VEGF-D promotes pulmonary oedema in hyperoxic acute lung injury.

PubMed

Sato, Teruhiko; Paquet-Fifield, Sophie; Harris, Nicole C; Roufail, Sally; Turner, Debra J; Yuan, Yinan; Zhang, You-Fang; Fox, Stephen B; Hibbs, Margaret L; Wilkinson-Berka, Jennifer L; Williams, Richard A; Stacker, Steven A; Sly, Peter D; Achen, Marc G

2016-06-01

Leakage of fluid from blood vessels, leading to oedema, is a key feature of many diseases including hyperoxic acute lung injury (HALI), which can occur when patients are ventilated with high concentrations of oxygen (hyperoxia). The molecular mechanisms driving vascular leak and oedema in HALI are poorly understood. VEGF-D is a protein that promotes blood vessel leak and oedema when overexpressed in tissues, but the role of endogenous VEGF-D in pathological oedema was unknown. To address these issues, we exposed Vegfd-deficient mice to hyperoxia. The resulting pulmonary oedema in Vegfd-deficient mice was substantially reduced compared to wild-type, as was the protein content of bronchoalveolar lavage fluid, consistent with reduced vascular leak. Vegf-d and its receptor Vegfr-3 were more highly expressed in lungs of hyperoxic, versus normoxic, wild-type mice, indicating that components of the Vegf-d signalling pathway are up-regulated in hyperoxia. Importantly, VEGF-D and its receptors were co-localized on blood vessels in clinical samples of human lungs exposed to hyperoxia; hence, VEGF-D may act directly on blood vessels to promote fluid leak. Our studies show that Vegf-d promotes oedema in response to hyperoxia in mice and support the hypothesis that VEGF-D signalling promotes vascular leak in human HALI. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Performance of Leak Compensation in All-Age ICU Ventilators During Volume-Targeted Neonatal Ventilation: A Lung Model Study.

PubMed

Itagaki, Taiga; Bennett, Desmond J; Chenelle, Christopher T; Fisher, Daniel F; Kacmarek, Robert M

2017-01-01

Volume-targeted ventilation is increasingly used in low birthweight infants because of the potential for reducing volutrauma and avoiding hypocapnea. However, it is not known what level of air leak is acceptable during neonatal volume-targeted ventilation when leak compensation is activated concurrently. Four ICU ventilators (Servo-i, PB980, V500, and Avea) were compared in available invasive volume-targeted ventilation modes (pressure control continuous spontaneous ventilation [PC-CSV] and pressure control continuous mandatory ventilation [PC-CMV]). The Servo-i and PB980 were tested with (+) and without (-) their proximal flow sensor. The V500 and Avea were tested with their proximal flow sensor as indicated by their manufacturers. An ASL 5000 lung model was used to simulate 4 neonatal scenarios (body weight 0.5, 1, 2, and 4 kg). The ASL 5000 was ventilated via an endotracheal tube with 3 different leaks. Two minutes of data were collected after each change in leak level, and the asynchrony index was calculated. Tidal volume (V T ) before and after the change in leak was assessed. The differences in delivered V T between before and after the change in leak were within ±5% in all scenarios with the PB980 (-/+) and V500. With the Servo-i (-/+), baseline V T was ≥10% greater than set V T during PC-CSV, and delivered V T markedly changed with leak. The Avea demonstrated persistent high V T in all leak scenarios. Across all ventilators, the median asynchrony index was 1% (interquartile range 0-27%) in PC-CSV and 1.8% (0-45%) in PC-CMV. The median asynchrony index was significantly higher in the Servo-i (-/+) than in the PB980 (-/+) and V500 in 1 and 2 kg scenarios during PC-CSV and PC-CMV. The PB980 and V500 were the only ventilators to acclimate to all leak scenarios and achieve targeted V T . Further clinical investigation is needed to validate the use of leak compensation during neonatal volume-targeted ventilation. Copyright © 2017 by Daedalus Enterprises.

Endotoxin increases pulmonary vascular protein permeability in the dog

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

Welsh, C.H.; Dauber, I.M.; Weil, J.V.

Endotoxin increases pulmonary vascular permeability consistently in some species but fails to reliably cause injury in the dog. We wondered whether this phenomenon depended on the method of injury assessment, as others have relied on edema measurement; we quantified injury by monitoring the rate of extravascular protein accumulation. /sup 113m/In-labeled protein and /sup 99m/Tc-labeled erythrocytes were injected into anesthetized dogs and monitored by an externally placed lung probe. A protein leak index, the rate of extravascular protein accumulation, was derived from the rate of increase in lung protein counts corrected for changes in intravascular protein activity. After administration of Salmonellamore » enteriditis endotoxin (4 micrograms/kg), the protein leak index was elevated 2.5-fold (41.1 +/- 4.6 X 10(-4) min-1) compared with control (16.0 +/- 2.8 X 10(-4) min-1). In contrast, wet-to-dry weight ratios failed to increase after endotoxin (4.6 +/- 0.8 vs. control values of 4.2 +/- 0.5 g/g dry bloodless lung). However, we observed that endotoxin increased lung dry weight (per unit body weight), which may have attenuated the change in wet-to-dry weight ratios. To determine whether low microvascular pressures following endotoxin attenuated edema formation, we increased pulmonary arterial wedge pressures in five dogs by saline infusion, which caused an increase in wet-to-dry weight ratios following endotoxin but no change in the five controls. We conclude that low dose endotoxin causes pulmonary vascular protein leak in the dog while edema formation is minimal or absent.« less

Patient and surgical factors influencing air leak after lung volume reduction surgery: lessons learned from the National Emphysema Treatment Trial.

PubMed

DeCamp, Malcolm M; Blackstone, Eugene H; Naunheim, Keith S; Krasna, Mark J; Wood, Douglas E; Meli, Yvonne M; McKenna, Robert J

2006-07-01

Although staple line buttressing is advocated to reduce air leak after lung volume reduction surgery (LVRS), its effectiveness is unknown. We sought to identify risk factors for air leak and its duration and to estimate its medical consequences for selecting optimal perioperative technique(s), such as buttressing technique, to preempt or treat post-LVRS air leak. Detailed air leak data were available for 552 of 580 patients receiving bilateral stapled LVRS in the National Emphysema Treatment Trial. Risk factors for prevalence and duration of air leak were identified by logistic and hazard function analyses. Medical consequences were estimated in propensity-matched pairs with and without air leak. Within 30 days of LVRS, 90% of patients developed air leak (median duration = 7 days). Its occurrence was more common and duration prolonged in patients with lower diffusing capacity (p = 0.06), upper lobe disease (p = 0.04), and important pleural adhesions (p = 0.007). Duration was also protracted in Caucasians (p < 0.0001), patients using inhaled steroids (p = 0.004), and those with lower 1-second forced expiratory volume (p = 0.0003). Surgical approach, buttressing, stapler brand, and intraoperative adjunctive procedures were not associated with fewer or less prolonged air leaks (p >/= 0.2). Postoperative complications occurred more often in matched patients experiencing air leak (57% vs 30%, p = 0.0004), and postoperative stay was longer (11.8 +/- 6.5 days vs 7.6 +/- 4.4 days, p = 0.0005). Air leak accompanies LVRS in 90% of patients, is often prolonged, and is associated with a more complicated and protracted hospital course. Its occurrence and duration are associated with characteristics of patients and their disease, not with a specific surgical technique.

