen-Chu; Wu, Yi-Cheng; Yeh, Chi-Ju; Liu, Chien-Ying; Hsieh, Ming-Ju; Yuan, Hsu-Chia; Ko, Po-Jen; Liu, Yun-Hen

2015-12-01

Transumbilical single-port surgery has been associated with less postoperative pain and offers better cosmetic outcomes than conventional 3-port laparoscopic surgery. This study compares the safety and efficacy of transumbilical thoracoscopy and conventional thoracoscopy for lung wedge resection. The animals (n = 16) were randomly assigned to the transumbilical thoracoscopic approach group (n = 8) or conventional thoracoscopic approach group (n = 8). Transumbilical lung resection was performed via an umbilical incision and a diaphragmatic incision. In the conventional thoracoscopic group, lung resection was completed through a thoracic incision. For both procedures, we compared the surgical outcomes, for example, operating time and operative complications; physiologic parameters, for example, respiratory rate and body temperature; inflammatory parameters, for example, white blood cell count; and pulmonary parameters, for example, arterial blood gas levels. The animals were euthanized 2 weeks after the surgery for gross and histologic evaluations. The lung wedge resection was successfully performed in all animals. There was no significant difference in the mean operating times or complications between the transumbilical and the conventional thoracoscopic approach groups. With regard to the physiologic impact of the surgeries, the transumbilical approach was associated with significant elevations in body temperature on postoperative day 1, when compared with the standard thoracoscopic approach. This study suggests that both approaches for performing lung wedge resection were comparable in efficacy and postoperative complications. © The Author(s) 2014.

Severe Acute Respiratory Syndrome Coronaviruses with Mutations in the E Protein Are Attenuated and Promising Vaccine Candidates

PubMed Central

Regla-Nava, Jose A.; Nieto-Torres, Jose L.; Jimenez-Guardeño, Jose M.; Fernandez-Delgado, Raul; Fett, Craig; Castaño-Rodríguez, Carlos; Perlman, Stanley; DeDiego, Marta L.

2015-01-01

ABSTRACT Severe acute respiratory syndrome coronavirus (SARS-CoV) causes a respiratory disease with a mortality rate of 10%. A mouse-adapted SARS-CoV (SARS-CoV-MA15) lacking the envelope (E) protein (rSARS-CoV-MA15-ΔE) is attenuated in vivo. To identify E protein regions and host responses that contribute to rSARS-CoV-MA15-ΔE attenuation, several mutants (rSARS-CoV-MA15-E*) containing point mutations or deletions in the amino-terminal or the carboxy-terminal regions of the E protein were generated. Amino acid substitutions in the amino terminus, or deletion of regions in the internal carboxy-terminal region of E protein, led to virus attenuation. Attenuated viruses induced minimal lung injury, diminished limited neutrophil influx, and increased CD4+ and CD8+ T cell counts in the lungs of BALB/c mice, compared to mice infected with the wild-type virus. To analyze the host responses leading to rSARS-CoV-MA15-E* attenuation, differences in gene expression elicited by the native and mutant viruses in the lungs of infected mice were determined. Expression levels of a large number of proinflammatory cytokines associated with lung injury were reduced in the lungs of rSARS-CoV-MA15-E*-infected mice, whereas the levels of anti-inflammatory cytokines were increased, both at the mRNA and protein levels. These results suggested that the reduction in lung inflammation together with a more robust antiviral T cell response contributed to rSARS-CoV-MA15-E* attenuation. The attenuated viruses completely protected mice against challenge with the lethal parental virus, indicating that these viruses are promising vaccine candidates. IMPORTANCE Human coronaviruses are important zoonotic pathogens. SARS-CoV caused a worldwide epidemic infecting more than 8,000 people with a mortality of around 10%. Therefore, understanding the virulence mechanisms of this pathogen and developing efficacious vaccines are of high importance to prevent epidemics from this and other human coronaviruses. Previously, we demonstrated that a SARS-CoV lacking the E protein was attenuated in vivo. Here, we show that small deletions and modifications within the E protein led to virus attenuation, manifested by minimal lung injury, limited neutrophil influx to the lungs, reduced expression of proinflammatory cytokines, increased anti-inflammatory cytokine levels, and enhanced CD4+ and CD8+ T cell counts in vivo, suggesting that these phenomena contribute to virus attenuation. The attenuated mutants fully protected mice from challenge with virulent virus. These studies show that mutations in the E protein are not well tolerated and indicate that this protein is an excellent target for vaccine development. PMID:25609816

Conditional analysis of mixed Poisson processes with baseline counts: implications for trial design and analysis.

PubMed

Cook, Richard J; Wei, Wei

2003-07-01

The design of clinical trials is typically based on marginal comparisons of a primary response under two or more treatments. The considerable gains in efficiency afforded by models conditional on one or more baseline responses has been extensively studied for Gaussian models. The purpose of this article is to present methods for the design and analysis of clinical trials in which the response is a count or a point process, and a corresponding baseline count is available prior to randomization. The methods are based on a conditional negative binomial model for the response given the baseline count and can be used to examine the effect of introducing selection criteria on power and sample size requirements. We show that designs based on this approach are more efficient than those proposed by McMahon et al. (1994).

Direct measurement of carbon-14 in carbon dioxide by liquid scintillation counting

NASA Technical Reports Server (NTRS)

Horrocks, D. L.

1969-01-01

Liquid scintillation counting technique is applied to the direct measurement of carbon-14 in carbon dioxide. This method has high counting efficiency and eliminates many of the basic problems encountered with previous techniques. The technique can be used to achieve a percent substitution reaction and is of interest as an analytical technique.

Nonlinear histogram binning for quantitative analysis of lung tissue fibrosis in high-resolution CT data

NASA Astrophysics Data System (ADS)

Zavaletta, Vanessa A.; Bartholmai, Brian J.; Robb, Richard A.

2007-03-01

Diffuse lung diseases, such as idiopathic pulmonary fibrosis (IPF), can be characterized and quantified by analysis of volumetric high resolution CT scans of the lungs. These data sets typically have dimensions of 512 x 512 x 400. It is too subjective and labor intensive for a radiologist to analyze each slice and quantify regional abnormalities manually. Thus, computer aided techniques are necessary, particularly texture analysis techniques which classify various lung tissue types. Second and higher order statistics which relate the spatial variation of the intensity values are good discriminatory features for various textures. The intensity values in lung CT scans range between [-1024, 1024]. Calculation of second order statistics on this range is too computationally intensive so the data is typically binned between 16 or 32 gray levels. There are more effective ways of binning the gray level range to improve classification. An optimal and very efficient way to nonlinearly bin the histogram is to use a dynamic programming algorithm. The objective of this paper is to show that nonlinear binning using dynamic programming is computationally efficient and improves the discriminatory power of the second and higher order statistics for more accurate quantification of diffuse lung disease.

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.

Inhaled gene therapy in lung cancer: proof-of-concept for nano-oncology and nanobiotechnology in the management of lung cancer.

PubMed

Zarogoulidis, Paul; Darwiche, Kaid; Hohenforst-Schmidt, Wolfgang; Huang, Haidong; Li, Qiang; Freitag, Lutz; Zarogoulidis, Konstantinos

2013-08-01

Lung cancer still remains one of the leading causes of death among cancer patients. Although novel targeted therapies have been established in everyday treatment practice, and conventional platinum-based doublets have demonstrated effective results regarding overall and progression-free survival, we have still failed to achieve long-term survival. Therefore, several strategies of applying locoregional therapy are under investigation. Aerosol chemotherapy is already under investigation and, taking this a step further, aerosol gene therapies with multiple delivery systems are being developed. Several efforts have demonstrated its efficiency and effectiveness, but there are still multiple factors that have to be considered and combined to achieve an overall more effective multifunctional treatment. In the current review, we present data regarding aerosol delivery systems, transporters, carriers, vectors, genes, toxicity, efficiency, specificity, lung microenvironment and delivery gene therapy systems. Finally, we present current studies and future perspectives.

Prevalence of respiratory symptoms and disorders among rice mill workers in India.

PubMed

Ghosh, Tirthankar; Gangopadhyay, Somnath; Das, Banibrata

2014-05-01

Lung function tests have become an integral part of assessment of pulmonary disease. Diseases of the respiratory system induced by occupational dusts are influenced by the duration of exposure. The aim of the study is to investigate the impairment of lung function and prevalence of respiratory symptoms among the rice mill workers. A total of 120 rice mill workers from three districts of Karnataka were included in this study. Fifty urban dwellers from the same socio-economic level were selected as controls. The study included clinical examination, assessment of respiratory symptoms, pulmonary function test, measurement of peak expiratory flow rate, absolute eosinophil count, ESR estimation, total IgE estimation and radiographic test. The present study has shown that the rice mill workers complained of several types of respiratory disorders like phlegm (40.8 %), dyspnea (44.2 %), chest tightness (26.7 %), cough (21.7 %), and nose irritation (27.5 %). Rice mill workers exposed to dust presented significantly (p < 0.05) lower levels of FVC (3.44 ± 0.11), FEV1 (2.73 ± 0.15) and PEFR (304.95 ± 28.79) than the controls. The rice mill workers are having significantly higher absolute eosinophil counts, total IgE and ESR than control groups. The hematological findings suggest that the harmful effects may be linked to both non-specific irritation and allergic responses to rice husk dust among rice mill workers. Dust exposure in the working environment affects the lung function values and increased the respiratory symptoms among the rice mill workers.

Cell Death, Inflammation, Tumor Burden, and Proliferation Blood Biomarkers Predict Lung Cancer Radiotherapy Response and Correlate With Tumor Volume and Proliferation Imaging.

PubMed

Salem, Ahmed; Mistry, Hitesh; Backen, Alison; Hodgson, Clare; Koh, Pek; Dean, Emma; Priest, Lynsey; Haslett, Kate; Trigonis, Ioannis; Jackson, Alan; Asselin, Marie-Claude; Dive, Caroline; Renehan, Andrew; Faivre-Finn, Corinne; Blackhall, Fiona

2018-05-01

There is an unmet need to develop noninvasive biomarkers to stratify patients in drug-radiotherapy trials. In this pilot study we investigated lung cancer radiotherapy response and toxicity blood biomarkers and correlated findings with tumor volume and proliferation imaging. Blood samples were collected before and during (day 21) radiotherapy. Twenty-six cell-death, hypoxia, angiogenesis, inflammation, proliferation, invasion, and tumor-burden biomarkers were evaluated. Clinical and laboratory data were collected. Univariate analysis was performed on small-cell and non-small-cell lung cancer (NSCLC) whereas multivariate analysis focused on NSCLC. Blood samples from 78 patients were analyzed. Sixty-one (78.2%) harbored NSCLC, 48 (61.5%) received sequential chemoradiotherapy. Of tested baseline biomarkers, undetectable interleukin (IL)-1b (hazard ratio [HR], 4.02; 95% confidence interval [CI], 2.04-7.93; P < .001) was the only significant survival covariate. Of routinely collected laboratory tests, high baseline neutrophil count was a significant survival covariate (HR, 1.07; 95% CI, 1.02-1.11; P = .017). Baseline IL-1b and neutrophil count were prognostic for survival in a multivariate model. The addition of day-21 cytokeratin-19 antigen modestly improved this model's survival prediction (concordance probability, 0.75-0.78). Chemotherapy (P < .001) and baseline keratinocyte growth factor (P = .019) predicted acute esophagitis, but only chemotherapy remained significant after Bonferroni correction. Baseline angioprotein-1 and hepatocyte growth factor showed a direct correlation with tumor volume whereas changes in vascular cell adhesion molecule 1 showed significant correlations with 18F-fluorothymidine (FLT) positron emission tomography (PET). Select biomarkers are prognostic after radiotherapy in this lung cancer series. The correlation between circulating biomarkers and 18F-FLT PET is shown, to our knowledge for the first time, highlighting their potential role as imaging surrogates. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Pulmonary neutrophil recruitment and bronchial reactivity in formaldehyde-exposed rats are modulated by mast cells and differentially by neuropeptides and nitric oxide

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

Lino dos Santos Franco, Adriana; Damazo, Amilcar Sabino; Post-Graduation in Morphology, UNIFESP, EPM, Sao Paulo

2006-07-01

We have used a pharmacological approach to study the mechanisms underlying the rat lung injury and the airway reactivity changes induced by inhalation of formaldehyde (FA) (1% formalin solution, 90 min once a day, 4 days). The reactivity of isolated tracheae and intrapulmonary bronchi were assessed in dose-response curves to methacholine (MCh). Local and systemic inflammatory phenomena were evaluated in terms of leukocyte countings in bronchoalveolar lavage (BAL) fluid, blood, bone marrow lavage and spleen. Whereas the tracheal reactivity to MCh did not change, a significant bronchial hyporesponsiveness (BHR) was found after FA inhalation as compared with naive rats. Also,more » FA exposure significantly increased the total cell numbers in BAL, in peripheral blood and in the spleen, but did not modify the counts in bone marrow. Capsaicin hindered the increase of leukocyte number recovered in BAL fluid after FA exposure. Both compound 48/80 and indomethacin were able to prevent the lung neutrophil influx after FA, but indomethacin had no effect on that of mononuclear cells. Following FA inhalation, the treatment with sodium cromoglycate (SCG), but not with the nitric oxide (NO) synthase inhibitor L-NAME, significantly reduced the total cell number in BAL. Compound 48/80, L-NAME and SCG significantly prevented BHR to MCh after FA inhalation, whereas capsaicin was inactive in this regard. On the other hand, indomethacin exacerbated BHR. These data suggest that after FA inhalation, the resulting lung leukocyte influx and BHR may involve nitric oxide, airway sensory fibers and mast cell-derived mediators. The effect of NO seemed to be largely restricted to the bronchial tonus, whereas neuropeptides appeared to be linked to the inflammatory response, therefore indicating that the mechanisms responsible for the changes of airway responsiveness caused by FA may be separate from those underlying its inflammatory lung effects.« less

Methotrexate-induced Hypersensitivity Pneumonitis appearing after 30 years of use: a case report.

PubMed

Salehi, Mashal; Miller, Robertha; Khaing, Myint

2017-06-28

Methotrexate has been implicated in a variety of lung complications, one of which is hypersensitivity pneumonitis. Hypersensitivity pneumonitis most often occurs within the first year of starting low-dose orally administered methotrexate. We present a case of methotrexate-induced hypersensitivity pneumonitis after 30 years of methotrexate use, which is the first case to be reported so far. A 77-year-old African American woman with a history of rheumatoid arthritis presented with progressively worsening shortness of breath and nonproductive cough. She was on a daily dose of 2.5 mg of methotrexate that had been orally administered for the last 30 years. A physical examination was significant for fever of 38.2 °C (100.8 °F), tachycardia, bilateral basal crackles, and oxygen saturation of 88% on room air. A laboratory work up was significant for normal white blood cell count, increased eosinophil count of 18.3%, and erythrocyte sedimentation rate of 111 mm/hour. Sputum cultures were negative for any bacterial pathogens including acid-fast bacilli. Influenza and respiratory syncytial viral infection were ruled out. A (1-3)-B-D-glucan assay (Fungitell®) was within normal limits. Pulmonary embolism was ruled out and echocardiography was normal. A chest X-ray showed hazy opacity with prominent reticulation within the upper lung fields bilaterally, right greater than the left with no pleural effusion. Lung computed tomography revealed nonspecific bilateral upper lung opacification. A pulmonary function test was significant for no obstruction, normal maximum voluntary ventilation, and no restriction, with mildly decreased diffusion. Methotrexate was stopped, and our patient was started on prednisone 60 mg orally administered daily with dramatic clinical and radiologic improvement. Methotrexate-induced hypersensitivity pneumonitis usually occurs in the initial few weeks to months of starting treatment with methotrexate; however, it can occur late during therapy too, and prompt diagnosis is crucial as it is a reversible condition when diagnosed early.

Improvements in lung lavage to increase its effectiveness in removing inhaled radionuclides

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

Muggenburg, B.A.; Guilmette, R.A.; Romero, L.M.

Lung lavage has been shown to be an effective method to remove insoluble radionuclides deposited and retained in the lung, but the treatment has been limited to the effective removal of only about 50% of the retained material. Reported here is change in lavage technique that slightly increases the effectiveness and the addition of high-frequency chest wall oscillation. The latter increased the effectiveness of the lavage procedure but also caused significant physiological complications. These studies were conducted in adult male and female beagles. The aerosol in the first study was {sup 239}PuO{sub 2} heat-treated at 850{degrees}C, obtained as powder frommore » a commercial V-blending process. The dogs briefly inhaled the aerosol per nasi. The tissue content at death and the amount of {sup 239}Pu excreted and in the recovered lung lavage fluid was determined by radiochemical methods{sup 5}. These values were used to reconstruct the initial pulmonary burden of {sup 239} and the amount of {sup 239}Pu removed by lavage. In the second study, with the HFCWO, the aerosol was {sup 85}Sr fused in aluminosilicate particles. The IPB of {sup 85}Sr was determined by whole-body counting. The excreta and recovered lung lavage fluids were also assayed for {sup 85}Sr activity.« less

Can body composition be used to optimize the dose of platinum chemotherapy in lung cancer? A feasibility study.

PubMed

Crosby, Vincent; D'Souza, Catherine; Bristow, Carina; Proffitt, Amy; Hussain, Asmah; Potter, Vanessa; Hennig, Ivo; O'Connor, Richard; Baracos, Vickie; Wilcock, Andrew

2017-04-01

Current methods of dosing platinum-based chemotherapy are suboptimal. Potentially, taking lean body mass into account may help. To inform the design of a future study, we first examined the feasibility and acceptability of such an approach using dual-energy X-ray absorptiometry (DEXA) and explored aspects suggestive of over- and under-dosing. Patients with lung cancer offered platinum-based chemotherapy over 1 year were identified and, if eligible, invited to take part in a prospective feasibility study. Questionnaires examined acceptability of the DEXA scan and of a future study that randomized between traditional dosing and one adjusted according to body composition. Dose-limiting toxicity (DLT) and a lack of neutropenia explored potential over- and under-dosing, respectively. Of the 173 patients offered chemotherapy, 123 (71%) were ineligible, mostly because of failing entry criteria (84, 49%). Of the 50 approached, 18 (36%) participated, most receiving carboplatin, with 17 providing data. All found a DEXA scan acceptable; other assessments were fully completed, except nadir and pre-chemotherapy blood counts. Most (94%) were prepared to take part in a future study, although the additional hospital visits for a nadir blood count were unpopular with some. Five (29%) patients experienced six episodes of DLT which resulted in discontinuation (3), dose reduction (2) or change to a less toxic regimen (1). Nine (60%) patients experienced either no (2) or inconsistent (7) neutropenia. A randomized trial appears acceptable and feasible in patients receiving carboplatin. Adjustment of our entry criteria and avoiding a hospital visit for a nadir blood count should aid recruitment.

Generation of a novel phase-space-based cylindrical dose kernel for IMRT optimization.

PubMed

Zhong, Hualiang; Chetty, Indrin J

2012-05-01

Improving dose calculation accuracy is crucial in intensity-modulated radiation therapy (IMRT). We have developed a method for generating a phase-space-based dose kernel for IMRT planning of lung cancer patients. Particle transport in the linear accelerator treatment head of a 21EX, 6 MV photon beam (Varian Medical Systems, Palo Alto, CA) was simulated using the EGSnrc/BEAMnrc code system. The phase space information was recorded under the secondary jaws. Each particle in the phase space file was associated with a beamlet whose index was calculated and saved in the particle's LATCH variable. The DOSXYZnrc code was modified to accumulate the energy deposited by each particle based on its beamlet index. Furthermore, the central axis of each beamlet was calculated from the orientation of all the particles in this beamlet. A cylinder was then defined around the central axis so that only the energy deposited within the cylinder was counted. A look-up table was established for each cylinder during the tallying process. The efficiency and accuracy of the cylindrical beamlet energy deposition approach was evaluated using a treatment plan developed on a simulated lung phantom. Profile and percentage depth doses computed in a water phantom for an open, square field size were within 1.5% of measurements. Dose optimized with the cylindrical dose kernel was found to be within 0.6% of that computed with the nontruncated 3D kernel. The cylindrical truncation reduced optimization time by approximately 80%. A method for generating a phase-space-based dose kernel, using a truncated cylinder for scoring dose, in beamlet-based optimization of lung treatment planning was developed and found to be in good agreement with the standard, nontruncated scoring approach. Compared to previous techniques, our method significantly reduces computational time and memory requirements, which may be useful for Monte-Carlo-based 4D IMRT or IMAT treatment planning.

Chest Low-Dose Computed Tomography for Early Lung Cancer Diagnosis as an Opportunity to Diagnose Vertebral Fractures in HIV-Infected Smokers, an ANRS EP48 HIV CHEST Substudy.

PubMed

Thouvenin, Yann; Makinson, Alain; Cournil, Amandine; Eymard-Duvernay, Sabrina; Lentz, Pierre; Delemazure, Anne-Sophie; Corneloup, Olivier; Fabre, Sylvie; Quesnoy, Mylène; Poire, Sylvain; Brillet, Pierre-Yves; Cyteval, Catherine; Reynes, Jacques; Le Moing, Vincent

2015-07-01

To estimate the prevalence of vertebral fractures on chest low-dose computed tomography (LDCT) in HIV-infected smokers. Cross-sectional study of vertebral fractures visualized on chest LDCT from a multicenter prospective cohort evaluating feasibility of chest LDCT for early lung cancer diagnosis in HIV-infected subjects. Subjects were included if 40 years or older, had been active smokers within the last 3 years of at least 20 pack-years, and had a CD4 T-lymphocyte nadir cell count <350 per microliter and an actual CD4 T-cell count >100 cells per microliter. Spinal reconstructed sagittal planes obtained from chest axial native acquisitions were blindly read by a musculoskeletal imaging specialist. Assessment of the fractured vertebra used Genant semiquantitative method. The study end point was the prevalence of at least 1 vertebral fracture. Three hundred ninety-seven subjects were included. Median age was 49.5 years, median smoking history was 30 pack-years, median last CD4 count was 584 cells per microliter, and median CD4 nadir count was 168 cells per microliter; 90% of subjects had a viral load below 50 copies per milliliter. At least 1 fracture was visible in 46 (11.6%) subjects. In multivariate analysis, smoking ≥40 packs-years [OR = 2.5; 95% CI: (1.2 to 5.0)] was associated with an increased risk of vertebral fracture, while HIV viral load <200 copies per milliliter [OR = 0.3; 95% CI: (0.1 to 0.9)] was protective. Prevalence of vertebral fractures on chest LDCT was 11.6% in this high-risk population. Smoking cessation and early introduction of antiretroviral therapy for prevention of vertebral fractures could be beneficial. Chest LDCT is an opportunity to diagnose vertebral fractures.

SCOTCH: Secure Counting Of encrypTed genomiC data using a Hybrid approach.

PubMed

Chenghong, Wang; Jiang, Yichen; Mohammed, Noman; Chen, Feng; Jiang, Xiaoqian; Al Aziz, Md Momin; Sadat, Md Nazmus; Wang, Shuang

2017-01-01

As genomic data are usually at large scale and highly sensitive, it is essential to enable both efficient and secure analysis, by which the data owner can securely delegate both computation and storage on untrusted public cloud. Counting query of genotypes is a basic function for many downstream applications in biomedical research (e.g., computing allele frequency, calculating chi-squared statistics, etc.). Previous solutions show promise on secure counting of outsourced data but the efficiency is still a big limitation for real world applications. In this paper, we propose a novel hybrid solution to combine a rigorous theoretical model (homomorphic encryption) and the latest hardware-based infrastructure (i.e., Software Guard Extensions) to speed up the computation while preserving the privacy of both data owners and data users. Our results demonstrated efficiency by using the real data from the personal genome project.

SCOTCH: Secure Counting Of encrypTed genomiC data using a Hybrid approach

PubMed Central

Chenghong, Wang; Jiang, Yichen; Mohammed, Noman; Chen, Feng; Jiang, Xiaoqian; Al Aziz, Md Momin; Sadat, Md Nazmus; Wang, Shuang

2017-01-01

As genomic data are usually at large scale and highly sensitive, it is essential to enable both efficient and secure analysis, by which the data owner can securely delegate both computation and storage on untrusted public cloud. Counting query of genotypes is a basic function for many downstream applications in biomedical research (e.g., computing allele frequency, calculating chi-squared statistics, etc.). Previous solutions show promise on secure counting of outsourced data but the efficiency is still a big limitation for real world applications. In this paper, we propose a novel hybrid solution to combine a rigorous theoretical model (homomorphic encryption) and the latest hardware-based infrastructure (i.e., Software Guard Extensions) to speed up the computation while preserving the privacy of both data owners and data users. Our results demonstrated efficiency by using the real data from the personal genome project. PMID:29854245

Electroporation-mediated Delivery of Genes in Rodent Models of Lung Contusion

PubMed Central

Machado-Aranda, David; Raghavendran, Krishnan

2015-01-01

Several of the biological processes involved in the pathogenesis of acute lung injury and acute respiratory distress syndrome after lung contusion are regulated at a genetic and epigenetic level. Thus, strategies to manipulate gene expression in this context are highly desirable not only to elucidate the mechanisms involved but also to look for potential therapies. In the present chapter, we describe mouse and rat models of inducing blunt thoracic injury followed by electroporation-mediated gene delivery to the lung. Electroporation is a highly efficient and easily reproducible technique that allows circumvention of several of lung gene delivery challenges and safety issues present with other forms of lung gene therapy. PMID:24510825

A new approach for measuring the work and quality of histopathology reporting.

PubMed

Sharma, Vijay; Davey, Jonathan G N; Humphreys, Catherine; Johnston, Peter W

2013-07-01

Cancer datasets drive report quality, but require more work to inform compliant reports. The aim of this study was to correlate the number of words with measures of quality, to examine the impact of the drive for improved quality on the workload of histopathology reporting over time. We examined the first 10 reports of colon, breast, renal, lung and ovarian carcinoma, melanoma resection, nodal lymphoma appendicitis and seborrhoeic keratosis (SK) issued in 1991, 2001 and 2011. Correlations were analysed using Pearson's partial correlation coefficients. Word count increased significantly over time for most specimen types examined. Word count almost always correlated with units of information, indicating that the word count was a good measure of the amount of information contained within the reports; this correlation was preserved following correction for the effect of time. A good correlation with compliance with cancer datasets was also observed, but was weakened or lost following correction for the increase in word count and units of information that occurred between time points. These data indicate that word count could potentially be used as a measure of information content if its integrity and usefulness are continuously validated. Further prospective studies are required to assess and validate this approach. © 2013 John Wiley & Sons Ltd.

Efficient Genotyping of KRAS Mutant Non-Small Cell Lung Cancer Using a Multiplexed Droplet Digital PCR Approach.

PubMed

Pender, Alexandra; Garcia-Murillas, Isaac; Rana, Sareena; Cutts, Rosalind J; Kelly, Gavin; Fenwick, Kerry; Kozarewa, Iwanka; Gonzalez de Castro, David; Bhosle, Jaishree; O'Brien, Mary; Turner, Nicholas C; Popat, Sanjay; Downward, Julian

2015-01-01

Droplet digital PCR (ddPCR) can be used to detect low frequency mutations in oncogene-driven lung cancer. The range of KRAS point mutations observed in NSCLC necessitates a multiplex approach to efficient mutation detection in circulating DNA. Here we report the design and optimisation of three discriminatory ddPCR multiplex assays investigating nine different KRAS mutations using PrimePCR™ ddPCR™ Mutation Assays and the Bio-Rad QX100 system. Together these mutations account for 95% of the nucleotide changes found in KRAS in human cancer. Multiplex reactions were optimised on genomic DNA extracted from KRAS mutant cell lines and tested on DNA extracted from fixed tumour tissue from a cohort of lung cancer patients without prior knowledge of the specific KRAS genotype. The multiplex ddPCR assays had a limit of detection of better than 1 mutant KRAS molecule in 2,000 wild-type KRAS molecules, which compared favourably with a limit of detection of 1 in 50 for next generation sequencing and 1 in 10 for Sanger sequencing. Multiplex ddPCR assays thus provide a highly efficient methodology to identify KRAS mutations in lung adenocarcinoma.

Efficient Genotyping of KRAS Mutant Non-Small Cell Lung Cancer Using a Multiplexed Droplet Digital PCR Approach

PubMed Central

Pender, Alexandra; Garcia-Murillas, Isaac; Rana, Sareena; Cutts, Rosalind J.; Kelly, Gavin; Fenwick, Kerry; Kozarewa, Iwanka; Gonzalez de Castro, David; Bhosle, Jaishree; O’Brien, Mary; Turner, Nicholas C.; Popat, Sanjay; Downward, Julian

2015-01-01

Droplet digital PCR (ddPCR) can be used to detect low frequency mutations in oncogene-driven lung cancer. The range of KRAS point mutations observed in NSCLC necessitates a multiplex approach to efficient mutation detection in circulating DNA. Here we report the design and optimisation of three discriminatory ddPCR multiplex assays investigating nine different KRAS mutations using PrimePCR™ ddPCR™ Mutation Assays and the Bio-Rad QX100 system. Together these mutations account for 95% of the nucleotide changes found in KRAS in human cancer. Multiplex reactions were optimised on genomic DNA extracted from KRAS mutant cell lines and tested on DNA extracted from fixed tumour tissue from a cohort of lung cancer patients without prior knowledge of the specific KRAS genotype. The multiplex ddPCR assays had a limit of detection of better than 1 mutant KRAS molecule in 2,000 wild-type KRAS molecules, which compared favourably with a limit of detection of 1 in 50 for next generation sequencing and 1 in 10 for Sanger sequencing. Multiplex ddPCR assays thus provide a highly efficient methodology to identify KRAS mutations in lung adenocarcinoma. PMID:26413866

Fixed-Radius Point Counts in Forests: Factors Influencing Effectiveness and Efficiency

Treesearch

Daniel R. Petit; Lisa J. Petit; Victoria A. Saab; Thomas E. Martin

1995-01-01

The effectiveness of fixed-radius point counts in quantifying abundance and richness of bird species in oak-hickory, pine-hardwoods, mixed-mesophytic, beech-maple, and riparian cottonwood forests was evaluated in Arkansas, Ohio, Kentucky, and Idaho. Effects of count duration and numbers of stations and visits per stand were evaluated in May to July 1991 by conducting...

Use of Submicron Vaterite Particles Serves as an Effective Delivery Vehicle to the Respiratory Portion of the Lung

PubMed Central

Gusliakova, Olga; Atochina-Vasserman, Elena N.; Sindeeva, Olga; Sindeev, Sergey; Pinyaev, Sergey; Pyataev, Nikolay; Revin, Viktor; Sukhorukov, Gleb B.; Gorin, Dmitry; Gow, Andrew J.

2018-01-01

Nano- and microencapsulation has proven to be a useful technique for the construction of drug delivery vehicles for use in vascular medicine. However, the possibility of using these techniques within the lung as an inhalation delivery mechanism has not been previously considered. A critical element of particle delivery to the lung is the degree of penetrance that can be achieved with respect to the airway tree. In this study we examined the effectiveness of near infrared (NIR) dye (Cy7) labeled calcium carbonate (vaterite) particles of 3.15, 1.35, and 0.65 μm diameter in reaching the respiratory portion of the lung. First of all, it was shown that, interaction vaterite particles and the components of the pulmonary surfactant occurs a very strong retardation of the recrystallization and dissolution of the particles, which can subsequently be used to create systems with a prolonging release of bioactive substances after the particles penetrate the distal sections of the lungs. Submicro- and microparticles, coated with Cy7 labeled albumin as a model compound, were delivered to mouse lungs via tracheostomy with subsequent imaging performed 24, 48, and 72 h after delivery by in vivo fluorescence. 20 min post administration particles of all three sizes were visible in the lung, with the deepest penetrance observed with 0.65 μm particles. In vivo biodistribution was confirmed by fluorescence tomography imaging of excised organs post 72 h. Laser scanning confocal microscopy shows 0.65 μm particles reaching the alveolar space. The delivery of fluorophore to the blood was assessed using Cy7 labeled 0.65 μm particles. Cy7 labeled 0.65 μm particles efficiently delivered fluorescent material to the blood with a peak 3 h after particle administration. The pharmacokinetics of NIR fluorescence dye will be shown. These studies establish that by using 0.65 μm particles loaded with Cy7 we can efficiently access the respiratory portion of the lung, which represents a potentially efficient delivery mechanism for both the lung and the vasculature.

Use of Submicron Vaterite Particles Serves as an Effective Delivery Vehicle to the Respiratory Portion of the Lung.

PubMed

Gusliakova, Olga; Atochina-Vasserman, Elena N; Sindeeva, Olga; Sindeev, Sergey; Pinyaev, Sergey; Pyataev, Nikolay; Revin, Viktor; Sukhorukov, Gleb B; Gorin, Dmitry; Gow, Andrew J

2018-01-01

Nano- and microencapsulation has proven to be a useful technique for the construction of drug delivery vehicles for use in vascular medicine. However, the possibility of using these techniques within the lung as an inhalation delivery mechanism has not been previously considered. A critical element of particle delivery to the lung is the degree of penetrance that can be achieved with respect to the airway tree. In this study we examined the effectiveness of near infrared (NIR) dye (Cy7) labeled calcium carbonate (vaterite) particles of 3.15, 1.35, and 0.65 μm diameter in reaching the respiratory portion of the lung. First of all, it was shown that, interaction vaterite particles and the components of the pulmonary surfactant occurs a very strong retardation of the recrystallization and dissolution of the particles, which can subsequently be used to create systems with a prolonging release of bioactive substances after the particles penetrate the distal sections of the lungs. Submicro- and microparticles, coated with Cy7 labeled albumin as a model compound, were delivered to mouse lungs via tracheostomy with subsequent imaging performed 24, 48, and 72 h after delivery by in vivo fluorescence. 20 min post administration particles of all three sizes were visible in the lung, with the deepest penetrance observed with 0.65 μm particles. In vivo biodistribution was confirmed by fluorescence tomography imaging of excised organs post 72 h. Laser scanning confocal microscopy shows 0.65 μm particles reaching the alveolar space. The delivery of fluorophore to the blood was assessed using Cy7 labeled 0.65 μm particles. Cy7 labeled 0.65 μm particles efficiently delivered fluorescent material to the blood with a peak 3 h after particle administration. The pharmacokinetics of NIR fluorescence dye will be shown. These studies establish that by using 0.65 μm particles loaded with Cy7 we can efficiently access the respiratory portion of the lung, which represents a potentially efficient delivery mechanism for both the lung and the vasculature.

[Classification and Risk-factor Analysis of Postoperative Cardio-pulmonary 
Complications after Lobectomy in Patients with Stage I Non-small Cell Lung Cancer].

PubMed

Lai, Yutian; Su, Jianhua; Wang, Mingming; Zhou, Kun; Du, Heng; Huang, Jian; Che, Guowei

2016-05-20

There are incresing lung cancer patients detected and diagnosed at the intermediate stage when the pre-malignant or early lesions are amenable to resection and cure, owing to the progress of medical technology, the renewal of detection methods, the popularity of medical screening and the improvement of social health consciousness. The aim of this study is to investigate the risk factors of the occurrence of postoperative cardio-pulmonary complications in stage I non-small cell lung cancer (NSCLC) patients, based on routine laboratory tests, basic characteristics, and intraoperative variables in hospital. The 421 patients after lobectomy in patients with stage I NSCLC at the West China Hospital of Sichuan University from January 2012 to December 2013 were included into the study and stratified into complication group and non-complication group, according to whether to occur postoperative cardio-pulmonary complications after lobectomy in 30 days. Of them, 64 (15.2%) patients were finally identified and selected into the complication group, compared with 357 (84.8%) in non-complication group: pneumonia (8.8%, 37/421) was the primary complication, and other main complications included atelectasis (5.9%, 25/421), pleural effusion (≥middle) (5.0%, 21/421), persistent air leak (3.6%, 15/421); The operation time (P=0.007), amount of blood loss (P=0.034), preoperative chronic obstructive pulmonary disease (COPD) (P=0.027), white blood cell (WBC) count (P<0.001), neutrophil-lymphocyte ratio (NLR) (P<0.001) were significantly different between the two groups. According to the binary logistics regression analysis, preoperative COPD (OR=0.031, 95%CI: 0.012-0.078, P<0.001) and WBC count (OR=1.451, 95%CI: 1.212-1.736, P<0.001) were independent risk factors for postoperative cardio-pulmonary complications. Among an array of clinical variables in hospital, operation time, preoperative white blood cell count, preoperative COPD, may be the independent risk factors of the occurrence of postoperative cardio-pulmonary complications.

An Automatic Detection System of Lung Nodule Based on Multi-Group Patch-Based Deep Learning Network.

PubMed

Jiang, Hongyang; Ma, He; Qian, Wei; Gao, Mengdi; Li, Yan

2017-07-14

High-efficiency lung nodule detection dramatically contributes to the risk assessment of lung cancer. It is a significant and challenging task to quickly locate the exact positions of lung nodules. Extensive work has been done by researchers around this domain for approximately two decades. However, previous computer aided detection (CADe) schemes are mostly intricate and time-consuming since they may require more image processing modules, such as the computed tomography (CT) image transformation, the lung nodule segmentation and the feature extraction, to construct a whole CADe system. It is difficult for those schemes to process and analyze enormous data when the medical images continue to increase. Besides, some state of the art deep learning schemes may be strict in the standard of database. This study proposes an effective lung nodule detection scheme based on multi-group patches cut out from the lung images, which are enhanced by the Frangi filter. Through combining two groups of images, a four-channel convolution neural networks (CNN) model is designed to learn the knowledge of radiologists for detecting nodules of four levels. This CADe scheme can acquire the sensitivity of 80.06% with 4.7 false positives per scan and the sensitivity of 94% with 15.1 false positives per scan. The results demonstrate that the multi-group patch-based learning system is efficient to improve the performance of lung nodule detection and greatly reduce the false positives under a huge amount of image data.

Waveguide integrated low noise NbTiN nanowire single-photon detectors with milli-Hz dark count rate

PubMed Central

Schuck, Carsten; Pernice, Wolfram H. P.; Tang, Hong X.

2013-01-01

Superconducting nanowire single-photon detectors are an ideal match for integrated quantum photonic circuits due to their high detection efficiency for telecom wavelength photons. Quantum optical technology also requires single-photon detection with low dark count rate and high timing accuracy. Here we present very low noise superconducting nanowire single-photon detectors based on NbTiN thin films patterned directly on top of Si3N4 waveguides. We systematically investigate a large variety of detector designs and characterize their detection noise performance. Milli-Hz dark count rates are demonstrated over the entire operating range of the nanowire detectors which also feature low timing jitter. The ultra-low dark count rate, in combination with the high detection efficiency inherent to our travelling wave detector geometry, gives rise to a measured noise equivalent power at the 10−20 W/Hz1/2 level. PMID:23714696

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

Smith, T; Graham, C L; Sundsmo, T

This procedure provides instructions for the calibration and use of the Canberra iSolo Low Background Alpha/Beta Counting System (iSolo) that is used for counting air filters and swipe samples. This detector is capable of providing radioisotope identification (e.g., it can discriminate between radon daughters and plutonium). This procedure includes step-by-step instructions for: (1) Performing periodic or daily 'Background' and 'Efficiency QC' checks; (2) Setting-up the iSolo for counting swipes and air filters; (3) Counting swipes and air filters for alpha and beta activity; and (4) Annual calibration.

Color quench correction for low level Cherenkov counting.

PubMed

Tsroya, S; Pelled, O; German, U; Marco, R; Katorza, E; Alfassi, Z B

2009-05-01

The Cherenkov counting efficiency varies strongly with color quenching, thus correction curves must be used to obtain correct results. The external (152)Eu source of a Quantulus 1220 liquid scintillation counting (LSC) system was used to obtain a quench indicative parameter based on spectra area ratio. A color quench correction curve for aqueous samples containing (90)Sr/(90)Y was prepared. The main advantage of this method over the common spectra indicators is its usefulness also for low level Cherenkov counting.

The development of strategy use in elementary school children: working memory and individual differences.

PubMed

Imbo, Ineke; Vandierendonck, André

2007-04-01

The current study tested the development of working memory involvement in children's arithmetic strategy selection and strategy efficiency. To this end, an experiment in which the dual-task method and the choice/no-choice method were combined was administered to 10- to 12-year-olds. Working memory was needed in retrieval, transformation, and counting strategies, but the ratio between available working memory resources and arithmetic task demands changed across development. More frequent retrieval use, more efficient memory retrieval, and more efficient counting processes reduced the working memory requirements. Strategy efficiency and strategy selection were also modified by individual differences such as processing speed, arithmetic skill, gender, and math anxiety. Short-term memory capacity, in contrast, was not related to children's strategy selection or strategy efficiency.

CPAP of 4 cm H(2)O Has no short-term benefit at term in infants with BPD.

PubMed

Sandberg, Kenneth L; Hjalmarson, Ola

2012-01-01

Lung development and function is compromised at term in infants with bronchopulmonary dysplasia (BPD), characterized by reduced functional residual capacity (FRC) and impaired gas-mixing efficiency in distal airways. To determine whether continuous positive airway pressure (CPAP) improves FRC, ventilation, distal airway function, and gas exchange in spontaneously breathing infants with BPD. Twenty-one infants with BPD (median birth weight 0.72 kg (range 0.50-1.27) and median gestational age 26 weeks (range 23-28)) were studied before and after CPAP of 4 cm H(2)O was applied by a facemask system. A multiple-breath nitrogen washout method was used to assess FRC, ventilation, and gas-mixing efficiency. Moment analysis and lung clearance index was calculated from the nitrogen-decay curve for assessment of gas-mixing efficiency. Transcutaneous (Tc) PO(2)/PCO(2) was monitored during stable infant conditions before each washout test. When CPAP was raised from 0 to 4 cm H(2)O, FRC increased significantly together with a significant increase in moment ratios (M(1)/M(0) and M(2)/M(0)). Tc PO(2) decreased significantly and the breathing pattern changed, with significantly reduced respiratory rate, minute ventilation, and alveolar ventilation. There was also an increase in tidal volume and dead space. CPAP of 4 cm H(2)O applied with a facemask at term to infants with BPD did not improve ventilation, gas-mixing efficiency in distal airways, or oxygenation despite an increase in FRC. We speculate that instead of promoting recruitment of unventilated lung volumes, increasing the end-expiratory pressure in infants with BPD may lead to an overexpansion of already ventilated parts of the lung, causing further compromise of lung function. Copyright © 2012 S. Karger AG, Basel.

Reducing Bottlenecks to Improve the Efficiency of the Lung Cancer Care Delivery Process: A Process Engineering Modeling Approach to Patient-Centered Care.

PubMed

Ju, Feng; Lee, Hyo Kyung; Yu, Xinhua; Faris, Nicholas R; Rugless, Fedoria; Jiang, Shan; Li, Jingshan; Osarogiagbon, Raymond U

2017-12-01

The process of lung cancer care from initial lesion detection to treatment is complex, involving multiple steps, each introducing the potential for substantial delays. Identifying the steps with the greatest delays enables a focused effort to improve the timeliness of care-delivery, without sacrificing quality. We retrospectively reviewed clinical events from initial detection, through histologic diagnosis, radiologic and invasive staging, and medical clearance, to surgery for all patients who had an attempted resection of a suspected lung cancer in a community healthcare system. We used a computer process modeling approach to evaluate delays in care delivery, in order to identify potential 'bottlenecks' in waiting time, the reduction of which could produce greater care efficiency. We also conducted 'what-if' analyses to predict the relative impact of simulated changes in the care delivery process to determine the most efficient pathways to surgery. The waiting time between radiologic lesion detection and diagnostic biopsy, and the waiting time from radiologic staging to surgery were the two most critical bottlenecks impeding efficient care delivery (more than 3 times larger compared to reducing other waiting times). Additionally, instituting surgical consultation prior to cardiac consultation for medical clearance and decreasing the waiting time between CT scans and diagnostic biopsies, were potentially the most impactful measures to reduce care delays before surgery. Rigorous computer simulation modeling, using clinical data, can provide useful information to identify areas for improving the efficiency of care delivery by process engineering, for patients who receive surgery for lung cancer.

Azithromycin analogue CSY0073 attenuates lung inflammation induced by LPS challenge

PubMed Central

Balloy, V; Deveaux, A; Lebeaux, D; Tabary, O; le Rouzic, P; Ghigo, J M; Busson, P F; Boëlle, P Y; Guez, J Guez; Hahn, U; Clement, A; Chignard, M; Corvol, H; Burnet, M; Guillot, L

2014-01-01

Background and Purpose Azithromycin is a macrolide antibiotic with anti-inflammatory and immunomodulating effects. Long-term azithromycin therapy in patients with chronic lung diseases such as cystic fibrosis has been associated with increased antimicrobial resistance, emergence of hypermutable strains, ototoxicity and cardiac toxicity. The aim of this study was to assess the anti-inflammatory effects of the non-antibiotic azithromycin derivative CSY0073. Experimental Approach We compared the effects of CSY0073 with those of azithromycin in experiments on bacterial cultures, Pseudomonas aeruginosa biofilm, lung cells and mice challenged intranasally with P. aeruginosa LPS. Key Results In contrast to azithromycin, CSY0073 did not inhibit the growth of P. aeruginosa, Staphylococcus aureus or Haemophilus influenzae and had no effect on an established P. aeruginosa biofilm. Bronchoalveolar lavage (BAL) fluids and lung homogenates collected after the LPS challenge in mice showed that CSY0073 and azithromycin (200 mg·kg−1, i.p.) decreased neutrophil counts at 24 h and TNF-α, CXCL1 and CXCL2 levels in the BAL fluid after 3 h and IL-6, CXCL2 and IL-1β levels in the lung after 3 h compared with the vehicle. However, only azithromycin reduced IL-1β levels in the lung 24 h post LPS challenge. CSY0073 and azithromycin similarly diminished the production of pro-inflammatory cytokines by macrophages, but not lung epithelial cells, exposed to P. aeruginosa LPS. Conclusions and Implications Unlike azithromycin, CSY0073 had no antibacterial effects but it did have a similar anti-inflammatory profile to that of azithromycin. Hence, CSY0073 may have potential as a long-term treatment for patients with chronic lung diseases. PMID:24417187

Pulmonary inflammation and tumor induction in lung tumor susceptible A/J and resistant C57BL/6J mice exposed to welding fume.

PubMed

Zeidler-Erdely, Patti C; Kashon, Michael L; Battelli, Lori A; Young, Shih-Houng; Erdely, Aaron; Roberts, Jenny R; Reynolds, Steven H; Antonini, James M

2008-09-08

Welding fume has been categorized as "possibly carcinogenic" to humans. Our objectives were to characterize the lung response to carcinogenic and non-carcinogenic metal-containing welding fumes and to determine if these fumes caused increased lung tumorigenicity in A/J mice, a lung tumor susceptible strain. We exposed male A/J and C57BL/6J, a lung tumor resistant strain, by pharyngeal aspiration four times (once every 3 days) to 85 mug of gas metal arc-mild steel (GMA-MS), GMA-stainless steel (SS), or manual metal arc-SS (MMA-SS) fume, or to 25.5 mug soluble hexavalent chromium (S-Cr). Shams were exposed to saline vehicle. Bronchoalveolar lavage (BAL) was done at 2, 7, and 28 days post-exposure. For the lung tumor study, gross tumor counts and histopathological changes were assessed in A/J mice at 48 and 78 weeks post-exposure. BAL revealed notable strain-dependent differences with regards to the degree and resolution of the inflammatory response after exposure to the fumes. At 48 weeks, carcinogenic metal-containing GMA-SS fume caused the greatest increase in tumor multiplicity and incidence, but this was not different from sham. By 78 weeks, tumor incidence in the GMA-SS group versus sham approached significance (p = 0.057). A significant increase in perivascular/peribronchial lymphoid infiltrates for the GMA-SS group versus sham and an increased persistence of this fume in lung cells compared to the other welding fumes was found. The increased persistence of GMA-SS fume in combination with its metal composition may trigger a chronic, but mild, inflammatory state in the lung possibly enhancing tumorigenesis in this susceptible mouse strain.

Pulmonary inflammation and tumor induction in lung tumor susceptible A/J and resistant C57BL/6J mice exposed to welding fume

PubMed Central

Zeidler-Erdely, Patti C; Kashon, Michael L; Battelli, Lori A; Young, Shih-Houng; Erdely, Aaron; Roberts, Jenny R; Reynolds, Steven H; Antonini, James M

2008-01-01

Background Welding fume has been categorized as "possibly carcinogenic" to humans. Our objectives were to characterize the lung response to carcinogenic and non-carcinogenic metal-containing welding fumes and to determine if these fumes caused increased lung tumorigenicity in A/J mice, a lung tumor susceptible strain. We exposed male A/J and C57BL/6J, a lung tumor resistant strain, by pharyngeal aspiration four times (once every 3 days) to 85 μg of gas metal arc-mild steel (GMA-MS), GMA-stainless steel (SS), or manual metal arc-SS (MMA-SS) fume, or to 25.5 μg soluble hexavalent chromium (S-Cr). Shams were exposed to saline vehicle. Bronchoalveolar lavage (BAL) was done at 2, 7, and 28 days post-exposure. For the lung tumor study, gross tumor counts and histopathological changes were assessed in A/J mice at 48 and 78 weeks post-exposure. Results BAL revealed notable strain-dependent differences with regards to the degree and resolution of the inflammatory response after exposure to the fumes. At 48 weeks, carcinogenic metal-containing GMA-SS fume caused the greatest increase in tumor multiplicity and incidence, but this was not different from sham. By 78 weeks, tumor incidence in the GMA-SS group versus sham approached significance (p = 0.057). A significant increase in perivascular/peribronchial lymphoid infiltrates for the GMA-SS group versus sham and an increased persistence of this fume in lung cells compared to the other welding fumes was found. Conclusion The increased persistence of GMA-SS fume in combination with its metal composition may trigger a chronic, but mild, inflammatory state in the lung possibly enhancing tumorigenesis in this susceptible mouse strain. PMID:18778475

Parecoxib reduced ventilation induced lung injury in acute respiratory distress syndrome.

PubMed

Meng, Fan-You; Gao, Wei; Ju, Ying-Nan

2017-03-29

Cyclooxygenase-2 (COX-2) contributes to ventilation induced lung injury (VILI) and acute respiratory distress syndrome (ARDS). The objective of present study was to observe the therapeutic effect of parecoxib on VILI in ARDS. In this parallel controlled study performed at Harbin Medical University, China between January 2016 and March 2016, 24 rats were randomly allocated into sham group (S), volume ventilation group/ARDS (VA), parecoxib/volume ventilation group/ARDS (PVA). Rats in the S group only received anesthesia; rats in the VA and PVA group received intravenous injection of endotoxin to induce ARDS, and then received ventilation. Rats in the VA and PVA groups were treated with intravenous injection of saline or parecoxib. The ratio of arterial oxygen pressure to fractional inspired oxygen (PaO 2 /FiO 2 ), the wet to dry weight ratio of lung tissue, inflammatory factors in serum and bronchoalveolar lavage fluid (BALF), and histopathologic analyses of lung tissue were examined. In addition, survival was calculated at 24 h after VILI. Compared to the VA group, in the PVA group, PaO 2 /FiO 2 was significantly increased; lung tissue wet to dry weight ratio; macrophage and neutrophil counts, total protein and neutrophil elastase levels in BALF; tumor necrosis factor-α, interleukin-1β, and prostaglandin E 2 levels in BALF and serum; and myeloperoxidase (MPO) activity, malondialdehyde levels, and Bax and COX-2 protein levels in lung tissue were significantly decreased, while Bcl-2 protein levels were significantly increased. Lung histopathogical changes and apoptosis were reduced by parecpxib in the PVA group. Survival was increased in the PVA group. Parecoxib improves gas exchange and epithelial permeability, decreases edema, reduces local and systemic inflammation, ameliorates lung injury and apoptosis, and increases survival in a rat model of VILI.

Anti-sFlt-1 Therapy Preserves Lung Alveolar and Vascular Growth in Antenatal Models of Bronchopulmonary Dysplasia.

PubMed

Wallace, Bradley; Peisl, Amelie; Seedorf, Gregory; Nowlin, Taylor; Kim, Christina; Bosco, Jennifer; Kenniston, Jon; Keefe, Dennis; Abman, Steven H

2018-03-15

Pregnancies complicated by antenatal stress, including preeclampsia (PE) and chorioamnionitis (CA), increase the risk for bronchopulmonary dysplasia (BPD) in preterm infants, but biologic mechanisms linking prenatal factors with BPD are uncertain. Levels of sFlt-1 (soluble fms-like tyrosine kinase 1), an endogenous antagonist to VEGF (vascular endothelial growth factor), are increased in amniotic fluid and maternal blood in PE and associated with CA. Because impaired VEGF signaling has been implicated in the pathogenesis of BPD, we hypothesized that fetal exposure to sFlt-1 decreases lung growth and causes abnormal lung structure and pulmonary hypertension during infancy. To test this hypothesis, we studied the effects of anti-sFlt-1 monoclonal antibody (mAb) treatment on lung growth in two established antenatal models of BPD that mimic PE and CA induced by intraamniotic (i.a.) injections of sFlt-1 or endotoxin, respectively. In experimental PE, mAb was administered by three different approaches, including antenatal treatment by either i.a. instillation or maternal uterine artery infusion, or by postnatal intraperitoneal injections. With each strategy, mAb therapy improved infant lung structure as assessed by radial alveolar count, vessel density, right ventricular hypertrophy, and lung function. As found in the PE model, the adverse lung effects of i.a. endotoxin were also reduced by antenatal or postnatal mAb therapy. We conclude that treatment with anti-sFlt-1 mAb preserves lung structure and function and prevents right ventricular hypertrophy in two rat models of BPD of antenatal stress and speculate that early mAb therapy may provide a novel strategy for the prevention of BPD.

Detection of circulating tumor cells using oHSV1-hTERT-GFP in lung cancer.

PubMed

Gao, Hongjun; Liu, Wenjing; Yang, Shaoxing; Zhang, Wen; Li, Xiaoyan; Qin, Haifeng; Wang, Weixia; Zhao, Changyun

2018-01-01

This study was conducted to evaluate the clinical utility of the oHSV1-hTERT-GFP circulating tumor cell (CTC) detection method in the peripheral blood of patients with lung cancer by comparing its sensitivity to the CellSearch CTC detection method. The oHSV1-hTERT-GFP and CellSearch CTC detection methods were compared using peripheral blood samples of patients pathologically diagnosed with lung cancer. A total of 240 patients with lung cancer were recruited, including 89 patients who were newly diagnosed and 151 patients who had previously received treatment. Sixty-six newly diagnosed patients were evaluated using both methods. The CTC detection rates were 71.2% and 33.3% using the oHSV1-hTERT-GFP and CellSearch methods, respectively; this difference was statistically significant (P = 0.000). Among the entire cohort (n = 240), the CTC detection rate using the oHSV1-hTERT-GFP method was 76.3%, with a CTC count of 0-81. The CTC detection rates were 76.7%, 68.9%, and 76.3% in patients with squamous cell carcinoma, adenocarcinoma, and small cell lung cancer, respectively. There was no statistically significant difference in the CTC detection rates between these different pathological subtypes (P = 0.738). The CTC detection rates of 79.8% and 74.4% in patients with stage I-III and IV lung cancer, respectively, were not significantly different (P = 0.427). The oHSV1-hTERT-GFP method is highly effective for detecting CTCs in patients with lung cancer, independent of pathological type and disease stage, and is ideal for large-scale clinical applications. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Vitamin E isoform γ-tocotrienol protects against emphysema in cigarette smoke-induced COPD.

PubMed

Peh, Hong Yong; Tan, W S Daniel; Chan, Tze Khee; Pow, Chen Wei; Foster, Paul S; Wong, W S Fred

2017-09-01

Inflammation and oxidative stress contribute to emphysema in COPD. Although corticosteroids are the standard of care for COPD, they do not reduce oxidative stress, and a subset of patients is steroid-resistant. Vitamin E isoform γ-tocotrienol possesses both anti-inflammatory and anti-oxidative properties that may protect against emphysema. We aimed to establish the therapeutic potential of γ-tocotrienol in cigarette smoke-induced COPD models in comparison with prednisolone. BALB/c mice were exposed to cigarette smoke for 2 weeks or 2 months. γ-Tocotrienol and prednisolone were given orally. Bronchoalveolar lavage (BAL) fluid and lung tissues were assessed for inflammation, oxidative damage, and regulation of transcription factor activities. Emphysema and lung function were also evaluated. γ-Tocotrienol dose-dependently reduced cigarette smoke-induced BAL fluid neutrophil counts and levels of cytokines, chemokines and oxidative damage biomarkers, and pulmonary pro-inflammatory and pro-oxidant gene expression, but restored lung endogenous antioxidant activities. γ-Tocotrienol acted by inhibiting nuclear translocation of STAT3 and NF-κB, and up-regulating Nrf2 activation in the lungs. In mice exposed to 2-month cigarette smoke, γ-tocotrienol ameliorated bronchial epithelium thickening and destruction of alveolar sacs in lungs, and improved lung functions. In comparison with prednisolone, γ-tocotrienol demonstrated better anti-oxidative efficacy, and protection against emphysema and lung function in COPD. We revealed for the first time the anti-inflammatory and antioxidant efficacies of γ-tocotrienol in cigarette smoke-induced COPD models. In addition, γ-tocotrienol was able to attenuate emphysematous lesions and improve lung function in COPD. γ-Tocotrienol may have therapeutic potential for the treatment of COPD. Copyright © 2017 Elsevier Inc. All rights reserved.

Inhalation exposure to sulfur mustard in the guinea pig model: Clinical, biochemical and histopathological characterization of respiratory injuries

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

Allon, Nahum, E-mail: nahuma@iibr.gov.i; Amir, Adina; Manisterski, Eliau

2009-12-01

Guinea pigs (GP) were exposed (head only) in individual plethysmographs to various concentrations of sulfur mustard vapor, determined online, using FTIR attached to flow chamber. The LCt{sub 50} and the inhaled LD{sub 50} were calculated at different time points post exposure. Surviving animals were monitored for clinical symptoms, respiratory parameters and body weight changes for up to 30 days. Clinical symptoms were noted at 3 h post exposure, characterized by erythematic and swelling nose with extensive mucous secretion (with or without bleeding). At 6 h post exposure most of the guinea pigs had breathing difficulties, rhonchi and dyspnea and fewmore » deaths were noted. These symptoms peaked at 48 h and were noted up to 8 days, associated with few additional deaths. Thereafter, a spontaneous healing was noted, characterized by recovery of respiratory parameters and normal weight gain with almost complete apparent healing within 2 weeks. Histopathological evaluation of lungs and trachea in the surviving GPs at 4 weeks post exposure revealed a dose-dependent residual injury in both lung and trachea expressed by abnormal recovery of the tracheal epithelium concomitant with a dose-dependent increase in cellular volume in the lungs. These abnormal epithelial regeneration and lung remodeling were accompanied with significant changes in protein, LDH, differential cell count and glutathione levels in the bronchoalveolar lavage (BAL). It is suggested that the abnormal epithelial growth and cellular infiltration into the lung as well as the continuous lung inflammation could cause recurrent lung injury similar to that reported for HD exposed human casualties.« less

Morinda citrifolia edible leaf extract enhanced immune response against lung cancer.

PubMed

Lim, Swee-Ling; Goh, Yong-Meng; Noordin, M Mustapha; Rahman, Heshu S; Othman, Hemn H; Abu Bakar, Nurul Ain; Mohamed, Suhaila

2016-02-01

Lung cancer causes 1.4 million deaths annually. In the search for functional foods as complementary therapies against lung cancer, the immuno-stimulatory properties of the vegetable Morinda citrifolia leaves were investigated and compared with the anti-cancer drug erlotinib. Lung tumour-induced BALB/c mice were fed with 150 mg kg(-1) or 300 mg kg(-1) body weight of the leaf extract, or erlotinib (50 mg kg(-1) body-weight) for 21 days. The 300 mg kg(-1) body weight extract significantly (and dose-dependently) suppressed lung tumour growth; the extract worked more effectively than the 50 mg kg(-1) body weight erlotinib treatment. The extract significantly increased blood lymphocyte counts, and spleen tissue B cells, T cells and natural killer cells, and reduced the epidermal growth factor receptor (EGFR) which is a lung adenocarcinoma biomarker. The extract also suppressed the cyclooxygenase 2 (COX2) inflammatory markers, and enhanced the tumour suppressor gene (phosphatase and tensin homolog, PTEN). It inhibited tumour growth cellular gene (transformed mouse 3T3 cell double minute 2 (MDM2), V-raf-leukemia viral oncogene 1 (RAF1), and mechanistic target of rapamycin (MTOR)) mRNA expression in the tumours. The extract is rich in scopoletin and epicatechin, which are the main phenolic compounds. The 300 mg kg(-1)Morinda citrifolia leaf 50% ethanolic extract showed promising potential as a complementary therapeutic dietary supplement which was more effective than the 50 mg kg(-1) erlotinib in suppressing lung adenocarcinoma. Part of the mechanisms involved enhancing immune responses, suppressing proliferation and interfering with various tumour growth signalling pathways.

Inhibition of EphA2/EphrinA1 signal attenuates lipopolysaccharide-induced lung injury.

PubMed

Hong, Ji Young; Shin, Mi Hwa; Douglas, Ivor S; Chung, Kyung Soo; Kim, Eun Young; Jung, Ji Ye; Kang, Young Ae; Kim, Se Kyu; Chang, Joon; Kim, Young Sam; Park, Moo Suk

2016-11-01

Eph-Ephrin signalling mediates various cellular processes, including vasculogenesis, angiogenesis, cell migration, axon guidance, fluid homoeostasis and repair after injury. Although previous studies have demonstrated that stimulation of the EphA receptor induces increased vascular permeability and inflammatory response in lung injury, the detailed mechanisms of EphA2 signalling are unknown. In the present study, we evaluated the role of EphA2 signalling in mice with lipopolysaccharide (LPS)-induced lung injury. Acute LPS exposure significantly up-regulated EphA2 and EphrinA1 expression. Compared with LPS+IgG mice (IgG instillation after LPS exposure), LPS+EphA2 mAb mice [EphA2 monoclonal antibody (mAb) instillation posttreatment after LPS exposure] had attenuated lung injury and reduced cell counts and protein concentration of bronchoalveolar lavage fluid (BALF). EphA2 mAb posttreatment down-regulated the expression of phosphoinositide 3-kinases (PI3K) 110γ, phospho-Akt, phospho-NF-κB p65, phospho-Src and phospho-S6K in lung lysates. In addition, inhibiting the EphA2 receptor augmented the expression of E-cadherin, which is involved in cell-cell adhesion. Our study identified EphA2 receptor as an unrecognized modulator of several signalling pathways-including PI3K-Akt-NF-kB, Src-NF-κB, E-cadherin and mTOR-in LPS-induced lung injury. These results suggest that EphA2 receptor inhibitors may function as novel therapeutic agents for LPS-induced lung injury. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Intratracheal instillation of pravastatin for the treatment of murine allergic asthma: a lung-targeted approach to deliver statins

PubMed Central

Zeki, Amir A; Bratt, Jennifer M; Chang, Kevin Y; Franzi, Lisa M; Ott, Sean; Silveria, Mark; Fiehn, Oliver; Last, Jerold A; Kenyon, Nicholas J

2015-01-01

Systemic treatment with statins mitigates allergic airway inflammation, TH2 cytokine production, epithelial mucus production, and airway hyperreactivity (AHR) in murine models of asthma. We hypothesized that pravastatin delivered intratracheally would be quantifiable in lung tissues using mass spectrometry, achieve high drug concentrations in the lung with minimal systemic absorption, and mitigate airway inflammation and structural changes induced by ovalbumin. Male BALB/c mice were sensitized to ovalbumin (OVA) over 4 weeks, then exposed to 1% OVA aerosol or filtered air (FA) over 2 weeks. Mice received intratracheal instillations of pravastatin before and after each OVA exposure (30 mg/kg). Ultra performance liquid chromatography – mass spectrometry was used to quantify plasma, lung, and bronchoalveolar lavage fluid (BALF) pravastatin concentration. Pravastatin was quantifiable in mouse plasma, lung tissue, and BALF (BALF > lung > plasma for OVA and FA groups). At these concentrations pravastatin inhibited airway goblet cell hyperplasia/metaplasia, and reduced BALF levels of cytokines TNFα and KC, but did not reduce BALF total leukocyte or eosinophil cell counts. While pravastatin did not mitigate AHR, it did inhibit airway hypersensitivity (AHS). In this proof-of-principle study, using novel mass spectrometry methods we show that pravastatin is quantifiable in tissues, achieves high levels in mouse lungs with minimal systemic absorption, and mitigates some pathological features of allergic asthma. Inhaled pravastatin may be beneficial for the treatment of asthma by having direct airway effects independent of a potent anti-inflammatory effect. Statins with greater lipophilicity may achieve better anti-inflammatory effects warranting further research. PMID:25969462

The effect of low level laser therapy on ventilator-induced lung injury in mice (Conference Presentation)

NASA Astrophysics Data System (ADS)

Szabari, Margit V.; Miller, Alyssa J.; Hariri, Lida P.; Hamblin, Michael R.; Musch, Guido; Stroh, Helene; Suter, Melissa J.

2016-03-01

Although mechanical ventilation (MV) is necessary to support gas exchange in critically ill patients, it can contribute to the development of lung injury and multiple organ dysfunction. It is known that high tidal volume (Vt) MV can cause ventilator-induced lung injury (VILI) in healthy lungs and increase the mortality of patients with Acute Respiratory Distress Syndrome. Low level laser therapy (LLLT) has demonstrated to have anti-inflammatory effects. We investigated whether LLLT could alleviate inflammation from injurious MV in mice. Adult mice were assigned to 2 groups: VILI+LLLT group (3 h of injurious MV: Vt=25-30 ml/kg, respiratory rate (RR)=50/min, positive end-expiratory pressure (PEEP)=0 cmH20, followed by 3 h of protective MV: Vt=9 ml/kg, RR=140/min, PEEP=2 cmH20) and VILI+no LLLT group. LLLT was applied during the first 30 min of the MV (810 nm LED system, 5 J/cm2, 1 cm above the chest). Respiratory impedance was measured in vivo with forced oscillation technique and lung mechanics were calculated by fitting the constant phase model. At the end of the MV, bronchoalveolar lavage (BAL) was performed and inflammatory cells counted. Lungs were removed en-bloc and fixed for histological evaluation. We hypothesize that LLLT can reduce lung injury and inflammation from VILI. This therapy could be translated into clinical practice, where it can potentially improve outcomes in patients requiring mechanical ventilation in the operating room or in the intensive care units.

Low-dose AgNPs reduce lung mechanical function and innate immune defense in the absence of cellular toxicity.

PubMed

Botelho, Danielle J; Leo, Bey Fen; Massa, Christopher B; Sarkar, Srijata; Tetley, Terry D; Chung, Kian Fan; Chen, Shu; Ryan, Mary P; Porter, Alexandra E; Zhang, Junfeng; Schwander, Stephan K; Gow, Andrew J

2016-01-01

Multiple studies have examined the direct cellular toxicity of silver nanoparticles (AgNPs). However, the lung is a complex biological system with multiple cell types and a lipid-rich surface fluid; therefore, organ level responses may not depend on direct cellular toxicity. We hypothesized that interaction with the lung lining is a critical determinant of organ level responses. Here, we have examined the effects of low dose intratracheal instillation of AgNPs (0.05 μg/g body weight) 20 and 110 nm diameter in size, and functionalized with citrate or polyvinylpyrrolidone. Both size and functionalization were significant factors in particle aggregation and lipid interaction in vitro. One day post-intratracheal instillation lung function was assessed, and bronchoalveolar lavage (BAL) and lung tissue collected. There were no signs of overt inflammation. There was no change in surfactant protein-B content in the BAL but there was loss of surfactant protein-D with polyvinylpyrrolidone (PVP)-stabilized particles. Mechanical impedance data demonstrated a significant increase in pulmonary elastance as compared to control, greatest with 110 nm PVP-stabilized particles. Seven days post-instillation of PVP-stabilized particles increased BAL cell counts, and reduced lung function was observed. These changes resolved by 21 days. Hence, AgNP-mediated alterations in the lung lining and mechanical function resolve by 21 days. Larger particles and PVP stabilization produce the largest disruptions. These studies demonstrate that low dose AgNPs elicit deficits in both mechanical and innate immune defense function, suggesting that organ level toxicity should be considered.

Projected Clinical, Resource Use, and Fiscal Impacts of Implementing Low-Dose Computed Tomography Lung Cancer Screening in Medicare.

PubMed

Roth, Joshua A; Sullivan, Sean D; Goulart, Bernardo H L; Ravelo, Arliene; Sanderson, Joanna C; Ramsey, Scott D

2015-07-01

The Centers for Medicare and Medicaid Services (CMS) recently issued a national coverage determination that provides reimbursement for low-dose computed tomography (CT) lung cancer screening for enrollees age 55 to 77 years with ≥ 30-pack-year smoking history who currently smoke or quit in the last 15 years. The clinical, resource use, and fiscal impacts of this change in screening coverage policy remain uncertain. We developed a simulation model to forecast the 5-year health outcome impacts of the CMS low-dose CT screening policy in Medicare compared with no screening. The model used data from the National Lung Screening Trial, CMS enrollment statistics and reimbursement schedules, and peer-reviewed literature. Outcomes included counts of screening examinations, patient cases of lung cancer detected, stage distribution, and total and per-enrollee per-month fiscal impact. Over 5 years, we project that low-dose CT screening will result in 10.7 million more low-dose CT scans, 52,000 more lung cancers detected, and increased overall expenditure of $6.8 billion ($2.22 per Medicare enrollee per month). The most fiscally impactful factors were the average cost-per-screening episode, proportion of enrollees eligible for screening, and cost of treating stage I lung cancer. Low-dose CT screening is expected to increase lung cancer diagnoses, shift stage at diagnosis toward earlier stages, and substantially increase Medicare expenditures over a 5-year time horizon. These projections can inform planning efforts by Medicare administrators, contracted health care providers, and other stakeholders. Copyright © 2015 by American Society of Clinical Oncology.

Effects of positive end-expiratory pressure and recruitment maneuvers in a ventilator-induced injury mouse model

PubMed Central

Franzi, Lisa M.; Linderholm, Angela L.; Last, Jerold A.; Adams, Jason Y.; Harper, Richart W.

2017-01-01

Background Positive-pressure mechanical ventilation is an essential therapeutic intervention, yet it causes the clinical syndrome known as ventilator-induced lung injury. Various lung protective mechanical ventilation strategies have attempted to reduce or prevent ventilator-induced lung injury but few modalities have proven effective. A model that isolates the contribution of mechanical ventilation on the development of acute lung injury is needed to better understand biologic mechanisms that lead to ventilator-induced lung injury. Objectives To evaluate the effects of positive end-expiratory pressure and recruitment maneuvers in reducing lung injury in a ventilator-induced lung injury murine model in short- and longer-term ventilation. Methods 5–12 week-old female BALB/c mice (n = 85) were anesthetized, placed on mechanical ventilation for either 2 hrs or 4 hrs with either low tidal volume (8 ml/kg) or high tidal volume (15 ml/kg) with or without positive end-expiratory pressure and recruitment maneuvers. Results Alteration of the alveolar-capillary barrier was noted at 2 hrs of high tidal volume ventilation. Standardized histology scores, influx of bronchoalveolar lavage albumin, proinflammatory cytokines, and absolute neutrophils were significantly higher in the high-tidal volume ventilation group at 4 hours of ventilation. Application of positive end-expiratory pressure resulted in significantly decreased standardized histology scores and bronchoalveolar absolute neutrophil counts at low- and high-tidal volume ventilation, respectively. Recruitment maneuvers were essential to maintain pulmonary compliance at both 2 and 4 hrs of ventilation. Conclusions Signs of ventilator-induced lung injury are evident soon after high tidal volume ventilation (as early as 2 hours) and lung injury worsens with longer-term ventilation (4 hrs). Application of positive end-expiratory pressure and recruitment maneuvers are protective against worsening VILI across all time points. Dynamic compliance can be used guide the frequency of recruitment maneuvers to help ameloriate ventilator-induced lung injury. PMID:29112971

Chromium in stainless steel welding fume suppresses lung defense responses against bacterial infection in rats.

PubMed

Antonini, James M; Roberts, Jenny R

2007-04-01

Pulmonary infections have been reported to be increased in welders. Previous animal studies have indicated that manual metal arc, stainless steel welding fume (MMA-SS) increased susceptibility to lung infections. MMA-SS is composed of a complex of metals (e.g., iron, chromium, nickel). The objective was to determine which metal component of MMA-SS welding fume alters lung defense responses. At Day 0, rats were intratracheally instilled one time with saline or MMA-SS at a concentration of 2 mg/rat. Additional rats were treated with the metal constituents, Fe(2)O(3), NiO, or Cr(2)Na(2)O(7) alone or in combination, at concentrations that are present in the dose used for MMA-SS treatment. At Day 3, rats were intratracheally inoculated with 5 x 10(3) Listeria monocytogenes. At Days 6, 8 and 10, homogenized left lungs were cultured, and colony-forming units were counted after an overnight incubation to assess pulmonary bacterial clearance. At Day 3 (prior to infection) and at Days 6, 8 and 10, right lungs were lavaged to recover cells and fluid from the airspaces to measure lung injury, inflammation, and cytokine secretion. The production of reactive oxygen species by phagocytes recovered from the lungs was measured. Exposure to MMA-SS, soluble Cr, or the mixture of all three metals before infection significantly increased bacterial lung burden and tissue damage when compared to control. Animals treated with NiO or Fe(2)O(3) did not differ from control. Animals pre-treated with soluble Cr had alterations in inflammation and in the production of different cytokines (TNFalpha, IL-6, IL-2, and IL-12) involved in lung immune responses. This study indicates that soluble Cr present in MMA-SS is likely the primary component responsible for the suppression of lung defense responses associated with stainless steel welding fumes.

siRNA delivery targeting to the lung via agglutination-induced accumulation and clearance of cationic tetraamino fullerene.

PubMed

Minami, Kosuke; Okamoto, Koji; Doi, Kent; Harano, Koji; Noiri, Eisei; Nakamura, Eiichi

2014-05-12

The efficient treatment of lung diseases requires lung-selective delivery of agents to the lung. However, lung-selective delivery is difficult because the accumulation of micrometer-sized carriers in the lung often induces inflammation and embolization-related toxicity. Here we demonstrate a lung-selective delivery system of small interfering RNA (siRNA) by controlling the size of carrier vehicle in blood vessels. The carrier is made of tetra(piperazino)fullerene epoxide (TPFE), a water-soluble cationic tetraamino fullerene. TPFE and siRNA form sub-micrometer-sized complexes in buffered solution and these complexes agglutinate further with plasma proteins in the bloodstream to form micrometer-sized particles. The agglutinate rapidly clogs the lung capillaries, releases the siRNA into lung cells to silence expression of target genes, and is then cleared rapidly from the lung after siRNA delivery. We applied our delivery system to an animal model of sepsis, indicating the potential of TPFE-based siRNA delivery for clinical applications.

siRNA delivery targeting to the lung via agglutination-induced accumulation and clearance of cationic tetraamino fullerene

NASA Astrophysics Data System (ADS)

Minami, Kosuke; Okamoto, Koji; Doi, Kent; Harano, Koji; Noiri, Eisei; Nakamura, Eiichi

2014-05-01

The efficient treatment of lung diseases requires lung-selective delivery of agents to the lung. However, lung-selective delivery is difficult because the accumulation of micrometer-sized carriers in the lung often induces inflammation and embolization-related toxicity. Here we demonstrate a lung-selective delivery system of small interfering RNA (siRNA) by controlling the size of carrier vehicle in blood vessels. The carrier is made of tetra(piperazino)fullerene epoxide (TPFE), a water-soluble cationic tetraamino fullerene. TPFE and siRNA form sub-micrometer-sized complexes in buffered solution and these complexes agglutinate further with plasma proteins in the bloodstream to form micrometer-sized particles. The agglutinate rapidly clogs the lung capillaries, releases the siRNA into lung cells to silence expression of target genes, and is then cleared rapidly from the lung after siRNA delivery. We applied our delivery system to an animal model of sepsis, indicating the potential of TPFE-based siRNA delivery for clinical applications.

siRNA delivery targeting to the lung via agglutination-induced accumulation and clearance of cationic tetraamino fullerene

PubMed Central

MINAMI, Kosuke; OKAMOTO, Koji; DOI, Kent; HARANO, Koji; NOIRI, Eisei; NAKAMURA, Eiichi

2014-01-01

The efficient treatment of lung diseases requires lung-selective delivery of agents to the lung. However, lung-selective delivery is difficult because the accumulation of micrometer-sized carriers in the lung often induces inflammation and embolization-related toxicity. Here we demonstrate a lung-selective delivery system of small interfering RNA (siRNA) by controlling the size of carrier vehicle in blood vessels. The carrier is made of tetra(piperazino)fullerene epoxide (TPFE), a water-soluble cationic tetraamino fullerene. TPFE and siRNA form sub-micrometer-sized complexes in buffered solution and these complexes agglutinate further with plasma proteins in the bloodstream to form micrometer-sized particles. The agglutinate rapidly clogs the lung capillaries, releases the siRNA into lung cells to silence expression of target genes, and is then cleared rapidly from the lung after siRNA delivery. We applied our delivery system to an animal model of sepsis, indicating the potential of TPFE-based siRNA delivery for clinical applications. PMID:24814863

Localization of lung fields in HRCT images using a deep convolution neural network

NASA Astrophysics Data System (ADS)

Kumar, Abhishek; Agarwala, Sunita; Dhara, Ashis Kumar; Mukhopadhyay, Sudipta; Nandi, Debashis; Garg, Mandeep; Khandelwal, Niranjan; Kalra, Naveen

2018-02-01

Lung field segmentation is a prerequisite step for the development of a computer-aided diagnosis system for interstitial lung diseases observed in chest HRCT images. Conventional methods of lung field segmentation rely on a large gray value contrast between lung fields and surrounding tissues. These methods fail on lung HRCT images with dense and diffused pathology. An efficient prepro- cessing could improve the accuracy of segmentation of pathological lung field in HRCT images. In this paper, a convolution neural network is used for localization of lung fields in HRCT images. The proposed method provides an optimal bounding box enclosing the lung fields irrespective of the presence of diffuse pathology. The performance of the proposed algorithm is validated on 330 lung HRCT images obtained from MedGift database on ZF and VGG networks. The model achieves a mean average precision of 0.94 with ZF net and a slightly better performance giving a mean average precision of 0.95 in case of VGG net.

QSAR and docking based semi-synthesis and in vitro evaluation of 18 β-glycyrrhetinic acid derivatives against human lung cancer cell line A-549.

PubMed

Yadav, Dharmendra Kumar; Kalani, Komal; Khan, Feroz; Srivastava, Santosh Kumar

2013-12-01

For the prediction of anticancer activity of glycyrrhetinic acid (GA-1) analogs against the human lung cancer cell line (A-549), a QSAR model was developed by forward stepwise multiple linear regression methodology. The regression coefficient (r(2)) and prediction accuracy (rCV(2)) of the QSAR model were taken 0.94 and 0.82, respectively in terms of correlation. The QSAR study indicates that the dipole moments, size of smallest ring, amine counts, hydroxyl and nitro functional groups are correlated well with cytotoxic activity. The docking studies showed high binding affinity of the predicted active compounds against the lung cancer target EGFR. These active glycyrrhetinic acid derivatives were then semi-synthesized, characterized and in-vitro tested for anticancer activity. The experimental results were in agreement with the predicted values and the ethyl oxalyl derivative of GA-1 (GA-3) showed equal cytotoxic activity to that of standard anticancer drug paclitaxel.