The Chitinase-like Proteins Breast Regression Protein-39 and YKL-40 Regulate Hyperoxia-induced Acute Lung Injury

PubMed Central

Sohn, Myung Hyun; Kang, Min-Jong; Matsuura, Hiroshi; Bhandari, Vineet; Chen, Ning-Yuan; Lee, Chun Geun; Elias, Jack A.

2010-01-01

Rationale: Prolonged exposure to 100% O2 causes hyperoxic acute lung injury (HALI), characterized by alveolar epithelial cell injury and death. We previously demonstrated that the murine chitinase-like protein, breast regression protein (BRP)–39 and its human homolog, YKL-40, inhibit cellular apoptosis. However, the regulation and roles of these molecules in hyperoxia have not been addressed. Objectives: We hypothesized that BRP-39 and YKL-40 (also called chitinase-3–like 1) play important roles in the pathogenesis of HALI. Methods: We characterized the regulation of BRP-39 during HALI and the responses induced by hyperoxia in wild-type mice, BRP-39–null (−/−) mice, and BRP-39−/− mice in which YKL-40 was overexpressed in respiratory epithelium. We also compared the levels of tracheal aspirate YKL-40 in premature newborns with respiratory failure. Measurements and Main Results: These studies demonstrate that hyperoxia inhibits BRP-39 in vivo in the murine lung and in vitro in epithelial cells. They also demonstrate that BRP-39−/− mice have exaggerated permeability, protein leak, oxidation, inflammatory, chemokine, and epithelial apoptosis responses, and experience premature death in 100% O2. Lastly, they demonstrate that YKL-40 ameliorates HALI, prolongs survival in 100% O2, and rescues the exaggerated injury response in BRP-39−/− animals. In accord with these findings, the levels of tracheal aspirate YKL-40 were lower in premature infants treated with hyperoxia for respiratory failure who subsequently experienced bronchopulmonary dysplasia or death compared with those that did not experience these complications. Conclusions: These studies demonstrate that hyperoxia inhibits BRP-39/YKL-40, and that BRP-39 and YKL-40 are critical regulators of oxidant injury, inflammation, and epithelial apoptosis in the murine and human lung. PMID:20558631

Scintigraphy for pulmonary capillary protein leak. Final report, 1 October 1981-30 September 1985

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

Sugerman, H.J.; Tatum, J.L.; Hirsch, J.I.

1986-06-01

Computerized scintigraphy, employing the gamma camera, has been used to study the dynamics of the pulmonary capillary membrane leak of 99m-technetium-tagged human serum albumin (Tc-HSA). In preliminary canine studies, the severity of an oleic acid-induced albumin leak was proportional to the slope of lung: heart radioactivity ratio and was more sensitive than arterial blood gases or standard chest roentgenograms. This rising ratio is called slope of injury slope index. A number of agents were studied in an attempt to prevent oleic acid-induced pulmonary microvascular injury. Following a series of five control dogs, five dogs each were studied with each ofmore » the following agents: methylprednisolone, ibuprofen, the superoxide radical scavenger, MK-44, and, in three dogs, calcium gluconate. None of these agents was able to alter the rise in lung: heart radioactivity ratio following oleic acid injury. A septic pig model was developed for study of bacterially induced ARDS. Septic-induced ARDS and multi-system organ failure are probably secondary to the systemic release of several mediators of inflammation, treatment will probably require a combination of anti-inflammatory agents. This should impact significantly on the mortality and morbidity of septic complications in traumatized combat soldiers.« less

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

Mitochondrial proton and electron leaks.

PubMed

Jastroch, Martin; Divakaruni, Ajit S; Mookerjee, Shona; Treberg, Jason R; Brand, Martin D

2010-01-01

Mitochondrial proton and electron leak have a major impact on mitochondrial coupling efficiency and production of reactive oxygen species. In the first part of this chapter, we address the molecular nature of the basal and inducible proton leak pathways, and their physiological importance. The basal leak is unregulated, and a major proportion can be attributed to mitochondrial anion carriers, whereas the proton leak through the lipid bilayer appears to be minor. The basal proton leak is cell-type specific and correlates with metabolic rate. The inducible leak through the ANT (adenine nucleotide translocase) and UCPs (uncoupling proteins) can be activated by fatty acids, superoxide or lipid peroxidation products. The physiological role of inducible leak through UCP1 in mammalian brown adipose tissue is heat production, whereas the roles of non-mammalian UCP1 and its paralogous proteins, in particular UCP2 and UCP3, are not yet resolved. The second part of the chapter focuses on the electron leak that occurs in the mitochondrial electron transport chain. Exit of electrons prior to the reduction of oxygen to water at cytochrome c oxidase causes superoxide production. As the mechanisms of electron leak are crucial to understanding their physiological relevance, we summarize the mechanisms and topology of electron leak from complexes I and III in studies using isolated mitochondria. We also highlight recent progress and challenges of assessing electron leak in the living cell. Finally, we emphasize the importance of proton and electron leak as therapeutic targets in body mass regulation and insulin secretion.

Malondialdehyde-acetaldehyde (MAA) adducted protein inhalation causes lung injury

PubMed Central

Wyatt, T. A.; Kharbanda, K. K.; McCaskill, M. L.; Tuma, D. J.; Yanov, D.; DeVasure, J.; Sisson, J. H.

2011-01-01

In addition to cigarette smoking, alcohol exposure is also associated with increased lung infections and decreased mucociliary clearance. However, little research has been conducted on the combination effects of alcohol and cigarette smoke on lungs. Previously, we have demonstrated in a mouse model that the combination of cigarette smoke and alcohol exposure results in the formation of a very stable hybrid malondialdehyde-acetaldehyde (MAA)-adducted protein in the lung. In in vitro studies, MAA-adducted protein stimulates bronchial epithelial cell interleukin-8 via the activation of protein kinase C epsilon (PKCε). We hypothesized that direct MAA-adducted protein exposure in the lungs would mimic such a combination of smoke and alcohol exposure leading to airway inflammation. To test this hypothesis, C57BL/6J female mice were intranasally instilled with either saline, 30 µL of 50 µg/mL BSA-MAA, or unadducted BSA for up to 3 wk. Likewise, human lung surfactant proteins A and D (SPA, SPD) were purified from human pulmonary proteinosis lung lavage fluid and successfully MAA-adducted in vitro. Similar to BSA-MAA, SPD-MAA was instilled into mouse lungs. Lungs were necropsied and assayed for histopathology, PKCε activation, and lung lavage chemokines. In control mice instilled with saline, normal lungs had few inflammatory cells. No significant effects were observed in un-adducted BSA- or SPD-instilled mice. However, when mice were instilled with BSA-MAA or SPD-MAA for 3 wk, a significant peribronchiolar localization of inflammatory cells was observed. Both BSA-MAA and SPD-MAA stimulated increased lung lavage neutrophils and caused a significant elevation in the chemokine, KC, which is a functional homologue to human interleukin-8. Likewise, MAA-adducted protein stimulated the activation of airway and lung slice PKCε. These data support that MAA-adducted protein induces a pro-inflammatory response in the lungs and that lung surfactant protein is a biologically