Identification of TRA2B-DNAH5 fusion as a novel oncogenic driver in human lung squamous cell carcinoma

PubMed Central

Li, Fei; Fang, Zhaoyuan; Zhang, Jian; Li, Chen; Liu, Hongyan; Xia, Jufeng; Zhu, Hongwen; Guo, Chenchen; Qin, Zhen; Li, Fuming; Han, Xiangkun; Wang, Yuetong; Feng, Yan; Wang, Ye; Zhang, Wenjing; Wang, Zuoyun; Jin, Yujuan; Sun, Yihua; Wei, Wenyi; Zeng, Rong; Chen, Haiquan; Ji, Hongbin

2016-01-01

Lung squamous cell carcinoma (SCC) is one of the major subtypes of lung cancer. Our current knowledge of oncogenic drivers in this specific subtype of lung cancer is largely limited compared with lung adenocarcinoma (ADC). Through exon array analyses, molecular analyses and functional studies, we here identify the TRA2B-DNAH5 fusion as a novel oncogenic driver in lung SCC. We found that this gene fusion occurs exclusively in lung SCC (3.1%, 5/163), but not in lung ADC (0/119). Through mechanistic studies, we further revealed that this TRA2B-DNAH5 fusion promotes lung SCC malignant progression through regulating a SIRT6-ERK1/2-MMP1 signaling axis. We show that inhibition of ERK1/2 activation using selumetinib efficiently inhibits the growth of lung SCC with TRA2B-DNAH5 fusion expression. These findings improve our current knowledge of oncogenic drivers in lung SCC and provide a potential therapeutic strategy for lung SCC patients with TRA2B-DNAH5 fusion. PMID:27670699

Physiological rules for the heart, lungs and other pressure-based organs

PubMed Central

Camilleri, Liberato; Manché, Alexander; Gatt, Ruben; Gauci, Marilyn; Camilleri-Podesta, Marie-Therese; Grima, Joseph N.; Chetcuti, Stanley

2017-01-01

Background The adherence of the heart to physical laws, such as Laplace’s Law, may act as a measure of the organ’s relative efficiency. Allometric relationships were investigated to assess the heart’s efficiency concerning end-diastolic and end-systolic volumes, cardiac pressurization energy, cardiac output and mass. Methods Data to generate allometric relationships was obtained using a literature search, identifying heart and lung data across different mammalian and bird species. Statistical analysis was carried out using ordinary least squares (OLS) estimation. Results Near isometric relationships exist between body mass and seven parameters indicating no “efficiency of size” with scaling of the heart, and size-matching of the heart to the lungs and whole body. Even though there was equal efficiency in pressurization energy generation, cardiac output was maximally efficient in small mammals <10 kg and birds; the human heart reached only 71% efficiency. This loss in cardiac efficiency with increasing body mass can be explained by the aortic cross-section that scales following the three-quarter allometry law, compared to end-systolic and end-diastolic volumes that scale isometrically. The heart is therefore throttled by a relatively small aorta at large body size. Conclusions Mammalian and avian hearts operate at similar efficiencies, demonstrating a high degree of symmorphosis, however cardiac output efficiency decreases in larger animals due to a relatively negative aortic cross-section allometry. This work has a myriad of potential applications including explaining cardiac dysfunction in athletes, patient-prosthesis mismatch in aortic valve replacement and why heavy exercise is associated with a worse prognosis than mild or moderate exercise. PMID:29268387

Multiple-Event, Single-Photon Counting Imaging Sensor

NASA Technical Reports Server (NTRS)

Zheng, Xinyu; Cunningham, Thomas J.; Sun, Chao; Wang, Kang L.

2011-01-01

The single-photon counting imaging sensor is typically an array of silicon Geiger-mode avalanche photodiodes that are monolithically integrated with CMOS (complementary metal oxide semiconductor) readout, signal processing, and addressing circuits located in each pixel and the peripheral area of the chip. The major problem is its single-event method for photon count number registration. A single-event single-photon counting imaging array only allows registration of up to one photon count in each of its pixels during a frame time, i.e., the interval between two successive pixel reset operations. Since the frame time can t be too short, this will lead to very low dynamic range and make the sensor merely useful for very low flux environments. The second problem of the prior technique is a limited fill factor resulting from consumption of chip area by the monolithically integrated CMOS readout in pixels. The resulting low photon collection efficiency will substantially ruin any benefit gained from the very sensitive single-photon counting detection. The single-photon counting imaging sensor developed in this work has a novel multiple-event architecture, which allows each of its pixels to register as more than one million (or more) photon-counting events during a frame time. Because of a consequently boosted dynamic range, the imaging array of the invention is capable of performing single-photon counting under ultra-low light through high-flux environments. On the other hand, since the multiple-event architecture is implemented in a hybrid structure, back-illumination and close-to-unity fill factor can be realized, and maximized quantum efficiency can also be achieved in the detector array.

Designing primers and evaluation of the efficiency of propidium monoazide - Quantitative polymerase chain reaction for counting the viable cells of Lactobacillus gasseri and Lactobacillus salivarius.

PubMed

Lai, Chieh-Hsien; Wu, Sih-Rong; Pang, Jen-Chieh; Ramireddy, Latha; Chiang, Yu-Cheng; Lin, Chien-Ku; Tsen, Hau-Yang

2017-07-01

The purpose of this study is to evaluate the efficiency of using propidium monoazide (PMA) real-time quantitative polymerase chain reaction (qPCR) to count the viable cells of Lactobacillus gasseri and Lactobacillus salivarius in probiotic products. Based on the internal transcription spacer and 23S rRNA genes, two primer sets specific for these two Lactobacillus species were designed. For a probiotic product, the total deMan Rogosa Sharpe plate count was 8.65±0.69 log CFU/g, while for qPCR, the cell counts of L. gasseri and L. salivarius were 8.39±0.14 log CFU/g and 8.57±0.24 log CFU/g, respectively. Under the same conditions, for its heat-killed product, qPCR counts for L. gasseri and L. salivarius were 6.70±0.16 log cells/g and 7.67±0.20 log cells/g, while PMA-qPCR counts were 5.33±0.18 log cells/g and 5.05±0.23 log cells/g, respectively. For cell dilutions with a viable cell count of 8.5 log CFU/mL for L. gasseri and L. salivarius, after heat killing, the PMA-qPCR count for both Lactobacillus species was near 5.5 log cells/mL. When the PMA-qPCR counts of these cell dilutions were compared before and after heat killing, although some DNA might be lost during the heat killing, significant qPCR signals from dead cells, i.e., about 4-5 log cells/mL, could not be reduced by PMA treatment. Increasing PMA concentrations from 100 μM to 200 μM or light exposure time from 5 minutes to 15 minutes had no or, if any, only minor effect on the reduction of qPCR signals from their dead cells. Thus, to differentiate viable lactic acid bacterial cells from dead cells using the PMA-qPCR method, the efficiency of PMA to reduce the qPCR signals from dead cells should be notable. Copyright © 2016. Published by Elsevier B.V.

Eosinophil count, allergies, and rejection in pediatric heart transplant recipients.

PubMed

Arbon, Kate S; Albers, Erin; Kemna, Mariska; Law, Sabrina; Law, Yuk

2015-08-01

Allograft rejection and long-term immunosuppression remain significant challenges in pediatric heart transplantation. Pediatric recipients are known to have fewer rejection episodes and to develop more allergic conditions than adults. A T-helper 2 cell dominant phenotype, manifested clinically by allergies and an elevated eosinophil count, may be associated with immunologic quiescence in transplant recipients. This study assessed whether the longitudinal eosinophil count and an allergic phenotype were associated with freedom from rejection. This single-center, longitudinal, observational study included 86 heart transplant patients monitored from 1994 to 2011. Post-transplant biannual complete blood counts, allergic conditions, and clinical characteristics related to rejection risk were examined. At least 1 episode of acute cellular rejection (ACR) occurred in 38 patients (44%), antibody-mediated rejection (AMR) occurred in 11 (13%), and 49 patients (57%) were diagnosed with an allergic condition. Patients with ACR or AMR had a lower eosinophil count compared with non-rejectors (p = 0.011 and p = 0.022, respectively). In the multivariable regression analysis, the presence of panel reactive antibodies to human leukocyte antigen I (p = 0.014) and the median eosinophil count (p = 0.011) were the only independent covariates associated with AMR. Eosinophil count (p = 0.010) and female sex (p = 0.009) were independent risk factors for ACR. Allergic conditions or young age at transplant were not protective from rejection. This study demonstrates a novel association between a high eosinophil count and freedom from rejection. Identifying a biomarker for low rejection risk may allow a reduction in immunosuppression. Further investigation into the role of the T-helper 2 cell phenotype and eosinophils in rejection quiescence is warranted. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

HSP90 Inhibition Suppresses Lipopolysaccharide-Induced Lung Inflammation In Vivo

PubMed Central

Lilja, Andrew; Weeden, Clare E.; McArthur, Kate; Nguyen, Thao; Donald, Alastair; Wong, Zi Xin; Dousha, Lovisa; Bozinovski, Steve; Vlahos, Ross; Burns, Christopher J.; Asselin-Labat, Marie-Liesse; Anderson, Gary P.

2015-01-01

Inflammation is an important component of cancer diathesis and treatment-refractory inflammation is a feature of many chronic degenerative lung diseases. HSP90 is a 90kDa protein which functions as an ATP-dependent molecular chaperone that regulates the signalling conformation and expression of multiple protein client proteins especially oncogenic mediators. HSP90 inhibitors are in clinical development as cancer therapies but the myeleosuppressive and neutropenic effect of first generation geldanamycin-class inhibitors has confounded studies on the effects on HSP90 inhibitors on inflammation. To address this we assessed the ability of Ganetespib, a non-geldanamycin HSP90 blocker, to suppress lipopolysaccharide (LPS)-induced cellular infiltrates, proteases and inflammatory mediator and transcriptional profiles. Ganetespib (10–100mg/kg, i.v.) did not directly cause myelosuppression, as assessed by video micrography and basal blood cell count, but it strongly and dose-dependently suppressed LPS-induced neutrophil mobilization into blood and neutrophil- and mononuclear cell-rich steroid-refractory lung inflammation. Ganetespib also suppressed B cell and NK cell accumulation, inflammatory cytokine and chemokine induction and MMP9 levels. These data identify non-myelosuppresssive HSP90 inhibitors as potential therapies for inflammatory diseases refractory to conventional therapy, in particular those of the lung. PMID:25615645

Clinical initiatives linking Japanese and Swedish healthcare resources on cancer studies utilizing Biobank Repositories.

PubMed

Nishimura, Toshihide; Kawamura, Takeshi; Sugihara, Yutaka; Bando, Yasuhiko; Sakamoto, Shigeru; Nomura, Masaharu; Ikeda, Norihiko; Ohira, Tatsuo; Fujimoto, Junichiro; Tojo, Hiromasa; Hamakubo, Takao; Kodama, Tatsuhiko; Andersson, Roland; Fehniger, Thomas E; Kato, Harubumi; Marko-Varga, György

2014-12-01

The Tokyo Medical University Hospital in Japan and the Lund University hospital in Sweden have recently initiated a research program with the objective to impact on patient treatment by clinical disease stage characterization (phenotyping), utilizing proteomics sequencing platforms. By sharing clinical experiences, patient treatment principles, and biobank strategies, our respective clinical teams in Japan and Sweden will aid in the development of predictive and drug related protein biomarkers. Data from joint lung cancer studies are presented where protein expression from Neuro- Endocrine lung cancer (LCNEC) phenotype patients can be separated from Small cell- (SCLC) and Large Cell lung cancer (LCC) patients by deep sequencing and spectral counting analysis. LCNEC, a subtype of large cell carcinoma (LCC), is characterized by neuroendocrine differentiation that small cell lung carcinoma (SCLC) shares. Pre-therapeutic histological distinction between LCNEC and SCLC has so far been problematic, leading to adverse clinical outcome. An establishment of protein targets characteristic of LCNEC is quite helpful for decision of optimal therapeutic strategy by diagnosing individual patients. Proteoform annotation and clinical biobanking is part of the HUPO initiative (http://www.hupo.org) within chromosome 10 and chromosome 19 consortia.

Case study: three acute 241Am inhalation exposures with DTPA therapy.

PubMed

Carbaugh, Eugene H; Lynch, Timothy P; Cannon, Curt N; Lewis, Loren L

2010-10-01

Three workers incurred inhalation exposures to Am oxide as a result of waste sorting and compaction activities. The exposure magnitudes were not fully recognized until the following day when an in-vivo lung count identified a significant lung deposition of Am in a male worker, and DTPA chelation therapy was initiated. Two additional workers (one female and one male) were then identified as sufficiently exposed to also warrant therapy. In-vivo bioassay measurements were performed over the ensuing 6 mo to quantify the 241Am activity in the lungs, liver, and skeleton. Urine and fecal samples were collected and showed readily detectable 241Am. Clinical lab tests and medical evaluations all showed normal results. There were no significant adverse clinical health effects from the therapy. The estimated 241Am inhalation intakes for the three workers were 1,800 Bq, 630 Bq, and 150 Bq. Lung retention showed somewhat longer pulmonary clearance half-times than standard inhalation class W or absorption Type M assumptions. The three subjects underwent slightly different therapy regimens, with therapy effectiveness factors (defined as the ratio of the reference doses without therapy relative to the final assessed doses) of 4.5, 1.9, and 1.7, respectively.

Design, synthesis, and structure–activity relationships of 2-benzylidene-1-indanone derivatives as anti-inflammatory agents for treatment of acute lung injury

PubMed Central

Chen, Hongjin; Fang, Bo; Qiu, Yinda; Chen, Xianxin; Chen, Lingfeng; Shu, Sheng; Zhang, Yali; Zhao, Yunjie; Liu, Zhiguo; Liang, Guang

2018-01-01

Purpose The purpose of this study was to design and synthesize novel 2-benzylidene-1-indanone derivatives for treatment of acute lung injury. Methods A series of 39 novel 2-benzylidene-indanone structural derivatives were synthesized and evaluated for anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated murine primary macrophages. Results Most of the obtained compounds effectively inhibited the LPS-induced expression of IL-6 and TNF-α. The most active compound, 8f, was found to significantly reduce LPS-induced pulmonary inflammation, as reflected by reductions in the concentration of total protein, inflammatory cell count, as well as the lung wet/dry ratio in bronchoalveolar lavage (BAL) fluid. Furthermore, 8f effectively inhibited mRNA expression of several inflammatory cytokines after LPS challenge in vitro and in vivo. Administration of 8f also blocked LPS-induced activation of the proinflammatory NF-κB/MAPK signaling pathway. Conclusion The simple synthetic preparation and biological properties of these derivatives make these 2-benzylidene-indanone scaffolds promising new entities for the development of anti-inflammatory therapeutics for the treatment of acute lung injury. PMID:29719375

A preliminary study of the effect of guaiphenesin on mucociliary clearance from the human lung

PubMed Central

Thomson, M. L.; Pavia, D.; McNicol, M. W.

1973-01-01

Thomson, M. L., Pavia, D., and McNicol, M. W. (1973).Thorax, 28, 742-747. A preliminary study of the effect of guaiphenesin on mucociliary clearance from the human lung. The effect of guaiphenesin (administered as Robitussin1) on mucociliary clearance has been assessed in 15 subjects from the rate of removal from the lung of previously inhaled radioactive tracer particles. The guaiphenesin was compared with a positive control preparation consisting of the guaiphenesin vehicle only in two double-blind crossover trials. The first trial examined eight aged `healthy' volunteer subjects and the second trial examined seven chronic bronchitic patients. Sequential gamma counts were made from the whole lung by scintillation counters for 6 hours after inhalation and the chest was also scanned rectilinearly. In the first 5 hours after inhalation the mean rate of removal of particles and therefore of secretions was faster after guaiphenesin than after the control preparation. This difference was not statistically significant in the healthy volunteers but achieved significance (P <0·05) in the chronic bronchitic patients. Lung scans after inhaling the tracer aerosol indicated that on average the initial penetration of the particles into the lung was similar in the guaiphenesin and control runs. The faster clearance after guaiphenesin was unlikely to be due to bulk movements of mucus caused by coughing since the mean frequency of coughing during the experiment was somewhat less after the drug. PMID:4595814

Hyperoxia Exacerbates Postnatal Inflammation-Induced Lung Injury in Neonatal BRP-39 Null Mutant Mice Promoting the M1 Macrophage Phenotype

PubMed Central

Syed, Mansoor A.

2013-01-01

Rationale. Hyperoxia exposure to developing lungs—critical in the pathogenesis of bronchopulmonary dysplasia—may augment lung inflammation by inhibiting anti-inflammatory mediators in alveolar macrophages. Objective. We sought to determine the O2-induced effects on the polarization of macrophages and the role of anti-inflammatory BRP-39 in macrophage phenotype and neonatal lung injury. Methods. We used RAW264.7, peritoneal, and bone marrow derived macrophages for polarization (M1/M2) studies. For in vivo studies, wild-type (WT) and BRP-39−/− mice received continuous exposure to 21% O2 (control mice) or 100% O2 from postnatal (PN) 1 to PN7 days, along with intranasal lipopolysaccharide (LPS) administered on alternate days (PN2, -4, and -6). Lung histology, bronchoalveolar lavage (BAL) cell counts, BAL protein, and cytokines measurements were performed. Measurements and Main Results. Hyperoxia differentially contributed to macrophage polarization by enhancing LPS induced M1 and inhibiting interleukin-4 induced M2 phenotype. BRP-39 absence led to further enhancement of the hyperoxia and LPS induced M1 phenotype. In addition, BRP-39−/− mice were significantly more sensitive to LPS plus hyperoxia induced lung injury and mortality compared to WT mice. Conclusions. These findings collectively indicate that BRP-39 is involved in repressing the M1 proinflammatory phenotype in hyperoxia, thereby deactivating inflammatory responses in macrophages and preventing neonatal lung injury. PMID:24347826

CT-assessed large airway involvement and lung function decline in eosinophilic asthma: The association between induced sputum eosinophil differential counts and airway remodeling.

PubMed

Inoue, Hideki; Ito, Isao; Niimi, Akio; Matsumoto, Hisako; Matsuoka, Hirofumi; Jinnai, Makiko; Takeda, Tomoshi; Oguma, Tsuyoshi; Otsuka, Kojiro; Nakaji, Hitoshi; Tajiri, Tomoko; Iwata, Toshiyuki; Nagasaki, Tadao; Kanemitsu, Yoshihiro; Mishima, Michiaki

2016-11-01

Eosinophilic asthma (EA) is a distinct clinical phenotype characterized by eosinophilic airway inflammation and airway remodeling. Few studies have used computed tomography (CT) scanning to assess the association between sputum eosinophil differential counts and airway involvement. We aimed to investigate the clinical characteristics and airway involvement of EA, and to examine the correlation between induced sputum eosinophil differential counts and CT-assessed airway remodeling. We retrospectively divided 63 patients with stable asthma receiving inhaled corticosteroids into 2 groups: 26 patients with EA (sputum eosinophil >3%) and 37 patients with non-eosinophilic asthma (NEA). Clinical measurements such as spirometry, fractional exhaled nitric oxide levels (FeNO), and CT-assessed indices of airway involvement were compared between the groups. Multivariate analysis was performed to identify determinants of the percentage of wall area (WA%). The EA group had significantly longer asthma duration, lower pulmonary function, and higher FeNO than the NEA group. Also, the EA group had higher WA% and smaller airway luminal area than the NEA group. Sputum eosinophil differential counts and WA% were positively correlated. The multivariate linear regression analysis showed that the factors associated with WA% included sputum eosinophil differential counts, age, and body mass index. However, asthma duration was not associated with WA%. Our CT-assessed findings demonstrated large airway involvement in EA, and we observed a positive association between induced sputum eosinophil differential counts and WA%. The findings indicate that induced sputum eosinophil differential counts may be associated with airway remodeling in patients with stable asthma.

Numerical simulation of volume-controlled mechanical ventilated respiratory system with 2 different lungs.

PubMed

Shi, Yan; Zhang, Bolun; Cai, Maolin; Zhang, Xiaohua Douglas

2017-09-01

Mechanical ventilation is a key therapy for patients who cannot breathe adequately by themselves, and dynamics of mechanical ventilation system is of great significance for life support of patients. Recently, models of mechanical ventilated respiratory system with 1 lung are used to simulate the respiratory system of patients. However, humans have 2 lungs. When the respiratory characteristics of 2 lungs are different, a single-lung model cannot reflect real respiratory system. In this paper, to illustrate dynamic characteristics of mechanical ventilated respiratory system with 2 different lungs, we propose a mathematical model of mechanical ventilated respiratory system with 2 different lungs and conduct experiments to verify the model. Furthermore, we study the dynamics of mechanical ventilated respiratory system with 2 different lungs. This research study can be used for improving the efficiency and safety of volume-controlled mechanical ventilation system. Copyright © 2016 John Wiley & Sons, Ltd.

Technology Development for High Efficiency Optical Communications

NASA Technical Reports Server (NTRS)

Farr, William H.

2012-01-01

Deep space optical communications is a significantly more challenging operational domain than near Earth space optical communications, primarily due to effects resulting from the vastly increased range between transmitter and receiver. The NASA Game Changing Development Program Deep Space Optical Communications Project is developing four key technologies for the implementation of a high efficiency telecommunications system that will enable greater than 10X the data rate of a state-of-the-art deep space RF system (Ka-band) for similar transceiver mass and power burden on the spacecraft. These technologies are a low mass spacecraft disturbance isolation assembly, a flight qualified photon counting detector array, a high efficiency flight laser amplifier and a high efficiency photon counting detector array for the ground-based receiver.

Performance Comparisons of Jet and Mesh Nebulizers Using Different Interfaces in Simulated Spontaneously Breathing Adults and Children.

PubMed

Ari, Arzu; de Andrade, Armele Dornelas; Sheard, Meryl; AlHamad, Bshayer; Fink, James B

2015-08-01

Different types of nebulizers and interfaces are used for the treatment of adults and children with pulmonary diseases. The purpose of this study was to determine the efficiency of a mesh nebulizer (MN) with a proprietary adapter and a jet nebulizer (JN) under different configurations in adult and pediatric models of spontaneous breathing. We hypothesize that delivery efficiency of JN and MN will differ depending on the interface used during aerosol therapy in simulated spontaneously breathing adult and pediatric models. While we expect that aerosol delivery with JN will be less efficient than MN, we also hypothesize that lung deposition obtained with the adult lung model will be more than that with the pediatric lung model in all conditions tested in this study. A lung model using a teaching manikin connected to a sinusoidal pump via a collecting filter at the level of the bronchi simulating a spontaneously breathing adult (Vt 500 mL, RR 15 bpm, I:E ratio 1:2) or pediatric patient (Vt 150 mL, RR 25 bpm, I:E ratio 1:2). Albuterol sulfate (2.5 mg/3 mL) was aerosolized with JN (Mistymax 10, Airlife) or MN (Aerogen Solo(®), Aerogen) with the Adapter (Aerogen Solo(®) Adapter, Aerogen Ltd, Galway, Ireland) using mouthpiece, aerosol mask, and valved-mask in adults and the dragon mask, aerosol mask, and valved-mask in pediatrics (n=3). The Adapter, specifically designed for MN, was attached to all the interfaces used in this study with supplemental oxygen of 2 lpm, and in addition, the MP was tested with no additional flow in the adult model. The JN was driven with 10 lpm based on the manufacturer's label. Drug was eluted from the filter and analyzed via spectrophotometry. Descriptive statistics, dependent t-test and one-way analysis of variance were used for data analysis. Significant level was set at 0.05. In adults, delivery efficiency of JN with the valved mask was significantly greater than that with the aerosol mask (p=0.01). Aerosol delivery of JN with the mouthpiece was not statistically significant from the valved mask (p=0.123) and the aerosol mask (p=0.193). Drug delivery with MN with mouthpiece (15.42±1.4%) and valved-mask (15.15±1.1%) was greater than the open aerosol mask (7.54±0.39%; p=0.0001) in the adult lung model. With no flow mouthpiece delivery increased>2 fold (34.9±3.1%; p=.0001) compared to use of 2 lpm of flow. Using the JN with the pediatric model deposition with valved-mask (5.3±0.8%), dragon mask (4.7±0.9%), and aerosol mask (4.1±0.3%) were similar (p>0.05); while drug delivery with MN via valved-mask (11.1±0.7%) was greater than the dragon mask (6.44±0.3%; p=0.002) and aerosol mask (4.6±0.4%; p=0.002), and the dragon mask was more efficient than the open aerosol mask (p=0.009) CONCLUSION: The type of nebulizer and interface used for aerosol therapy affects delivery efficiency in these simulated spontaneously breathing adult and pediatric models. Drug delivery was greatest with the valved-mouthpiece and mask with JN and MN, while the standard aerosol mask was least efficient in these simulated spontaneously breathing adult and pediatric lung models. Delivery efficiency of JN was less than MN in all conditions tested in this study except in the aerosol mask. Lung deposition obtained with the adult lung model was more than that with the pediatric lung model.

A novel concentration and viability detection method for Brettanomyces using the Cellometer image cytometry.

PubMed

Martyniak, Brian; Bolton, Jason; Kuksin, Dmitry; Shahin, Suzanne M; Chan, Leo Li-Ying

2017-01-01

Brettanomyces spp. can present unique cell morphologies comprised of excessive pseudohyphae and budding, leading to difficulties in enumerating cells. The current cell counting methods include manual counting of methylene blue-stained yeasts or measuring optical densities using a spectrophotometer. However, manual counting can be time-consuming and has high operator-dependent variations due to subjectivity. Optical density measurement can also introduce uncertainties where instead of individual cells counted, an average of a cell population is measured. In contrast, by utilizing the fluorescence capability of an image cytometer to detect acridine orange and propidium iodide viability dyes, individual cell nuclei can be counted directly in the pseudohyphae chains, which can improve the accuracy and efficiency of cell counting, as well as eliminating the subjectivity from manual counting. In this work, two experiments were performed to demonstrate the capability of Cellometer image cytometer to monitor Brettanomyces concentrations, viabilities, and budding/pseudohyphae percentages. First, a yeast propagation experiment was conducted to optimize software counting parameters for monitoring the growth of Brettanomyces clausenii, Brettanomyces bruxellensis, and Brettanomyces lambicus, which showed increasing cell concentrations, and varying pseudohyphae percentages. The pseudohyphae formed during propagation were counted either as multiple nuclei or a single multi-nuclei organism, where the results of counting the yeast as a single multi-nuclei organism were directly compared to manual counting. Second, a yeast fermentation experiment was conducted to demonstrate that the proposed image cytometric analysis method can monitor the growth pattern of B. lambicus and B. clausenii during beer fermentation. The results from both experiments displayed different growth patterns, viability, and budding/pseudohyphae percentages for each Brettanomyces species. The proposed Cellometer image cytometry method can improve efficiency and eliminate operator-dependent variations of cell counting compared with the traditional methods, which can potentially improve the quality of beverage products employing Brettanomyces yeasts.

The piecewise-linear dynamic attenuator reduces the impact of count rate loss with photon-counting detectors

NASA Astrophysics Data System (ADS)

Hsieh, Scott S.; Pelc, Norbert J.

2014-06-01

Photon counting x-ray detectors (PCXDs) offer several advantages compared to standard energy-integrating x-ray detectors, but also face significant challenges. One key challenge is the high count rates required in CT. At high count rates, PCXDs exhibit count rate loss and show reduced detective quantum efficiency in signal-rich (or high flux) measurements. In order to reduce count rate requirements, a dynamic beam-shaping filter can be used to redistribute flux incident on the patient. We study the piecewise-linear attenuator in conjunction with PCXDs without energy discrimination capabilities. We examined three detector models: the classic nonparalyzable and paralyzable detector models, and a ‘hybrid’ detector model which is a weighted average of the two which approximates an existing, real detector (Taguchi et al 2011 Med. Phys. 38 1089-102 ). We derive analytic expressions for the variance of the CT measurements for these detectors. These expressions are used with raw data estimated from DICOM image files of an abdomen and a thorax to estimate variance in reconstructed images for both the dynamic attenuator and a static beam-shaping (‘bowtie’) filter. By redistributing flux, the dynamic attenuator reduces dose by 40% without increasing peak variance for the ideal detector. For non-ideal PCXDs, the impact of count rate loss is also reduced. The nonparalyzable detector shows little impact from count rate loss, but with the paralyzable model, count rate loss leads to noise streaks that can be controlled with the dynamic attenuator. With the hybrid model, the characteristic count rates required before noise streaks dominate the reconstruction are reduced by a factor of 2 to 3. We conclude that the piecewise-linear attenuator can reduce the count rate requirements of the PCXD in addition to improving dose efficiency. The magnitude of this reduction depends on the detector, with paralyzable detectors showing much greater benefit than nonparalyzable detectors.

SU-F-T-687: Comparison of SPECT/CT-Based Methodologies for Estimating Lung Dose from Y-90 Radioembolization

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

Kost, S; Yu, N; Lin, S

2016-06-15

Purpose: To compare mean lung dose (MLD) estimates from 99mTc macroaggregated albumin (MAA) SPECT/CT using two published methodologies for patients treated with {sup 90}Y radioembolization for liver cancer. Methods: MLD was estimated retrospectively using two methodologies for 40 patients from SPECT/CT images of 99mTc-MAA administered prior to radioembolization. In these two methods, lung shunt fractions (LSFs) were calculated as the ratio of scanned lung activity to the activity in the entire scan volume or to the sum of activity in the lung and liver respectively. Misregistration of liver activity into the lungs during SPECT acquisition was overcome by excluding lungmore » counts within either 2 or 1.5 cm of the diaphragm apex respectively. Patient lung density was assumed to be 0.3 g/cm{sup 3} or derived from CT densitovolumetry respectively. Results from both approaches were compared to MLD determined by planar scintigraphy (PS). The effect of patient size on the difference between MLD from PS and SPECT/CT was also investigated. Results: Lung density from CT densitovolumetry is not different from the reference density (p = 0.68). The second method resulted in lung dose of an average 1.5 times larger lung dose compared to the first method; however the difference between the means of the two estimates was not significant (p = 0.07). Lung dose from both methods were statistically different from those estimated from 2D PS (p < 0.001). There was no correlation between patient size and the difference between MLD from PS and both SPECT/CT methods (r < 0.22, p > 0.17). Conclusion: There is no statistically significant difference between MLD estimated from the two techniques. Both methods are statistically different from conventional PS, with PS overestimating dose by a factor of three or larger. The difference between lung doses estimated from 2D planar or 3D SPECT/CT is not dependent on patient size.« less

CFD simulation of aerosol delivery to a human lung via surface acoustic wave nebulization.

PubMed

Yousefi, Morteza; Pourmehran, Oveis; Gorji-Bandpy, Mofid; Inthavong, Kiao; Yeo, Leslie; Tu, Jiyuan

2017-12-01

Administration of drug in the form of particles through inhalation is generally preferable in the treatment of respiratory disorders. Conventional inhalation therapy devices such as inhalers and nebulizers, nevertheless, suffer from low delivery efficiencies, wherein only a small fraction of the inhaled drug reaches the lower respiratory tract. This is primarily because these devices are not able to produce a sufficiently fine drug mist that has aerodynamic diameters on the order of a few microns. This study employs computational fluid dynamics to investigate the transport and deposition of the drug particles produced by a new aerosolization technique driven by surface acoustic waves (SAWs) into an in silico lung model geometrically reconstructed using computed tomography scanning. The particles generated by the SAW are released in different locations in a spacer chamber attached to a lung model extending from the mouth to the 6th generation of the lung bronchial tree. An Eulerian approach is used to solve the Navier-Stokes equations that govern the airflow within the respiratory tract, and a Lagrangian approach is adopted to track the particles, which are assumed to be spherical and inert. Due to the complexity of the lung geometry, the airflow patterns vary as it penetrates deeper into the lung. High inertia particles tend to deposit at locations where the geometry experiences a significant reduction in cross section. Our findings, nevertheless, show that the injection location can influence the delivery efficiency: Injection points close to the spacer centerline result in deeper penetration into the lung. Additionally, we found that the ratio of drug particles entering the right lung is significantly higher than the left lung, independent of the injection location. This is in good agreement with this fact that the most of airflow enters to the right lobes.

Integrated four-channel all-fiber up-conversion single-photon-detector with adjustable efficiency and dark count.

PubMed

Zheng, Ming-Yang; Shentu, Guo-Liang; Ma, Fei; Zhou, Fei; Zhang, Hai-Ting; Dai, Yun-Qi; Xie, Xiuping; Zhang, Qiang; Pan, Jian-Wei

2016-09-01

Up-conversion single photon detector (UCSPD) has been widely used in many research fields including quantum key distribution, lidar, optical time domain reflectrometry, and deep space communication. For the first time in laboratory, we have developed an integrated four-channel all-fiber UCSPD which can work in both free-running and gate modes. This compact module can satisfy different experimental demands with adjustable detection efficiency and dark count. We have characterized the key parameters of the UCSPD system.

Effect of hyperinflation on inspiratory function of the diaphragm.

PubMed

Minh, V D; Dolan, G F; Konopka, R F; Moser, K M

1976-01-01

The inspiratory efficiency of the diaphragm during unilateral and bilateral phrenic stimulation (UEPS and BEPS) with constant stimulus was studied in seven dogs from FRC to 120% TLC. Alveolar pressures (PAl) were recorded during relaxation, BEPS and UEPS at each lung volume in the closed respiratory system. From the PAl-lung volume curves, tidal volume (VT), and pressure developed by the diaphragm (Pmus) were derived. Results are summarized below. a) Hyperinflation impaired the inspiratory efficiency of the diaphragm which behaved as an expiratory muscle beyond the lung volume of 103.7% TLC (Vinef). b) The diaphragm during UEPS became expiratory at the same Vinef as during (BEPS. C) The VT-lung volume relationship was linear during BEPS, allowing simple quantitation of VT loss with hyperinflation and prediction of Vinef. d) With only one phrenic nerve stimulated, the functional loss is less pronounced in VT than in Pmus, as compared to BEPS, indicating that the respiratory system was more compliant during UEPS than BEPS. This compliance difference from UEPS to BEPS diminished with severe hyperinflation.

Social media use for occupational lung disease.

PubMed

Harber, Philip; Leroy, Gondy

2017-04-01

Social media have great impact on all aspects of life throughout the world. The utilization of social media for occupational lung disease, however, has been much more limited. This article summarizes recent literature concerning social media for occupational lung disease and identifies areas for additional use. Social media are used in six relevant areas: information dissemination, peer-to-peer communication, survey research data collection, participatory research and exposome data acquisition, assessing public concerns, and knowledge generation. There are very clear advantages for information dissemination from experts to workers and on a peer-to-peer basis, although variable credibility and accuracy concerns persist. For research, social media have been used for acquiring data posted for nonresearch purposes and for efficiently collecting information specifically for research. The benefits of efficiency, democracy, and very large data sources may counterbalance concerns about inadequate specification of recruitment strategies and limited control over data quality. The potential benefits of using social media for lung health-workplace interactions are much greater than the very limited current utilization.

Longitudinal monitoring of whole body counter NaI(TI) detector efficiency

USDA-ARS?s Scientific Manuscript database

Assessing accuracy of radiation counting systems over time is critical. We examined long-term WBC performance in detail. Efficiency factors for 54 detectors were updated annually over several years. Newer efficiency values were compared with baseline and with annual values. Overall system efficiency...

Impaired anti-fibrotic effect of bone marrow-derived mesenchymal stem cell in a mouse model of pulmonary paracoccidioidomycosis

PubMed Central

Arango, Julián Camilo; Puerta-Arias, Juan David; Pino-Tamayo, Paula Andrea; Salazar-Peláez, Lina María; Rojas, Mauricio

2017-01-01

Bone marrow-derived mesenchymal stem cells (BMMSCs) have been consider as a promising therapy in fibrotic diseases. Experimental models suggest that BMMSCs may be used as an alternative therapy to treat chemical- or physical-induced pulmonary fibrosis. We investigated the anti-fibrotic potential of BMMSCs in an experimental model of lung fibrosis by infection with Paracoccidioides brasiliensis. BMMSCs were isolated and purified from BALB/c mice using standardized methods. BALB/c male mice were inoculated by intranasal infection of 1.5x106 P. brasiliensis yeasts. Then, 1x106 BMMSCs were administered intra venous at 8th week post-infection (p.i.). An additional group of mice was treated with itraconazole (ITC) two weeks before BMMSCs administration. Animals were sacrificed at 12th week p.i. Histopathological examination, fibrocytes counts, soluble collagen and fibrosis-related genes expression in lungs were evaluated. Additionally, human fibroblasts were treated with homogenized lung supernatants (HLS) to determine induction of collagen expression. Histological analysis showed an increase of granulomatous inflammatory areas in BMMSCs-treated mice. A significant increase of fibrocytes count, soluble collagen and collagen-3α1, TGF-β3, MMP-8 and MMP-15 genes expression were also observed in those mice. Interestingly, when combined therapy BMMSCs/ITC was used there is a decrease of TIMP-1 and MMP-13 gene expression in infected mice. Finally, human fibroblasts stimulated with HLS from infected and BMMSCs-transplanted mice showed a higher expression of collagen I. In conclusion, our findings indicate that late infusion of BMMSCs into mice infected with P. brasiliensis does not have any anti-fibrotic effect; possibly because their interaction with the fungus promotes collagen expression and tissue remodeling. PMID:29040281

Dibutyryl cAMP effects on thromboxane and leukotriene production in decompression-induced lung injury

NASA Technical Reports Server (NTRS)

Little, T. M.; Butler, B. D.

1997-01-01

Decompression-induced venous bubble formation has been linked to increased neutrophil counts, endothelial cell injury, release of vasoactive eicosanoids, and increased vascular membrane permeability. These actions may account for inflammatory responses and edema formation. Increasing the intracellular cAMP has been shown to decrease eicosanoid production and edema formation in various models of lung injury. Reduction of decompression-induced inflammatory responses was evaluated in decompressed rats pretreated with saline (controls) or dibutyryl cAMP (DBcAMP, an analog of cAMP). After pretreatment, rats were exposed to either 616 kPa for 120 min or 683 kPa for 60 min. The observed increases in extravascular lung water ratios (pulmonary edema), bronchoalveolar lavage, and pleural protein in the saline control group (683 kPa) were not evident with DBcAMP treatment. DBcAMP pretreatment effects were also seen with the white blood cell counts and the percent of neutrophils in the bronchoalveolar lavage. Urinary levels of thromboxane B2, 11-dehydrothromboxane B2, and leukotriene E4 were significantly increased with the 683 kPa saline control decompression exposure. DBcAMP reduced the decompression-induced leukotriene E4 production in the urine. Plasma levels of thromboxane B2, 11-dehydrothromboxane B2, and leukotriene E4 were increased with the 683-kPa exposure groups. DBcAMP treatment did not affect these changes. The 11-dehydrothromboxane B2 and leukotriene E4 levels in the bronchoalveolar lavage were increased with the 683 kPa exposure and were reduced with the DBcAMP treatment. Our results indicate that DBcAMP has the capability to reduce eicosanoid production and limit membrane permeability and subsequent edema formation in rats experiencing decompression sickness.

Association between proximity to major roads and sputum cell counts

PubMed Central

Wallace, Julie; D’silva, Liesel; Brannan, John; Hargreave, Frederick E; Kanaroglou, Pavlos; Nair, Parameswaran

2011-01-01

BACKGROUND: Air pollution caused by motor vehicle emissions has been associated with exacerbations of obstructive airway diseases; however, the nature of the resulting bronchitis has not been quantified. OBJECTIVE: To examine whether proximity to major roads or highways is associated with an increase in sputum neutrophils or eosinophils, and to evaluate the effect of proximity to roads on spirometry and exacerbations in patients with asthma. METHODS: A retrospective study of 485 sputum cell counts from patients attending a tertiary chest clinic in Hamilton, Ontario, identified eosinophilic or neutrophilic bronchitis. Patients’ residences were geocoded to the street network of Hamilton using geographic information system software. Associations among bronchitis, lung function, and proximity to major roads and highways were examined using multinomial logistic and multivariate linear regression analyses adjusted for patient age, smoking status and corticosteroid medications. RESULTS: Patients living within 1000 m of highways showed an increased risk of bronchitis (OR 3.8 [95% CI 1.0 to 13.7]; P<0.05), particularly neutrophilic bronchitis (OR 4.7 [95% CI 1.2 to 18.7]; P<0.05) as well as an increased risk of an asthma diagnosis (OR 1.9 [95% CI 1.0 to 3.4]; P<0.05). Patients living within 300 m of a major road were at increased risk for an asthma exacerbation (OR 1.9 [95% CI 1.5 to 15.5]; P<0.01) and lower lung function, particularly in women (P=0.036). CONCLUSION: In patients with airway diseases, living close to a highway or major road was associated with neutrophilic bronchitis, an increased risk of asthma diagnosis, asthma exacerbations and lower lung function. PMID:21369545

Assessment of inhibitory potential of Pothos scandens L. on ovalbumin-induced airway hyperresponsiveness in balb/c mice.

PubMed

Gupta, Saurabh; Basavan, Duraiswamy; Muthureddy Nataraj, Satish Kumar; Raju, K Rama Satyanarayana; Babu, U V; L M, Sharath Kumar; Gupta, Renu

2014-01-01

Pothos scandens L. was used in Indian traditional medicine as an antiasthmatic drug. The ethanolic and aqueous extracts were prepared with aerial parts of P. scandens (PSE & PSA). ESI MS/MS of PSE ethanolic extract was carried out for the determination of chemical constituents. CP1 is isolated from the PSE, structurally confirmed with NMR and LCMS/MS. PSE, PSA and CP1 are evaluated against ovalbumin (OVA) induced airway hyperresponsiveness (AHR) in balb/c mice. The test drugs are administered p.o. prior to challenge with aerosolized 2.5% w/v OVA. Total and differential leucocyte count, nitrite (NO2), nitrate (NO3), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-13 (IL-13) are estimated in bronchoalveolar lavage fluid (BALF). Similarly, myeloperoxidase (MPO), malonaldehyde (MDA) and total lung protein (TLP) are estimated in the lungs. The results reveal a significant increase in total and differential leucocyte count, NO2, NO3, TNF-α, IL-6, and IL-13 in OVA induced AHR. However, these parameters are significantly decreased in PSE and PSA tested doses (PSE 100 & 200mg/kg). While, treatment with CP1 is less effective at 5 & 10mg/kg doses. Similar observations obtain for MPO and MDA in lungs. However, the mean value indicated that the PSE at 200mg/kg showed a significant restoration in all the parameters. Pro-inflammatory mediators are known to be responsible for AHR. Histopathology revealed justifies the effectiveness. The present investigations suggest PSE are interesting molecules for further research for asthma, with an approach through pro-inflammatory inhibitory pathway. P. scandens is a potential herbal medicine for allergy induced asthma. Copyright © 2013 Elsevier B.V. All rights reserved.

Analysis of Trace Elements in Rat Bronchoalveolar Lavage Fluid by Inductively Coupled Plasma Mass Spectrometry.

PubMed

Qamar, Wajhul; Al-Ghadeer, Abdul Rahman; Ali, Raisuddin; Abuelizz, Hatem A

2017-08-01

The main objective was to determine the elemental profile of the lung lining fluid of rats which are used as model animals in various experiments. Lung lining fluid elemental constitution obtained after bronchoalveolar lavage fluid (BALF) was analyzed by inductively coupled plasma mass spectrometry (ICP-MS) to determine the biological trace elements along with calcium and magnesium. BALF was collected from healthy rats using a tracheal cannula. However, cells in BALF were counted to monitor any underlying inflammatory lung condition. Cell free BALF samples were processed and analyzed for the elements including magnesium (Mg), calcium (Ca), chromium (Cr), manganese (Mn), iron (Fe), nickel (Ni), copper (Cu), zinc (Zn), selenium (Se), bromine (Br), and iodine (I). In view of this, calcium concentration was the highest (6318.08 ± 3094.3 μg/L) and copper concentration was the lowest (0.89 ± 0.21 μg/L). The detected elements, from high to low concentration, include Ca > Mg > Fe > Br > I > Cr > Ni > Zn > Mn > Se > Cu. Pearson's correlation analysis revealed no significant correlation between cell count and concentration of any of the element detected in BALF. Correlation analysis also revealed significant positive correlation among Fe, I, Cr, Ni, and Mn. Ca was found to be correlated negatively with Cu and positively with Se. Br and Mg found to be positively correlated with each other. Zn remained the only element that was not found to be correlated with any of the elements in the rat BALF.

Cefepime and amikacin synergy in vitro and in vivo against a ceftazidime-resistant strain of Enterobacter cloacae.

PubMed

Mimoz, O; Jacolot, A; Padoin, C; Tod, M; Samii, K; Petitjean, O

1998-03-01

The activities of cefepime and amikacin alone or in combination against an isogenic pair of Enterobacter cloacae strains (wild type and stably derepressed, ceftazidime-resistant mutant) were compared using an experimental model of pneumonia in non-leucopenic rats. Animals were infected by administering 8.4 log10 cfu of E. cloacae intratracheally, and therapy was initiated 12 h later. At that time, the animals' lungs showed bilateral pneumonia and contained more than 7 log10 E. cloacae cfu/g tissue. Because rats eliminate amikacin and cefepime much more rapidly than humans, renal impairment was induced in all animals to simulate the pharmacokinetic parameters of humans. In-vitro susceptibilities showed an inoculum effect with cefepime proportional to the bacterial titre against the two strains, but more pronounced with the stably derepressed mutant strain, whereas with bacterial concentrations of up to 7 log10 cfu/mL, no inoculum effect was observed with amikacin. In-vitro killing indicated that antibiotic combinations were synergic only at intermediate concentrations. At peak concentrations, the combination was merely as effective as amikacin alone. At trough concentrations, a non-significant trend towards the superiority of the combination over each antibiotic alone was noted. Moreover, cefepime was either bacteriostatic or permitted regrowth of the organisms in the range of antibiotic concentrations tested. Although each antibiotic alone failed to decrease bacterial counts in the lungs, regardless of the susceptibility of the strain used, the combination of both antibiotics was synergic and induced a significant decrease in the lung bacterial count 24 h after starting therapy when compared with tissue bacterial numbers in untreated animals or animals treated with either antibiotic alone. No resistant clones emerged during treatment with any of the antibiotic regimens studied.

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

Cancer Burden in the HIV-Infected Population in the United States

PubMed Central

Pfeiffer, Ruth M.; Gail, Mitchell H.; Hall, H. Irene; Chaturvedi, Anil K.; Bhatia, Kishor; Uldrick, Thomas S.; Yarchoan, Robert; Goedert, James J.; Engels, Eric A.

2011-01-01

Background Effective antiretroviral therapy has reduced the risk of AIDS and dramatically prolonged the survival of HIV-infected people in the United States. Consequently, an increasing number of HIV-infected people are at risk of non-AIDS-defining cancers that typically occur at older ages. We estimated the annual number of cancers in the HIV-infected population, both with and without AIDS, in the United States. Methods Incidence rates for individual cancer types were obtained from the HIV/AIDS Cancer Match Study by linking 15 HIV and cancer registries in the United States. Estimated counts of the US HIV-infected and AIDS populations were obtained from Centers for Disease Control and Prevention surveillance data. We obtained estimated counts of AIDS-defining (ie, Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer) and non-AIDS-defining cancers in the US AIDS population during 1991–2005 by multiplying cancer incidence rates and AIDS population counts, stratified by year, age, sex, race and ethnicity, transmission category, and AIDS-relative time. We tested trends in counts and standardized incidence rates using linear regression models. We multiplied overall cancer rates and HIV-only (HIV infected, without AIDS) population counts, available from 34 US states during 2004–2007, to estimate cancers in the HIV-only population. All statistical tests were two-sided. Results The US AIDS population expanded fourfold from 1991 to 2005 (96 179 to 413 080) largely because of an increase in the number of people aged 40 years or older. During 1991–2005, an estimated 79 656 cancers occurred in the AIDS population. From 1991–1995 to 2001–2005, the estimated number of AIDS-defining cancers decreased by greater than threefold (34 587 to 10 325 cancers; Ptrend < .001), whereas non-AIDS-defining cancers increased by approximately threefold (3193 to 10 059 cancers; Ptrend < .001). From 1991–1995 to 2001–2005, estimated counts increased for anal (206 to 1564 cancers), liver (116 to 583 cancers), prostate (87 to 759 cancers), and lung cancers (875 to 1882 cancers), and Hodgkin lymphoma (426 to 897 cancers). In the HIV-only population in 34 US states, an estimated 2191 non-AIDS-defining cancers occurred during 2004–2007, including 454 lung, 166 breast, and 154 anal cancers. Conclusions Over a 15-year period (1991–2005), increases in non-AIDS-defining cancers were mainly driven by growth and aging of the AIDS population. This growing burden requires targeted cancer prevention and treatment strategies. PMID:21483021

Poly(amidoamine) Dendrimer Nanocarriers and Their Aerosol Formulations for siRNA Delivery to the Lung Epithelium

PubMed Central

2015-01-01

Small interfering RNA (siRNA)-based therapies have great promise in the treatment of a number of prevalent pulmonary disorders including lung cancer, asthma and cystic fibrosis. However, progress in this area has been hindered due to the lack of carriers that can efficiently deliver siRNA to lung epithelial cells, and also due to challenges in developing oral inhalation (OI) formulations for the regional administration of siRNA and their carriers to the lungs. In this work we report the ability of generation four, amine-terminated poly(amidoamine) (PAMAM) dendrimer (G4NH2)–siRNA complexes (dendriplexes) to silence the enhanced green fluorescent protein (eGFP) gene on A549 lung alveolar epithelial cells stably expressing eGFP. We also report the formulation of the dendriplexes and their aerosol characteristics in propellant-based portable OI devices. The size and gene silencing ability of the dendriplexes was seen not to be a strong function of the N/P ratio. Silencing efficiencies of up to 40% are reported. Stable dispersions of the dendriplexes encapsulated in mannitol and also in a biodegradable and water-soluble co-oligomer were prepared in hydrofluoroalkane (HFA)-based pressurized metered-dose inhalers (pMDIs). Their aerosol characteristics were very favorable, and conducive to deep lung deposition, with respirable fractions of up to 77%. Importantly, siRNA formulated as dendriplexes in pMDIs was shown to keep its integrity after the particle preparation processes, and also after long-term exposures to HFA. The relevance of this study stems from the fact that this is the first work to report the formulation of inhalable siRNA with aerosol properties suitable to deep lung deposition using pMDIs devices that are the least expensive and most widely used portable inhalers. This study is relevant because, also for the first time, it shows that siRNA–G4NH2 dendriplexes can efficiently target lung alveolar epithelial A549 cells and silence genes even after siRNA has been exposed to the propellant environment. PMID:24811243

Distribution of extravascular fluid volumes in isolated perfused lungs measured with H215O.

PubMed Central

Jones, T; Jones, H A; Rhodes, C G; Buckingham, P D; Hughes, J M

1976-01-01

The distributions per unit volume of extravascular water (EVLW), blood volume, and blood flow were measured in isolated perfused vertical dog lungs. A steady-state tracer technique was employed using oxygen-15, carbon-11, and nitrogen-13 isotopes and external scintillation counting of the 511-KeV annihilation radiation common to all three radionuclides. EVLW, and blood volume and flow increased from apex to base in all preparations, but the gradient of increasing flow exceeded that for blood and EVLW volumes. The regional distributions of EVLW and blood volume were almost identical. With increasing edema, lower-zone EVLW increased slightly relative to that in the upper zone. There was no change in the distribution of blood volume or flow until gross edema (100% wt gain) occurred when lower zone values were reduced. In four lungs the distribution of EVLW was compared with wet-to-dry ratios from lung biopsies taken immediately afterwards. Whereas the isotopically measured EVLW increased from apex to base, the wet-to-dry weight ratios remained essentially uniform. We concluded that isotopic methods measure only an "exchangeable" water pool whose volume is dependent on regional blood flow and capillary recruitment. Second, the isolated perfused lung can accommodate up to 60% wt gain without much change in the regional distribution of EVLW, volume, or flow. PMID:765354

Case Report: Analytical Electron Microscopy of Lung Granulomas Associated with Exposure to Coating Materials Carried by Glass Wool Fibers

PubMed Central

Ferreira, Angela S.; Moreira, Valéria B.; Castro, Marcos César S.; Soares, Porfírio J.; Algranti, Eduardo; Andrade, Leonardo R.

2010-01-01

Context Man-made vitreous fibers (MMVFs) are noncrystalline inorganic fibrous material used for thermal and acoustical insulation (e.g., rock wool, glass wool, glass microfibers, and refractory ceramic fibers). Neither epidemiologic studies of human exposure nor animal studies have shown a noticeable hazardous effect of glass wools on health. However, MMVFs have been anecdotally associated with granulomatous lung disease in several case reports. Case presentation Here, we describe the case of a patient with multiple bilateral nodular opacities who was exposed to glass wool fibers and coating materials for 7 years. Bronchoalveolar lavage fluid revealed an increased total cell count (predominantly macrophages) with numerous cytoplasmic particles. Lung biopsy showed peribronchiolar infiltration of lymphoid cells and many foreign-body–type granulomas. Alveolar macrophages had numerous round and elongated platelike particles inside the cytoplasm. X-ray microanalysis of these particles detected mainly oxygen/aluminum/silicon and oxygen/magnesium/silicon, compatible with kaolinite and talc, respectively. No elemental evidence for glass fibers was found in lung biopsy. Discussion The contribution of analytical electron microscopy applied in the lung biopsy was imperative to confirm the diagnosis of pneumoconiosis associated with a complex occupational exposure that included both MMVFs and coating materials. Relevance to clinical or professional practice This case study points out the possible participation of other components (coating materials), beyond MMVFs, in the etiology of pneumoconiosis. PMID:20123612

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).

Anti-citrullinated protein antibodies are associated with neutrophil extracellular traps in the sputum in relatives of rheumatoid arthritis patients

PubMed Central

Demoruelle, M. Kristen; Harrall, Kylie K.; Ho, Linh; Purmalek, Monica M.; Seto, Nickie L.; Rothfuss, Heather M.; Weisman, Michael H.; Solomon, Joshua J.; Fischer, Aryeh; Okamoto, Yuko; Kelmenson, Lindsay B.; Parish, Mark C.; Feser, Marie; Fleischer, Chelsie; Anderson, Courtney; Mahler, Michael; Norris, Jill M.; Kaplan, Mariana J.; Cherrington, Brian D.; Holers, V. Michael; Deane, Kevin D.

2017-01-01

Objectives Studies suggest that rheumatoid arthritis (RA)-related autoimmunity is initiated at a mucosal site. However, the factors associated with the mucosal generation of this autoimmunity are unknown, especially in individuals who are at-risk for future RA. Therefore, we tested anti-cyclic citrullinated peptide (anti-CCP) antibodies in the sputum of RA-free first-degree relatives (FDRs) of RA patients and patients with classifiable RA. Methods We evaluated induced sputum and serum from 67 FDRs and 20 RA subjects for anti-CCP-IgA and anti-CCP-IgG, with cut-off levels for positivity determined in a control population. Sputum was also evaluated for cell counts, neutrophil extracellular traps (NETs) using sandwich ELISAs for protein/nucleic acid complexes, and total citrulline. Results Sputum anti-CCP-IgA and/or anti-CCP-IgG was positive in 17/67 (25%) FDRs and 14/20 (70%) RA subjects, including a portion of FDRs who were serum anti-CCP negative. In FDRs, elevations of sputum anti-CCP-IgA and anti-CCP-IgG were associated with elevated sputum cell counts and levels of NET complexes. Anti-CCP-IgA was associated with ever-smoking and elevated sputum citrulline levels. Conclusions Anti-CCP is elevated in the sputum of FDRs, including seronegative FDRs, suggesting the lung may be one site of anti-CCP generation in this population. The association of anti-CCP with elevated cell counts and NET levels in FDRs supports a hypothesis that local airway inflammation and NET formation may drive anti-CCP production in the lung and may promote the early stages of RA development. Longitudinal studies are needed to follow the evolution of these processes relative to the development of systemic autoimmunity and articular RA. PMID:28182854

Initial assessment of image quality for low-dose PET: evaluation of lesion detectability

NASA Astrophysics Data System (ADS)

Schaefferkoetter, Joshua D.; Yan, Jianhua; Townsend, David W.; Conti, Maurizio

2015-07-01

In the context of investigating the potential of low-dose PET imaging for screening applications, we developed methods to assess small lesion detectability as a function of the number of counts in the scan. We present here our methods and preliminary validation using tuberculosis cases. FDG-PET data from seventeen patients presenting diffuse hyper-metabolic lung lesions were selected for the study, to include a wide range of lesion sizes and contrasts. Reduced doses were simulated by randomly discarding events in the PET list mode, and ten realizations at each simulated dose were generated and reconstructed. The data were grouped into 9 categories determined by the number of included true events, from  >40 M to  <250 k counts. The images reconstructed from the original full statistical set were used to identify lung lesions, and each was, at every simulated dose, quantified by 6 parameters: lesion metabolic volume, lesion-to-background contrast, mean lesion tracer uptake, standard deviation of activity measurements (across realizations), lesion signal-to-noise ratio (SNR), and Hotelling observer SNR. Additionally, a lesion-detection task including 550 images was presented to several experienced image readers for qualitative assessment. Human observer performances were ranked using receiver operating characteristic analysis. The observer results were correlated with the lesion image measurements and used to train mathematical observer models. Absolute sensitivities and specificities of the human observers, as well as the area under the ROC curve, showed clustering and performance similarities among images produced from 5 million or greater counts. The results presented here are from a clinically realistic but highly constrained experiment, and more work is needed to validate these findings with a larger patient population.

Initial assessment of image quality for low-dose PET: evaluation of lesion detectability.

PubMed

Schaefferkoetter, Joshua D; Yan, Jianhua; Townsend, David W; Conti, Maurizio

2015-07-21

In the context of investigating the potential of low-dose PET imaging for screening applications, we developed methods to assess small lesion detectability as a function of the number of counts in the scan. We present here our methods and preliminary validation using tuberculosis cases. FDG-PET data from seventeen patients presenting diffuse hyper-metabolic lung lesions were selected for the study, to include a wide range of lesion sizes and contrasts. Reduced doses were simulated by randomly discarding events in the PET list mode, and ten realizations at each simulated dose were generated and reconstructed. The data were grouped into 9 categories determined by the number of included true events, from  >40 M to  <250 k counts. The images reconstructed from the original full statistical set were used to identify lung lesions, and each was, at every simulated dose, quantified by 6 parameters: lesion metabolic volume, lesion-to-background contrast, mean lesion tracer uptake, standard deviation of activity measurements (across realizations), lesion signal-to-noise ratio (SNR), and Hotelling observer SNR. Additionally, a lesion-detection task including 550 images was presented to several experienced image readers for qualitative assessment. Human observer performances were ranked using receiver operating characteristic analysis. The observer results were correlated with the lesion image measurements and used to train mathematical observer models. Absolute sensitivities and specificities of the human observers, as well as the area under the ROC curve, showed clustering and performance similarities among images produced from 5 million or greater counts. The results presented here are from a clinically realistic but highly constrained experiment, and more work is needed to validate these findings with a larger patient population.

Population pharmacokinetic-pharmacodynamic modeling and model-based prediction of docetaxel-induced neutropenia in Japanese patients with non-small cell lung cancer.

PubMed

Fukae, Masato; Shiraishi, Yoshimasa; Hirota, Takeshi; Sasaki, Yuka; Yamahashi, Mika; Takayama, Koichi; Nakanishi, Yoichi; Ieiri, Ichiro

2016-11-01

Docetaxel is used to treat many cancers, and neutropenia is the dose-limiting factor for its clinical use. A population pharmacokinetic-pharmacodynamic (PK-PD) model was introduced to predict the development of docetaxel-induced neutropenia in Japanese patients with non-small cell lung cancer (NSCLC). Forty-seven advanced or recurrent Japanese patients with NSCLC were enrolled. Patients received 50 or 60 mg/m 2 docetaxel as monotherapy, and blood samples for a PK analysis were collected up to 24 h after its infusion. Laboratory tests including absolute neutrophil count data and demographic information were used in population PK-PD modeling. The model was built by NONMEM 7.2 with a first-order conditional estimation using an interaction method. Based on the final model, a Monte Carlo simulation was performed to assess the impact of covariates on and the predictability of neutropenia. A three-compartment model was employed to describe PK data, and the PK model adequately described the docetaxel concentrations observed. Serum albumin (ALB) was detected as a covariate of clearance (CL): CL (L/h) = 32.5 × (ALB/3.6) 0.965  × (WGHT/70) 3/4 . In population PK-PD modeling, a modified semi-mechanistic myelosuppression model was applied, and characterization of the time course of neutrophil counts was adequate. The covariate selection indicated that α1-acid glycoprotein (AAG) was a predictor of neutropenia. The model-based simulation also showed that ALB and AAG negatively correlated with the development of neutropenia and that the time course of neutrophil counts was predictable. The developed model may facilitate the prediction and care of docetaxel-induced neutropenia.

Cyto-adherence of Mycoplasma mycoides subsp. mycoides to bovine lung epithelial cells.

PubMed

Aye, Racheal; Mwirigi, Martin Kiogora; Frey, Joachim; Pilo, Paola; Jores, Joerg; Naessens, Jan

2015-02-07

Mycoplasma mycoides subsp. mycoides (Mmm) is the causative agent of contagious bovine pleuropneumonia (CBPP), a respiratory disease of cattle, whereas the closely related Mycoplasma mycoides subsp. capri (Mmc) is a goat pathogen. Cyto-adherence is a crucial step in host colonization by mycoplasmas and subsequent pathogenesis. The aim of this study was to investigate the interactions between Mmm and mammalian host cells by establishing a cyto-adherence flow cytometric assay and comparing tissue and species specificity of Mmm and Mmc strains. There were little significant differences in the adherence patterns of eight different Mmm strains to adult bovine lung epithelial cells. However, there was statistically significant variation in binding to different host cells types. Highest binding was observed with lung epithelial cells, intermediate binding with endothelial cells and very low binding with fibroblasts, suggesting the presence of effective adherence of Mmm on cells lining the airways of the lung, which is the target organ for this pathogen, possibly by high expression of a specific receptor. However, binding to bovine fetal lung epithelial cells was comparably low; suggesting that the lack of severe pulmonary disease seen in many infected young calves can be explained by reduced expression of a specific receptor. Mmm bound with high efficiency to adult bovine lung cells and less efficiently to calves or goat lung cells. The data show that cyto-adherence of Mmm is species- and tissue- specific confirming its role in colonization of the target host and subsequent infection and development of CBPP.

Volume calculation of CT lung lesions based on Halton low-discrepancy sequences

NASA Astrophysics Data System (ADS)

Li, Shusheng; Wang, Liansheng; Li, Shuo

2017-03-01

Volume calculation from the Computed Tomography (CT) lung lesions data is a significant parameter for clinical diagnosis. The volume is widely used to assess the severity of the lung nodules and track its progression, however, the accuracy and efficiency of previous studies are not well achieved for clinical uses. It remains to be a challenging task due to its tight attachment to the lung wall, inhomogeneous background noises and large variations in sizes and shape. In this paper, we employ Halton low-discrepancy sequences to calculate the volume of the lung lesions. The proposed method directly compute the volume without the procedure of three-dimension (3D) model reconstruction and surface triangulation, which significantly improves the efficiency and reduces the complexity. The main steps of the proposed method are: (1) generate a certain number of random points in each slice using Halton low-discrepancy sequences and calculate the lesion area of each slice through the proportion; (2) obtain the volume by integrating the areas in the sagittal direction. In order to evaluate our proposed method, the experiments were conducted on the sufficient data sets with different size of lung lesions. With the uniform distribution of random points, our proposed method achieves more accurate results compared with other methods, which demonstrates the robustness and accuracy for the volume calculation of CT lung lesions. In addition, our proposed method is easy to follow and can be extensively applied to other applications, e.g., volume calculation of liver tumor, atrial wall aneurysm, etc.

Subchronic inhalation toxicity of gold nanoparticles

PubMed Central

2011-01-01

Background Gold nanoparticles are widely used in consumer products, including cosmetics, food packaging, beverages, toothpaste, automobiles, and lubricants. With this increase in consumer products containing gold nanoparticles, the potential for worker exposure to gold nanoparticles will also increase. Only a few studies have produced data on the in vivo toxicology of gold nanoparticles, meaning that the absorption, distribution, metabolism, and excretion (ADME) of gold nanoparticles remain unclear. Results The toxicity of gold nanoparticles was studied in Sprague Dawley rats by inhalation. Seven-week-old rats, weighing approximately 200 g (males) and 145 g (females), were divided into 4 groups (10 rats in each group): fresh-air control, low-dose (2.36 × 104 particle/cm3, 0.04 μg/m3), middle-dose (2.36 × 105 particle/cm3, 0.38 μg/m3), and high-dose (1.85 × 106 particle/cm3, 20.02 μg/m3). The animals were exposed to gold nanoparticles (average diameter 4-5 nm) for 6 hours/day, 5 days/week, for 90-days in a whole-body inhalation chamber. In addition to mortality and clinical observations, body weight, food consumption, and lung function were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for hematology and clinical chemistry tests, and organ weights were measured. Cellular differential counts and cytotoxicity measurements, such as albumin, lactate dehydrogenase (LDH), and total protein were also monitored in a cellular bronchoalveolar lavage (BAL) fluid. Among lung function test measurements, tidal volume and minute volume showed a tendency to decrease comparing control and dose groups during the 90-days of exposure. Although no statistically significant differences were found in cellular differential counts, histopathologic examination showed minimal alveoli, an inflammatory infiltrate with a mixed cell type, and increased macrophages in the high-dose rats. Tissue distribution of gold nanoparticles showed a dose-dependent accumulation of gold in only lungs and kidneys with a gender-related difference in gold nanoparticles content in kidneys. Conclusions Lungs were the only organ in which there were dose-related changes in both male and female rats. Changes observed in lung histopathology and function in high-dose animals indicate that the highest concentration (20 μg/m3) is a LOAEL and the middle concentration (0.38 μg/m3) is a NOAEL for this study. PMID:21569586

The peroxisome proliferator-activated receptor agonist pioglitazone and 5-lipoxygenase inhibitor zileuton have no effect on lung inflammation in healthy volunteers by positron emission tomography in a single-blind placebo-controlled cohort study.

PubMed

Chen, Delphine L; Huang, Howard J; Byers, Derek E; Shifren, Adrian; Belikoff, Bryan; Engle, Jacquelyn T; Arentson, Elizabeth; Kemp, Debra; Phillips, Sharon; Scherrer, David E; Fujiwara, Hideji; Spayd, Katherine J; Brooks, Frank J; Pierce, Richard A; Castro, Mario; Isakow, Warren

2018-01-01

Anti-inflammatory drug development efforts for lung disease have been hampered in part by the lack of noninvasive inflammation biomarkers and the limited ability of animal models to predict efficacy in humans. We used 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in a human model of lung inflammation to assess whether pioglitazone, a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, and zileuton, a 5-lipoxygenase inhibitor, reduce lung inflammation. For this single center, single-blind, placebo-controlled cohort study, we enrolled healthy volunteers sequentially into the following treatment cohorts (N = 6 per cohort): pioglitazone plus placebo, zileuton plus placebo, or dual placebo prior to bronchoscopic endotoxin instillation. 18F-FDG uptake pre- and post-endotoxin was quantified as the Patlak graphical analysis-determined Ki (primary outcome measure). Secondary outcome measures included the mean standard uptake value (SUVmean), post-endotoxin bronchoalveolar lavage (BAL) cell counts and differentials and blood adiponectin and urinary leukotriene E4 (LTE4) levels, determined by enzyme-linked immunosorbent assay, to verify treatment compliance. One- or two-way analysis of variance assessed for differences among cohorts in the outcome measures (expressed as mean ± standard deviation). Ten females and eight males (29±6 years of age) completed all study procedures except for one volunteer who did not complete the post-endotoxin BAL. Ki and SUVmean increased in all cohorts after endotoxin instillation (Ki increased by 0.0021±0.0019, 0.0023±0.0017, and 0.0024±0.0020 and SUVmean by 0.47±0.14, 0.55±0.15, and 0.54±0.38 in placebo, pioglitazone, and zileuton cohorts, respectively, p<0.001) with no differences among treatment cohorts (p = 0.933). Adiponectin levels increased as expected with pioglitazone treatment but not urinary LTE4 levels as expected with zileuton treatment. BAL cell counts (p = 0.442) and neutrophil percentage (p = 0.773) were similar among the treatment cohorts. Endotoxin-induced lung inflammation in humans is not responsive to pioglitazone or zileuton, highlighting the challenge in translating anti-inflammatory drug efficacy results from murine models to humans. ClinicalTrials.gov NCT01174056.

The peroxisome proliferator-activated receptor agonist pioglitazone and 5-lipoxygenase inhibitor zileuton have no effect on lung inflammation in healthy volunteers by positron emission tomography in a single-blind placebo-controlled cohort study

PubMed Central

Huang, Howard J.; Byers, Derek E.; Shifren, Adrian; Belikoff, Bryan; Engle, Jacquelyn T.; Arentson, Elizabeth; Kemp, Debra; Phillips, Sharon; Scherrer, David E.; Fujiwara, Hideji; Spayd, Katherine J.; Brooks, Frank J.; Pierce, Richard A.; Castro, Mario; Isakow, Warren

2018-01-01

Background Anti-inflammatory drug development efforts for lung disease have been hampered in part by the lack of noninvasive inflammation biomarkers and the limited ability of animal models to predict efficacy in humans. We used 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in a human model of lung inflammation to assess whether pioglitazone, a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, and zileuton, a 5-lipoxygenase inhibitor, reduce lung inflammation. Methods For this single center, single-blind, placebo-controlled cohort study, we enrolled healthy volunteers sequentially into the following treatment cohorts (N = 6 per cohort): pioglitazone plus placebo, zileuton plus placebo, or dual placebo prior to bronchoscopic endotoxin instillation. 18F-FDG uptake pre- and post-endotoxin was quantified as the Patlak graphical analysis-determined Ki (primary outcome measure). Secondary outcome measures included the mean standard uptake value (SUVmean), post-endotoxin bronchoalveolar lavage (BAL) cell counts and differentials and blood adiponectin and urinary leukotriene E4 (LTE4) levels, determined by enzyme-linked immunosorbent assay, to verify treatment compliance. One- or two-way analysis of variance assessed for differences among cohorts in the outcome measures (expressed as mean ± standard deviation). Results Ten females and eight males (29±6 years of age) completed all study procedures except for one volunteer who did not complete the post-endotoxin BAL. Ki and SUVmean increased in all cohorts after endotoxin instillation (Ki increased by 0.0021±0.0019, 0.0023±0.0017, and 0.0024±0.0020 and SUVmean by 0.47±0.14, 0.55±0.15, and 0.54±0.38 in placebo, pioglitazone, and zileuton cohorts, respectively, p<0.001) with no differences among treatment cohorts (p = 0.933). Adiponectin levels increased as expected with pioglitazone treatment but not urinary LTE4 levels as expected with zileuton treatment. BAL cell counts (p = 0.442) and neutrophil percentage (p = 0.773) were similar among the treatment cohorts. Conclusions Endotoxin-induced lung inflammation in humans is not responsive to pioglitazone or zileuton, highlighting the challenge in translating anti-inflammatory drug efficacy results from murine models to humans. Trial registration ClinicalTrials.gov NCT01174056. PMID:29414995

Inhaled chemotherapy in lung cancer: future concept of nanomedicine

PubMed Central

Zarogoulidis, Paul; Chatzaki, Ekaterini; Porpodis, Konstantinos; Domvri, Kalliopi; Hohenforst-Schmidt, Wolfgang; Goldberg, Eugene P; Karamanos, Nikos; Zarogoulidis, Konstantinos

2012-01-01

Regional chemotherapy was first used for lung cancer 30 years ago. Since then, new methods of drug delivery and pharmaceuticals have been investigated in vitro, and in animals and humans. An extensive review of drug delivery systems, pharmaceuticals, patient monitoring, methods of enhancing inhaled drug deposition, safety and efficacy, and also additional applications of inhaled chemotherapy and its advantages and disadvantages are presented. Regional chemotherapy to the lung parenchyma for lung cancer is feasible and efficient. Safety depends on the chemotherapy agent delivered to the lungs and is dose-dependent and time-dependent. Further evaluation is needed to provide data regarding early lung cancer stages, and whether regional chemotherapy can be used as neoadjuvant or adjuvant treatment. Finally, inhaled chemotherapy could one day be administered at home with fewer systemic adverse effects. PMID:22619512

Division of methods for counting helminths' eggs and the problem of efficiency of these methods.

PubMed

Jaromin-Gleń, Katarzyna; Kłapeć, Teresa; Łagód, Grzegorz; Karamon, Jacek; Malicki, Jacek; Skowrońska, Agata; Bieganowski, Andrzej

2017-03-21

From the sanitary and epidemiological aspects, information concerning the developmental forms of intestinal parasites, especially the eggs of helminths present in our environment in: water, soil, sandpits, sewage sludge, crops watered with wastewater are very important. The methods described in the relevant literature may be classified in various ways, primarily according to the methodology of the preparation of samples from environmental matrices prepared for analysis, and the sole methods of counting and chambers/instruments used for this purpose. In addition, there is a possibility to perform the classification of the research methods analyzed from the aspect of the method and time of identification of the individuals counted, or the necessity for staining them. Standard methods for identification of helminths' eggs from environmental matrices are usually characterized by low efficiency, i.e. from 30% to approximately 80%. The efficiency of the method applied may be measured in a dual way, either by using the method of internal standard or the 'Split/Spike' method. While measuring simultaneously in an examined object the efficiency of the method and the number of eggs, the 'actual' number of eggs may be calculated by multiplying the obtained value of the discovered eggs of helminths by inverse efficiency.

Neutrophil elastase inhibitor, ONO-5046, modulates acid-induced lung and systemic injury in rabbits.

PubMed

Kaneko, K; Kudoh, I; Hattori, S; Yamada, H; Ohara, M; Wiener-Kronish, J; Okumura, F

1997-09-01

Acid instillation leads to direct lung and to secondary systemic organ injury, probably via activated macrophages and neutrophils. This study investigated the effects of neutrophil elastase on organ injury after unilateral lung acid instillation by administrating a specific neutrophil elastase inhibitor, ONO-5046, before acid instillation. Three groups of anesthetized rabbits (n = 12 in each group) underwent tracheostomies, and instillations were made into their right lower lobe airspaces with either phosphate buffered saline (pH, 7.4; volume, 1.2 ml/kg; n = 12) or HCl (pH, 1.25; volume, 1.2 ml/kg; n = 24). In half of the acid-instilled rabbits, ONO-5046, 10 mg/kg, was given intravenously 15 min before the HCl instillation, and then 10 mg x kg(-1) x h(-1) of the drug was continuously infused throughout the experiment. The other groups of animals received the vehicle intravenously. Anesthesia and mechanical ventilation was continued for 8 h, whereas arterial blood gases were sampled intermittently. Eight hours after saline or acid instillation, the animals were killed, and their lungs, heart, kidneys, liver, and small intestines were harvested. Wet-to-dry weight ratios (W/ D) and myeloperoxidase (MPO) assays of these organs were done, and elastase assays on the bronchoalveolar lavage fluids (BALF) obtained from each lung also were performed. Pretreatment with ONO-5046 attenuated the physiologic changes seen in the vehicle-treated animals. Significant decreases in W/D of the noninstilled lungs and of the small intestine and normalization of the oxygenation of the experimental animals occurred. The ONO-5046 pretreatment did not affect the neutrophil sequestration in the lungs or in the other organs as determined by neutrophil counts in BALF and by the MPO assays. A neutrophil elastase inhibitor, ONO-5046, administered immediately before acid instillation attenuated the physiologic changes seen in the vehicle-treated animals. The drug blocked neutrophil elastase but did not block neutrophil sequestration in the lungs, although the drug improved measurements of lung injury.

Immunodeficiency, AIDS-related pneumonia, and risk of lung cancer among HIV-infected individuals.

PubMed

Marcus, Julia L; Leyden, Wendy A; Chao, Chun R; Horberg, Michael A; Klein, Daniel B; Quesenberry, Charles P; Towner, William J; Silverberg, Michael J

2017-04-24

The objective is to clarify the role of immunodeficiency and pneumonia in elevated lung cancer risk among HIV-infected individuals. Cohort study of HIV-infected and HIV-uninfected adults in a large integrated healthcare system in California during 1996-2011. We used Poisson models to obtain rate ratios for lung cancer associated with HIV infection, overall and stratified by recent CD4 cells/μl (HIV-uninfected as reference group), with χ tests for trends across CD4 strata. Fully adjusted models included demographics, cancer risk factors (smoking, drug/alcohol abuse, overweight/obesity), and prior pneumonia. Among 24 768 HIV-infected and 257 600 HIV-uninfected individuals, the lung cancer rate per 100 000 person-years was 66 (n = 80 events) for HIV-infected and 33 (n = 506 events) for HIV-uninfected individuals [rate ratio 2.0, 95% confidence interval (CI): 1.7-2.2]. Overall, HIV-infected individuals were at increased risk of lung cancer after adjustment for demographics and cancer risk factors (rate ratio 1.4, 95% CI: 1.1-1.7), but not after additional adjustment for pneumonia (rate ratio 1.2, 95% CI: 0.9-1.6). Lower CD4 cell counts were associated with higher risk of lung cancer in unadjusted and demographics-adjusted models (P < 0.001 for all), but this trend did not remain after adjustment for cancer risk factors and pneumonia. Compared with HIV-uninfected individuals, HIV-infected individuals with CD4 less than 200 cells/μl were not at increased risk of lung cancer in fully adjusted models. The increased lung cancer risk among HIV patients is attributable to differences in demographics, risk factors such as smoking, and history of pneumonia. Immunodeficiency does not appear to have an independent effect on lung cancer risk.

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.

Three-dimensional computed tomographic volumetry precisely predicts the postoperative pulmonary function.

PubMed

Kobayashi, Keisuke; Saeki, Yusuke; Kitazawa, Shinsuke; Kobayashi, Naohiro; Kikuchi, Shinji; Goto, Yukinobu; Sakai, Mitsuaki; Sato, Yukio

2017-11-01

It is important to accurately predict the patient's postoperative pulmonary function. The aim of this study was to compare the accuracy of predictions of the postoperative residual pulmonary function obtained with three-dimensional computed tomographic (3D-CT) volumetry with that of predictions obtained with the conventional segment-counting method. Fifty-three patients scheduled to undergo lung cancer resection, pulmonary function tests, and computed tomography were enrolled in this study. The postoperative residual pulmonary function was predicted based on the segment-counting and 3D-CT volumetry methods. The predicted postoperative values were compared with the results of postoperative pulmonary function tests. Regarding the linear correlation coefficients between the predicted postoperative values and the measured values, those obtained using the 3D-CT volumetry method tended to be higher than those acquired using the segment-counting method. In addition, the variations between the predicted and measured values were smaller with the 3D-CT volumetry method than with the segment-counting method. These results were more obvious in COPD patients than in non-COPD patients. Our findings suggested that the 3D-CT volumetry was able to predict the residual pulmonary function more accurately than the segment-counting method, especially in patients with COPD. This method might lead to the selection of appropriate candidates for surgery among patients with a marginal pulmonary function.

Transfection efficiency and uptake process of polyplexes in human lung endothelial cells: a comparative study in non-polarized and polarized cells.