Malfolded Protein Structure and Proteostasis in Lung Diseases

PubMed Central

Balch, William E.; Sznajder, Jacob I.; Budinger, Scott; Finley, Daniel; Laposky, Aaron D.; Cuervo, Ana Maria; Benjamin, Ivor J.; Barreiro, Esther; Morimoto, Richard I.; Postow, Lisa; Weissman, Allan M.; Gail, Dorothy; Banks-Schlegel, Susan; Croxton, Thomas

2014-01-01

Recent discoveries indicate that disorders of protein folding and degradation play a particularly important role in the development of lung diseases and their associated complications. The overarching purpose of the National Heart, Lung, and Blood Institute workshop on “Malformed Protein Structure and Proteostasis in Lung Diseases” was to identify mechanistic and clinical research opportunities indicated by these recent discoveries in proteostasis science that will advance our molecular understanding of lung pathobiology and facilitate the development of new diagnostic and therapeutic strategies for the prevention and treatment of lung disease. The workshop's discussion focused on identifying gaps in scientific knowledge with respect to proteostasis and lung disease, discussing new research advances and opportunities in protein folding science, and highlighting novel technologies with potential therapeutic applications for diagnosis and treatment. PMID:24033344

Malfolded protein structure and proteostasis in lung diseases.

PubMed

Balch, William E; Sznajder, Jacob I; Budinger, Scott; Finley, Daniel; Laposky, Aaron D; Cuervo, Ana Maria; Benjamin, Ivor J; Barreiro, Esther; Morimoto, Richard I; Postow, Lisa; Weissman, Allan M; Gail, Dorothy; Banks-Schlegel, Susan; Croxton, Thomas; Gan, Weiniu

2014-01-01

Recent discoveries indicate that disorders of protein folding and degradation play a particularly important role in the development of lung diseases and their associated complications. The overarching purpose of the National Heart, Lung, and Blood Institute workshop on "Malformed Protein Structure and Proteostasis in Lung Diseases" was to identify mechanistic and clinical research opportunities indicated by these recent discoveries in proteostasis science that will advance our molecular understanding of lung pathobiology and facilitate the development of new diagnostic and therapeutic strategies for the prevention and treatment of lung disease. The workshop's discussion focused on identifying gaps in scientific knowledge with respect to proteostasis and lung disease, discussing new research advances and opportunities in protein folding science, and highlighting novel technologies with potential therapeutic applications for diagnosis and treatment.

Fissureless fissure-last video-assisted thoracoscopic lobectomy for all lung lobes: a better alternative to decrease the incidence of prolonged air leak?

PubMed

Stamenovic, Davor; Bostanci, Korkut; Messerschmidt, Antje; Jahn, Tillmann; Schneider, Thomas

2016-07-01

Prolonged air leak (PAL) after major lung resections is a common postoperative complication that leads to extended length of hospital stay (LOS) and increased hospital costs. Dissection of the lung tissue through the fissure may increase the incidence of PAL especially in the patients with incomplete fissures. The objective of this study was to evaluate the impact of the fissureless fissure-last technique in VATS lobectomy on immediate outcome, especially relating to air leak and LOS. This is an observational analysis on prospectively collected data of a single thoracic surgery unit. A total of 54 consecutive patients underwent VATS lobectomy and mediastinal lymphadenectomy-in 24 patients conventional VATS lobectomy (Group 1), in 30 patients fissureless VATS lobectomy (Group 2) was performed. The two groups were compared according to preoperative, operative and postoperative parameters. No differences were found when comparing patient characteristics, operation time (M1 = 185 min; M2 = 176 min; P = 0.52) and number of staplers used (M1 = 6.2; M2 = 7.7; P = 0.088). The presence of air leak (P = 0.004; RR = 3.5), PAL (P = 0.003; RR = 10), in days with chest tube (M1 = 7.2; M2 = 4.2; P = 0.028) and LOS (M1 = 12.7; M2 = 8.9; P = 0.020) was significantly more frequent in patients that underwent conventional VATS lobectomy. Focusing on the air leak, significance was present in male gender (P = 0.034; RR = 2.41), higher ASA (M1 = 3.04; M2 = 2.67; P = 0.012), postoperative complications other than air leak (P = 0.001; RR = 5.78) and age between groups with and without air leak (M1 = 63.9; M2 = 74.1; P < 0.001). Fissureless fissure-last VATS lobectomy is a feasible and equivalent to conventional VATS lobectomy in terms of operation time, stapler use and complications. Fissureless fissure-last VATS lobectomy, however, appears to be a superior technique to conventional VATS lobectomy in terms of preventing PAL and reducing the LOS. © The Author 2016. Published by Oxford

Protein profiles associated with survival in lung adenocarcinoma

PubMed Central

Chen, Guoan; Gharib, Tarek G; Wang, Hong; Huang, Chiang-Ching; Kuick, Rork; Thomas, Dafydd G.; Shedden, Kerby A.; Misek, David E.; Taylor, Jeremy M. G.; Giordano, Thomas J.; Kardia, Sharon L. R.; Iannettoni, Mark D.; Yee, John; Hogg, Philip J.; Orringer, Mark B.; Hanash, Samir M.; Beer, David G.

2003-01-01

Morphologic assessment of lung tumors is informative but insufficient to adequately predict patient outcome. We previously identified transcriptional profiles that predict patient survival, and here we identify proteins associated with patient survival in lung adenocarcinoma. A total of 682 individual protein spots were quantified in 90 lung adenocarcinomas by using quantitative two-dimensional polyacrylamide gel electrophoresis analysis. A leave-one-out cross-validation procedure using the top 20 survival-associated proteins identified by Cox modeling indicated that protein profiles as a whole can predict survival in stage I tumor patients (P = 0.01). Thirty-three of 46 survival-associated proteins were identified by using mass spectrometry. Expression of 12 candidate proteins was confirmed as tumor-derived with immunohistochemical analysis and tissue microarrays. Oligonucleotide microarray results from both the same tumors and from an independent study showed mRNAs associated with survival for 11 of 27 encoded genes. Combined analysis of protein and mRNA data revealed 11 components of the glycolysis pathway as associated with poor survival. Among these candidates, phosphoglycerate kinase 1 was associated with survival in the protein study, in both mRNA studies and in an independent validation set of 117 adenocarcinomas and squamous lung tumors using tissue microarrays. Elevated levels of phosphoglycerate kinase 1 in the serum were also significantly correlated with poor outcome in a validation set of 107 patients with lung adenocarcinomas using ELISA analysis. These studies identify new prognostic biomarkers and indicate that protein expression profiles can predict the outcome of patients with early-stage lung cancer. PMID:14573703

Digital air leak monitoring after lobectomy for primary lung cancer in patients with moderate COPD: can a fast-tracking algorithm reduce postoperative costs and complications?

PubMed

Filosso, P L; Ruffini, E; Solidoro, P; Molinatti, M; Bruna, M C; Oliaro, A

2010-06-01

Prolonged air leaks remain one of the most important complication after pulmonary resection. The aim of this study was to test a new fast-track chest tube removal protocol using a new drainage system, which digitally records postoperative air leaks, compared to the traditional one, with subjective visual air leak assessment. Patients with moderate COPD undergoing lobectomy for primary lung cancer at the Department of Thoracic Surgery of the University of Torino were randomised in two groups with different chest drainage systems and different removal protocols: in Group A the drainage was removed after digitally recordered measurement of air leaks; in Group B the tube was removed according to the air leaks visualization by bubbling in the water column. The following variables were evaluated: first and second drainage removal day; overall hospital length of stay; overall hospitalization costs. First and second drainages were removed sooner in those patients with the digital drainage system. An earlier drainage removal is associated with significative reduction in hospital length of stay and overall hospitalization costs. The digital and continuous air leak measurement reduces the hospital length of stay by a more accurate and reproductive air leaks measurement. Further studies are mandatory to corroborate our preliminary results.

Sensitivity of scintigraphy for detection of pulmonary capillary albumin leak in canine oleic acid ARDS

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

Sugerman, H.J.; Strash, A.M.; Hirsch, J.I.

1981-07-01

Computerized gamma scintigraphy was shown in this study to be a sensitive technique for the detection and kinetic analysis of a pulmonary capillary protein leak. A rising lung:heart radioactivity of slope of injury was found at each dose of intravenous oleic acid in dogs from 0.01 to 0.20 ml/kg (p less than 0.01). This slope of injury was proportional to the dose of oleic acid (r . +0.97; p less than 0.004) and was more sensitive than changes in arterial oxygen tension, standard chest radiography, bloodless wet:dry lung weight, or alveolar epithelial membrane permeability. Only standard light microscopy and rightmore » lymphatic duct flow were able to document the leakage of protein detected by gamma scintigraphy at 0.01 ml/kg oleic acid.« less

Lung protein leakage in feline septic shock.

PubMed

Schützer, K M; Larsson, A; Risberg, B; Falk, A

1993-06-01

The aim of the present study was to explore lung microvascular leakage of protein and water in a feline model of septic shock, using a double isotope technique with external gamma camera detection and gravimetric lung water measurements. The experiments were performed on artificially ventilated cats. One group of cats (n = 8) was given an infusion of live Escherichia coli bacteria, and another group (n = 5) served as a control group receiving saline. Plasma transferrin was radiolabeled in vivo with indium-113m-chloride, and erythrocytes were labeled with technetium-99m. The distribution of these isotopes in the lungs was continuously measured with a gamma camera. A normalized slope index (NSI) was calculated, indicative of the transferrin accumulation corrected for changes in local blood volume that reflect protein leakage. In the septic group there was a protein leakage after bacterial infusion, with a NSI of 39 x 10(-4) +/- 5 x 10(-4) min-1 (mean +/- SEM), and the PaO2 diminished from 21 +/- 1 to 9.5 +/- 1 kPa. In control cats a slight protein leakage with a NSI of 9 +/- 10(-4) +/- 2 x 10(-4) min-1 was detected, probably caused by the operative procedure, but PaO2 did not change. Wet-to-dry-weight ratios of postmortem lungs were not significantly different between the groups. It was concluded that an intravenous infusion of live E. coli bacteria induces a lung capillary protein leakage without increased lung water and a concomitantly disturbed gas exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet Vascular Endothelial Growth Factor is a Potential Mediator of Transfusion-Related Acute Lung Injury.

PubMed

Maloney, James P; Ambruso, Daniel R; Voelkel, Norbert F; Silliman, Christopher C

The occurrence of non-hemolytic transfusion reactions is highest with platelet and plasma administration. Some of these reactions are characterized by endothelial leak, especially transfusion related acute lung injury (TRALI). Elevated concentrations of inflammatory mediators secreted by contaminating leukocytes during blood product storage may contribute to such reactions, but platelet-secreted mediators may also contribute. We hypothesized that platelet storage leads to accumulation of the endothelial permeability mediator vascular endothelial growth factor (VEGF), and that intravascular administration of exogenous VEGF leads to extensive binding to its lung receptors. Single donor, leukocyte-reduced apheresis platelet units were sampled over 5 days of storage. VEGF protein content of the centrifuged supernatant was determined by ELISA, and the potential contribution of VEGF from contaminating leukocytes was quantified. Isolated-perfused rat lungs were used to study the uptake of radiolabeled VEGF administered intravascularly, and the effect of unlabeled VEGF on lung leak. There was a time-dependent release of VEGF into the plasma fraction of the platelet concentrates (62 ± 9 pg/ml on day one, 149 ± 23 pg/ml on day 5; mean ± SEM, p<0.01, n=8) and a contribution by contaminating leukocytes was excluded. Exogenous 125I-VEGF bound avidly and specifically to the lung vasculature, and unlabeled VEGF in the lung perfusate caused vascular leak. Rising concentrations of VEGF occur during storage of single donor platelet concentrates due to platelet secretion or disintegration, but not due to leukocyte contamination. Exogenous VEGF at these concentrations rapidly binds to its receptors in the lung vessels. At higher VEGF concentrations, VEGF causes vascular leak in uninjured lungs. These data provide further evidence that VEGF may contribute to the increased lung permeability seen in TRALI associated with platelet products.

New technique to prevent prolonged air leak: use of 'Tachosuture' technique.

PubMed

Nishida, Tatsuya; Mikami, Iwao; Fujii, Yoshitaka

2017-02-01

Prolonged air leak (defined as air leak >7 days), caused by pulmonary resection or alveolar-pleural fistula, increases postoperative morbidity, prolongs hospital stay and increases healthcare costs. We describe a new technique ('Tachosuture' technique) to prevent prolonged air leak. The key point of this new technique is that air leak is classified into three types and an absorbable suture is added to a TachoSil ® patch in each type to prevent detachment from the lung parenchyma. Between August 2013 and March 2016, 40 patients underwent thoracoscopic surgery using 'Tachosuture' technique. Postoperative air leak always stopped within 3 days (95% confidence interval for the absence of prolonged air leak: 92.5-100%). It is considered that this simple technique is useful to prevent prolonged air leak.

Intraoperative air leak measured after lobectomy is associated with postoperative duration of air leak.