PubMed

Mennesson, Eric; Erbacher, Patrick; Piller, Véronique; Kieda, Claudine; Midoux, Patrick; Pichon, Chantal

2005-06-01

Following systemic administration, polyplexes must cross the endothelium barrier to deliver genes to the target cells underneath. To design an efficient gene delivery system into lung epithelium, we evaluated capture and transfection efficiencies of DNA complexed with either Jet-PEI (PEI-polyplexes) or histidylated polylysine (His-polyplexes) in human lung microvascular endothelial cells (HLMEC) and tracheal epithelial cells. After optimizing growth conditions to obtain a tight HLMEC monolayer, we characterized uptake of polyplexes by flow cytometry and evaluated their transfection efficiency. Polyplexes were formulated as small particles. YOYO-labelled plasmid fluorescence intensity and luciferase activity were used as readouts for uptake and gene expression, respectively. PEI-polyplexes were more efficiently taken up than His-polyplexes by both non-polarized (2-fold) and polarized HLMEC (10-fold). They were mainly internalized by a clathrin-dependent pathway whatever the cell state. In non-polarized cells, His-polyplexes entered also mainly via a clathrin-dependent pathway but with an involvement of cholesterol. The cell polarization decreased this way and a clathrin-independent pathway became predominant. PEI-polyplexes transfected more efficiently HLMEC than His-polyplexes (10(7) vs. 10(5) relative light units (RLU)/mg of proteins) with a more pronounced difference in polarized cells. In contrast, no negative effect of the cell polarization was observed with tracheal epithelial cells in which both polyplexes had comparable efficiency. We show that the efficiency of polyplex uptake by HLMEC and their internalization mechanism are polymer-dependent. By contrast with His-polyplexes, the HLMEC polarization has little influence on the uptake process and on the transfection efficiency of PEI-polyplexes. Copyright (c) 2005 John Wiley & Sons, Ltd.

Single Photon Counting UV Solar-Blind Detectors Using Silicon and III-Nitride Materials

PubMed Central

Nikzad, Shouleh; Hoenk, Michael; Jewell, April D.; Hennessy, John J.; Carver, Alexander G.; Jones, Todd J.; Goodsall, Timothy M.; Hamden, Erika T.; Suvarna, Puneet; Bulmer, J.; Shahedipour-Sandvik, F.; Charbon, Edoardo; Padmanabhan, Preethi; Hancock, Bruce; Bell, L. Douglas

2016-01-01

Ultraviolet (UV) studies in astronomy, cosmology, planetary studies, biological and medical applications often require precision detection of faint objects and in many cases require photon-counting detection. We present an overview of two approaches for achieving photon counting in the UV. The first approach involves UV enhancement of photon-counting silicon detectors, including electron multiplying charge-coupled devices and avalanche photodiodes. The approach used here employs molecular beam epitaxy for delta doping and superlattice doping for surface passivation and high UV quantum efficiency. Additional UV enhancements include antireflection (AR) and solar-blind UV bandpass coatings prepared by atomic layer deposition. Quantum efficiency (QE) measurements show QE > 50% in the 100–300 nm range for detectors with simple AR coatings, and QE ≅ 80% at ~206 nm has been shown when more complex AR coatings are used. The second approach is based on avalanche photodiodes in III-nitride materials with high QE and intrinsic solar blindness. PMID:27338399

Direct Detection Electron Energy-Loss Spectroscopy: A Method to Push the Limits of Resolution and Sensitivity.

PubMed

Hart, James L; Lang, Andrew C; Leff, Asher C; Longo, Paolo; Trevor, Colin; Twesten, Ray D; Taheri, Mitra L

2017-08-15

In many cases, electron counting with direct detection sensors offers improved resolution, lower noise, and higher pixel density compared to conventional, indirect detection sensors for electron microscopy applications. Direct detection technology has previously been utilized, with great success, for imaging and diffraction, but potential advantages for spectroscopy remain unexplored. Here we compare the performance of a direct detection sensor operated in counting mode and an indirect detection sensor (scintillator/fiber-optic/CCD) for electron energy-loss spectroscopy. Clear improvements in measured detective quantum efficiency and combined energy resolution/energy field-of-view are offered by counting mode direct detection, showing promise for efficient spectrum imaging, low-dose mapping of beam-sensitive specimens, trace element analysis, and time-resolved spectroscopy. Despite the limited counting rate imposed by the readout electronics, we show that both core-loss and low-loss spectral acquisition are practical. These developments will benefit biologists, chemists, physicists, and materials scientists alike.

FPGA-based photon-counting phase-modulation fluorometer and a brief comparison with that operated in a pulsed-excitation mode

NASA Astrophysics Data System (ADS)

Iwata, Tetsuo; Taga, Takanori; Mizuno, Takahiko

2018-02-01

We have constructed a high-efficiency, photon-counting phase-modulation fluorometer (PC-PMF) using a field-programmable gate array, which is a modified version of the photon-counting fluorometer (PCF) that works in a pulsed-excitation mode (Iwata and Mizuno in Meas Sci Technol 28:075501, 2017). The common working principle for both is the simultaneous detection of the photoelectron pulse train, which covers 64 ns with a 1.0-ns resolution time (1.0 ns/channel). The signal-gathering efficiency was improved more than 100 times over that of conventional time-correlated single-photon-counting at the expense of resolution time depending on the number of channels. The system dead time for building a histogram was eliminated, markedly shortening the measurement time for fluorescent samples with moderately high quantum yields. We describe the PC-PMF and make a brief comparison with the pulsed-excitation PCF in precision, demonstrating the potential advantage of PC-PMF.

Single Photon Counting UV Solar-Blind Detectors Using Silicon and III-Nitride Materials.

PubMed

Nikzad, Shouleh; Hoenk, Michael; Jewell, April D; Hennessy, John J; Carver, Alexander G; Jones, Todd J; Goodsall, Timothy M; Hamden, Erika T; Suvarna, Puneet; Bulmer, J; Shahedipour-Sandvik, F; Charbon, Edoardo; Padmanabhan, Preethi; Hancock, Bruce; Bell, L Douglas

2016-06-21

Ultraviolet (UV) studies in astronomy, cosmology, planetary studies, biological and medical applications often require precision detection of faint objects and in many cases require photon-counting detection. We present an overview of two approaches for achieving photon counting in the UV. The first approach involves UV enhancement of photon-counting silicon detectors, including electron multiplying charge-coupled devices and avalanche photodiodes. The approach used here employs molecular beam epitaxy for delta doping and superlattice doping for surface passivation and high UV quantum efficiency. Additional UV enhancements include antireflection (AR) and solar-blind UV bandpass coatings prepared by atomic layer deposition. Quantum efficiency (QE) measurements show QE > 50% in the 100-300 nm range for detectors with simple AR coatings, and QE ≅ 80% at ~206 nm has been shown when more complex AR coatings are used. The second approach is based on avalanche photodiodes in III-nitride materials with high QE and intrinsic solar blindness.

Single photon detection in a waveguide-coupled Ge-on-Si lateral avalanche photodiode.

PubMed

Martinez, Nicholas J D; Gehl, Michael; Derose, Christopher T; Starbuck, Andrew L; Pomerene, Andrew T; Lentine, Anthony L; Trotter, Douglas C; Davids, Paul S

2017-07-10

We examine gated-Geiger mode operation of an integrated waveguide-coupled Ge-on-Si lateral avalanche photodiode (APD) and demonstrate single photon detection at low dark count for this mode of operation. Our integrated waveguide-coupled APD is fabricated using a selective epitaxial Ge-on-Si growth process resulting in a separate absorption and charge multiplication (SACM) design compatible with our silicon photonics platform. Single photon detection efficiency and dark count rate is measured as a function of temperature in order to understand and optimize performance characteristics in this device. We report single photon detection of 5.27% at 1310 nm and a dark count rate of 534 kHz at 80 K for a Ge-on-Si single photon avalanche diode. Dark count rate is the lowest for a Ge-on-Si single photon detector in this range of temperatures while maintaining competitive detection efficiency. A jitter of 105 ps was measured for this device.

CXC chemokine ligand 4 (CXCL4) is predictor of tumour angiogenic activity and prognostic biomarker in non-small cell lung cancer (NSCLC) patients undergoing surgical treatment.

PubMed

Spaks, Artjoms; Svirina, Darja; Spaka, Irina; Jaunalksne, Inta; Breiva, Donats; Tracums, Ilmars; Krievins, Dainis

2016-07-01

To evaluate the association of CXC chemokine ligand 4 (CXCL4) plasma levels with tumour angiogenesis in non-small cell lung cancer (NSCLC) and to assess association of CXCL4 with clinical outcomes. Fifty patients with early stage NSCLC who underwent pulmonary resection. CXCL4 levels were analysed by ELISA. Angiogenesis was assessed by immunohistochemistry, and microvessel density (MVD) count. There was positive correlation between MVD and CXCL4 levels. Patients with higher CXCL4 levels had worse overall and disease-free survival. Plasma levels of CXCL4 are associated with tumour vascularity. Increased CXCL4 levels in NSCLC patients undergoing treatment may indicate active cancer-induced angiogenesis associated with relapse and worse outcome.

Modeling the frequency-dependent detective quantum efficiency of photon-counting x-ray detectors.

PubMed

Stierstorfer, Karl

2018-01-01

To find a simple model for the frequency-dependent detective quantum efficiency (DQE) of photon-counting detectors in the low flux limit. Formula for the spatial cross-talk, the noise power spectrum and the DQE of a photon-counting detector working at a given threshold are derived. Parameters are probabilities for types of events like single counts in the central pixel, double counts in the central pixel and a neighboring pixel or single count in a neighboring pixel only. These probabilities can be derived in a simple model by extensive use of Monte Carlo techniques: The Monte Carlo x-ray propagation program MOCASSIM is used to simulate the energy deposition from the x-rays in the detector material. A simple charge cloud model using Gaussian clouds of fixed width is used for the propagation of the electric charge generated by the primary interactions. Both stages are combined in a Monte Carlo simulation randomizing the location of impact which finally produces the required probabilities. The parameters of the charge cloud model are fitted to the spectral response to a polychromatic spectrum measured with our prototype detector. Based on the Monte Carlo model, the DQE of photon-counting detectors as a function of spatial frequency is calculated for various pixel sizes, photon energies, and thresholds. The frequency-dependent DQE of a photon-counting detector in the low flux limit can be described with an equation containing only a small set of probabilities as input. Estimates for the probabilities can be derived from a simple model of the detector physics. © 2017 American Association of Physicists in Medicine.

Metyrapone Alleviates Deleterious Effects of Maternal Food Restriction on Lung Development and Growth of Rat Offspring

PubMed Central

Paek, David S.; Sakurai, Reiko; Saraswat, Aditi; Li, Yishi; Khorram, Omid; Torday, John S.

2015-01-01

Maternal food restriction (MFR) causes intrauterine growth restriction, a known risk factor for developing chronic lung disease. However, it is unknown whether this negative outcome is gender specific or preventable by blocking the MFR-induced hyperglucocorticoidism. Using a well-established rat model, we used metyrapone (MTP), an inhibitor of glucocorticoid synthesis, to study the MFR-induced lung changes on postnatal day (p) 21 in a gender-specific manner. From embryonic day 10 until delivery, pregnant dams were fed either an ad libitum diet or a 50% caloric restricted diet with or without MTP supplementation. Postnatally, the offspring were fed ad libitum from healthy dams until p21. Morphometric, Western blot, and immunohistochemical analysis of the lungs demonstrated that MTP mitigated the MFR-mediated decrease in alveolar count, decrease in adipogenic protein peroxisome proliferator-activated receptor γ, increase in myogenic proteins (fibronectin, α-smooth muscle actin, and calponin), increase in Wnt signaling intermediates (lymphoid enhancer-binding factor 1 and β-catenin), and increase in glucocorticoid receptor (GR) levels. The MFR-induced lung phenotype and the effects of MTP were similar in both genders. To elucidate the mechanism of MFR-induced shift of the adipogenic-to-myogenic phenotype, lung fibroblasts were used to independently study the effects of (1) nutrient restriction and (2) excess steroid exposure. Nutrient deprivation increased myogenic proteins, Wnt signaling intermediates, and GR, all changes blocked by protein supplementation. MTP also blocked, likely by normalizing nicotinamide adenine dinucleotide phosphate levels, the corticosterone-induced increase in myogenic proteins, but had no effect on GR levels. In summary, protein restriction and increased glucocorticoid levels appear to be the key players in MFR-induced lung disease, affecting both genders. PMID:24916330

Metyrapone alleviates deleterious effects of maternal food restriction on lung development and growth of rat offspring.

PubMed

Paek, David S; Sakurai, Reiko; Saraswat, Aditi; Li, Yishi; Khorram, Omid; Torday, John S; Rehan, Virender K

2015-02-01

Maternal food restriction (MFR) causes intrauterine growth restriction, a known risk factor for developing chronic lung disease. However, it is unknown whether this negative outcome is gender specific or preventable by blocking the MFR-induced hyperglucocorticoidism. Using a well-established rat model, we used metyrapone (MTP), an inhibitor of glucocorticoid synthesis, to study the MFR-induced lung changes on postnatal day (p) 21 in a gender-specific manner. From embryonic day 10 until delivery, pregnant dams were fed either an ad libitum diet or a 50% caloric restricted diet with or without MTP supplementation. Postnatally, the offspring were fed ad libitum from healthy dams until p21. Morphometric, Western blot, and immunohistochemical analysis of the lungs demonstrated that MTP mitigated the MFR-mediated decrease in alveolar count, decrease in adipogenic protein peroxisome proliferator-activated receptor γ, increase in myogenic proteins (fibronectin, α-smooth muscle actin, and calponin), increase in Wnt signaling intermediates (lymphoid enhancer-binding factor 1 and β-catenin), and increase in glucocorticoid receptor (GR) levels. The MFR-induced lung phenotype and the effects of MTP were similar in both genders. To elucidate the mechanism of MFR-induced shift of the adipogenic-to-myogenic phenotype, lung fibroblasts were used to independently study the effects of (1) nutrient restriction and (2) excess steroid exposure. Nutrient deprivation increased myogenic proteins, Wnt signaling intermediates, and GR, all changes blocked by protein supplementation. MTP also blocked, likely by normalizing nicotinamide adenine dinucleotide phosphate levels, the corticosterone-induced increase in myogenic proteins, but had no effect on GR levels. In summary, protein restriction and increased glucocorticoid levels appear to be the key players in MFR-induced lung disease, affecting both genders. © The Author(s) 2014.

Development of an automated size-based filtration system for isolation of circulating tumor cells in lung cancer patients.

PubMed

Yagi, Satomi; Koh, Yasuhiro; Akamatsu, Hiroaki; Kanai, Kuninobu; Hayata, Atsushi; Tokudome, Nahomi; Akamatsu, Keiichiro; Endo, Katsuya; Nakamura, Seita; Higuchi, Masayuki; Kanbara, Hisashige; Nakanishi, Masanori; Ueda, Hiroki; Yamamoto, Nobuyuki

2017-01-01

Circulating tumor cells (CTCs), defined as tumor cells circulating in the peripheral blood of patients with solid tumors, are relatively rare. Diagnosis using CTCs is expected to help in the decision-making for precision cancer medicine. We have developed an automated microcavity array (MCA) system to detect CTCs based on the differences in size and deformability between tumor cells and normal blood cells. Herein, we evaluated the system using blood samples from non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) patients. To evaluate the recovery of CTCs, preclinical experiments were performed by spiking NSCLC cell lines (NCI-H820, A549, NCI-H23 and NCI-H441) into peripheral whole blood samples from healthy volunteers. The recovery rates were 70% or more in all cell lines. For clinical evaluation, 6 mL of peripheral blood was collected from 50 patients with advanced lung cancer and from 10 healthy donors. Cells recovered on the filter were stained. We defined CTCs as DAPI-positive, cytokeratin-positive, and CD45-negative cells under the fluorescence microscope. The 50 lung cancer patients had a median age of 72 years (range, 48-85 years); 76% had NSCLC and 20% had SCLC, and 14% were at stage III disease whereas 86% were at stage IV. One or more CTCs were detected in 80% of the lung cancer patients (median 2.5). A comparison of the CellSearch system with our MCA system, using the samples from NSCLC patients, confirmed the superiority of our system (median CTC count, 0 versus 11 for CellSearch versus MCA; p = 0.0001, n = 17). The study results suggest that our MCA system has good clinical potential for diagnosing CTCs in lung cancer.

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

PubMed

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

2011-01-01

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

Short-term inhalation of stainless steel welding fume causes sustained lung toxicity but no tumorigenesis in lung tumor susceptible A/J mice.

PubMed

Zeidler-Erdely, Patti C; Battelli, Lori A; Stone, Sam; Chen, Bean T; Frazer, David G; Young, Shih-Houng; Erdely, Aaron; Kashon, Michael L; Andrews, Ronnee; Antonini, James M

2011-02-01

Debate exists as to whether welding fume is carcinogenic, but epidemiological evidence suggests that welders are an at-risk population for development of lung cancer. Our objective was to expose, by inhalation, lung tumor susceptible (A/J) and resistant C57BL/6J (B6) mice to stainless steel (SS) welding fume containing carcinogenic metals and characterize the lung-inflammatory and tumorigenic response. Male mice were exposed to air or gas metal arc (GMA)-SS welding fume at 40 mg/m(3)×3 h/day for 6 and 10 days. At 1, 4, 7, 10, 14, and 28 days after 10 days of exposure, bronchoalveolar lavage (BAL) was done. Lung cytotoxicity, permeability, inflammatory cytokines, and cell differentials were analyzed. For the lung tumor study, gross tumor counts and histopathological changes were assessed in A/J mice at 78 weeks after 6 and 10 days of exposure. Inhalation of GMA-SS fume caused an early, sustained macrophage and lymphocyte response followed by a gradual neutrophil influx and the magnitudes of these differed between the mouse strains. Monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor-α (TNF-α) were increased in both strains while the B6 also had increased interleukin-6 (IL-6) protein. BAL measures of cytotoxicity and damage were similar between the strains and significantly increased at all time points. Histopathology and tumorigenesis were unremarkable at 78 weeks. In conclusion, GMA-SS welding fume induced a significant and sustained inflammatory response in both mouse strains with no recovery by 28 days. Under our exposure conditions, GMA-SS exposure resulted in no significant tumor development in A/J mice.

Endothelin-1–Rho kinase interactions impair lung structure and cause pulmonary hypertension after bleomycin exposure in neonatal rat pups

PubMed Central

Tseng, Nancy; Seedorf, Gregory; Kuhn, Katherine; Abman, Steven H.

2016-01-01

Bronchopulmonary dysplasia (BPD) is the chronic lung disease associated with premature birth, characterized by impaired vascular and alveolar growth. In neonatal rats bleomycin decreases lung growth and causes pulmonary hypertension (PH), which is poorly responsive to nitric oxide. In the developing lung, through Rho kinase (ROCK) activation, ET-1 impairs endothelial cell function; however, whether ET-1–ROCK interactions contribute to impaired vascular and alveolar growth in experimental BPD is unknown. Neonatal rats were treated daily with intraperitoneal bleomycin with and without selective ETA (BQ123/BQ610) and ETB (BQ788) receptor blockers, nonselective ET receptor blocker (ETRB) (bosentan), or fasudil (ROCK inhibitor). At day 14, lungs were harvested for morphometrics, and measurements of Fulton's index (RV/LV+S), medial wall thickness (MWT), and vessel density. Lung ET-1 protein and ROCK activity (phospho-MYPT-1:total MYPT-1 ratio) were also measured by Western blot analysis. Bleomycin increased lung ET-1 protein expression by 65%, RV/LV+S by 60%, mean linear intercept (MLI) by 212%, and MWT by 140% and decreased radial alveolar count (RAC) and vessel density by 40 and 44%, respectively (P < 0.01 for each comparison). After bleomycin treatment, fasudil and bosentan partially restored RAC and vessel density and decreased MLI, RV/LV+S, and MWT to normal values. Bleomycin increased ROCK activity by 120%, which was restored to normal values by bosentan but not selective ETRB. We conclude that ET-1–ROCK interactions contribute to decreased alveolar and vascular growth and PH in experimental BPD. We speculate that nonselective ETRB and ROCK inhibitors may be effective in the treatment of infants with BPD and PH. PMID:27760762

Endothelin-1-Rho kinase interactions impair lung structure and cause pulmonary hypertension after bleomycin exposure in neonatal rat pups.

PubMed

Gien, Jason; Tseng, Nancy; Seedorf, Gregory; Kuhn, Katherine; Abman, Steven H

2016-12-01

Bronchopulmonary dysplasia (BPD) is the chronic lung disease associated with premature birth, characterized by impaired vascular and alveolar growth. In neonatal rats bleomycin decreases lung growth and causes pulmonary hypertension (PH), which is poorly responsive to nitric oxide. In the developing lung, through Rho kinase (ROCK) activation, ET-1 impairs endothelial cell function; however, whether ET-1-ROCK interactions contribute to impaired vascular and alveolar growth in experimental BPD is unknown. Neonatal rats were treated daily with intraperitoneal bleomycin with and without selective ET A (BQ123/BQ610) and ET B (BQ788) receptor blockers, nonselective ET receptor blocker (ETRB) (bosentan), or fasudil (ROCK inhibitor). At day 14, lungs were harvested for morphometrics, and measurements of Fulton's index (RV/LV+S), medial wall thickness (MWT), and vessel density. Lung ET-1 protein and ROCK activity (phospho-MYPT-1:total MYPT-1 ratio) were also measured by Western blot analysis. Bleomycin increased lung ET-1 protein expression by 65%, RV/LV+S by 60%, mean linear intercept (MLI) by 212%, and MWT by 140% and decreased radial alveolar count (RAC) and vessel density by 40 and 44%, respectively (P < 0.01 for each comparison). After bleomycin treatment, fasudil and bosentan partially restored RAC and vessel density and decreased MLI, RV/LV+S, and MWT to normal values. Bleomycin increased ROCK activity by 120%, which was restored to normal values by bosentan but not selective ETRB. We conclude that ET-1-ROCK interactions contribute to decreased alveolar and vascular growth and PH in experimental BPD. We speculate that nonselective ETRB and ROCK inhibitors may be effective in the treatment of infants with BPD and PH. Copyright © 2016 the American Physiological Society.

Sustained hyperoxia-induced NF-κB activation improves survival and preserves lung development in neonatal mice

PubMed Central

McKenna, Sarah; Michaelis, Katherine A.; Agboke, Fadeke; Liu, Thanh; Han, Kristie; Yang, Guang; Dennery, Phyllis A.

2014-01-01

Oxygen toxicity contributes to the pathogenesis of bronchopulmonary dysplasia (BPD). Neonatal mice exposed to hyperoxia develop a simplified lung structure that resembles BPD. Sustained activation of the transcription factor NF-κB and increased expression of protective target genes attenuate hyperoxia-induced mortality in adults. However, the effect of enhancing hyperoxia-induced NF-κB activity on lung injury and development in neonatal animals is unknown. We performed this study to determine whether sustained NF-κB activation, mediated through IκBβ overexpression, preserves lung development in neonatal animals exposed to hyperoxia. Newborn wild-type (WT) and IκBβ-overexpressing (AKBI) mice were exposed to hyperoxia (>95%) or room air from day of life (DOL) 0–14, after which all animals were kept in room air. Survival curves were generated through DOL 14. Lung development was assessed using radial alveolar count (RAC) and mean linear intercept (MLI) at DOL 3 and 28 and pulmonary vessel density at DOL 28. Lung tissue was collected, and NF-κB activity was assessed using Western blot for IκB degradation and NF-κB nuclear translocation. WT mice demonstrated 80% mortality through 14 days of exposure. In contrast, AKBI mice demonstrated 60% survival. Decreased RAC, increased MLI, and pulmonary vessel density caused by hyperoxia in WT mice were significantly attenuated in AKBI mice. These findings were associated with early and sustained NF-κB activation and expression of cytoprotective target genes, including vascular endothelial growth factor receptor 2. We conclude that sustained hyperoxia-induced NF-κB activation improves neonatal survival and preserves lung development. Potentiating early NF-κB activity after hyperoxic exposure may represent a therapeutic intervention to prevent BPD. PMID:24748603

Budesonide ameliorates lung injury induced by large volume ventilation.

PubMed

Ju, Ying-Nan; Yu, Kai-Jiang; Wang, Guo-Nian

2016-06-04

Ventilation-induced lung injury (VILI) is a health problem for patients with acute respiratory dysfunction syndrome. The aim of this study was to investigate the effectiveness of budesonide in treating VILI. Twenty-four rats were randomized to three groups: a ventilation group, ventilation/budesonide group, and sham group were ventilated with 30 ml/kg tidal volume or only anesthesia for 4 hor saline or budesonide airway instillation immediately after ventilation. The PaO2/FiO2and wet-to-dry weight ratios, protein concentration, neutrophil count, and neutrophil elastase levels in bronchoalveolar lavage fluid (BALF) and the levels of inflammation-related factors were examined. Histological evaluation of and apoptosis measurement inthe lung were conducted. Compared with that in the ventilation group, the PaO2/FiO2 ratio was significantly increased by treatment with budesonide. The lung wet-to-dry weight ratio, total protein, neutrophil elastase level, and neutrophilcount in BALF were decreased in the budesonide group. The BALF and plasma tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, intercellular adhesion molecule (ICAM)-1, and macrophage inflammatory protein (MIP)-2 levels were decreased, whereas the IL-10 level was increased in the budesonide group. The phosphorylated nuclear factor (NF)-kBlevels in lung tissue were inhibited by budesonide. The histological changes in the lung and apoptosis were reduced by budesonide treatment. Bax, caspase-3, and cleaved caspase-3 were down-regulated, and Bcl-2 was up-regulated by budesonide. Budesonide ameliorated lung injury induced by large volume ventilation, likely by improving epithelial permeability, decreasing edema, inhibiting local and systemic inflammation, and reducing apoptosis in VILI.

Dimethyl sulfoxide in a 10% concentration has no effect on oxidation stress induced by ovalbumin-sensitization in a guinea-pig model of allergic asthma.

PubMed

Mikolka, P; Mokra, D; Drgova, A; Petras, M; Mokry, J

2012-04-01

In allergic asthma, activated cells produce various substances including reactive oxygen species (ROS). As heterogenic pathophysiology of asthma results to different response to the therapy, testing novel interventions continues. Because of water-insolubility of some potentially beneficial drugs, dimethyl sulfoxide (DMSO) is often used as a solvent. Based on its antioxidant properties, this study evaluated effects of DMSO on mobilization of leukocytes into the lungs, and oxidation processes induced by ovalbumin (OVA)-sensitization in a guinea-pig model of allergic asthma. Guinea-pigs were divided into OVA-sensitized and naive animals. One group of OVA-sensitized animals and one group of naive animals were pretreated with 10% DMSO, the other two groups were given saline. After sacrificing animals, blood samples were taken and total antioxidant status (TAS) in the plasma was determined. Left lungs were saline-lavaged and differential leukocyte count in bronchoalveolar lavage fluid (BAL) was made. Right lung tissue was homogenized, TAS and products of lipid and protein oxidation were determined in the lung homogenate and in isolated mitochondria. OVA-sensitization increased total number of cells and percentages of eosinophils and neutrophils in BAL fluid; increased lipid and protein oxidation in the lung homogenate and mitochondria, and decreased TAS in the lungs and plasma compared with naive animals. However, no differences were observed in DMSO-instilled animals compared to controls. In conclusion, OVA-sensitization increased mobilization of leukocytes into the lungs and elevated production of ROS, accompanied by decrease in TAS. 10% DMSO had no effect on lipid and protein oxidation in a guinea-pig model of allergic asthma.

Topoisomerase I peptide-loaded dendritic cells induce autoantibody response as well as skin and lung fibrosis.

PubMed

Mehta, Heena; Goulet, Philippe-Olivier; Nguyen, Vinh; Pérez, Gemma; Koenig, Martial; Senécal, Jean-Luc; Sarfati, Marika

2016-12-01

DNA Topoisomerase I (TopoI) is a candidate autoantigen for diffuse cutaneous systemic sclerosis (dcSSc) associated with fatal lung disease. Dendritic cells (DCs) contribute to bleomycin-induced lung fibrosis. However, the possibility that TopoI-loaded DCs are involved in the initiation and/or perpetuation of dcSSc has not been explored. Here, we show that immunization with TopoI peptide-loaded DCs induces anti-TopoI autoantibody response and long-term fibrosis. Mice were repeatedly immunized with unpulsed DCs or DCs loaded with either TOPOIA or TOPOIB peptides, selected from different regions of TopoI. At week 12 after initial DC immunization, TOPOIA DCs but not TOPOIB DCs immunization induced mixed inflammation and fibrosis in lungs and skin. At a late time point (week 18), both TOPOIA DCs and TOPOIB DCs groups displayed increased alpha-smooth muscle actin expression in lungs and dermis along with skin fibrosis distal from the site of injection when compared with unpulsed DCs. Both TopoI peptide-DC-immunized groups developed IgG2a anti-TopoI autoantibody response. At week 10, signs of perivascular, peribronchial, and parenchymal pulmonary inflammation were already observed in the TOPOIA DCs group, together with transient elevation in bronchoalveolar lavage cell counts, IL-17A expression, and CXCL4 production, a biomarker of early human dcSSc. Collectively, TopoI peptide DCs induce progressive autoantibody response as well as development of protracted skin and lung dcSSc-like disease. Pronounced lung inflammation, transient IL-17A, and CXCL4 expression precede fibrosis development. Our immunization strategy, that uses self immune system and autoantigen, will help to further investigate the pathogenesis of this complex autoimmune disorder with unmet medical needs.

Prevention and management of lung cancer in China.

PubMed

Hong, Qun-Ying; Wu, Guo-Ming; Qian, Gui-Sheng; Hu, Cheng-Ping; Zhou, Jian-Ying; Chen, Liang-An; Li, Wei-Min; Li, Shi-Yue; Wang, Kai; Wang, Qi; Zhang, Xiao-Ju; Li, Jing; Gong, Xin; Bai, Chun-Xue

2015-09-01

Lung cancer is the leading cause of cancer-related death worldwide. In China, the incidence of lung cancer has grown rapidly, resulting in a large social and economic burden. Several researchers have devoted their studies to lung cancer and have demonstrated that there are many risk factors for lung cancer in China, including tobacco use, environmental pollution, food, genetics, and chronic obstructive pulmonary disease. However, the lung cancer incidence is still growing rapidly in China, and there is an even higher incidence among the younger generation. One explanation may be the triple-neglect situation, in which medical policies that neglect prevention, diagnosis, and supportive care have increased patients' mortality and reduced their quality of life. Therefore, it is necessary to enhance the efficiency of prevention and early diagnosis not only by focusing more attention on treatment but also by drawing more attention to supportive care for patients with lung cancer. © 2015 American Cancer Society.

Current and future molecular diagnostics in non-small-cell lung cancer.

PubMed

Li, Chun Man; Chu, Wing Ying; Wong, Di Lun; Tsang, Hin Fung; Tsui, Nancy Bo Yin; Chan, Charles Ming Lok; Xue, Vivian Wei Wen; Siu, Parco Ming Fai; Yung, Benjamin Yat Ming; Chan, Lawrence Wing Chi; Wong, Sze Chuen Cesar

2015-01-01

The molecular investigation of lung cancer has opened up an advanced area for the diagnosis and therapeutic management of lung cancer patients. Gene alterations in cancer initiation and progression provide not only information on molecular changes in lung cancer but also opportunities in advanced therapeutic regime by personalized targeted therapy. EGFR mutations and ALK rearrangement are important predictive biomarkers for the efficiency of tyrosine kinase inhibitor treatment in lung cancer patients. Moreover, epigenetic aberration and microRNA dysregulation are recent advances in the early detection and monitoring of lung cancer. Although a wide range of molecular tests are available, standardization and validation of assay protocols are essential for the quality of the test outcome. In this review, current and new advancements of molecular biomarkers for non-small-cell lung cancer will be discussed. Recommendations on future development of molecular diagnostic services will also be explored.

Protein and microRNA biomarkers from lavage, urine, and serum in military personnel evaluated for dyspnea

PubMed Central

2014-01-01

Background We have identified candidate protein and microRNA (miRNA) biomarkers for dyspnea by studying serum, lavage fluid, and urine from military personnel who reported serious respiratory symptoms after they were deployed to Iraq or Afghanistan. Methods Forty-seven soldiers with the complaint of dyspnea who enrolled in the STudy of Active Duty Military Personnel for Environmental Dust Exposure (STAMPEDE) underwent comprehensive pulmonary evaluations at the San Antonio Military Medical Center. The evaluation included fiber-optic bronchoscopy with bronchoalveolar lavage. The clinical findings from the STAMPEDE subjects pointed to seven general underlying diagnoses or findings including airway hyperreactivity, asthma, low diffusivity of carbon monoxide, and abnormal cell counts. The largest category was undiagnosed. As an exploratory study, not a classification study, we profiled proteins or miRNAs in lavage fluid, serum, or urine in this group to look for any underlying molecular patterns that might lead to biomarkers. Proteins in lavage fluid and urine were identified by accurate mass tag (database-driven) proteomics methods while miRNAs were profiled by a hybridization assay applied to serum, urine, and lavage fluid. Results Over seventy differentially expressed proteins were reliably identified both from lavage and from urine in forty-eight dyspnea subjects compared to fifteen controls with no known lung disorder. Six of these proteins were detected both in urine and lavage. One group of subjects was distinguished from controls by expressing a characteristic group of proteins. A related group of dyspnea subjects expressed a unique group of miRNAs that included one miRNA that was differentially overexpressed in all three fluids studied. The levels of several miRNAs also showed modest but direct associations with several standard clinical measures of lung health such as forced vital capacity or gas exchange efficiency. Conclusions Candidate proteins and miRNAs associated with the general diagnosis of dyspnea have been identified in subjects with differing medical diagnoses. Since these markers can be measured in readily obtained clinical samples, further studies are possible that test the value of these findings in more formal classification or case–control studies in much larger cohorts of subjects with specific lung diseases such as asthma, emphysema, or some other well-defined lung disease. PMID:25282157

Protein and microRNA biomarkers from lavage, urine, and serum in military personnel evaluated for dyspnea.

PubMed

Brown, Joseph N; Brewer, Heather M; Nicora, Carrie D; Weitz, Karl K; Morris, Michael J; Skabelund, Andrew J; Adkins, Joshua N; Smith, Richard D; Cho, Ji-Hoon; Gelinas, Richard

2014-10-05

We have identified candidate protein and microRNA (miRNA) biomarkers for dyspnea by studying serum, lavage fluid, and urine from military personnel who reported serious respiratory symptoms after they were deployed to Iraq or Afghanistan. Forty-seven soldiers with the complaint of dyspnea who enrolled in the STudy of Active Duty Military Personnel for Environmental Dust Exposure (STAMPEDE) underwent comprehensive pulmonary evaluations at the San Antonio Military Medical Center. The evaluation included fiber-optic bronchoscopy with bronchoalveolar lavage. The clinical findings from the STAMPEDE subjects pointed to seven general underlying diagnoses or findings including airway hyperreactivity, asthma, low diffusivity of carbon monoxide, and abnormal cell counts. The largest category was undiagnosed. As an exploratory study, not a classification study, we profiled proteins or miRNAs in lavage fluid, serum, or urine in this group to look for any underlying molecular patterns that might lead to biomarkers. Proteins in lavage fluid and urine were identified by accurate mass tag (database-driven) proteomics methods while miRNAs were profiled by a hybridization assay applied to serum, urine, and lavage fluid. Over seventy differentially expressed proteins were reliably identified both from lavage and from urine in forty-eight dyspnea subjects compared to fifteen controls with no known lung disorder. Six of these proteins were detected both in urine and lavage. One group of subjects was distinguished from controls by expressing a characteristic group of proteins. A related group of dyspnea subjects expressed a unique group of miRNAs that included one miRNA that was differentially overexpressed in all three fluids studied. The levels of several miRNAs also showed modest but direct associations with several standard clinical measures of lung health such as forced vital capacity or gas exchange efficiency. Candidate proteins and miRNAs associated with the general diagnosis of dyspnea have been identified in subjects with differing medical diagnoses. Since these markers can be measured in readily obtained clinical samples, further studies are possible that test the value of these findings in more formal classification or case-control studies in much larger cohorts of subjects with specific lung diseases such as asthma, emphysema, or some other well-defined lung disease.

Protein and microRNA biomarkers from lavage, urine, and serum in military personnel evaluated for dyspnea

DOE PAGES

Brown, Joseph N.; Brewer, Heather M.; Nicora, Carrie D.; ...

2014-10-05

Background: We have identified candidate protein and microRNA (miRNA) biomarkers for dyspnea by studying serum, lavage fluid, and urine from military personnel who reported serious respiratory symptoms after they were deployed to Iraq or Afghanistan. Methods: Forty-seven soldiers with the complaint of dyspnea who enrolled in the STudy of Active Duty Military Personnel for Environmental Dust Exposure (STAMPEDE) underwent comprehensive pulmonary evaluations at the San Antonio Military Medical Center. The evaluation included fiber-optic bronchoscopy with bronchoalveolar lavage. The clinical findings from the STAMPEDE subjects pointed to seven general underlying diagnoses or findings including airway hyperreactivity, asthma, low diffusivity of carbonmore » monoxide, and abnormal cell counts. The largest category was undiagnosed. As an exploratory study, not a classification study, we profiled proteins or miRNAs in lavage fluid, serum, or urine in this group to look for any underlying molecular patterns that might lead to biomarkers. Proteins in lavage fluid and urine were identified by accurate mass tag (database-driven) proteomics methods while miRNAs were profiled by a hybridization assay applied to serum, urine, and lavage fluid. Results: Over seventy differentially expressed proteins were reliably identified both from lavage and from urine in forty-eight dyspnea subjects compared to fifteen controls with no known lung disorder. Six of these proteins were detected both in urine and lavage. One group of subjects was distinguished from controls by expressing a characteristic group of proteins. A related group of dyspnea subjects expressed a unique group of miRNAs that included one miRNA that was differentially overexpressed in all three fluids studied. The levels of several miRNAs also showed modest but direct associations with several standard clinical measures of lung health such as forced vital capacity or gas exchange efficiency. Conclusions: Candidate proteins and miRNAs associated with the general diagnosis of dyspnea have been identified in subjects with differing medical diagnoses. Since these markers can be measured in readily obtained clinical samples, further studies are possible that test the value of these findings in more formal classification or case–control studies in much larger cohorts of subjects with specific lung diseases such as asthma, emphysema, or some other well-defined lung disease.« less

Protein and microRNA biomarkers from lavage, urine, and serum in military personnel evaluated for dyspnea

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

Brown, Joseph N.; Brewer, Heather M.; Nicora, Carrie D.

Background: We have identified candidate protein and microRNA (miRNA) biomarkers for dyspnea by studying serum, lavage fluid, and urine from military personnel who reported serious respiratory symptoms after they were deployed to Iraq or Afghanistan. Methods: Forty-seven soldiers with the complaint of dyspnea who enrolled in the STudy of Active Duty Military Personnel for Environmental Dust Exposure (STAMPEDE) underwent comprehensive pulmonary evaluations at the San Antonio Military Medical Center. The evaluation included fiber-optic bronchoscopy with bronchoalveolar lavage. The clinical findings from the STAMPEDE subjects pointed to seven general underlying diagnoses or findings including airway hyperreactivity, asthma, low diffusivity of carbonmore » monoxide, and abnormal cell counts. The largest category was undiagnosed. As an exploratory study, not a classification study, we profiled proteins or miRNAs in lavage fluid, serum, or urine in this group to look for any underlying molecular patterns that might lead to biomarkers. Proteins in lavage fluid and urine were identified by accurate mass tag (database-driven) proteomics methods while miRNAs were profiled by a hybridization assay applied to serum, urine, and lavage fluid. Results: Over seventy differentially expressed proteins were reliably identified both from lavage and from urine in forty-eight dyspnea subjects compared to fifteen controls with no known lung disorder. Six of these proteins were detected both in urine and lavage. One group of subjects was distinguished from controls by expressing a characteristic group of proteins. A related group of dyspnea subjects expressed a unique group of miRNAs that included one miRNA that was differentially overexpressed in all three fluids studied. The levels of several miRNAs also showed modest but direct associations with several standard clinical measures of lung health such as forced vital capacity or gas exchange efficiency. Conclusions: Candidate proteins and miRNAs associated with the general diagnosis of dyspnea have been identified in subjects with differing medical diagnoses. Since these markers can be measured in readily obtained clinical samples, further studies are possible that test the value of these findings in more formal classification or case–control studies in much larger cohorts of subjects with specific lung diseases such as asthma, emphysema, or some other well-defined lung disease.« less

A biomechanical analysis of common lunge tasks in badminton.