PubMed

Brunelli, Alessandro; Salati, Michele; Pompili, Cecilia; Gentili, Paolo; Sabbatini, Armando

2017-11-01

To verify the association between the air leak objectively measured intraoperatively (IAL) using the ventilator and the air leak duration after pulmonary lobectomy. Prospective analysis on 111 patients submitted to pulmonary lobectomy (33 by video-assisted thoracic surgery). After resection, objective assessment of air leak (in milliliter per minute) was performed before closure of the chest by measuring the difference between a fixed inspired and expired volume, using a tidal volume of 8 ml/kg, a respiratory rate of 10 and a positive-end expiratory pressure of 5 cmH2O. A multivariable analysis was performed for identifying factors associated with duration of postoperative air leak. Average IAL was 158 ml/min (range 0-1500 ml/min). The best cut-off (receiver-operating characteristics analysis) associated with air leak longer than 5 days was 500 ml/min. Nine patients had IAL >500 ml/min (8%). They had a longer duration of postoperative air leak compared with those with a lower IAL (mean values, 10.1 days, SD 8.8 vs 1.5 days, SD 4.9 P < 0.001). The following variables remained associated with days of air leak duration after multivariable regression: left side resection (P = 0.018), upper site resection (P = 0.031) and IAL >500 ml/min (P < 0.001). The following equation estimating the days of air leak duration was generated: 1.7 + 2.4 × left side + 2.2 × upper site + 8.8 × IAL >500. The air leak measurement using the ventilator parameters after lung resection may assist in estimating the risk of postoperative prolonged air leak. An IAL > 500 ml/min may warrant the use of intraoperative preventative measures, particularly after video-assisted thoracic surgery lobectomy where a submersion test is often unreliable. © 2017 European Society of Cardiology and European Atherosclerosis Association. All rights reserved. For permissions please email: journals.permissions@oup.com.

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.

Capillary leak syndrome: etiologies, pathophysiology, and management.

PubMed

Siddall, Eric; Khatri, Minesh; Radhakrishnan, Jai

2017-07-01

In various human diseases, an increase in capillary permeability to proteins leads to the loss of protein-rich fluid from the intravascular to the interstitial space. Although sepsis is the disease most commonly associated with this phenomenon, many other diseases can lead to a "sepsis-like" syndrome with manifestations of diffuse pitting edema, exudative serous cavity effusions, noncardiogenic pulmonary edema, hypotension, and, in some cases, hypovolemic shock with multiple-organ failure. The term capillary leak syndrome has been used to describe this constellation of disease manifestations associated with an increased capillary permeability to proteins. Diseases other than sepsis that can result in capillary leak syndrome include the idiopathic systemic capillary leak syndrome or Clarkson's disease, engraftment syndrome, differentiation syndrome, the ovarian hyperstimulation syndrome, hemophagocytic lymphohistiocytosis, viral hemorrhagic fevers, autoimmune diseases, snakebite envenomation, and ricin poisoning. Drugs including some interleukins, some monoclonal antibodies, and gemcitabine can also cause capillary leak syndrome. Acute kidney injury is commonly seen in all of these diseases. In addition to hypotension, cytokines are likely to be important in the pathophysiology of acute kidney injury in capillary leak syndrome. Fluid management is a critical part of the treatment of capillary leak syndrome; hypovolemia and hypotension can cause organ injury, whereas capillary leakage of administered fluid can worsen organ edema leading to progressive organ injury. The purpose of this article is to discuss the diseases other than sepsis that produce capillary leak and review their collective pathophysiology and treatment. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Application of the coaxial smart drain in patients with a large air leak following anatomic lung resection: a prospective multicenter phase II analysis of efficacy and safety

PubMed Central

Filosso, Pier Luigi; Pompili, Cecilia; Olivetti, Stefania; Roffinella, Matteo; Imperatori, Andrea; Brunelli, Alessandro

2018-01-01

Background The presence of air leak following lung resection remains a frequent problem, which may prolong hospital stay and increase hospital costs. In the past, some studies documented the efficacy of soft and flexible chest tube in patients who underwent thoracic surgery. Nevertheless, safety in case of post-operative large air or liquid leak remains questionable. The objective of this study was to verify through a multicentre study the safety and the effectiveness of the coaxial chest tube in a consecutive series of selected patients who underwent anatomical pulmonary resection and with an active and large air leak. Methods Between October 2016 and September 2017, data from patients submitted to anatomical lung resection with curative intent and operated in two Department of Thoracic Surgery of two different were prospectively collected. The inclusion criteria consisted in the presence of an air leak greater than 50 mL/min measured with a digital drainage system during the 3 postoperative hours. A descriptive statistic was used to report the incidence of complications assumed to be associated with the use of the coaxial drain. Results Forty-eight consecutive patients (27 males) submitted to lobectomy (37 patients: 77%) or anatomic segmentectomies (11 patients) were included in the analyses. Thirty-four operations (71%) were performed by video-assisted thoracic surgery (VATS). The median duration of chest tubes was 13 days [interquartile range (IQR), 4–19] and the median duration of air leak was 9 days (IQR, 2–17.5). No patient had undrained postoperative pleural effusion judged to require an additional chest tube placement. There were 12 (25%) cases of clinically or radiologically significant surgical emphysema; in none of these patients any additional procedure or re-operation was required, and they were treated conservatively by increasing the level of suction. Conclusions Our experience with this novel Coaxial Drain was satisfactory with no clinically

Application of the coaxial smart drain in patients with a large air leak following anatomic lung resection: a prospective multicenter phase II analysis of efficacy and safety.

PubMed

Guerrera, Francesco; Filosso, Pier Luigi; Pompili, Cecilia; Olivetti, Stefania; Roffinella, Matteo; Imperatori, Andrea; Brunelli, Alessandro

2018-01-01

The presence of air leak following lung resection remains a frequent problem, which may prolong hospital stay and increase hospital costs. In the past, some studies documented the efficacy of soft and flexible chest tube in patients who underwent thoracic surgery. Nevertheless, safety in case of post-operative large air or liquid leak remains questionable. The objective of this study was to verify through a multicentre study the safety and the effectiveness of the coaxial chest tube in a consecutive series of selected patients who underwent anatomical pulmonary resection and with an active and large air leak. Between October 2016 and September 2017, data from patients submitted to anatomical lung resection with curative intent and operated in two Department of Thoracic Surgery of two different were prospectively collected. The inclusion criteria consisted in the presence of an air leak greater than 50 mL/min measured with a digital drainage system during the 3 postoperative hours. A descriptive statistic was used to report the incidence of complications assumed to be associated with the use of the coaxial drain. Forty-eight consecutive patients (27 males) submitted to lobectomy (37 patients: 77%) or anatomic segmentectomies (11 patients) were included in the analyses. Thirty-four operations (71%) were performed by video-assisted thoracic surgery (VATS). The median duration of chest tubes was 13 days [interquartile range (IQR), 4-19] and the median duration of air leak was 9 days (IQR, 2-17.5). No patient had undrained postoperative pleural effusion judged to require an additional chest tube placement. There were 12 (25%) cases of clinically or radiologically significant surgical emphysema; in none of these patients any additional procedure or re-operation was required, and they were treated conservatively by increasing the level of suction. Our experience with this novel Coaxial Drain was satisfactory with no clinically relevant complication caused using this drain

No air leak on PPV does not exclude tracheobronchial injury after blunt chest trauma.

PubMed

Ong, Victor Yeok Kein; Tan, Kenneth Hock Soon

2008-04-01

Tracheobronchial injuries are commonly associated with persistent air leak with pneumothoraces especially when on positive pressure ventilation (PPV). Injuries with absence of these features together with collapse of the lung and consequent low arterial oxygen tension while on PPV are less well recognised. We present a patient with traumatic aortic dissection and preoperatively undiagnosed complete transaction of the left main bronchus following blunt chest trauma. He had no persistent air leak with lower lung lobe collapse despite undergoing PPV and had low arterial oxygen tension which failed to respond to appropriate oxygen therapy.

[Tripartite-motif protein 25 and pyruvate kinase M2 protein expression in non-small cell lung cancer].

PubMed

Jing, Huai-Zhi; Qiu, Feng; Chen, Shi-Zhi; Su, Lin; Qu, Can

2015-03-01

To investigate the expression of tripartite-motif protein 25 (TRIM25) and pyruvate kinase M2 (PKM2) protein in non-small cell lung cancer (NSCLC) and explore their role in the occurrence and progression of NSCLC. The expressions of TRIM25 and PKM2 protein were detected in 60 NSCLC specimens and 20 adjacent normal lung tissue (>5 cm from the lesions) with immunofluorescence histochemical method and in 10 fresh specimens of NSCLC with Western blotting. The results were analyzed in relation with the clinicopathological features of the patients. The positivity rates of TRIM25 expression was 45% in the 60 lung carcinoma specimens, significantly higher than that in the 20 normal lung tissues (10%, P=0.005). TRIM25 protein was expressed in 28.6% of lung adenocarcinoma tissues and in 59.4% of squamous carcinoma tissues (P=0.017). TRIM25 protein expression was positively correlated with the TNM stages and lymph node metastasis of NSCLC (P<0.05). The expressions of PKM2 protein in 60 cases of lung carcinoma was 73.3%,while in 20 cases of normal lung tissues the expressions was 30%(P=0.001). The positivity rates of PKM2 expression differed significantly between lung adenocarcinoma and squamous carcinoma (57.1% vs 87.5%, P=0.008). An inverse correlation was noted between TRIM25 and PKM2 expressions (P=0.026). TRIM25 and PKM2 protein may participate in the occurrence and progression of NSCLC, and their expressions are inversely correlated.

Glycoxidation and inflammatory markers in patients on treatment with PMMA-based protein-leaking dialyzers.

PubMed

Galli, Francesco; Benedetti, Serena; Floridi, Ardesio; Canestrari, Franco; Piroddi, Marta; Buoncristiani, Emanuela; Buoncristiani, Umberto

2005-02-01

High-molecular-weight solutes such as glycation and oxidation protein products are putative proinflammatory mediators found in the uremic blood. The elimination of these and other large solutes by protein-leaking dialyzers (PLD) might help to correct the inflammatory status of maintenance hemodialysis (HD) patients. Two matched groups of 13 standard 3 times/week HD patients were treated for 6 months with PMMA-based PLD and non-protein-leaking dialyzers (NPLD), respectively. At baseline, 1, 3, and 6 months, we measured the blood levels of the inflammatory cytokines IL-1beta, TNF-alpha, IL-6, the acute-phase protein C-reactive protein (CRP), the adhesion molecules ICAM-1, VCAM-1, and selectine-E, the chemotaxis factors MCP-1, and the glycation and oxidation protein end products pentosidine, protein carbonyls, and AOPP. In all the patients at baseline, pre-HD levels of glycation and oxidation protein markers, and inflammatory parameters were significantly higher than in healthy control subjects (P < 0.01 or greater). After 6 months, in the group on treatment with PLD, but not in that on NPLD, there was a significant decrease (P < 0.05 or greater) of pre-HD values of total pentosidine (mainly represented by pentosidine in serum albumin; -43%), protein carbonyls (-42%), AOPP (-38%), and the inflammatory cytokines IL-1beta (-49%), IL-6 (-39%), and TNF-alpha (-20%), while IL-10 and INF-gamma increased by 67% and 37%, respectively. Proinflammatory cytokines, and particularly IL-6, showed a positive correlation with the levels of circulating pentosidine. Protidemia was not significantly modified at the end of the study in both the groups. The results in this pilot study show that the removal of large solutes by PLD can improve some indices of chronic inflammation in HD patients. Further studies are required to determine the relevance of the individual solutes removed with PLD as proinflammatory mediators in the uremic environment.

A clinical prediction model for prolonged air leak after pulmonary resection.

PubMed

Attaar, Adam; Winger, Daniel G; Luketich, James D; Schuchert, Matthew J; Sarkaria, Inderpal S; Christie, Neil A; Nason, Katie S

2017-03-01

Prolonged air leak increases costs and worsens outcomes after pulmonary resection. We aimed to develop a clinical prediction tool for prolonged air leak using pretreatment and intraoperative variables. Patients who underwent pulmonary resection for lung cancer/nodules (from January 2009 to June 2014) were stratified by prolonged parenchymal air leak (>5 days). Using backward stepwise logistic regression with bootstrap resampling for internal validation, candidate variables were identified and a nomogram risk calculator was developed. A total of 2317 patients underwent pulmonary resection for lung cancer/nodules. Prolonged air leak (8.6%, n = 200) was associated with significantly longer hospital stay (median 10 vs 4 days; P < .001). Final model variables associated with increased risk included low percent forced expiratory volume in 1 second, smoking history, bilobectomy, higher annual surgeon caseload, previous chest surgery, Zubrod score >2, and interaction terms for right-sided thoracotomy and wedge resection by thoracotomy. Wedge resection, higher body mass index, and unmeasured percent forced expiratory volume in 1 second were protective. Derived nomogram discriminatory accuracy was 76% (95% confidence interval [CI], 0.72-0.79) and facilitated patient stratification into low-, intermediate- and high-risk groups with monotonic increase in observed prolonged air leaks (2.0%, 8.9%, and 19.2%, respectively; P < .001). Patients at intermediate and high risk were 4.80 times (95% CI, 2.86-8.07) and 11.86 times (95% CI, 7.21-19.52) more likely to have prolonged air leak compared with patients at low risk. Using readily available candidate variables, our nomogram predicts increasing risk of prolonged air leak with good discriminatory ability. Risk stratification can support surgical decision making, and help initiate proactive, patient-specific surgical management. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc

Current and Prospective Protein Biomarkers of Lung Cancer

PubMed Central

Zamay, Tatiana N.; Zamay, Galina S.; Kolovskaya, Olga S.; Zukov, Ruslan A.; Petrova, Marina M.; Gargaun, Ana; Berezovski, Maxim V.