PubMed

Kuntze, Gregor; Mansfield, Neil; Sellers, William

2010-01-01

The lunge is regularly used in badminton and is recognized for the high physical demands it places on the lower limbs. Despite its common occurrence, little information is available on the biomechanics of lunging in the singles game. A video-based pilot study confirmed the relatively high frequency of lunging, approximately 15% of all movements, in competitive singles games. The biomechanics and performance characteristics of three badminton-specific lunge tasks (kick, step-in, and hop lunge) were investigated in the laboratory with nine experienced male badminton players. Ground reaction forces and kinematic data were collected and lower limb joint kinetics calculated using an inverse dynamics approach. The step-in lunge was characterized by significantly lower mean horizontal reaction force at drive-off and lower mean peak hip joint power than the kick lunge. The hop lunge resulted in significantly larger mean reaction forces during loading and drive-off phases, as well as significantly larger mean peak ankle joint moments and knee and ankle joint powers than the kick or step-in lunges. These findings indicate that, within the setting of this investigation, the step-in lunge may be beneficial for reducing the muscular demands of lunge recovery and that the hop lunge allows for higher positive power output, thereby presenting an efficient lunging method.

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.

INTERPRETATIONS AND LIMITATION OF PULMONARY FUNCTION TESTING IN SMALL LABORATORY ANIMALS

EPA Science Inventory

Pulmonary function tests are tools available to the researcher and clinician to evaluate the ability of the lung to perform its essential function of gas exchange. o meet this principal function, the lung needs to operate efficiently with minimal mechanical work as well as provid...

Improving the counting efficiency in time-correlated single photon counting experiments by dead-time optimization

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

Peronio, P.; Acconcia, G.; Rech, I.

Time-Correlated Single Photon Counting (TCSPC) has been long recognized as the most sensitive method for fluorescence lifetime measurements, but often requiring “long” data acquisition times. This drawback is related to the limited counting capability of the TCSPC technique, due to pile-up and counting loss effects. In recent years, multi-module TCSPC systems have been introduced to overcome this issue. Splitting the light into several detectors connected to independent TCSPC modules proportionally increases the counting capability. Of course, multi-module operation also increases the system cost and can cause space and power supply problems. In this paper, we propose an alternative approach basedmore » on a new detector and processing electronics designed to reduce the overall system dead time, thus enabling efficient photon collection at high excitation rate. We present a fast active quenching circuit for single-photon avalanche diodes which features a minimum dead time of 12.4 ns. We also introduce a new Time-to-Amplitude Converter (TAC) able to attain extra-short dead time thanks to the combination of a scalable array of monolithically integrated TACs and a sequential router. The fast TAC (F-TAC) makes it possible to operate the system towards the upper limit of detector count rate capability (∼80 Mcps) with reduced pile-up losses, addressing one of the historic criticisms of TCSPC. Preliminary measurements on the F-TAC are presented and discussed.« less

Gas Transfer in Cellularized Collagen-Membrane Gas Exchange Devices.

PubMed

Lo, Justin H; Bassett, Erik K; Penson, Elliot J N; Hoganson, David M; Vacanti, Joseph P

2015-08-01

Chronic lower respiratory disease is highly prevalent in the United States, and there remains a need for alternatives to lung transplant for patients who progress to end-stage lung disease. Portable or implantable gas oxygenators based on microfluidic technologies can address this need, provided they operate both efficiently and biocompatibly. Incorporating biomimetic materials into such devices can help replicate native gas exchange function and additionally support cellular components. In this work, we have developed microfluidic devices that enable blood gas exchange across ultra-thin collagen membranes (as thin as 2 μm). Endothelial, stromal, and parenchymal cells readily adhere to these membranes, and long-term culture with cellular components results in remodeling, reflected by reduced membrane thickness. Functionally, acellular collagen-membrane lung devices can mediate effective gas exchange up to ∼288 mL/min/m(2) of oxygen and ∼685 mL/min/m(2) of carbon dioxide, approaching the gas exchange efficiency noted in the native lung. Testing several configurations of lung devices to explore various physical parameters of the device design, we concluded that thinner membranes and longer gas exchange distances result in improved hemoglobin saturation and increases in pO2. However, in the design space tested, these effects are relatively small compared to the improvement in overall oxygen and carbon dioxide transfer by increasing the blood flow rate. Finally, devices cultured with endothelial and parenchymal cells achieved similar gas exchange rates compared with acellular devices. Biomimetic blood oxygenator design opens the possibility of creating portable or implantable microfluidic devices that achieve efficient gas transfer while also maintaining physiologic conditions.

Surfactant protein-A nanobody-conjugated liposomes loaded with methylprednisolone increase lung-targeting specificity and therapeutic effect for acute lung injury.

PubMed

Li, Nan; Weng, Dong; Wang, Shan-Mei; Zhang, Yuan; Chen, Shan-Shan; Yin, Zhao-Fang; Zhai, Jiali; Scoble, Judy; Williams, Charlotte C; Chen, Tao; Qiu, Hui; Wu, Qin; Zhao, Meng-Meng; Lu, Li-Qin; Mulet, Xavier; Li, Hui-Ping

2017-11-01

The advent of nanomedicine requires novel delivery vehicles to actively target their site of action. Here, we demonstrate the development of lung-targeting drug-loaded liposomes and their efficacy, specificity and safety. Our study focuses on glucocorticoids methylprednisolone (MPS), a commonly used drug to treat lung injuries. The steroidal molecule was loaded into functionalized nano-sterically stabilized unilamellar liposomes (NSSLs). Targeting functionality was performed through conjugation of surfactant protein A (SPANb) nanobodies to form MPS-NSSLs-SPANb. MPS-NSSLs-SPANb exhibited good size distribution, morphology, and encapsulation efficiency. Animal experiments demonstrated the high specificity of MPS-NSSLs-SPANb to the lung. Treatment with MPS-NSSLs-SPANb reduced the levels of TNF-α, IL-8, and TGF-β1 in rat bronchoalveolar lavage fluid and the expression of NK-κB in the lung tissues, thereby alleviating lung injuries and increasing rat survival. The nanobody functionalized nanoparticles demonstrate superior performance to treat lung injury when compared to that of antibody functionalized systems.

Emphysema and soluble CD14 are associated with pulmonary nodules in HIV-infected patients: implications for lung cancer screening.

PubMed

Triplette, Matthew; Sigel, Keith M; Morris, Alison; Shahrir, Shahida; Wisnivesky, Juan P; Kong, Chung Y; Diaz, Phillip T; Petraglia, Alycia; Crothers, Kristina

2017-07-31

Lung cancer screening may benefit HIV-infected (HIV) smokers because of an elevated risk of lung cancer, but may have unique harms because of HIV-specific risk factors for false-positive screens. This study seeks to understand whether inflammatory biomarkers and markers of chronic lung disease are associated with noncalcified nodules at least 4 mm (NCN) in HIV compared with uninfected patients. This is a cohort study of Examinations of HIV-Associated Lung Emphysema (EXHALE), including 158 HIV and 133 HIV-uninfected participants. Participants underwent a laboratory assessment [including measurement of D-dimer, interleukin 6, and soluble CD14 (sCD14)], chest computed tomography (CT), and pulmonary function testing. We created multivariable logistic regression models to determine predictors of NCN in the participants stratified by HIV status, with attention to semiqualitative scoring of radiographic emphysema, markers of pulmonary function, and inflammatory biomarkers. Of the 291 participants, 69 had NCN on chest CT. As previously reported, there was no difference in prevalence of these nodules by HIV status. Emphysema and elevated sCD14 demonstrated an association with NCN in HIV participants independent of smoking status, CD4 cell count, HIV viral load, and pulmonary function. Emphysema and sCD14, a marker of immune activation, was associated with a higher prevalence of NCN on chest CT in HIV participants. Patients with chronic immune activation and emphysema may be at higher risk for both false-positive findings and incident lung cancer, thus screening in this group requires further study to understand the balance of benefits and harms.

Evaluation of large format electron bombarded virtual phase CCDs as ultraviolet imaging detectors

NASA Technical Reports Server (NTRS)

Opal, Chet B.; Carruthers, George R.

1989-01-01

In conjunction with an external UV-sensitive cathode, an electron-bombarded CCD may be used as a high quantum efficiency/wide dynamic range photon-counting UV detector. Results are presented for the case of a 1024 x 1024, 18-micron square pixel virtual phase CCD used with an electromagnetically focused f/2 Schmidt camera, which yields excellent simgle-photoevent discrimination and counting efficiency. Attention is given to the vacuum-chamber arrangement used to conduct system tests and the CCD electronics and data-acquisition systems employed.

Negative Avalanche Feedback Detectors for Photon-Counting Optical Communications

NASA Technical Reports Server (NTRS)

Farr, William H.

2009-01-01

Negative Avalanche Feedback photon counting detectors with near-infrared spectral sensitivity offer an alternative to conventional Geiger mode avalanche photodiode or phototube detectors for free space communications links at 1 and 1.55 microns. These devices demonstrate linear mode photon counting without requiring any external reset circuitry and may even be operated at room temperature. We have now characterized the detection efficiency, dark count rate, after-pulsing, and single photon jitter for three variants of this new detector class, as well as operated these uniquely simple to use devices in actual photon starved free space optical communications links.

Small Nodules Localization on CT Images of Lungs

NASA Astrophysics Data System (ADS)

Snezhko, E. V.; Kharuzhyk, S. A.; Tuzikov, A. V.; Kovalev, V. A.

2017-05-01

According to the World Health Organization (WHO) lung cancer remains the leading cause of death of men among all malignant tumors [1, 2]. One of the reasons of such a statistics is the fact that the lung cancer is hardly diagnosed on the yearly stages when it is almost asymptomatic. The purpose of this paper is to present a Computer-Aided Diagnosis (CAD) software developed for assistance of early detection of nodules in CT lung images including solitary pulmonary nodules (SPN) as well as multiple nodules. The efficiency of nodule localization was intended to be as high as the level of the best practice. The software developed supports several functions including lungs segmentation, selection of nodule candidates and nodule candidates filtering.

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.

Lung Microbiota Changes Associated with Chronic Pseudomonas aeruginosa Lung Infection and the Impact of Intravenous Colistimethate Sodium

PubMed Central

Collie, David; Glendinning, Laura; Govan, John; Wright, Steven; Thornton, Elisabeth; Tennant, Peter; Doherty, Catherine; McLachlan, Gerry

2015-01-01

Background Exacerbations associated with chronic lung infection with Pseudomonas aeruginosa are a major contributor to morbidity, mortality and premature death in cystic fibrosis. Such exacerbations are treated with antibiotics, which generally lead to an improvement in lung function and reduced sputum P. aeruginosa density. This potentially suggests a role for the latter in the pathogenesis of exacerbations. However, other data suggesting that changes in P. aeruginosa sputum culture status may not reliably predict an improvement in clinical status, and data indicating no significant changes in either total bacterial counts or in P. aeruginosa numbers in sputum samples collected prior to pulmonary exacerbation sheds doubt on this assumption. We used our recently developed lung segmental model of chronic Pseudomonas infection in sheep to investigate the lung microbiota changes associated with chronic P. aeruginosa lung infection and the impact of systemic therapy with colistimethate sodium (CMS). Methodology/Principal Findings We collected protected specimen brush (PSB) samples from sheep (n = 8) both prior to and 14 days after establishment of chronic local lung infection with P aeruginosa. Samples were taken from both directly infected lung segments (direct) and segments spatially remote to such sites (remote). Four sheep were treated with daily intravenous injections of CMS between days 7 and 14, and four were treated with a placebo. Necropsy examination at d14 confirmed the presence of chronic local lung infection and lung pathology in every direct lung segment. The predominant orders in lung microbiota communities before infection were Bacillales, Actinomycetales and Clostridiales. While lung microbiota samples were more likely to share similarities with other samples derived from the same lung, considerable within- and between-animal heterogeneity could be appreciated. Pseudomonadales joined the aforementioned list of predominant orders in lung microbiota communities after infection. Whilst treatment with CMS appeared to have little impact on microbial community composition after infection, or the change undergone by communities in reaching that state, when Gram negative organisms (excluding Pseudomonadales) were considered together as a group there was a significant decrease in their relative proportion that was only observed in the sheep treated with CMS. With only one exception the reduction was seen in both direct and remote lung segments. This reduction, coupled with generally increasing or stable levels of Pseudomonadales, meant that the proportion of the latter relative to total Gram negative bacteria increased in all bar one direct and one remote lung segment. Conclusions/Significance The proportional increase in Pseudomonadales relative to other Gram negative bacteria in the lungs of sheep treated with systemic CMS highlights the potential for such therapies to inadvertently select or create a niche for bacteria seeding from a persistent source of chronic infection. PMID:26544950

Laboratory productivity and the rate of manual peripheral blood smear review: a College of American Pathologists Q-Probes study of 95,141 complete blood count determinations performed in 263 institutions.

PubMed

Novis, David A; Walsh, Molly; Wilkinson, David; St Louis, Mary; Ben-Ezra, Jonathon

2006-05-01

Automated laboratory hematology analyzers are capable of performing differential counts on peripheral blood smears with greater precision and more accurate detection of distributional and morphologic abnormalities than those performed by manual examinations of blood smears. Manual determinations of blood morphology and leukocyte differential counts are time-consuming, expensive, and may not always be necessary. The frequency with which hematology laboratory workers perform manual screens despite the availability of labor-saving features of automated analyzers is unknown. To determine the normative rates with which manual peripheral blood smears were performed in clinical laboratories, to examine laboratory practices associated with higher or lower manual review rates, and to measure the effects of manual smear review on the efficiency of generating complete blood count (CBC) determinations. From each of 3 traditional shifts per day, participants were asked to select serially, 10 automated CBC specimens, and to indicate whether manual scans and/or reviews with complete differential counts were performed on blood smears prepared from those specimens. Sampling continued until a total of 60 peripheral smears were reviewed manually. For each specimen on which a manual review was performed, participants indicated the patient's age, hemoglobin value, white blood cell count, platelet count, and the primary reason why the manual review was performed. Participants also submitted data concerning their institutions' demographic profiles and their laboratories' staffing, work volume, and practices regarding CBC determinations. The rates of manual reviews and estimations of efficiency in performing CBC determinations were obtained from the data. A total of 263 hospitals and independent laboratories, predominantly located in the United States, participating in the College of American Pathologists Q-Probes Program. There were 95,141 CBC determinations examined in this study; participants reviewed 15,423 (16.2%) peripheral blood smears manually. In the median institution (50th percentile), manual reviews of peripheral smears were performed on 26.7% of specimens. Manual differential count review rates were inversely associated with the magnitude of platelet counts that were required by laboratory policy to trigger smear reviews and with the efficiency of generating CBC reports. Lower manual differential count review rates were associated with laboratory policies that allowed manual reviews solely on the basis of abnormal automated red cell parameters and that precluded performing repeat manual reviews within designated time intervals. The manual scan rate elevated with increased number of hospital beds. In more than one third (35.7%) of the peripheral smears reviewed manually, participants claimed to have learned additional information beyond what was available on automated hematology analyzer printouts alone. By adopting certain laboratory practices, it may be possible to reduce the rates of manual reviews of peripheral blood smears and increase the efficiency of generating CBC results.

Assessing avian richness in remnant wetlands: Towards an improved methodology

USGS Publications Warehouse

Krzys, Greg; Waite, Thomas A.; Stapanian, Martin; Vucetich, John A.

2002-01-01

Because the North American Breeding Bird Survey provides inadequate coverage of wetland habitat, the Wetland Breeding Bird Survey was recently established in Ohio, USA. This program relies on volunteers to conduct 3 counts at each monitored wetland. Currently, all counts are conducted during the morning. Under the premise that volunteer participation could be increased by allowing evening counts, we evaluated the potential for modifying the methodology. We evaluated the sampling efficiency of all 3-count combinations of morning and evening counts using data collected at 14 wetlands. Estimates of overall species richness decreased with increasing numbers of evening counts. However, this pattern did not hold when analyses were restricted to wetland-dependent species or those of conservation concern. Our findings suggest that it would be reasonable to permit evening counts, particularly if the data are to be used to monitor wetland dependent species and those of concern.

Asbestos lung burden and asbestosis after occupational and environmental exposure in an asbestos cement manufacturing area: a necropsy study

PubMed Central

Magnani, C.; Mollo, F.; Paoletti, L.; Bellis, D.; Bernardi, P.; Betta, P.; Botta, M.; Falchi, M.; Ivaldi, C.; Pavesi, M.

1998-01-01

OBJECTIVE: The largest Italian asbestos cement factory had been active in Casale Monferrato until 1986: in previous studies a substantial increase in the incidence of pleural mesothelioma was found among residents without occupational exposure to asbestos. To estimate exposure to asbestos in the population, this study evaluated the presence of histological asbestosis and the lung burden of asbestos fibres (AFs) and asbestos bodies (ABs). METHODS: The study comprises the consecutive series of necropsies performed at the Hospital of Casale Monferrato between 1985 and 1988. A sample of lung parenchima was collected and stored for 48 out of 55 necropsies. The AF concentration was measured with a TEM electron microscope with x ray mineralogical analysis. The ABs were counted and fibrosis evaluated by optical microscopy. The nearest relative of each subject was interviewed on occupational and residential history. Mineralogical and histological analyses and interviews were conducted in 1993-4. RESULTS: Statistical analyses included 41 subjects with AF, AB count, and interview. Subjects without occupational exposure who ever lived in Casale Monferrato had an average concentration of 1500 AB/g dried weight (gdw); Seven of 18 presented with asbestosis or small airway lung disease (SAL). G2 asbestosis was diagnosed in two women with no occupational asbestos exposure. One of them had been teaching at a school close to the factory for 12 years. Ten subjects had experienced occupational asbestos exposure, seven in asbestos cement production: mean concentrations were 1.032 x 10(6) AF/gdw and 96,280 AB/gdw. Eight of the 10 had asbestosis or SAL. CONCLUSION: The high concentration of ABs and the new finding of environmental asbestosis confirm that high asbestos concentration was common in the proximity of the factory. Subjects not occupationally exposed and ever living in Casale Monferrato tended to have higher AB concentration than subjects never living in the town (difference not significant). The concentrations of ABs and AFs were higher than those found in other studies on nonoccupationally exposed subjects.   PMID:9924446

[Effect of CsA bleomycin-induced interstitial pulmonary disease in mice].

PubMed

Ren, Ying; Yang, Hui; Zhu, Ping; Fan, Chun-mei; Wang, Yan-hong; Li, Jia; Liu, Hui

2012-03-01

To observe the therapeutic effect of cyclosporine A (CsA) on bleomycin (BLM) induced pulmonary fibrosis and to investigate its mechanism. One hundred and twenty C57BL/6 female mice were divided randomly into five groups: BLM model group, control saline group, CsA30 mg treatment group, CsA50 mg treatment group and control treatment group. Treatment groups and model groups were administrated BLM intratracheally to induce interstitial pulmonary disease model, with control saline group administrated with equal volume of normal saline instead. Mice in treatment groups were intraperitoneal injected with CsA, while control treatment group were injected with equal volume of normal saline instead. On the 4th, 7th and 14th day after administration, 8 mice of each group were sacrificed, and the peripheral blood was obtained to count total leucocytes with counting chamber and quantify CD4(+); T cells, CD14(+); monocytes and CD19(+); B cells by flow cytometry (FCM). Bronchoalveolar levage fluid was harvested for cell counting and Giemsa staining. Lung tissues were harvested for immunohistochemical staining and pathological examination. The quantity of total leucocyte was higher in BLM model group than those in control saline group.The proportion of CD14(+); T cells and CD19(+);B cells in BLM model group were increased markedly than those in control saline group on the 4th, 7th and 14th day post BLM. With CsA treatment, The proportion of CD14(+); T cells was lower than BLM model group at the same time point, especially on the 4th day. The proportion of CD19(+); B cells were significantly lower than those of BLM model group at the same time point(7 d, 14 d). The total and classification of cells of BLM model group were increased markedly than those in control saline group, and decreased obviously in the treatment groups at the same time point. Examination of lung tissues: With the prolonged time of BLM administration, it showed wider alveolar septum, more collagen deposition, as well as more infiltrating inflammatory cells which consisted of generous lymphocyte and few mononuclear macrophages than those in saline control group. With the prolonged time of CsA injection, the interstitial pulmonary inflammation was remissive, and there was less fibroblast infiltration and collagen deposition in pulmonary interstitium and periphery of bronchiole. Alveolar epithelial cells, bronchiolar epithelial cells, mononuclear macrophages, neutrophils and lymphocytes were demonstrated to express CD147, there was higher CD147 expression in BLM model group than those in CsA treatment groups. CsA may heal BLM induced interstitial pulmonary disease by blocking CD147-CypA interaction, then decreasing chemotaxis for the immunocyte, and reducing migration of immunocytes to the lung and collagen deposition in the lung.

Visual versus mechanised leucocyte differential counts: costing and evaluation of traditional and Hemalog D methods.

PubMed

Hudson, M J; Green, A E

1980-11-01

Visual differential counts were examined for efficiency, cost effectiveness, and staff acceptability within our laboratory. A comparison with the Hemalog D system was attempted. The advantages and disadvantages of each system are enumerated and discussed in the context of a large general hospital.

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.

Effect of total body irradiation on late lung effects: hidden dangers.

PubMed

Johnston, Carl J; Manning, Casey; Hernady, Eric; Reed, Christina; Thurston, Sally W; Finkelstein, Jacob N; Williams, Jacqueline P

2011-08-01

In our ongoing investigation into the consequences of a radiological terrorism or nuclear dispersion event, we assessed whether a dose range that is believed to be sub-threshold for the development of lung endpoints results in late pathological changes and, secondarily, whether those late changes affect the lung's ability to respond to subsequent challenge. C57BL/6J mice received total body irradiation (0.5-10 Gy) and were followed for 6-18 months after irradiation. At 12 and 15 months, a subset of mice was exposed to a second challenge (aerosolised lipopolysaccharide [LPS]). Cytokines shown to be upregulated early (hours) following irradiation (interleukin [IL]6, keratinocyte chemoattractant [KC], IL1B, and IL1R2) demonstrated increases in messenger ribose nucleic acid (mRNA) expression at late time points, beginning at nine months. Although persistent, dose-dependent increases in T cell counts were seen, no other overt changes in pathophysiology were observed. Nonetheless, animals that were exposed to a secondary challenge at late time points demonstrated an increased inflammatory cell recruitment and persistence in response relative to controls. We propose that, following doses that elicit little change in pathophysiology, sub-clinical radiation-induced injury increases the lungs' susceptibility to a secondary challenge, possibly through a radiation-induced alteration in the immune defense system.

Ginseng ameliorates chronic histopathologic changes in a murine model of asthma.

PubMed

Babayigit, Arzu; Olmez, Duygu; Karaman, Ozkan; Bagriyanik, H Alper; Yilmaz, Osman; Kivcak, Bijen; Erbil, Guven; Uzuner, Nevin

2008-01-01

Currently, asthma therapies are effective in reducing inflammation but airway remodeling is poorly responsive to these agents. New therapeutic options that have fewer side effects and reverse chronic changes in the lungs are essential. This study aimed to determine the efficacy of oral administration of ginseng on lung histopathology in a murine model of chronic asthma. BALB/c mice were divided into four groups: control, placebo, ginseng, and dexamethasone. All mice except those in the control group were sensitized and challenged with ovalbumin. Then, mice in the ginseng group were given 2 gr/kg per day of ginseng and mice in the dexamethasone group received 1 mg/kg per day of dexamethasone via orogastic gavage once daily for 1 week. Lung histopathology was evaluated by using light and electron microscopy in all groups. All of the chronic changes of airways in the ginseng group were significantly ameliorated when compared with the placebo group. When compared with the dexamethasone group, the ginseng group had significantly lower numbers of mast cell count. Thicknesses of basement membrane, epithelium, and subepithelial smooth muscle were not statistically different between the ginseng and dexamethasone groups. Goblet cell numbers were much more reduced in the dexamethasone group. Ginseng is effective in resolving the established chronic histopathological changes of the lungs in the murine model of asthma.

The total alkaloids of Aconitum tanguticum protect against lipopolysaccharide-induced acute lung injury in rats.

PubMed

Wu, Guotai; Du, Lidong; Zhao, Lei; Shang, Ruofeng; Liu, Dongling; Jing, Qi; Liang, Jianping; Ren, Yuan

2014-09-29

Aconitum tanguticum has been widely used as a remedy for infectious diseases in traditional Tibetan medicine in China. The total alkaloids of Aconitum tanguticum (TAA) are the main active components of Aconitum tanguticum and have been demonstrated to be effective in suppressing inflammation. Our aim was to investigate the protective effects of TAA on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in rats. TAA was extracted in 95% ethanol and purified in chloroform. After vacuum drying, the TAA powder was dissolved in dimethyl sulfoxide. Adult male Sprague-Dawley rats were randomly divided into six groups. Rats were given dexamethasone (DXM, 4 mg/kg) or TAA (60 mg/kg, 30 mg/kg) before LPS injection. The PaO2and PaO2/FiO2 values, lung wet/dry (W/D) weight ratio and histological changes in lung tissue were measured. The cell counts, protein concentration, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid (BALF), and myeloperoxidase (MPO) activity in lung tissue were determined at 6, 12 or 24 h after LPS treatment. In addition, the NF-κ B activation in lung tissue was analyzed by western blot. In ALI rats, TAA significantly reduced the lung W/D ratio and increased the value of PaO2 or PaO2/FiO2 at 6, 12 or 24 h after LPS challenge. TAA also reduced the total protein concentration and the number of total cells, neutrophils or lymphocytes in BALF. In addition, TAA decreased MPO activity in the lung and attenuated histological changes in the lung. Furthermore, TAA inhibited the concentration of TNF-α, IL-6 and IL-1β in BALF at 6, 12 or 24 h after LPS treatment. Further study demonstrated that TAA significantly inhibited NF-κ B activation in lung tissue. The current study proved that TAA exhibited a potent protective effect on LPS-induced ALI in rats through its anti-inflammatory activity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

TU-G-BRA-01: Assessing Radiation-Induced Reductions in Regional Lung Perfusion Following Stereotactic Radiotherapy for Lung Cancer

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

McGurk, R; Green, R; Lawrence, M

2015-06-15

Purpose: The dose-dependent nature of radiation therapy (RT)-induced lung injury following hypo-fractionated stereotactic RT is unclear. We herein report preliminary results of a prospective study assessing the magnitude of RT-induced reductions in regional lung perfusion following hypo-fractionated stereotactic RT. Methods: Four patients undergoing hypo-fractionated stereotactic lung RT (SBRT: 12 Gy x 4 fractions or 10 Gy x 5 fractions) had a pre-treatment SPECT (single-photon emission computed tomography) perfusion scan providing a 3D map of regional lung perfusion. Scans were repeated 3–6 months post-treatment. Pre- and post SPECT scans were registered to the planning CT scan (and hence the 3D dosemore » data). Changes in regional perfusion (counts per cc on the pre-post scans) were computed in regions of the lung exposed to different doses of radiation (in 5 Gy intervals), thus defining a dose-response function. SPECT scans were internally normalized to the regions receiving <5 Gy. Results: At 3 months post-RT, the changes in perfusion are highly variable. At 6 months, there is a consistent dose-dependent reduction in regional perfusion. The average percent decline in regional perfusion was 10% at 15–20 Gy, 20% at 20–25 Gy, and 30% at 25–30 Gy representing a relatively linear dose response with an approximate 2% reduction per Gray for doses in excess of 10 Gy. There was a subtle increase in perfusion in the lung receiving <10 Gy. Conclusion: Hypo-fractionated stereotactic RT appears to cause a dose-dependent reduction in regional lung perfusion. There appears to be a threshold effect with no apparent perfusion loss at doses <10 Gy, though this might be in part due to the normalization technique used. Additional data is needed from a larger number of patients to better assess this issue. This sort of data can be used to assist optimizing RT treatment plans that minimize the risk of lung injury. Partly supported by the NIH (CA69579) and the Lance Armstrong Foundation.« less

Hierarchical pulmonary target nanoparticles via inhaled administration for anticancer drug delivery.

PubMed

Chen, Rui; Xu, Liu; Fan, Qin; Li, Man; Wang, Jingjing; Wu, Li; Li, Weidong; Duan, Jinao; Chen, Zhipeng

2017-11-01

Inhalation administration, compared with intravenous administration, significantly enhances chemotherapeutic drug exposure to the lung tissue and may increase the therapeutic effect for pulmonary anticancer. However, further identification of cancer cells after lung deposition of inhaled drugs is necessary to avoid side effects on normal lung tissue and to maximize drug efficacy. Moreover, as the action site of the major drug was intracellular organelles, drug target to the specific organelle is the final key for accurate drug delivery. Here, we designed a novel multifunctional nanoparticles (MNPs) for pulmonary antitumor and the material was well-designed for hierarchical target involved lung tissue target, cancer cell target, and mitochondrial target. The biodistribution in vivo determined by UHPLC-MS/MS method was employed to verify the drug concentration overwhelmingly increasing in lung tissue through inhaled administration compared with intravenous administration. Cellular uptake assay using A549 cells proved the efficient receptor-mediated cell endocytosis. Confocal laser scanning microscopy observation showed the location of MNPs in cells was mitochondria. All results confirmed the intelligent material can progressively play hierarchical target functions, which could induce more cell apoptosis related to mitochondrial damage. It provides a smart and efficient nanocarrier platform for hierarchical targeting of pulmonary anticancer drug. So far, this kind of material for pulmonary mitochondrial-target has not been seen in other reports.

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

NASA Astrophysics Data System (ADS)

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

2017-03-01

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

Fusarium Infection in Lung Transplant Patients

PubMed Central

Carneiro, Herman A.; Coleman, Jeffrey J.; Restrepo, Alejandro; Mylonakis, Eleftherios

2013-01-01

Fusarium is a fungal pathogen of immunosuppressed lung transplant patients associated with a high mortality in those with severe and persistent neutropenia. The principle portal of entry for Fusarium species is the airways, and lung involvement almost always occurs among lung transplant patients with disseminated infection. In these patients, the immunoprotective mechanisms of the transplanted lungs are impaired, and they are, therefore, more vulnerable to Fusarium infection. As a result, fusariosis occurs in up to 32% of lung transplant patients. We studied fusariosis in 6 patients following lung transplantation who were treated at Massachusetts General Hospital during an 8-year period and reviewed 3 published cases in the literature. Cases were identified by the microbiology laboratory and through discharge summaries. Patients presented with dyspnea, fever, nonproductive cough, hemoptysis, and headache. Blood tests showed elevated white blood cell counts with granulocytosis and elevated inflammatory markers. Cultures of Fusarium were isolated from bronchoalveolar lavage, blood, and sputum specimens. Treatments included amphotericin B, liposomal amphotericin B, caspofungin, voriconazole, and posaconazole, either alone or in combination. Lung involvement occurred in all patients with disseminated disease and it was associated with a poor outcome. The mortality rate in this group of patients was high (67%), and of those who survived, 1 patient was treated with a combination of amphotericin B and voriconazole, 1 patient with amphotericin B, and 1 patient with posaconazole. Recommended empirical treatment includes voriconazole, amphotericin B or liposomal amphotericin B first-line, and posaconazole for refractory disease. High-dose amphotericin B is recommended for treatment of most cases of fusariosis. The echinocandins (for example, caspofungin, micafungin, anidulafungin) are generally avoided because Fusarium species have intrinsic resistance to them. Treatment should ideally be based on the Fusarium isolate, susceptibility testing, and host-specific factors. Prognosis of fusariosis in the immunocompromised is directly related to a patient’s immune status. Prevention of Fusarium infection is recommended with aerosolized amphotericin B deoxycholate, which also has activity against other important fungi. PMID:21200188

[Cigarette smoking in different manners induces acute lung injury in rats].

PubMed

Xiao, Weiqiang; Zhou, Guojun; Xu, Chengyun; Xu, Jian; Huang, Fangfang; Lu, Xinbo; Li, Xia; Wu, Ximei

2016-05-25

Objective: To investigate the effects of cigarette smoking in different manners on acute lung injury in rats. Methods: The commercially available cigarettes with tar of 1,5, 11 mg were smoked in Canada depth smoking (health canada method, HCM) manner, and those with tar of 11 mg were also smoked in international standard (ISO) smoking manner. Rats were fixed and exposed to mainstream in a manner of nose-mouth exposure. After 28 days, the bronchoalveolar lavage fluids from left lung were collected for counting and classification of inflammatory cells and determination of pro-inflammatory cytokines IL-1β and TNF-α. The right lungs were subjected to histological examination and determination of myeloperoxidase (MPO) and superoxide dismutase (SOD) activities and glutathione, reactive oxygen species (ROS) and malondialdehyde (MDA) levels. Results: In both HCM and ISO manners, the degree of lung injury was closely related to the tar content of cigarettes, and significant decrease in the body weight of rats was observed after smoking for one week. In a HCM manner, smoking with cigarette of 11 mg tar resulted in robust infiltration of macrophages, lymphocytes and neutrophils into lungs, significant increase in IL-1β and TNF-α levels and MPO activities, and significant decrease in GSH levels and SOD activities and increase in ROS and MDA levels (all P <0.05). Smoking with cigarette of 5 mg tar led to moderate increase in IL-1β and TNF-α levels, and MPO activities (all P <0.05), and moderate decrease in GSH levels and SOD activities and increase of ROS and MDA levels (all P <0.05). However, smoking with cigarette of 1 mg tar affected neither inflammatory cell infiltration nor IL-1β and TNF-α levels. Conclusion: Cigarette smoking in nose-mouth exposure manner can induce acute lung injury in rats; and the degree of lung injury is closely related to the content of tar and other hazards in cigarettes.

Halothane reduces the early lipopolysaccharide-induced lung inflammation in mechanically ventilated rats.

PubMed

Giraud, O; Seince, P F; Rolland, C; Leçon-Malas, V; Desmonts, J M; Aubier, M; Dehoux, M

2000-12-01

Several studies suggest that anesthetics modulate the immune response. The aim of this study was to investigate the effect of halothane and thiopental on the lung inflammatory response. Rats submitted or not to intratracheal (IT) instillation of lipopolysaccharides (LPS) were anesthetized with either halothane (0. 5, 1, or 1.5%) or thiopental (60 mg. kg(-1)) and mechanically ventilated for 4 h. Control rats were treated or not by LPS without anesthesia. Lung inflammation was assessed by total and differential cell counts in bronchoalveolar lavage fluids (BALF) and by cytokine measurements (tumor necrosis factor-alpha [TNF-alpha], interleukin-6 [IL-6], macrophage inflammatory protein-2 [MIP-2], and monocyte chemoattractant protein-1 [MCP-1]) in BALF and lung homogenates. In the absence of LPS treatment, neither halothane nor thiopental modified the moderate inflammatory response induced by tracheotomy or mechanical ventilation. Cell recruitment and cytokine concentrations were increased in all groups receiving IT LPS. However, in halothane-anesthetized rats (halothane > or = 1%), but not in thiopental-anesthetized rats, the LPS-induced lung inflammation was altered in a dose-dependent manner. Indeed, when using 1% halothane, polymorphonuclear leukocyte (PMN) recruitment was decreased by 55% (p < 0.001) and TNF-alpha, IL-6, and MIP-2 concentrations in BALF and lung homogenates were decreased by more than 60% (p < 0.001) whereas total protein and MCP-1 concentrations remained unchanged. The decrease of MIP-2 (observed at the protein and messenger RNA [mRNA] level) was strongly correlated to the decrease of PMN recruitment (r = 0.73, p < 0.05). This halothane-reduced lung inflammatory response was transient and was reversed 20 h after the end of the anesthesia. Our study shows that halothane > or = 1%, delivered during 4 h by mechanical ventilation, but not mechanical ventilation per se, alters the early LPS-induced lung inflammation in the rat, suggesting a specific effect of halothane on this response.

Ternary particles for effective vaccine delivery to the pulmonary system

NASA Astrophysics Data System (ADS)

Terry, Treniece La'shay

Progress in the fields of molecular biology and genomics has provided great insight into the pathogenesis of disease and the defense mechanisms of the immune system. This knowledge has lead to the classification of an array of abnormal genes, for which, treatment relies on cellular expression of proteins. The utility of DNA-based vaccines hold great promise for the treatment of genetically based and infectious diseases, which ranges from hemophilia, cystic fibrosis, and HIV. Synthetic delivery systems consisting of cationic polymers, such as polyethylenimine (PEI), are capable of condensing DNA into compact structures, maximizing cellular uptake of DNA and yielding high levels of protein expression. To date, short term expression is a major obstacle in the development of gene therapies and has halted their expansion in clinical applications. This study intends to develop a sustained release vaccine delivery system using PLA-PEG block copolymers encapsulating PEI:DNA polyplexes. To enhance the effectiveness of such DNA-based vaccines, resident antigen presenting cells, macrophages and dendritic cells, will be targeted within the alveoli regions of the lungs. Porous microspheres will be engineered with aerodynamic properties capable of achieving deep lung deposition. A fabrication technique using concentric nozzles will be developed to produce porous microspheres. It was observed that modifications in the dispersed to continuous phase ratios have the largest influence on particle size distributions, release rates and encapsulation efficiency which ranged form 80--95% with fourteen days of release. Amphiphilic block copolymers were also used to fabricate porous microspheres. The confirmation of PEG within the biodegradable polymer backbone was found to have a tremendous impact on the microsphere morphology and encapsulation efficiency which varied from 50--90%. Porous microspheres were capable of providing sustained gene expression when tested in vitro using the luciferase reporter gene plasmid DNA. Prolonged expression was obtained for 9 days. PLGA and PLA-PEG microspheres were administered in vivo by intra-tracheal instillation and produced an acute inflammatory response, as observed from the large presence of neutrophils. The response using PLA-PEG microspheres yielded a lower total cell count signifying the incorporation of PEG into the copolymer backbone enhances the biocompatibility of the delivery system.

High-Efficiency Promoter-Dependent Transduction by Adeno-Associated Virus Type 6 Vectors in Mouse Lung

PubMed Central

HALBERT, CHRISTINE L.; LAM, SIU-LING; MILLER, A. DUSTY

2014-01-01

The transduction efficiency of adeno-associated virus (AAV) vectors in various somatic tissues has been shown to depend heavily on the AAV type from which the vector capsid proteins are derived. Among the AAV types studied, AAV6 efficiently transduces cells of the airway epithelium, making it a good candidate for the treatment of lung diseases such as cystic fibrosis. Here we have evaluated the effects of various promoter sequences on transduction rates and gene expression levels in the lung. Of the strong viral promoters examined, the Rous sarcoma virus (RSV) promoter performed significantly better than a human cytomegalovirus (CMV) promoter in the airway epithelium. However, a hybrid promoter consisting of a CMV enhancer, β-actin promoter and splice donor, and a β-globin splice acceptor (CAG promoter) exhibited even higher expression than either of the strong viral promoters alone, showing a 38-fold increase in protein expression over the RSV promoter. In addition, we show that vectors containing either the RSV or CAG promoter expressed well in the nasal and tracheal epithelium. Transduction rates in the 90% range were achieved in many airways with the CAG promoter, showing that with the proper AAV capsid proteins and promoter sequences, highly efficient transduction can be achieved. PMID:17430088

Measurement of the Solar Electron Neutrino Flux with the Homestake Chlorine Detector

NASA Astrophysics Data System (ADS)

Cleveland, Bruce T.; Daily, Timothy; Davis, Raymond, Jr.; Distel, James R.; Lande, Kenneth; Lee, C. K.; Wildenhain, Paul S.; Ullman, Jack

1998-03-01

The Homestake Solar Neutrino Detector, based on the inverse beta-decay reaction νe + 37Cl --> 37Ar + e-, has been measuring the flux of solar neutrinos since 1970. The experiment has operated in a stable manner throughout this time period. All aspects of this detector are reviewed, with particular emphasis on the determination of the extraction and counting efficiencies, the key experimental parameters that are necessary to convert the measured 37Ar count rate to the solar neutrino production rate. A thorough consideration is also given to the systematics of the detector, including the measurement of the extraction and counting efficiencies and the nonsolar production of 37Ar. The combined result of 108 extractions is a solar neutrino-induced 37Ar production rate of 2.56 +/- 0.l6 (statistical) +/- 0.16 (systematic) SNU.

Preclinical Evaluation of 68Ga-MAA from Commercial Available 99mTc-MAA Kit

PubMed Central

Shanehsazzadeh, Saeed; Jalilian, Amir Reza; Lahooti, Afsaneh; Geramifar, Parham; Beiki, Davood; Yousefnia, Hassan; Rabiee, Amir; Mazidi, Mohammad; Mirshojaei, Seyedeh Fatemeh; Maus, Stephan

2017-01-01

99mTc-Macroaggregated Albumin (99mTc-MAA) has been used as a perfusion agent. This study described development of the 68Ga-MAA via commercially available kits from Pars-Isotopes Company as a 99mTc-MAA kit. 68Ge/68Ga generator was eluted with suprapure HCl (0.6 M, 6 mL) in 0.5 mL fractions. The two fractions with the highest 68GaCl3 activity were generally used for labeling purposes. After labeling, the final product was centrifuged 2 times to purify the solution. Five rats were sacrificed at each exact time interval (from 15 min to 2 h post injection) and the percentage of injected dose per gram (%ID/g) of each organ was measured by direct counting from 11 harvested organs of rats. The RTLC showed that labeling yields before centrifuges were 90% and 95% for Pars-Isotopes and GE kits, respectively and after centrifuges, they became 100%. The microscopic size examination showed a shift in the particle sizes post centrifuges and the biodistribution data revealed the efficiency and benefits of centrifuges in terms of preventing the of liver and bone marrow uptakes especially for Pars-Isotopes kits. Our results showed that after centrifuges of the final product, the lung uptakes increased from 89% to more than 97% of %ID/g after 5 min post injections. The whole procedure took less than 25 min from elution to the final product. Since 99mTc-MAA remained longer than 68Ga-MAA in the lung and 68Ga-MAA showed better image qualities, using 68Ga-MAA is recommended. PMID:29552050

Preclinical Evaluation of 68Ga-MAA from Commercial Available 99mTc-MAA Kit.

PubMed

Shanehsazzadeh, Saeed; Jalilian, Amir Reza; Lahooti, Afsaneh; Geramifar, Parham; Beiki, Davood; Yousefnia, Hassan; Rabiee, Amir; Mazidi, Mohammad; Mirshojaei, Seyedeh Fatemeh; Maus, Stephan

2017-01-01

99m Tc-Macroaggregated Albumin ( 99m Tc-MAA) has been used as a perfusion agent. This study described development of the 68 Ga-MAA via commercially available kits from Pars-Isotopes Company as a 99m Tc-MAA kit. 68 Ge/ 68 Ga generator was eluted with suprapure HCl (0.6 M, 6 mL) in 0.5 mL fractions. The two fractions with the highest 68 GaCl 3 activity were generally used for labeling purposes. After labeling, the final product was centrifuged 2 times to purify the solution. Five rats were sacrificed at each exact time interval (from 15 min to 2 h post injection) and the percentage of injected dose per gram (%ID/g) of each organ was measured by direct counting from 11 harvested organs of rats. The RTLC showed that labeling yields before centrifuges were 90% and 95% for Pars-Isotopes and GE kits, respectively and after centrifuges, they became 100%. The microscopic size examination showed a shift in the particle sizes post centrifuges and the biodistribution data revealed the efficiency and benefits of centrifuges in terms of preventing the of liver and bone marrow uptakes especially for Pars-Isotopes kits. Our results showed that after centrifuges of the final product, the lung uptakes increased from 89% to more than 97% of %ID/g after 5 min post injections. The whole procedure took less than 25 min from elution to the final product. Since 99m Tc-MAA remained longer than 68 Ga-MAA in the lung and 68 Ga-MAA showed better image qualities, using 68 Ga-MAA is recommended.

Association of sputum and blood eosinophil concentrations with clinical measures of COPD severity: an analysis of the SPIROMICS cohort.

PubMed

Hastie, Annette T; Martinez, Fernando J; Curtis, Jeffrey L; Doerschuk, Claire M; Hansel, Nadia N; Christenson, Stephanie; Putcha, Nirupama; Ortega, Victor E; Li, Xingnan; Barr, R Graham; Carretta, Elizabeth E; Couper, David J; Cooper, Christopher B; Hoffman, Eric A; Kanner, Richard E; Kleerup, Eric; O'Neal, Wanda K; Paine, Richard; Peters, Stephen P; Alexis, Neil E; Woodruff, Prescott G; Han, MeiLan K; Meyers, Deborah A; Bleecker, Eugene R

2017-12-01

Increased concentrations of eosinophils in blood and sputum in chronic obstructive pulmonary disease (COPD) have been associated with increased frequency of exacerbations, reduced lung function, and corticosteroid responsiveness. We aimed to assess whether high eosinophil concentrations in either sputum or blood are associated with a severe COPD phenotype, including greater exacerbation frequency, and whether blood eosinophils are predictive of sputum eosinophils. We did a multicentre observational study analysing comprehensive baseline data from SPIROMICS in patients with COPD aged 40-80 years who had a smoking history of at least 20 pack-years, recruited from six clinical sites and additional subsites in the USA between Nov 12, 2010, and April 21, 2015. Inclusion criteria for this analysis were SPIROMICS baseline visit data with complete blood cell counts and, in a subset, acceptable sputum counts. We stratified patients on the basis of blood and sputum eosinophil concentrations and compared their demographic characteristics, as well as results from questionnaires, clinical assessments, and quantitative CT (QCT). We also analysed whether blood eosinophil concentrations reliably predicted sputum eosinophil concentrations. This study is registered with ClinicalTrials.gov (NCT01969344). Of the 2737 patients recruited to SPIROMICS, 2499 patients were smokers and had available blood counts, and so were stratified by mean blood eosinophil count: 1262 patients with low (<200 cells per μL) and 1237 with high (≥200 cells per μL) blood eosinophil counts. 827 patients were eligible for stratification by mean sputum eosinophil percentage: 656 with low (<1·25%) and 171 with high (≥1·25%) sputum eosinophil percentages. The high sputum eosinophil group had significantly lower median FEV 1 percentage predicted than the low sputum eosinophil group both before (65·7% [IQR 51·8-81·3] vs 75·7% [59·3-90·2], p<0·0001) and after (77·3% [63·1-88·5] vs 82·9% [67·8-95·9], p=0·001) bronchodilation. QCT density measures for emphysema and air trapping were significantly higher in the high sputum eosinophil group than the low sputum eosinophil group. Exacerbations requiring corticosteroids treatment were more common in the high versus low sputum eosinophil group (p=0·002). FEV 1 percentage predicted was significantly different between low and high blood eosinophil groups, but differences were less than those observed between the sputum groups. The high blood eosinophil group had slightly increased airway wall thickness (0·02 mm difference, p=0·032), higher St George Respiratory Questionnaire symptom scores (p=0·037), and increased wheezing (p=0·018), but no evidence of an association with COPD exacerbations (p=0·35) or the other indices of COPD severity, such as emphysema measured by CT density, COPD assessment test scores, Body-mass index, airflow Obstruction, Dyspnea, and Exercise index, or Global Initiative for Chronic Obstructive Lung Disease stage. Blood eosinophil counts showed a weak but significant association with sputum eosinophil counts (receiver operating characteristic area under the curve of 0·64, p<0·0001), but with a high false-discovery rate of 72%. In a large, well characterised cohort of former and current smoking patients with a broad range of COPD severity, high concentrations of sputum eosinophils were a better biomarker than high concentrations of blood eosinophils to identify a patient subgroup with more severe disease, more frequent exacerbations, and increased emphysema by QCT. Blood eosinophils alone were not a reliable biomarker for COPD severity or exacerbations, or for sputum eosinophils. Clinical trials targeting eosinophilic inflammation in COPD should consider assessing sputum eosinophils. National Institutes of Health, and National Heart, Lung, and Blood Institute. Copyright © 2017 Elsevier Ltd. All rights reserved.

Breakdown of lung framework and an increase in pores of Kohn as initial events of emphysema and a cause of reduction in diffusing capacity.

PubMed

Yoshikawa, Akira; Sato, Shuntaro; Tanaka, Tomonori; Hashisako, Mikiko; Kashima, Yukio; Tsuchiya, Tomoshi; Yamasaki, Naoya; Nagayasu, Takeshi; Yamamoto, Hiroshi; Fukuoka, Junya

2016-01-01

Pulmonary emphysema is the pathological prototype of chronic obstructive pulmonary disease and is also associated with other lung diseases. We considered that observation with different approaches may provide new insights for the pathogenesis of emphysema. We reviewed tissue blocks of the lungs of 25 cases with/without emphysema and applied a three-dimensional observation method to the blocks. Based on the three-dimensional characteristics of the alveolar structure, we considered one face of the alveolar polyhedron as a structural unit of alveoli and called it a framework unit (FU). We categorized FUs based on their morphological characteristics and counted their number to evaluate the destructive changes in alveoli. We also evaluated the number and the area of pores of Kohn in FUs. We performed linear regression analysis to estimate the effect of these data on pulmonary function tests. In multivariable regression analysis, a decrease in the number of FUs without an alveolar wall led to a significant decrease in the diffusing capacity of the lung for carbon monoxide (DLCO) and DLCO per unit alveolar volume, and an increase in the area of pores of Kohn had a significant effect on an increase in residual capacity. A breakdown in the lung framework and an increase in pores of Kohn are associated with a decrease in DLCO and DLCO per unit alveolar volume with/without emphysema.

Effects of proton pump inhibitors on lung cancer precise radiotherapy-induced radiation pneumonitis.

PubMed

Su, QiaoLi; Wang, Duoning; Yuan, Bo; Liu, Feng; Lei, Yi; Li, Shuangqing

2014-11-01

The objective of this study was to explore the effects of proton pump inhibitors (PPIs) on the development and prognosis of lung cancer precise radiotherapy-induced radiation pneumonitis. Clinical materials of 84 lung cancer patients who had radiation pneumonitis after precise radiotherapy were retrospectively analyzed, and the patients were divided into PPI group and control group, according to whether or not PPIs were applied. The development and prognosis of patients and the effects of different doses of PPI on patient condition from two groups were compared. There were 57 PPI cases in PPI group and 27 cases in control group. Basic characteristics of patients were not statistically different between the two groups; however, white blood cell count, oxygenation indexes, blood gas pH, and lung imaging index were significantly different (p < 0.05), indicating that radiation pneumonitis tended to be more severe in PPI group. As regards effects of PPI on prognosis of two groups, remission rate of radiation pneumonia in PPI group was significantly less than that of the control group. Among 57 cases in PPI group, there were 31 patients applied with PPI ≤ 1DDD and 31 patients applied with PPI > 1DDD. In comparison of the various parameters of patients, 7 days after being applied with different doses of PPI, there were no significant differences between the parameters of radiation pneumonitis. PPIs should be cautiously utilized to avoid the effects of lung cancer radiotherapy-induced radiation pneumonia.

Synergistic effect of bolus exposure to zinc oxide nanoparticles on bleomycin-induced secretion of pro-fibrotic cytokines without lasting fibrotic changes in murine lungs.

PubMed

Wu, Wenting; Ichihara, Gaku; Hashimoto, Naozumi; Hasegawa, Yoshinori; Hayashi, Yasuhiko; Tada-Oikawa, Saeko; Suzuki, Yuka; Chang, Jie; Kato, Masashi; D'Alessandro-Gabazza, Corina N; Gabazza, Esteban C; Ichihara, Sahoko

2014-12-30

Zinc oxide (ZnO) nanoparticles are widely used in various products, and the safety evaluation of this manufactured material is important. The present study investigated the inflammatory and fibrotic effects of pulmonary exposure to ZnO nanoparticles in a mouse model of pulmonary fibrosis. Pulmonary fibrosis was induced by constant subcutaneous infusion of bleomycin (BLM). Female C57BL/6Jcl mice were divided into BLM-treated and non-treated groups. In each treatment group, 0, 10, 20 or 30 µg of ZnO nanoparticles were delivered into the lungs through pharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) and the lungs were sampled at Day 10 or 14 after administration. Pulmonary exposure by a single bolus of ZnO nanoparticles resulted in severe, but transient inflammatory infiltration and thickening of the alveolar septa in the lungs, along with the increase of total and differential cell counts in BLAF. The BALF level of interleukin (IL)-1β and transforming growth factor (TGF)-β was increased at Day 10 and 14, respectively. At Day 10, the synergistic effect of BLM and ZnO exposure was detected on IL-1β and monocyte chemotactic protein (MCP)-1 in BALF. The present study demonstrated the synergistic effect of pulmonary exposure to ZnO nanoparticles and subcutaneous infusion of BLM on the secretion of pro-fibrotic cytokines in the lungs.

Factors that increase diagnostic yield of surgical lung biopsy in pediatric oncology patients.

PubMed

Acker, Shannon N; Gonzales, Danielle; Ross, James T; Dishop, Megan K; Deterding, Robin R; Partrick, David A

2015-09-01

Recent data demonstrate that surgical lung biopsy in immunocompromised children, including oncology patients, alters therapy in only 50% of cases. We hypothesized that there are factors identifiable preoperatively which can predict the patients who will or will not benefit from surgical biopsy. We reviewed the medical records of all children with malignancy who underwent surgical lung biopsy between 2004 and 2013 at a single institution, excluding those children who had previously undergone a solid organ or bone marrow transplant. Eighty lung wedge biopsies were performed (median age 13 years, IQR 5.25-16; 63% male, n=50) 53 (66%) of which led to a change in patient management. The majority of biopsies were performed to diagnose a new mass or differentiate infection from metastases (mass group) (n=68, 85%), and 12 biopsies (15%) were performed to diagnose a known infection for antibiotic guidance (infection group). Children in the infection group were more likely to be febrile preoperatively, were more likely to be an inpatient preoperatively, and had a lower absolute neutrophil count at the time of biopsy. Patients in the infection group had higher postoperative mortality rates and higher rates of major complications. In pediatric oncology patients, surgical lung biopsy has a lower diagnostic yield and higher complication rate when performed for antibiotic guidance. Prior to proceeding with biopsy in this high-risk patient population, surgeons and oncologists should carefully weigh the potential risks and benefits. Copyright © 2015 Elsevier Inc. All rights reserved.

Synergistic Effect of Bolus Exposure to Zinc Oxide Nanoparticles on Bleomycin-Induced Secretion of Pro-Fibrotic Cytokines without Lasting Fibrotic Changes in Murine Lungs

PubMed Central

Wu, Wenting; Ichihara, Gaku; Hashimoto, Naozumi; Hasegawa, Yoshinori; Hayashi, Yasuhiko; Tada-Oikawa, Saeko; Suzuki, Yuka; Chang, Jie; Kato, Masashi; D’Alessandro-Gabazza, Corina N.; Gabazza, Esteban C.; Ichihara, Sahoko

2014-01-01

Zinc oxide (ZnO) nanoparticles are widely used in various products, and the safety evaluation of this manufactured material is important. The present study investigated the inflammatory and fibrotic effects of pulmonary exposure to ZnO nanoparticles in a mouse model of pulmonary fibrosis. Pulmonary fibrosis was induced by constant subcutaneous infusion of bleomycin (BLM). Female C57BL/6Jcl mice were divided into BLM-treated and non-treated groups. In each treatment group, 0, 10, 20 or 30 µg of ZnO nanoparticles were delivered into the lungs through pharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) and the lungs were sampled at Day 10 or 14 after administration. Pulmonary exposure by a single bolus of ZnO nanoparticles resulted in severe, but transient inflammatory infiltration and thickening of the alveolar septa in the lungs, along with the increase of total and differential cell counts in BLAF. The BALF level of interleukin (IL)-1β and transforming growth factor (TGF)-β was increased at Day 10 and 14, respectively. At Day 10, the synergistic effect of BLM and ZnO exposure was detected on IL-1β and monocyte chemotactic protein (MCP)-1 in BALF. The present study demonstrated the synergistic effect of pulmonary exposure to ZnO nanoparticles and subcutaneous infusion of BLM on the secretion of pro-fibrotic cytokines in the lungs. PMID:25561223

Material screening with HPGe counting station for PandaX experiment

NASA Astrophysics Data System (ADS)

Wang, X.; Chen, X.; Fu, C.; Ji, X.; Liu, X.; Mao, Y.; Wang, H.; Wang, S.; Xie, P.; Zhang, T.

2016-12-01

A gamma counting station based on high-purity germanium (HPGe) detector was set up for the material screening of the PandaX dark matter experiments in the China Jinping Underground Laboratory. Low background gamma rate of 2.6 counts/min within the energy range of 20 to 2700 keV is achieved due to the well-designed passive shield. The sentivities of the HPGe detetector reach mBq/kg level for isotopes like K, U, Th, and even better for Co and Cs, resulted from the low-background rate and the high relative detection efficiency of 175%. The structure and performance of the counting station are described in this article. Detailed counting results for the radioactivity in materials used by the PandaX dark-matter experiment are presented. The upgrading plan of the counting station is also discussed.

Measurement of X-ray emission efficiency for K-lines.

PubMed

Procop, M

2004-08-01

Results for the X-ray emission efficiency (counts per C per sr) of K-lines for selected elements (C, Al, Si, Ti, Cu, Ge) and for the first time also for compounds and alloys (SiC, GaP, AlCu, TiAlC) are presented. An energy dispersive X-ray spectrometer (EDS) of known detection efficiency (counts per photon) has been used to record the spectra at a takeoff angle of 25 degrees determined by the geometry of the secondary electron microscope's specimen chamber. Overall uncertainty in measurement could be reduced to 5 to 10% in dependence on the line intensity and energy. Measured emission efficiencies have been compared with calculated efficiencies based on models applied in standardless analysis. The widespread XPP and PROZA models give somewhat too low emission efficiencies. The best agreement between measured and calculated efficiencies could be achieved by replacing in the modular PROZA96 model the original expression for the ionization cross section by the formula given by Casnati et al. (1982) A discrepancy remains for carbon, probably due to the high overvoltage ratio.

High-Dose Neutron Detector Development Using 10B Coated Cells

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

Menlove, Howard Olsen; Henzlova, Daniela

2016-11-08

During FY16 the boron-lined parallel-plate technology was optimized to fully benefit from its fast timing characteristics in order to enhance its high count rate capability. To facilitate high count rate capability, a novel fast amplifier with timing and operating properties matched to the detector characteristics was developed and implemented in the 8” boron plate detector that was purchased from PDT. Each of the 6 sealed-cells was connected to a fast amplifier with corresponding List mode readout from each amplifier. The FY16 work focused on improvements in the boron-10 coating materials and procedures at PDT to significantly improve the neutron detectionmore » efficiency. An improvement in the efficiency of a factor of 1.5 was achieved without increasing the metal backing area for the boron coating. This improvement has allowed us to operate the detector in gamma-ray backgrounds that are four orders of magnitude higher than was previously possible while maintaining a relatively high counting efficiency for neutrons. This improvement in the gamma-ray rejection is a key factor in the development of the high dose neutron detector.« less

Ga-67 uptake in the lung in sarcoidosis

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

Johnson, D.G.; Johnson, S.M.; Harris, C.C.

1984-02-01

Images were obtained with Ga-67 and bronchopulmonary lavage performed in 21 patients with sarcoidosis (31 studies). The Ga-67 index, a semiquantitative criterion, was compared to a quantitative computer index based on lung:liver activity ratios; accuracy in predicting active alveolitis (defined by lavage lymphocyte counts) was assessed and differences between 24- and 48-hour studies examined. Computer activity ratios correlated well with the Ga-67 index, which had a sensitivity of 64%, specificity of 71%, 82%, and 77%, respectively, for the computer scores. Scores at 24 and 48 hours were similar. These results suggest that (a) Ga-67 scanning is useful in staging activitymore » in pulmonary sarcoidosis, (b) quantitative computer scores are accurate in predicting disease activity, and (c) scanning can be performed 24 or 48 hours after injection.« less

Platelet-lymphocyte ratio is an independent prognostic factor in patients with ALK-positive non-small-cell lung cancer.

PubMed

Han, Ying; Wang, Jing; Hong, Liping; Sun, Leina; Zhuang, Hongqing; Sun, Bingsheng; Wang, Hua; Zhang, Xinwei; Ren, Xiubao

2017-01-01

As the prognostic value of the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) is unclear in patients with ALK-positive non-small-cell lung cancer (NSCLC), this study assessed the importance of these factors was in this patient subset. In 173 patients with primary ALK-positive NSCLC at pathological stages I-IV, neutrophil, platelet, lymphocyte, D-dimer and eosinophil levels were recorded before starting treatment. The patients' median NLR and PLR values were 2.10 and 127.69, respectively. Univariate analyses showed that NLR and PLR values, the D-dimer level and the eosinophil count were all associated with survival. Although multivariate analysis showed PLR to be an independent prognostic factor for overall survival (p = 0.018), NLR was not. PLR is an independent prognostic factor in ALK-positive NSCLC.

Nonlinear dimensionality reduction of CT histogram based feature space for predicting recurrence-free survival in non-small-cell lung cancer

NASA Astrophysics Data System (ADS)

Kawata, Y.; Niki, N.; Ohmatsu, H.; Aokage, K.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, M.

2015-03-01

Advantages of CT scanners with high resolution have allowed the improved detection of lung cancers. In the recent release of positive results from the National Lung Screening Trial (NLST) in the US showing that CT screening does in fact have a positive impact on the reduction of lung cancer related mortality. While this study does show the efficacy of CT based screening, physicians often face the problems of deciding appropriate management strategies for maximizing patient survival and for preserving lung function. Several key manifold-learning approaches efficiently reveal intrinsic low-dimensional structures latent in high-dimensional data spaces. This study was performed to investigate whether the dimensionality reduction can identify embedded structures from the CT histogram feature of non-small-cell lung cancer (NSCLC) space to improve the performance in predicting the likelihood of RFS for patients with NSCLC.

Development of a personalized training system using the Lung Image Database Consortium and Image Database resource Initiative Database.

PubMed

Lin, Hongli; Wang, Weisheng; Luo, Jiawei; Yang, Xuedong

2014-12-01

The aim of this study was to develop a personalized training system using the Lung Image Database Consortium (LIDC) and Image Database resource Initiative (IDRI) Database, because collecting, annotating, and marking a large number of appropriate computed tomography (CT) scans, and providing the capability of dynamically selecting suitable training cases based on the performance levels of trainees and the characteristics of cases are critical for developing a efficient training system. A novel approach is proposed to develop a personalized radiology training system for the interpretation of lung nodules in CT scans using the Lung Image Database Consortium (LIDC) and Image Database Resource Initiative (IDRI) database, which provides a Content-Boosted Collaborative Filtering (CBCF) algorithm for predicting the difficulty level of each case of each trainee when selecting suitable cases to meet individual needs, and a diagnostic simulation tool to enable trainees to analyze and diagnose lung nodules with the help of an image processing tool and a nodule retrieval tool. Preliminary evaluation of the system shows that developing a personalized training system for interpretation of lung nodules is needed and useful to enhance the professional skills of trainees. The approach of developing personalized training systems using the LIDC/IDRL database is a feasible solution to the challenges of constructing specific training program in terms of cost and training efficiency. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

Evaluation of absolute measurement using a 4π plastic scintillator for the 4πβ-γ coincidence counting method.

PubMed

Unno, Y; Sanami, T; Sasaki, S; Hagiwara, M; Yunoki, A

2018-04-01

Absolute measurement by the 4πβ-γ coincidence counting method was conducted by two photomultipliers facing across a plastic scintillator to be focused on β ray counting efficiency. The detector was held with a through-hole-type NaI(Tl) detector. The results include absolutely determined activity and its uncertainty especially about extrapolation. A comparison between the obtained and known activities showed agreement within their uncertainties. Copyright © 2017 Elsevier Ltd. All rights reserved.

Integrating Lung Physiology, Immunology, and Tuberculosis.

PubMed

Torrelles, Jordi B; Schlesinger, Larry S

2017-08-01

Lungs are directly exposed to the air, have enormous surface area, and enable gas exchange in air-breathing animals. They are constantly 'attacked' by microbes from both outside and inside and thus possess a unique, highly regulated local immune defense system which efficiently allows for microbial clearance while minimizing damaging inflammatory responses. As a prototypic host-adapted airborne pathogen, Mycobacterium tuberculosis traverses the lung and has several 'interaction points' (IPs) which it must overcome to cause infection. These interactions are critical, not only from a pathogenesis perspective but also in considering the effectiveness of therapies and vaccines in the lungs. Here we discuss emerging views on immunologic interactions occurring in the lungs for M. tuberculosis and their impact on infection and persistence. Copyright © 2017 Elsevier Ltd. All rights reserved.

Circulating Cell Free Tumor DNA Detection as a Routine Tool for Lung Cancer Patient Management

PubMed Central

Vendrell, Julie A.; Mau-Them, Frédéric Tran; Béganton, Benoît; Godreuil, Sylvain; Coopman, Peter; Solassol, Jérôme

2017-01-01

Circulating tumoral DNA (ctDNA), commonly named “liquid biopsy”, has emerged as a new promising noninvasive tool to detect biomarker in several cancers including lung cancer. Applications involving molecular analysis of ctDNA in lung cancer have increased and encompass diagnosis, response to treatment, acquired resistance and prognosis prediction, while bypassing the problem of tumor heterogeneity. ctDNA may then help perform dynamic genetic surveillance in the era of precision medicine through indirect tumoral genomic information determination. The aims of this review were to examine the recent technical developments that allowed the detection of genetic alterations of ctDNA in lung cancer. Furthermore, we explored clinical applications in patients with lung cancer including treatment efficiency monitoring, acquired therapy resistance mechanisms and prognosis value. PMID:28146051

Boiling sheep liver or lung for 30 minutes is necessary and sufficient to kill Echinococcus granulosus protoscoleces in hydatid cysts

PubMed Central

Li, Jun; Wu, Chuanchuan; Wang, Hui; Liu, Huanyuan; Vuitton, Dominique A.; Wen, Hao; Zhang, Wenbao

2014-01-01

Proper disposal of carcasses and offal after home slaughter is difficult in poor and remote communities and therefore dogs readily have access to hydatid cysts containing offal from livestock, thus completing the parasite cycle of Echinococcus granulosus and putting communities at risk of cystic echinococcosis. Boiling livers and lungs which contain hydatid cysts could be a simple, efficient and energy- and time-saving way to kill the infectious protoscoleces. The aim of this study was to provide precise practical recommendations to livestock owners. Our results show that boiling the whole sheep liver and/or lung, with single or multiple hydatid cysts, for 30 min is necessary and sufficient to kill E. granulosus protoscoleces in hydatid cysts. Advertising on this simple rule in at-risk communities would be an efficient and cheap complement to other veterinary public health operations to control cystic echinococcosis. PMID:25456565

Adaptive Bloom Filter: A Space-Efficient Counting Algorithm for Unpredictable Network Traffic

NASA Astrophysics Data System (ADS)

Matsumoto, Yoshihide; Hazeyama, Hiroaki; Kadobayashi, Youki

The Bloom Filter (BF), a space-and-time-efficient hashcoding method, is used as one of the fundamental modules in several network processing algorithms and applications such as route lookups, cache hits, packet classification, per-flow state management or network monitoring. BF is a simple space-efficient randomized data structure used to represent a data set in order to support membership queries. However, BF generates false positives, and cannot count the number of distinct elements. A counting Bloom Filter (CBF) can count the number of distinct elements, but CBF needs more space than BF. We propose an alternative data structure of CBF, and we called this structure an Adaptive Bloom Filter (ABF). Although ABF uses the same-sized bit-vector used in BF, the number of hash functions employed by ABF is dynamically changed to record the number of appearances of a each key element. Considering the hash collisions, the multiplicity of a each key element on ABF can be estimated from the number of hash functions used to decode the membership of the each key element. Although ABF can realize the same functionality as CBF, ABF requires the same memory size as BF. We describe the construction of ABF and IABF (Improved ABF), and provide a mathematical analysis and simulation using Zipf's distribution. Finally, we show that ABF can be used for an unpredictable data set such as real network traffic.

Lung segmentation from HRCT using united geometric active contours

NASA Astrophysics Data System (ADS)

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

2007-12-01

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

SiRNA/DOX lodeded chitosan based nanoparticles: Development, Characterization and in vitro evaluation on A549 lung cancer cell line.

PubMed

Seifi-Najmi, M; Hajivalili, M; Safaralizadeh, R; Sadreddini, S; Esmaeili, S; Razavi, R; Ahmadi, M; Mikaeili, H; Baradaran, B; Shams-Asenjan, K; Yousefi, M

2016-09-30

High-mobility group AT-hook2 (HMGA2), involved in epithelial mesenchymal transition (EMT) process, has a pivotal role in lung cancer metastasis. Lung cancer therapy with HMGA2 suppressing small interfering RNA (siRNA) has been introduced recently while doxorubicin (DOX) has been used as a frequent cancer chemotherapy agent. Both reagents have been faced with obstacles in clinic which make them ineffective. NanoParticles (NPs) provided a platform for efficient co delivery of the anticancer drugs. The aim of this study was production and in vitro characterization of different pharmacological groups (siRNA, DOX or siRNA-DOX) of carboxymethyl dextran thrimethyl chitosan nanoparticles (CMDTMChiNPs) on cytotoxicity, gene expression, apoptosis and migration of metastatic lung cancer cell line (A-549). CMDTMChiNPs were synthesized and encapsulated with siRNA, DOX or siRNA-DOX. Then the effects of HMGA2 siRNA and DOX co delivery was assessed in A549 viability and target genes (HMGA2, Ecadherin, vimentin and MMP9) by MTT and real time PCR, respectively. In addition capability of apoptosis induction and anti-migratory features of formulated NPs were analyzed by flowcytometry and wound healing assays. SiRNA-DOX-CMDTM ChiNPs approximate size were 207±5 with poly dispersity index (PDI) and zeta potential of 0.4 and 16.3±0.3, respectively. NPs loaded with DOX and siRNA were the most efficient drug formulations in A549 cell cytotoxicity, altering of EMT markers, apoptosis induction and migration inhibition. Generally our results showed that co delivery of HMGA2 siRNA and DOX by novel designed CMDTMChiNPs is a new therapeutic approach with great potential efficiency for lung cancer treatment.

Contribution of the bronchial circulation to lung preservation.

PubMed

LoCicero, J; Massad, M; Matano, J; Greene, R; Dunn, M; Michaelis, L L

1991-05-01

Short preservation time still severely limits lung transplantation. To determine the effect of bronchial arterial flush preservation, we studied 54 dogs using the isolated perfused working lung model. After baseline measurements, lungs were flushed with lactated Ringer's solution (60 ml/kg at 8 degrees C) by one of three methods: pulmonary artery perfusion, bronchial artery perfusion through a 15 cm closed aortic segment, or simultaneous pulmonary-bronchial artery perfusion. These groups were further subdivided and tested after 0, 4, and 17 hours of storage at 4 degrees C (n = 6 each). Lungs were ventilated (flow rate 140 ml/kg/min; inspired oxygen fraction 0.21) and continuously reperfused with normothermic deoxygenated autologous blood in a closed loop. Measured variables were hemodynamics, aerodynamics, and leukocytes in bronchoalveolar lavage. Survival time was determined from initial reperfusion to failure of the lung to oxygenate. After 0 and 4 hours of storage, there was no significant difference in survival times. After 17 hours, lungs subjected to pulmonary-bronchial artery perfusion survived longer than those perfused via either the pulmonary or bronchial arteries alone (120 +/- 24 versus 38 +/- 14 or 52 +/- 16 minutes; p less than 0.01). Pulmonary artery pressure and resistance in all groups except at failure were never different from baseline values in the intact animal. Shunts in the pulmonary-bronchial artery perfusion groups were closest to baseline at onset (8% +/- 4%) and remained lower throughout reperfusion than in the groups subjected to pulmonary or bronchial artery perfusion alone. After 17 hours, static compliance of pulmonary artery-perfused lungs was worse than baseline (1.1 +/- 0.2 x 10(-2) versus 3.2 +/- 0.7 x 10(-2) L/cm H2O/sec; p less than 0.05), whereas compliance in the pulmonary-bronchial artery perfusion groups remained constant (3.6 +/- 1.5 x 10(-2) L/cm H2O/sec). Elastic work performed by lungs subjected to pulmonary-bronchial artery flushing at onset was significantly lower when these lungs were reperfused immediately (201 +/- 14 versus 295 +/- 35 gm-m/min for pulmonary artery-flushed lungs) or after 4 hours of storage (229 +/- 30 versus 290 +/- 24 gm-m/min for pulmonary artery-flushed lungs). Bronchoalveolar lavage after 17 hours in the group subjected to pulmonary bronchial artery flushing demonstrated leukocyte counts similar to those of intact lungs (45 +/- 5 versus 29 +/- 8/mm3) and significantly less than in lungs subjected to pulmonary or bronchial artery flushing (137 +/- 18 or 82 +/- 10/mm3, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Radon Detection and Counting

NASA Astrophysics Data System (ADS)

Peterson, David

2004-11-01

One of the daughter products of the naturally occuring U 238 decay chain is the colorless, odorless, inert gas radon. The daughter products of the radon, from Po 218 through Po 214, can remain in the lungs after breathing radon that has diffused into the atmosphere. Radon testing of homes before sale or purchase is necessary in many parts of the U.S. Testing can be accomplished by the simple procedure of exposing a canister of activated charcoal to the ambient air. Radon atoms in the air are adsorbed onto the surface of the charcoal, which is then sealed in the canister. Gamma rays of the daughter products of the radon, in particular Pb 214 and Bi 214, can then be detected in low background counting system. Radon remediation procedures are encouraged for radon activities in the air greater than 4 pCi/L.

Visual versus mechanised leucocyte differential counts: costing and evaluation of traditional and Hemalog D methods.

PubMed Central

Hudson, M J; Green, A E

1980-01-01

Visual differential counts were examined for efficiency, cost effectiveness, and staff acceptability within our laboratory. A comparison with the Hemalog D system was attempted. The advantages and disadvantages of each system are enumerated and discussed in the context of a large general hospital. PMID:7440760

LOW ENERGY COUNTING CHAMBERS

DOEpatents

Hayes, P.M.

1960-02-16

A beta particle counter adapted to use an end window made of polyethylene terephthalate was designed. The extreme thinness of the film results in a correspondingly high transmission of incident low-energy beta particles by the window. As a consequence, the counting efficiency of the present counter is over 40% greater than counters using conventional mica end windows.

Single photon detection using Geiger mode CMOS avalanche photodiodes

NASA Astrophysics Data System (ADS)

Lawrence, William G.; Stapels, Christopher; Augustine, Frank L.; Christian, James F.

2005-10-01

Geiger mode Avalanche Photodiodes fabricated using complementary metal-oxide-semiconductor (CMOS) fabrication technology combine high sensitivity detectors with pixel-level auxiliary circuitry. Radiation Monitoring Devices has successfully implemented CMOS manufacturing techniques to develop prototype detectors with active diameters ranging from 5 to 60 microns and measured detection efficiencies of up to 60%. CMOS active quenching circuits are included in the pixel layout. The actively quenched pixels have a quenching time less than 30 ns and a maximum count rate greater than 10 MHz. The actively quenched Geiger mode avalanche photodiode (GPD) has linear response at room temperature over six orders of magnitude. When operating in Geiger mode, these GPDs act as single photon-counting detectors that produce a digital output pulse for each photon with no associated read noise. Thermoelectrically cooled detectors have less than 1 Hz dark counts. The detection efficiency, dark count rate, and after-pulsing of two different pixel designs are measured and demonstrate the differences in the device operation. Additional applications for these devices include nuclear imaging and replacement of photomultiplier tubes in dosimeters.

Architecture and data processing alternatives for the TSE computer. Volume 3: Execution of a parallel counting algorithm using array logic (Tse) devices

NASA Technical Reports Server (NTRS)

Metcalfe, A. G.; Bodenheimer, R. E.

1976-01-01

A parallel algorithm for counting the number of logic-l elements in a binary array or image developed during preliminary investigation of the Tse concept is described. The counting algorithm is implemented using a basic combinational structure. Modifications which improve the efficiency of the basic structure are also presented. A programmable Tse computer structure is proposed, along with a hardware control unit, Tse instruction set, and software program for execution of the counting algorithm. Finally, a comparison is made between the different structures in terms of their more important characteristics.

Comparison of particle-exposure triggered pulmonary and systemic inflammation in mice fed with three different diets.

PubMed

Götz, Alexander A; Rozman, Jan; Rödel, Heiko G; Fuchs, Helmut; Gailus-Durner, Valérie; Hrabě de Angelis, Martin; Klingenspor, Martin; Stoeger, Tobias

2011-09-27

Obesity can be linked to disease risks such as diabetes and cardiovascular disorders, but recently, the adipose tissue (AT) macrophage also emerges as actively participating in inflammation and immune function, producing pro- and anti-inflammatory factors. Connections between the AT and chronic lung diseases, like emphysema and asthma and a protective role of adipocyte-derived proteins against acute lung injury were suggested.In this study we addressed the question, whether a diet challenge increases the inflammatory response in the alveolar and the blood compartment in response to carbon nanoparticles (CNP), as a surrogate for ambient/urban particulate air pollutants. Mice were fed a high caloric carbohydrate-rich (CA) or a fat-rich (HF) diet for six weeks and were compared to mice kept on a purified low fat (LF) diet, respectively. Bronchoalveolar lavage (BAL) and blood samples were taken 24 h after intratracheal CNP instillation and checked for cellular and molecular markers of inflammation. The high caloric diets resulted in distinct effects when compared with LF mice, respectively: CA resulted in increased body and fat mass without affecting blood cellular immunity. Conversely, HF activated the blood system, increasing lymphocyte and neutrophil counts, and resulted in slightly increased body fat content. In contrast to higher pro-inflammatory BAL Leptin in CA and HF mice, on a cellular level, both diets did not lead to an increased pro-inflammatory basal status in the alveolar compartment per se, nor did result in differences in the particle-triggered response. However both diets resulted in a disturbance of the alveolar capillary barrier as indicated by enhanced BAL protein and lactate-dehydrogenase concentrations. Systemically, reduced serum Adiponectin in HF mice might be related to the observed white blood cell increase. The increase in BAL pro-inflammatory factors in high caloric groups and reductions in serum concentrations of anti-inflammatory factors in HF mice, clearly show diet-specific effects, pointing towards augmented systemic inflammatory conditions. Our data suggest that extended feeding periods, leading to manifest obesity, are necessary to generate an increased susceptibility to particle-induced lung inflammation; although the diet-challenge already was efficient in driving pro-inflammatory systemic events.

A method for smoothing segmented lung boundary in chest CT images

NASA Astrophysics Data System (ADS)

Yim, Yeny; Hong, Helen

2007-03-01

To segment low density lung regions in chest CT images, most of methods use the difference in gray-level value of pixels. However, radiodense pulmonary vessels and pleural nodules that contact with the surrounding anatomy are often excluded from the segmentation result. To smooth lung boundary segmented by gray-level processing in chest CT images, we propose a new method using scan line search. Our method consists of three main steps. First, lung boundary is extracted by our automatic segmentation method. Second, segmented lung contour is smoothed in each axial CT slice. We propose a scan line search to track the points on lung contour and find rapidly changing curvature efficiently. Finally, to provide consistent appearance between lung contours in adjacent axial slices, 2D closing in coronal plane is applied within pre-defined subvolume. Our method has been applied for performance evaluation with the aspects of visual inspection, accuracy and processing time. The results of our method show that the smoothness of lung contour was considerably increased by compensating for pulmonary vessels and pleural nodules.

A Fast parallel tridiagonal algorithm for a class of CFD applications

NASA Technical Reports Server (NTRS)

Moitra, Stuti; Sun, Xian-He

1996-01-01

The parallel diagonal dominant (PDD) algorithm is an efficient tridiagonal solver. This paper presents for study a variation of the PDD algorithm, the reduced PDD algorithm. The new algorithm maintains the minimum communication provided by the PDD algorithm, but has a reduced operation count. The PDD algorithm also has a smaller operation count than the conventional sequential algorithm for many applications. Accuracy analysis is provided for the reduced PDD algorithm for symmetric Toeplitz tridiagonal (STT) systems. Implementation results on Langley's Intel Paragon and IBM SP2 show that both the PDD and reduced PDD algorithms are efficient and scalable.