2017-01-01

Lung cancer is a malignant lung tumor with various histological variants that arise from different cell types, such as bronchial epithelium, bronchioles, alveoli, or bronchial mucous glands. The clinical course and treatment efficacy of lung cancer depends on the histological variant of the tumor. Therefore, accurate identification of the histological type of cancer and respective protein biomarkers is crucial for adequate therapy. Due to the great diversity in the molecular-biological features of lung cancer histological types, detection is impossible without knowledge of the nature and origin of malignant cells, which release certain protein biomarkers into the bloodstream. To date, different panels of biomarkers are used for screening. Unfortunately, a uniform serum biomarker composition capable of distinguishing lung cancer types is yet to be discovered. As such, histological analyses of tumor biopsies and immunohistochemistry are the most frequently used methods for establishing correct diagnoses. Here, we discuss the recent advances in conventional and prospective aptamer based strategies for biomarker discovery. Aptamers like artificial antibodies can serve as molecular recognition elements for isolation detection and search of novel tumor-associated markers. Here we will describe how these small synthetic single stranded oligonucleotides can be used for lung cancer biomarker discovery and utilized for accurate diagnosis and targeted therapy. Furthermore, we describe the most frequently used in-clinic and novel lung cancer biomarkers, which suggest to have the ability of differentiating between histological types of lung cancer and defining metastasis rate. PMID:29137182

Fluid management in critically ill patients: the role of extravascular lung water, abdominal hypertension, capillary leak, and fluid balance

PubMed Central

2012-01-01

Introduction Capillary leak in critically ill patients leads to interstitial edema. Fluid overload is independently associated with poor prognosis. Bedside measurement of intra-abdominal pressure (IAP), extravascular lung water index (EVLWI), fluid balance, and capillary leak index (CLI) may provide a valuable prognostic tool in mechanically ventilated patients. Methods We performed an observational study of 123 mechanically ventilated patients with extended hemodynamic monitoring, analyzing process-of-care variables for the first week of ICU admission. The primary outcome parameter was 28-day mortality. ΔmaxEVLWI indicated the maximum difference between EVLWI measurements during ICU stay. Patients with a ΔmaxEVLWI <−2 mL/kg were called 'responders'. CLI was defined as C-reactive protein (milligrams per deciliter) over albumin (grams per liter) ratio and conservative late fluid management (CLFM) as even-to-negative fluid balance on at least two consecutive days. Results CLI had a biphasic course. ΔmaxEVLWI was lower if CLFM was achieved and in survivors (−2.4 ± 4.8 vs 1.0 ± 5.5 mL/kg, p = 0.001; −3.3 ± 3.8 vs 2.5 ± 5.3 mL/kg, p = 0.001, respectively). No CLFM achievement was associated with increased CLI and IAPmean on day 3 and higher risk to be nonresponder (odds ratio (OR) 2.76, p = 0.046; OR 1.28, p = 0.011; OR 5.52, p = 0.001, respectively). Responders had more ventilator-free days during the first week (2.5 ± 2.3 vs 1.5 ± 2.3, p = 0.023). Not achieving CLFM and being nonresponder were strong independent predictors of mortality (OR 9.34, p = 0.001 and OR 7.14, p = 0.001, respectively). Conclusion There seems to be an important correlation between CLI, EVLWI kinetics, IAP, and fluid balance in mechanically ventilated patients, associated with organ dysfunction and poor prognosis. In this context, we introduce the global increased permeability syndrome. PMID:22873410

ATM protein is deficient in over 40% of lung adenocarcinomas.

PubMed

Villaruz, Liza C; Jones, Helen; Dacic, Sanja; Abberbock, Shira; Kurland, Brenda F; Stabile, Laura P; Siegfried, Jill M; Conrads, Thomas P; Smith, Neil R; O'Connor, Mark J; Pierce, Andrew J; Bakkenist, Christopher J

2016-09-06

Lung cancer is the leading cause of cancer-related mortality in the USA and worldwide, and of the estimated 1.2 million new cases of lung cancer diagnosed every year, over 30% are lung adenocarcinomas. The backbone of 1st-line systemic therapy in the metastatic setting, in the absence of an actionable oncogenic driver, is platinum-based chemotherapy. ATM and ATR are DNA damage signaling kinases activated at DNA double-strand breaks (DSBs) and stalled and collapsed replication forks, respectively. ATM protein is lost in a number of cancer cell lines and ATR kinase inhibitors synergize with cisplatin to resolve xenograft models of ATM-deficient lung cancer. We therefore sought to determine the frequency of ATM loss in a tissue microarray (TMA) of lung adenocarcinoma. Here we report the validation of a commercial antibody (ab32420) for the identification of ATM by immunohistochemistry and estimate that 61 of 147 (41%, 95% CI 34%-50%) cases of lung adenocarcinoma are negative for ATM protein expression. As a positive control for ATM staining, nuclear ATM protein was identified in stroma and immune infiltrate in all evaluable cases. ATM loss in lung adenocarcinoma was not associated with overall survival. However, our preclinical findings in ATM-deficient cell lines suggest that ATM could be a predictive biomarker for synergy of an ATR kinase inhibitor with standard-of-care cisplatin. This could improve clinical outcome in 100,000's of patients with ATM-deficient lung adenocarcinoma every year.

ATM protein is deficient in over 40% of lung adenocarcinomas

PubMed Central

Villaruz, Liza C.; Jones, Helen; Dacic, Sanja; Abberbock, Shira; Kurland, Brenda F.; Stabile, Laura P.; Siegfried, Jill M.; Conrads, Thomas P.; Smith, Neil R.; O'Connor, Mark J.; Pierce, Andrew J.; Bakkenist, Christopher J.

2016-01-01

Lung cancer is the leading cause of cancer-related mortality in the USA and worldwide, and of the estimated 1.2 million new cases of lung cancer diagnosed every year, over 30% are lung adenocarcinomas. The backbone of 1st-line systemic therapy in the metastatic setting, in the absence of an actionable oncogenic driver, is platinum-based chemotherapy. ATM and ATR are DNA damage signaling kinases activated at DNA double-strand breaks (DSBs) and stalled and collapsed replication forks, respectively. ATM protein is lost in a number of cancer cell lines and ATR kinase inhibitors synergize with cisplatin to resolve xenograft models of ATM-deficient lung cancer. We therefore sought to determine the frequency of ATM loss in a tissue microarray (TMA) of lung adenocarcinoma. Here we report the validation of a commercial antibody (ab32420) for the identification of ATM by immunohistochemistry and estimate that 61 of 147 (41%, 95% CI 34%-50%) cases of lung adenocarcinoma are negative for ATM protein expression. As a positive control for ATM staining, nuclear ATM protein was identified in stroma and immune infiltrate in all evaluable cases. ATM loss in lung adenocarcinoma was not associated with overall survival. However, our preclinical findings in ATM-deficient cell lines suggest that ATM could be a predictive biomarker for synergy of an ATR kinase inhibitor with standard-of-care cisplatin. This could improve clinical outcome in 100,000's of patients with ATM-deficient lung adenocarcinoma every year. PMID:27259260

Sodium leak channel, non-selective contributes to the leak current in human myometrial smooth muscle cells from pregnant women.