Effect of Pressurized Metered Dose Inhaler Spray Characteristics and Particle Size Distribution on Drug Delivery Efficiency.

PubMed

Yousefi, Morteza; Inthavong, Kiao; Tu, Jiyuan

2017-10-01

A key issue in pulmonary drug delivery is improvement of the delivery device for effective and targeted treatment. Pressurized metered dose inhalers (pMDIs) are the most popular aerosol therapy device for treating lung diseases. This article studies the effect of spray characteristics: injection velocity, spray cone angle, particle size distribution (PSD), and its mass median aerodynamic diameter (MMAD) on drug delivery. An idealized oral airway geometry, extending from mouth to the main bronchus, was connected to a pMDI device. Inhalation flow rates of 15, 30, and 60 L/min were used and drug particle tracking was a one-way coupled Lagrangian model. The results showed that most particles deposited in the pharynx, where the airway has a reduced cross-sectional area. Particle deposition generally decreased with initial spray velocity and with increased spray cone angle for 30 and 60 L/min flow rates. However, for 15 L/min flow rate, the deposition increased slightly with an increase in the spray velocity and cone angle. The effect of spray cone angle was more significant than the initial spray velocity on particle deposition. When the MMAD of a PSD was reduced, the deposition efficiency also reduces, suggesting greater rates of particle entry into the lung. The deposition rate showed negligible change when the MMAD was more than 8 μm. Spray injection angle and velocity change the drug delivery efficacy; however, the efficiency shows more sensitivity to the injection angle. The 30 L/min airflow rate delivers spray particles to the lung more efficiently than 15 and 60 L/min airflow rate, and reducing MMAD can help increase drug delivery to the lung.

Open and closed-circuit endotracheal suctioning in acute lung injury: efficiency and effects on gas exchange.

PubMed

Lasocki, Sigismond; Lu, Qin; Sartorius, Alfonso; Fouillat, Dominique; Remerand, Francis; Rouby, Jean-Jacques

2006-01-01

Closed-circuit endotracheal suctioning (CES) is advocated for preventing hypoxemia caused by the loss of lung volume resulting from open endotracheal suctioning (OES). However, the efficiency of CES and OES on tracheal secretion removal has never been compared in patients with acute lung injury. The authors designed a two-part study aimed at comparing gas exchange and efficiency between OES and CES performed at two levels of negative pressure. Among 18 patients with acute lung injury, 9 underwent CES and OES at 3-h intervals in a random order using a negative pressure of -200 mmHg. Nine other patients underwent CES twice using two levels of negative pressure (-200 and -400 mmHg) applied in a random order. After each CES, a recruitment maneuver was performed using 20 consecutive hyperinflations. Tracheal aspirates were weighed after each suctioning procedure. Arterial blood gases were continuously recorded using an intravascular sensor. Open endotracheal suctioning induced a significant 18% decrease in arterial oxygen tension (Pa(O2)) (range, +13 to -71%) and an 8% increase in arterial carbon dioxide tension (Pa(CO2)) (range, -2 to +16%) that persisted 15 min after the end of the procedure. CES using -200 cm H2O did not change Pa(O2), but tracheal aspirate mass was lower compared with OES (0.6 +/- 1.0 vs. 3.2 +/- 5.1 g; P = 0.03). Increasing negative pressure to -400 cm H2O during CES did not change Pa(O2) but increased the tracheal aspirate mass (1.7 +/- 1.6 vs. 1.0 +/- 1.3 g; P = 0.02). Closed-circuit endotracheal suctioning followed by a recruitment maneuver prevents hypoxemia resulting from OES but decreases secretion removal. Increasing suctioning pressure enhances suctioning efficiency without impairing gas exchange.

A site-specific genetic modification for induction of pluripotency and subsequent isolation of derived lung alveolar epithelial type II cells.

PubMed

Yan, Qing; Quan, Yuan; Sun, Huanhuan; Peng, Xinmiao; Zou, Zhengyun; Alcorn, Joseph L; Wetsel, Rick A; Wang, Dachun

2014-02-01

Human induced pluripotent stem cells (hiPSCs) have great therapeutic potential in repairing defective lung alveoli. However, genetic abnormalities caused by vector integrations and low efficiency in generating hiPSCs, as well as difficulty in obtaining transplantable hiPSC-derived cell types are still major obstacles. Here we report a novel strategy using a single nonviral site-specific targeting vector with a combination of Tet-On inducible gene expression system, Cre/lox P switching gene expression system, and alveolar epithelial type II cell (ATIIC)-specific Neomycin(R) transgene expression system. With this strategy, a single copy of all of the required transgenes can be specifically knocked into a site immediately downstream of β-2-microglobulin (B2M) gene locus at a high frequency, without causing B2M dysfunction. Thus, the expression of reprogramming factors, Oct4, Sox2, cMyc, and Klf4, can be precisely regulated for efficient reprogramming of somatic cells into random integration-free or genetic mutation-free hiPSCs. The exogenous reprogramming factor transgenes can be subsequently removed after reprogramming by transient expression of Cre recombinase, and the resulting random integration-free and exogenous reprogramming factor-free hiPSCs can be selectively differentiated into a homogenous population of ATIICs. In addition, we show that these hiPSC-derived ATIICs exhibit ultrastructural characteristics and biological functions of normal ATIICs. When transplanted into bleomycin-challenged mice lungs, hiPSC-derived ATIICs efficiently remain and re-epithelialize injured alveoli to restore pulmonary function, preventing lung fibrosis and increasing survival without tumorigenic side effect. This strategy allows for the first time efficient generation of patient-specific ATIICs for possible future clinical applications. © 2013 AlphaMed Press.

A site-specific genetic modification for induction of pluripotency and subsequent isolation of derived lung alveolar epithelial type II cells

PubMed Central

Yan, Qing; Quan, Yuan; Sun, Huanhuan; Peng, Xinmiao; Zou, Zhengyun; Alcorn, Joseph L.; Wetsel, Rick A.; Wang, Dachun

2013-01-01

Human induced pluripotent stem cells (hiPSCs) have great therapeutic potential in repairing defective lung alveoli. However, genetic abnormalities caused by vector-integrations and low efficiency in generating hiPSCs, as well as difficulty in obtaining transplantable hiPSC-derived cell types, are still major obstacles. Here we report a novel strategy using a single non-viral site-specific-targeting vector with a combination of Tet-On inducible gene expression system, Cre/lox P switching gene expression system, and alveolar epithelial type II cell (ATIIC)-specific NeomycinR trangene expression system. With this strategy, a single copy of all of the required transgenes can be specifically knocked into a site immediately downstream of beta-2-microglobulin (B2M) gene locus at a high frequency, without causing B2M dysfunction. Thus, the expression of reprogramming factors, Oct4, Sox2, cMyc and Klf4, can be precisely regulated for efficient reprogramming of somatic cells into random-integration-free or genetic mutation-free hiPSCs. The exogenous reprogramming factor transgenes can be subsequently removed after reprogramming by transient expression of Cre recombinase, and the resulting random-integration-free and exogenous reprogramming-factor-free hiPSCs can be selectively differentiated into a homogenous population of ATIICs. In addition, we show that these hiPSC-derived ATIICs exhibit ultra-structural characteristics and biological functions of normal ATIICs. When transplanted into bleomycin-challenged mice lungs, hiPSC-derived ATIICs efficiently remain and re-epithelialize injured alveoli to restore pulmonary function, preventing lung fibrosis and increasing survival without tumorigenic side effect. This strategy allows for the first time efficient generation of patient-specific ATIICs for possible future clinical applications. PMID:24123810

[Automated analyser of organ cultured corneal endothelial mosaic].

PubMed

Gain, P; Thuret, G; Chiquet, C; Gavet, Y; Turc, P H; Théillère, C; Acquart, S; Le Petit, J C; Maugery, J; Campos, L

2002-05-01

Until now, organ-cultured corneal endothelial mosaic has been assessed in France by cell counting using a calibrated graticule, or by drawing cells on a computerized image. The former method is unsatisfactory because it is characterized by a lack of objective evaluation of the cell surface and hexagonality and it requires an experienced technician. The latter method is time-consuming and requires careful attention. We aimed to make an efficient, fast and easy to use, automated digital analyzer of video images of the corneal endothelium. The hardware included a PC Pentium III ((R)) 800 MHz-Ram 256, a Data Translation 3155 acquisition card, a Sony SC 75 CE CCD camera, and a 22-inch screen. Special functions for automated cell boundary determination consisted of Plug-in programs included in the ImageTool software. Calibration was performed using a calibrated micrometer. Cell densities of 40 organ-cultured corneas measured by both manual and automated counting were compared using parametric tests (Student's t test for paired variables and the Pearson correlation coefficient). All steps were considered more ergonomic i.e., endothelial image capture, image selection, thresholding of multiple areas of interest, automated cell count, automated detection of errors in cell boundary drawing, presentation of the results in an HTML file including the number of counted cells, cell density, coefficient of variation of cell area, cell surface histogram and cell hexagonality. The device was efficient because the global process lasted on average 7 minutes and did not require an experienced technician. The correlation between cell densities obtained with both methods was high (r=+0.84, p<0.001). The results showed an under-estimation using manual counting (2191+/-322 vs. 2273+/-457 cell/mm(2), p=0.046), compared with the automated method. Our automated endothelial cell analyzer is efficient and gives reliable results quickly and easily. A multicentric validation would allow us to standardize cell counts among cornea banks in our country.

Toll-like receptor 9 partially regulates lung inflammation induced following exposure to chicken barn air.

PubMed

Schneberger, David; Aulakh, Gurpreet; Channabasappa, Shankaramurthy; Singh, Baljit

2016-01-01

Exposure to animal barn air is an occupational hazard that causes lung dysfunction in barn workers. Respiratory symptoms experienced by workers are typically associated with endotoxin and TLR4 signalling, but within these environments gram negative bacteria constitute only a portion of the total microbial population. In contrast, unmethylated DNA can be found in all bacteria, some viruses, and mold. We hypothesized that in such environments TLR9, which binds unmethylated DNA, contributes to the overall immune responses in the lung. Using a mouse model, wild-type and TLR9(-/-) mice were exposed to chicken barn air for 1, 5, or 20 days. Blood serum and bronchiolar lavage fluid was tested against a panel of six TLR9-induced cytokines (IL-1β, IL-6, IL-10, IL-12, TNFα, and IFNγ) for changes in expression. Bronchiolar lavage fluid (BAL) was also tested for macrophage as well as monocyte migration. There were significant decreases in serum TNFα after a single day exposure in TLR9(-/-) mice. BAL concentrations of TNFα and IFNγ, as well as TNFα in serum in TLR9(-/-) mice were also reduced after barn exposure for 5 days. After 20 days of exposure IFNγ was significantly reduced in lavage of TLR9(-/-) mice. Myeloperoxidase (MPO) accumulation in the lung was reduced at 20 days of exposure in TLR9(-/-) mice, as was total lavage cell counts. However, Masson's staining revealed no apparent lung histological differences between any of the treatment groups. Taken together our data show TLR9 plays a partial role in lung inflammation induced following exposure to chicken barn air potentially through binding of unmethylated DNA.

Combining Carbon Ion Radiotherapy and Local Injection of {alpha}-Galactosylceramide-Pulsed Dendritic Cells Inhibits Lung Metastases in an In Vivo Murine Model

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

Ohkubo, Yu; Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi; Iwakawa, Mayumi, E-mail: mayumii@nirs.go.j

2010-12-01

Purpose: Our previous report indicated that carbon ion beam irradiation upregulated membrane-associated immunogenic molecules, underlining the potential clinical application of radioimmunotherapy. The antimetastatic efficacy of local combination therapy of carbon ion radiotherapy and immunotherapy was examined by use of an in vivo murine model. Methods and Materials: Tumors of mouse squamous cell carcinoma (NR-S1) cells inoculated in the legs of C3H/HeSlc mice were locally irradiated with a single 6-Gy dose of carbon ions (290 MeV/nucleon, 6-cm spread-out Bragg peak). Thirty-six hours after irradiation, {alpha}-galactosylceramide-pulsed dendritic cells (DCs) were injected into the leg tumor. We investigated the effects on distant lungmore » metastases by counting the numbers of lung tumor colonies, making pathologic observations, and assessing immunohistochemistry. Results: The mice with no treatment (control) presented with 168 {+-} 53.8 metastatic nodules in the lungs, whereas the mice that received the combination therapy of carbon ion irradiation and DCs presented with 2.6 {+-} 1.9 (P = 0.009) at 2 weeks after irradiation. Immunohistochemistry showed that intracellular adhesion molecule 1, which activates DCs, increased from 6 h to 36 h after irradiation in the local tumors of the carbon ion-irradiated group. The expression of S100A8 in lung tissue, a marker of the lung pre-metastatic phase, was decreased only in the group with a combination of carbon ions and DCs. Conclusions: The combination of carbon ion radiotherapy with the injection of {alpha}-galactosylceramide-pulsed DCs into the primary tumor effectively inhibited distant lung metastases.« less

Euthanasia and Lavage Mediated Effects on Bronchoalveolar Measures of Lung Injury and Inflammation.

PubMed

Tighe, Robert M; Birukova, Anastasiya; Yeager, Michael J; Reece, Sky W; Gowdy, Kymberly M

2018-02-26

Accurate and reproducible assessments of experimental lung injury and inflammation are critical to basic and translational research. In particular, investigators use varied methods of bronchoalveolar lavage and euthanasia but their impact to assessments of injury and inflammation are unknown. To define potential effects, we compared methods of lavage and euthanasia in uninjured mice and following a mild lung injury model (ozone). C57BL/6J male mice age 8-10 weeks underwent BAL following euthanasia with ketamine/xylazine, carbon dioxide (C0 2 ), or isoflurane. BAL methods included 800-μL instilled and withdrawn three times, and 1 or 3 passive fill(s) and drainage to 20cm H20. Parallel experiments were performed 24hr following 3hr of ozone (O 3 ) exposure at 2 parts per million (ppm). BAL total cell counts/differentials and total protein/albumin were determined. Lung histology was evaluated for lung inflammation/injury. BAL cells were cultured and stimulated with PBS, phorbol myristate acetate (PMA) or lipopolysaccharide (LPS) for 4hr and supernatants were evaluated for cytokine content. In uninjured mice, we observed differences due to the lavage and euthanasia methods. The lavage method increased uninjured and O 3 exposure total cells and total protein/albumin with 800-μL instillation having the highest values. Isoflurane increased uninjured total BAL cells, while C0 2 euthanasia increased the uninjured total protein/albumin levels. These effects limited the ability to detect differences in BAL injury measures following O 3 exposure. In conclusion, the method of lavage and euthanasia affects measures of lung inflammation/injury and should be considered a variable in model assessment.

Metabolism of styrene to styrene oxide and vinylphenols in cytochrome P450 2F2- and P450 2E1-knockout mouse liver and lung microsomes

PubMed Central

Shen, Shuijie; Li, Lei; Ding, Xinxin; Zheng, Jiang

2014-01-01

Pulmonary toxicity of styrene is initiated by cytochromes P450-dependent metabolic activation. P450 2E1 and P450 2F2 are considered to be two main cytochrome P450 (CYP) enzymes responsible for styrene metabolism in mice. The objective of the current study was to determine the correlation between the formation of styrene metabolites (i.e. styrene oxide and 4-vinylphenol) and pulmonary toxicity of styrene, using Cyp2e1- and Cyp2f2-null mouse models. Dramatic decrease in the formation of styrene glycol and 4-vinylphenol was found in Cyp2f2-null mouse lung microsomes, relative to that in the wild-type mouse lung microsomes. However, no significant difference in the production of the styrene metabolites was observed between lung microsomes obtained from Cyp2e1-null and the wild-type mice. The knock–out and wild-type mice were treated with styrene (6.0 mmol/kg, ip), and cell counts and LDH activity in bronchoalveolar lavage fluids were monitored to evaluate the pulmonary toxicity induced by styrene. Cyp2e1-null mice displayed similar susceptibility to lung toxicity of styrene as the wild-type animals. However, Cyp2f2-null mice were resistant to styrene-induced pulmonary toxicity. In conclusion, both P450 2E1 and P450 2F2 are responsible for the metabolic activation of styrene. The latter enzyme plays an important role in styrene-induced pulmonary toxicity. Both styrene oxide and 4-vinylphenol are suggested to participate in the development of lung injury induced by styrene. PMID:24320693

Metabolism of styrene to styrene oxide and vinylphenols in cytochrome P450 2F2- and P450 2E1-knockout mouse liver and lung microsomes.

PubMed

Shen, Shuijie; Li, Lei; Ding, Xinxin; Zheng, Jiang

2014-01-21

Pulmonary toxicity of styrene is initiated by cytochromes P450-dependent metabolic activation. P450 2E1 and P450 2F2 are considered to be two main cytochrome P450 enzymes responsible for styrene metabolism in mice. The objective of the current study was to determine the correlation between the formation of styrene metabolites (i.e., styrene oxide and 4-vinylphenol) and pulmonary toxicity of styrene, using Cyp2e1- and Cyp2f2-null mouse models. A dramatic decrease in the formation of styrene glycol and 4-vinylphenol was found in Cyp2f2-null mouse lung microsomes relative to that in the wild-type mouse lung microsomes; however, no significant difference in the production of the styrene metabolites was observed between lung microsomes obtained from Cyp2e1-null and the wild-type mice. The knockout and wild-type mice were treated with styrene (6.0 mmol/kg, ip), and cell counts and LDH activity in bronchoalveolar lavage fluids were monitored to evaluate the pulmonary toxicity induced by styrene. Cyp2e1-null mice displayed a susceptibility to lung toxicity of styrene similar to that of the wild-type animals; however, Cyp2f2-null mice were resistant to styrene-induced pulmonary toxicity. In conclusion, both P450 2E1 and P450 2F2 are responsible for the metabolic activation of styrene. The latter enzyme plays an important role in styrene-induced pulmonary toxicity. Both styrene oxide and 4-vinylphenol are suggested to participate in the development of lung injury induced by styrene.

Complications after 1000 lung radiofrequency ablation sessions in 420 patients: a single center's experiences.

PubMed

Kashima, Masataka; Yamakado, Koichiro; Takaki, Haruyuki; Kodama, Hiroshi; Yamada, Tomomi; Uraki, Junji; Nakatsuka, Atsuhiro

2011-10-01

This study retrospectively evaluates complications after lung radiofrequency ablation (RFA). Complications were assessed for each RFA session in 420 consecutive patients with 1403 lung tumors who underwent 1000 RFA sessions with a cool-tip RFA system. A major complication was defined as a grade 3 or 4 adverse event. Risk factors affecting frequent major complications that occurred with an incidence of 1% or more were detected using multivariate analysis. Four deaths (0.4% [4/1000]) related to RFA procedures occurred. Three patients died of interstitial pneumonia. The other patient died of hemothorax. The major complication rate was 9.8% (98/1000). Frequent major complications were aseptic pleuritis (2.3% [23/1000]), pneumonia (1.8% [18/1000]), lung abscess (1.6% [16/1000]), bleeding requiring blood transfusion (1.6% [16/1000]), pneumothorax requiring pleural sclerosis (1.6% [16/1000]), followed by bronchopleural fistula (0.4% [4/1000]), brachial nerve injury (0.3% [3/1000]), tumor seeding (0.1% [1/1000]), and diaphragm injury (0.1% [1/1000]). Puncture number (p < 0.02) and previous systemic chemotherapy (p < 0.05) were significant risk factors for aseptic pleuritis. Previous external beam radiotherapy (p < 0.001) and age (p < 0.02) were significant risk factors for pneumonia, as were emphysema (p < 0.02) for lung abscess, and serum platelet count (p < 0.002) and tumor size (p < 0.02) for bleeding. Emphysema (p < 0.02) was a significant risk factor for pneumothorax requiring pleural sclerosis. Lung RFA is a relatively safe procedure, but it can be fatal. Risk factors found in this study will help to stratify high-risk patients.

Cadmium-enriched cigarette smoke-induced cytological and biochemical alterations in rat lungs

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

Gairola, C.G.

Male Sprague-Dawley rats were exposed daily for 52 wk in a nose-only exposure system to smoke from the University of Kentucky 2R1 reference cigarettes (SM) or from cigarettes made of cadmium-enriched tobacco (Cd-SM). At sacrifice, the animals were evaluated by bronchoalveolar lavage (BAL) for inflammatory cell response in the lungs, and the cells so obtained were analyzed for phagocytosis of particles (latex and IgG-coated SRBCs) and for their ability to release oxidants upon phagocytic challenge. Additionally, lung tissues were analyzed for Cd levels and lung homogenate fractions were assayed for aryl hydrocarbon hydroxylase (AHH) as well as total and selenium-dependentmore » glutathione peroxidase (GSH-Px) activities. BAL cell counts showed a significant influx of inflammatory cells into the lungs of the Cd-SM group but not the SM group. The proportion of neutrophils in the BAL cells of the Cd-Sm group was elevated to 40 {plus minus} 9%, compared with less than 2% in the SM group. Phagocytosis of both types of particles by macrophages from SM and Cd-SM groups was similar to that of the control groups, except that a greater uptake of latex particles was seen is Cd-SM macrophages. The release of oxidants (superoxides and hydrogen peroxide) by the BAL cells was severely impaired in the Cd-SM group, whereas a slight stimulation was seen in the SM gropu. Pulmonary GSH-Px activity was the same in all groups. A significant induction of the pulmonary AHH activity was observed in the SM group only. The Cd levels in the lungs were approximately 8- and 200-fold greater than controls in SM and Cd-SM groups, respectively. These observation suggest a significant influence of tabacco Cd on the toxicity of cigarette smoke.« less

Early treatment of chlorine-induced airway hyperresponsiveness and inflammation with corticosteroids.

PubMed

Jonasson, Sofia; Wigenstam, Elisabeth; Koch, Bo; Bucht, Anders

2013-09-01

Chlorine (Cl2) is an industrial gas that is highly toxic and irritating when inhaled causing tissue damage and an acute inflammatory response in the airways followed by a long-term airway dysfunction. The aim of this study was to evaluate whether early anti-inflammatory treatment can protect against the delayed symptoms in Cl2-exposed mice. BALB/c mice were exposed by nose-only inhalation using 200ppm Cl2 during 15min. Assessment of airway hyperresponsiveness (AHR), inflammatory cell counts in bronchoalveolar lavage, occurrence of lung edema and lung fibrosis were analyzed 24h or 14days post-exposure. A single dose of the corticosteroid dexamethasone (10 or 100mg/kg) was administered intraperitoneally 1, 3, 6, or 12h following Cl2 exposure. High-dose of dexamethasone reduced the acute inflammation if administered within 6h after exposure but treated animals still displayed a significant lung injury. The effect of dexamethasone administered within 1h was dose-dependent; high-dose significantly reduced acute airway inflammation (100mg/kg) but not treatment with the relatively low-dose (10mg/kg). Both doses reduced AHR 14days later, while lung fibrosis measured as collagen deposition was not significantly reduced. The results point out that the acute inflammation in the lungs due to Cl2 exposure only partly is associated with the long-term AHR. We hypothesize that additional pathogenic mechanisms apart from the inflammatory reactions contribute to the development of long-term airway dysfunction. By using this mouse model, we have validated early administration of corticosteroids in terms of efficacy to prevent acute lung injury and delayed symptoms induced by Cl2 exposure. Copyright © 2013 Elsevier Inc. All rights reserved.

Bacterial infection profiles in lung cancer patients with febrile neutropenia

PubMed Central

2011-01-01

Background The chemotherapy used to treat lung cancer causes febrile neutropenia in 10 to 40% of patients. Although most episodes are of undetermined origin, an infectious etiology can be suspected in 30% of cases. In view of the scarcity of data on lung cancer patients with febrile neutropenia, we performed a retrospective study of the microbiological characteristics of cases recorded in three medical centers in the Picardy region of northern France. Methods We analyzed the medical records of lung cancer patients with neutropenia (neutrophil count < 500/mm3) and fever (temperature > 38.3°C). Results The study included 87 lung cancer patients with febrile neutropenia (mean age: 64.2). Two thirds of the patients had metastases and half had poor performance status. Thirty-three of the 87 cases were microbiologically documented. Gram-negative bacteria (mainly enterobacteriaceae from the urinary and digestive tracts) were identified in 59% of these cases. Staphylococcus species (mainly S. aureus) accounted for a high proportion of the identified Gram-positive bacteria. Bacteremia accounted for 60% of the microbiologically documented cases of fever. 23% of the blood cultures were positive. 14% of the infections were probably hospital-acquired and 14% were caused by multidrug-resistant strains. The overall mortality rate at day 30 was 33% and the infection-related mortality rate was 16.1%. Treatment with antibiotics was successful in 82.8% of cases. In a multivariate analysis, predictive factors for treatment failure were age >60 and thrombocytopenia < 20000/mm3. Conclusion Gram-negative species were the most frequently identified bacteria in lung cancer patients with febrile neutropenia. Despite the success of antibiotic treatment and a low-risk neutropenic patient group, mortality is high in this particular population. PMID:21707992

Bacterial infection profiles in lung cancer patients with febrile neutropenia.

PubMed

Lanoix, Jean-Philippe; Pluquet, Emilie; Lescure, Francois Xavier; Bentayeb, Houcine; Lecuyer, Emmanuelle; Boutemy, Marie; Dumont, Patrick; Jounieaux, Vincent; Schmit, Jean Luc; Dayen, Charles; Douadi, Youcef

2011-06-27

The chemotherapy used to treat lung cancer causes febrile neutropenia in 10 to 40% of patients. Although most episodes are of undetermined origin, an infectious etiology can be suspected in 30% of cases. In view of the scarcity of data on lung cancer patients with febrile neutropenia, we performed a retrospective study of the microbiological characteristics of cases recorded in three medical centers in the Picardy region of northern France. We analyzed the medical records of lung cancer patients with neutropenia (neutrophil count < 500/mm(3)) and fever (temperature > 38.3°C). The study included 87 lung cancer patients with febrile neutropenia (mean age: 64.2). Two thirds of the patients had metastases and half had poor performance status. Thirty-three of the 87 cases were microbiologically documented. Gram-negative bacteria (mainly enterobacteriaceae from the urinary and digestive tracts) were identified in 59% of these cases. Staphylococcus species (mainly S. aureus) accounted for a high proportion of the identified Gram-positive bacteria. Bacteremia accounted for 60% of the microbiologically documented cases of fever. 23% of the blood cultures were positive. 14% of the infections were probably hospital-acquired and 14% were caused by multidrug-resistant strains. The overall mortality rate at day 30 was 33% and the infection-related mortality rate was 16.1%. Treatment with antibiotics was successful in 82.8% of cases. In a multivariate analysis, predictive factors for treatment failure were age >60 and thrombocytopenia < 20000/mm(3). Gram-negative species were the most frequently identified bacteria in lung cancer patients with febrile neutropenia. Despite the success of antibiotic treatment and a low-risk neutropenic patient group, mortality is high in this particular population.

A no-decompression air dive and ultrasound lung comets.

PubMed

Dujic, Zeljko; Marinovic, Jasna; Obad, Ante; Ivancev, Vladimir; Breskovic, Toni; Jovovic, Pavle; Ljubkovic, Marko

2011-01-01

Increased accumulation of extravascular lung water after repetitive deep trimix dives was recently reported. This effect was evident 40 min post-dive, but in subsequent studies most signs of this lung congestion were not evident 2-3 h post-dive, indicating no major negative effects on respiratory gas exchange following deep dives. Whether this response is unique for trimix dives or also occurs in more frequent air dives is presently unknown. A single no-decompression field dive to 33 m with 20 min bottom time was performed by 12 male divers. Multiple ultrasound lung comets (ULC), bubble grade (BG), and single-breath lung diffusing capacity (DLCO) measurements were made before and up to 120 min after the dive. Median BG was rather high with maximal values observed at 40 min post-dive [median 4 (4-4)]. Arterialization of bubbles from the venous side was observed only in one diver lasting up to 60 min post-dive. Despite high BG, no DCS symptoms were noted. DLCO and ULC were unchanged after the dive at any time point (DLCO(corr) was 33.6 +/- 1.9 ml x min(-1) mmHg(-1) pre-dive, 32.7 +/- 3.8 ml x min(-1) x mmHg(-1) at 60 min post-dive, and 33.2 +/- 5.3 ml x min(-1) x mmHg(-1) at 120 min post-dive; ULC count was 4.1 +/- 1.9 pre-dive, 4.9 +/- 3.3 at 20 min post-dive, and 3.3 +/- 1.9 at 60 min post-dive. These preliminary findings show no evidence of increased accumulation of extravascular lung water in male divers after a single no-decompression air dive at the limits of accepted Norwegian diving tables.

Health risk among asbestos cement sheet manufacturing workers in Thailand.

PubMed

Phanprasit, Wantanee; Sujirarat, Dusit; Chaikittiporn, Chalermchai

2009-12-01

To assess asbestos exposure and calculate the relative risks of lung cancer among asbestos cement roof sheet workers and to predict the incidence rate of lung cancer caused by asbestos in Thailand. A cross-sectional study was conducted in four asbestos cement roof factories. Both area and personal air samples were collected and analyzed employing NIOSH method # 7400 and counting rule A for all procesess and activities. The time weight average exposures were calculated for each studied task using average area concentrations of the mill and personal concentrations. Then, cumulative exposures were estimated based on the past nation-wide air sampling concentrations and those from the present study. The relative risk (RR) of lung cancer among asbestos cement sheet workers was calculated and the number of asbestos related lung cancer case was estimated. The roof fitting polishers had the highest exposure to airborne asbestos fiber (0.73 fiber/ml). The highest average area concentration was at the conveyor to the de-bagger areas (0.02 fiber/ml). The estimated cumulative exposure for the workers performed studied-tasks ranged in between 90.13-115.65 fiber-years/ml while the relative risk of lung cancer calculated using US. EPA's model were 5.37-5.96. Based on the obtained RR, lung cancer among AC sheet in Thailand would be 2 case/year. In case that AC sheet will not be prohibited from being manufactured, even though only chrysotile is allowed, the surveillance system should be further developed and more seriously implemented. The better control measures for all processes must be implemented. Furthermore, due to the environmental persistence of asbestos fiber, its life cycle analysis should be conducted in order to control environmental exposure of general population.

High hydrostatic pressure affects antigenic pool in tumor cells: Implication for dendritic cell-based cancer immunotherapy.

PubMed

Urbanova, Linda; Hradilova, Nada; Moserova, Irena; Vosahlikova, Sarka; Sadilkova, Lenka; Hensler, Michal; Spisek, Radek; Adkins, Irena

2017-07-01

High hydrostatic pressure (HHP) can be used to generate dendritic cell (DC)-based active immunotherapy for prostate, lung and ovarian cancer. We showed here that HHP treatment of selected human cancer cell lines leads to a degradation of tumor antigens which depends on the magnitude of HHP applied and on the cancer cell line origin. Whereas prostate or ovarian cell lines displayed little protein antigen degradation with HHP treatment up to 300MPa after 2h, tumor antigens are hardly detected in lung cancer cell line after treatment with HHP 250MPa at the same time. On the other hand, quick reduction of tumor antigen-coding mRNA was observed at HHP 200MPa immediately after treatment in all cell lines tested. To optimize the DC-based active cellular therapy protocol for HHP-sensitive cell lines the immunogenicity of HHP-treated lung cancer cells at 150, 200 and 250MPa was compared. Lung cancer cells treated with HHP 150MPa display characteristics of immunogenic cell death, however cells are not efficiently phagocytosed by DC. Despite induction of the highest number of antigen-specific CD8 + T cells, 150 MPa-treated lung cancer cells survive in high numbers. This excludes their use in DC vaccine manufacturing. HHP of 200MPa treatment of lung cancer cells ensures the optimal ratio of efficient immunogenic killing and delivery of protein antigens in DC. These results represent an important pre-clinical data for generation of immunogenic killed lung cancer cells in ongoing NSCLC Phase I/II clinical trial using DC-based active cellular immunotherapy (DCVAC/LuCa). Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Generation of a Close-to-Native In Vitro System to Study Lung Cells-Extracellular Matrix Crosstalk.

PubMed

Garlíková, Zuzana; Silva, Ana Catarina; Rabata, Anas; Potěšil, David; Ihnatová, Ivana; Dumková, Jana; Koledová, Zuzana; Zdráhal, Zbyněk; Vinarský, Vladimír; Hampl, Aleš; Pinto-do-Ó, Perpétua; Nascimento, Diana Santos

2018-01-01

Extracellular matrix (ECM) is an essential component of the tissue microenvironment, actively shaping cellular behavior. In vitro culture systems are often poor in ECM constituents, thus not allowing for naturally occurring cell-ECM interactions. This study reports on a straightforward and efficient method for the generation of ECM scaffolds from lung tissue and its subsequent in vitro application using primary lung cells. Mouse lung tissue was subjected to decellularization with 0.2% sodium dodecyl sulfate, hypotonic solutions, and DNase. Resultant ECM scaffolds were devoid of cells and DNA, whereas lung ECM architecture of alveolar region and blood and airway networks were preserved. Scaffolds were predominantly composed of core ECM and ECM-associated proteins such as collagens I-IV, nephronectin, heparan sulfate proteoglycan core protein, and lysyl oxidase homolog 1, among others. When homogenized and applied as coating substrate, ECM supported the attachment of lung fibroblasts (LFs) in a dose-dependent manner. After ECM characterization and biocompatibility tests, a novel in vitro platform for three-dimensional (3D) matrix repopulation that permits live imaging of cell-ECM interactions was established. Using this system, LFs colonized the ECM scaffolds, displaying a close-to-native morphology in intimate interaction with the ECM fibers, and showed nuclear translocation of the mechanosensor yes-associated protein (YAP), when compared with cells cultured in two dimensions. In conclusion, we developed a 3D-like culture system, by combining an efficient decellularization method with a live-imaging culture platform, to replicate in vitro native lung cell-ECM crosstalk. This is a valuable system that can be easily applied to other organs for ECM-related drug screening, disease modeling, and basic mechanistic studies.

Cystic lung disease in birt-hogg-dubé syndrome: a case series of three patients.

PubMed

Kilincer, Abidin; Ariyurek, Orhan Macit; Karabulut, Nevzat

2014-06-01

Birt-Hogg-Dubé syndrome is characterized by clinical manifestations such as hamartomas of the skin, renal tumors and lung cysts with spontaneous pneumothoraces. Patients with Birt-Hogg-Dubé syndrome may present with only multiple lung cysts. We report the chest computerized tomography (CT) features of three patients with Birt-Hogg-Dubé syndrome. Each patient had multiple lung cysts of various sizes according to chest CT evaluation, most of which were located in lower lobes and related to pleura. The identification of unique characteristics in the chest CT of patients with Birt-Hogg-Dubé syndrome may provide an efficient mechanism for diagnosis.

Effects of High-Intensity Swimming on Lung Inflammation and Oxidative Stress in a Murine Model of DEP-Induced Injury

PubMed Central

Ávila, Leonardo C. M.; Bruggemann, Thayse R.; Bobinski, Franciane; da Silva, Morgana Duarte; Oliveira, Regiane Carvalho; Martins, Daniel Fernandes; Mazzardo-Martins, Leidiane; Duarte, Marta Maria Medeiros Frescura; de Souza, Luiz Felipe; Dafre, Alcir; Vieira, Rodolfo de Paula; Santos, Adair Roberto Soares; Bonorino, Kelly Cattelan; Hizume Kunzler, Deborah de C.

2015-01-01

Studies have reported that exposure to diesel exhaust particles (DEPs) induces lung inflammation and increases oxidative stress, and both effects are susceptible to changes via regular aerobic exercise in rehabilitation programs. However, the effects of exercise on lungs exposed to DEP after the cessation of exercise are not clear. Therefore, the aim of this study was to evaluate the effects of high-intensity swimming on lung inflammation and oxidative stress in mice exposed to DEP concomitantly and after exercise cessation. Male Swiss mice were divided into 4 groups: Control (n = 12), Swimming (30 min/day) (n = 8), DEP (3 mg/mL—10 μL/mouse) (n = 9) and DEP+Swimming (n = 8). The high-intensity swimming was characterized by an increase in blood lactate levels greater than 1 mmoL/L between 10th and 30th minutes of exercise. Twenty-four hours after the final exposure to DEP, the anesthetized mice were euthanized, and we counted the number of total and differential inflammatory cells in the bronchoalveolar fluid (BALF), measured the lung homogenate levels of IL-1β, TNF-α, IL-6, INF-ϫ, IL-10, and IL-1ra using ELISA, and measured the levels of glutathione, non-protein thiols (GSH-t and NPSH) and the antioxidant enzymes catalase and glutathione peroxidase (GPx) in the lung. Swimming sessions decreased the number of total cells (p<0.001), neutrophils and lymphocytes (p<0.001; p<0.05) in the BALF, as well as lung levels of IL-1β (p = 0.002), TNF-α (p = 0.003), IL-6 (p = 0.0001) and IFN-ϫ (p = 0.0001). However, the levels of IL-10 (p = 0.01) and IL-1ra (p = 0.0002) increased in the swimming groups compared with the control groups, as did the CAT lung levels (p = 0.0001). Simultaneously, swimming resulted in an increase in the GSH-t and NPSH lung levels in the DEP group (p = 0.0001 and p<0.002). We concluded that in this experimental model, the high-intensity swimming sessions decreased the lung inflammation and oxidative stress status during DEP-induced lung inflammation in mice. PMID:26332044

Effects of High-Intensity Swimming on Lung Inflammation and Oxidative Stress in a Murine Model of DEP-Induced Injury.

PubMed

Ávila, Leonardo C M; Bruggemann, Thayse R; Bobinski, Franciane; da Silva, Morgana Duarte; Oliveira, Regiane Carvalho; Martins, Daniel Fernandes; Mazzardo-Martins, Leidiane; Duarte, Marta Maria Medeiros Frescura; de Souza, Luiz Felipe; Dafre, Alcir; Vieira, Rodolfo de Paula; Santos, Adair Roberto Soares; Bonorino, Kelly Cattelan; Hizume Kunzler, Deborah de C

2015-01-01

Studies have reported that exposure to diesel exhaust particles (DEPs) induces lung inflammation and increases oxidative stress, and both effects are susceptible to changes via regular aerobic exercise in rehabilitation programs. However, the effects of exercise on lungs exposed to DEP after the cessation of exercise are not clear. Therefore, the aim of this study was to evaluate the effects of high-intensity swimming on lung inflammation and oxidative stress in mice exposed to DEP concomitantly and after exercise cessation. Male Swiss mice were divided into 4 groups: Control (n = 12), Swimming (30 min/day) (n = 8), DEP (3 mg/mL-10 μL/mouse) (n = 9) and DEP+Swimming (n = 8). The high-intensity swimming was characterized by an increase in blood lactate levels greater than 1 mmoL/L between 10th and 30th minutes of exercise. Twenty-four hours after the final exposure to DEP, the anesthetized mice were euthanized, and we counted the number of total and differential inflammatory cells in the bronchoalveolar fluid (BALF), measured the lung homogenate levels of IL-1β, TNF-α, IL-6, INF-ϫ, IL-10, and IL-1ra using ELISA, and measured the levels of glutathione, non-protein thiols (GSH-t and NPSH) and the antioxidant enzymes catalase and glutathione peroxidase (GPx) in the lung. Swimming sessions decreased the number of total cells (p<0.001), neutrophils and lymphocytes (p<0.001; p<0.05) in the BALF, as well as lung levels of IL-1β (p = 0.002), TNF-α (p = 0.003), IL-6 (p = 0.0001) and IFN-ϫ (p = 0.0001). However, the levels of IL-10 (p = 0.01) and IL-1ra (p = 0.0002) increased in the swimming groups compared with the control groups, as did the CAT lung levels (p = 0.0001). Simultaneously, swimming resulted in an increase in the GSH-t and NPSH lung levels in the DEP group (p = 0.0001 and p<0.002). We concluded that in this experimental model, the high-intensity swimming sessions decreased the lung inflammation and oxidative stress status during DEP-induced lung inflammation in mice.