PubMed

Reinl, Erin L; Cabeza, Rafael; Gregory, Ismail A; Cahill, Alison G; England, Sarah K

2015-10-01

Uterine contractions are tightly regulated by the electrical activity of myometrial smooth muscle cells (MSMCs). These cells require a depolarizing current to initiate Ca(2+) influx and induce contraction. Cationic leak channels, which permit a steady flow of cations into a cell, are known to cause membrane depolarization in many tissue types. Previously, a Gd(3+)-sensitive, Na(+)-dependent leak current was identified in the rat myometrium, but the presence of such a current in human MSMCs and the specific ion channel conducting this current was unknown. Here, we report the presence of a Na(+)-dependent leak current in human myometrium and demonstrate that the Na(+)-leak channel, NALCN, contributes to this current. We performed whole-cell voltage-clamp on fresh and cultured MSMCs from uterine biopsies of term, non-laboring women and isolated the leak currents by using Ca(2+) and K(+) channel blockers in the bath solution. Ohmic leak currents were identified in freshly isolated and cultured MSMCs with normalized conductances of 14.6 pS/pF and 10.0 pS/pF, respectively. The myometrial leak current was significantly reduced (P < 0.01) by treating cells with 10 μM Gd(3+) or by superfusing the cells with a Na(+)-free extracellular solution. Reverse transcriptase PCR and immunoblot analysis of uterine biopsies from term, non-laboring women revealed NALCN messenger RNA and protein expression in the myometrium. Notably, ∼90% knockdown of NALCN protein expression with lentivirus-delivered shRNA reduced the Gd(3+)-sensitive leak current density by 42% (P < 0.05). Our results reveal that NALCN, in part, generates the leak current in MSMCs and provide the basis for future research assessing NALCN as a potential molecular target for modulating uterine excitability. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Gestational Protein Restriction Increases Angiotensin II Production in Rat Lung1

PubMed Central

Gao, Haijun; Yallampalli, Uma; Yallampalli, Chandra

2013-01-01

ABSTRACT Gestational protein restriction (PR) alters the renin-angiotensin system in uterine arteries and placentas and elevates plasma levels of angiotensin II in pregnant rats. To date, how PR increases maternal plasma levels of angiotensin II remains unknown. In this study, we hypothesize that the expression and/or the activity of angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 (ACE) in lungs, but not kidneys and blood, largely contribute to elevated plasma angiotensin II levels in pregnant rats subject to gestational PR. Time-scheduled pregnant Sprague-Dawley rats were fed a normal or low-protein diet from Day 3 of pregnancy until euthanized at Day 19 or 22. Expressions of Ace and Ace2 (angiotens in I converting enzyme [peptidyl-dipeptidase A] 2) in lungs and kidneys from pregnant rats by quantitative real-time PCR and Western blotting, and the activities of these proteins in lungs, kidneys, and plasma, were measured. The mRNA levels of Ace and Ace2 in lungs were elevated by PR at both Days 19 and 22 of pregnancy. The abundance of ACE protein in lungs was increased, but ACE2 protein was decreased, by PR. The activities of ACE, but not ACE2, in lungs were increased by PR. PR did not change expressions of Ace and Ace2, the activities of both ACE and ACE2 in kidneys, and the abundance and activity of plasma ACE. These findings suggest that maternal lungs contribute to the elevated plasma levels of angiotensin II by increasing both the expression and the activity of ACE in response to gestational PR. PMID:23365412

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.

Pneumostasis of experimental air leaks with a new photopolymerized synthetic tissue sealant.

PubMed

Ranger, W R; Halpin, D; Sawhney, A S; Lyman, M; Locicero, J

1997-09-01

Air leak is a major contributor to increased length of stay and postoperative morbidity following pulmonary surgery. The effectiveness of a new photopolymerized synthetic hydrogel (FocalSeal, Focal, Inc., Lexington, MA) as a sealant for pulmonary air leaks was determined in 10 mongrel dogs (20-35 kg). The animals were anesthetized and underwent left-sided anterolateral thoracotomy with amputation of a 2 x 3-cm segment of the lung apex. Hemostasis was achieved and terminal bronchial openings of 1.5 to 3 mm with vigorous air leaks were identified. After successful injury, the dogs were randomly assigned to sealant (n = 5) or control (n = 5) groups. In treated animals, the sealant was applied by brushing the solution to the cut parenchymal surface and solidified while briefly interrupting ventilation (40-60 seconds) using visible illumination (450-550 nm) from a xenon light source. Controls received no sealant. A single chest tube was maintained at the injury site with a continuous negative pressure of 20 cm of water. All dogs were extubated and allowed to breathe spontaneously under sedation for 24 hours. Chest radiographs were taken postsurgery and presacrifice. All control animals (n = 5) showed persistent vigorous air leak for the duration of the 24-hour observation period. All treated air leaks resolved immediately, and four of five remained sealed throughout the observation period. One leak reappeared after 17 hours due to inadequate sealant thickness over a 3-mm terminal bronchus. Gross evaluation of the treatment group at the end of 24 hours demonstrated intact sealant well adherent to the parenchyma. No evidence of atelectasis or excessive edema was seen, and no sealant-related complications or toxic effects were noted. Radiologically, lungs were fully inflated. Histologic evaluation at 24 hours revealed no evidence of a strong cellular response to the synthetic sealant, and no fibrosis or adhesions were seen, the onset of the healing process was favorable

Smokestack leak in central serous chorioretinopathy.

PubMed

Bujarborua, Dhiren; Nagpal, Pran N; Deka, Manab

2010-03-01

unbound fluorescein molecules along with protein-laden heavy fluid in downward spread of the leak.

[The benefits of digital air leak assessment after pulmonary resection: prospective and comparative study].

PubMed

Mier, José M; Molins, Laureano; Fibla, Juan J

2010-06-01

Persistent air leaks represent the most common pulmonary complication after elective lung resection. Since there are insufficient data in the literature regarding variability in the withdrawal of postoperative pleural drainages, we have designed a prospective, consecutive and comparative study to evaluate if the use of digital devices (Thopaz and DigiVent) to measure postoperative air leak compared to a Pleur-Evac varies on deciding when to withdraw chest tubes after lung resection. A prospective, consecutive and comparative trial was conducted in 75 patients who underwent elective pulmonary resection for non small cell lung cancer. This study compared two digitals devices with the current analogue version in 75 patients. The digital and analogue groups had 26, 24, and 25 patients, respectively. Clinical population data were not statistically different between the groups. The withdrawal of the chest tube was Thopaz, 2.4 days; Digivent, 3.3 days and PleurEvac, 4.5 days. Patients and nurses were subjectively more comfortable with digital devices. Surgeons obtained more objective information with digital devices. The safety mechanism of the Thopaz was also subjectively better, and one patient was discharged home without complications after one week. The digital and continuous measurement of air leak instead of the currently used static analogue systems reduced the chest tube withdrawal and hospital stay by more accurately and reproducibly measuring air leak. Intrapleural pressure curves from the Digivent may also help predict the optimal chest tube setting for each patient. The Thopaz alarm mechanism is very useful to prevent deficiencies in the mechanism and do not required wall suction. Copyright (c) 2010 AEC. Published by Elsevier Espana. All rights reserved.

Protein regulator of cytokinesis-1 expression: prognostic value in lung squamous cell carcinoma patients

PubMed Central

Zhan, Ping; Xi, Guang-Min; Liu, Hong-Bing; Liu, Ya-Fang; Xu, Wu-Jian; Zhu, Qingqing; Zhou, Ze-Jun; Miao, Ying-Ying; Wang, Xiao-Xia; Jin, Jia-Jia

2017-01-01

Background Protein regulator of cytokinesis-1 (PRC1) has been shown to participate in the completion of cytokinesis, and it is dysregulated in cancer processes. However, its relevance in lung squamous cell carcinoma (SCC) remained largely unknown. We aimed to study the expression pattern of PRC1 and assess its clinical significance in lung SCC. Methods PRC1 protein expression in human lung SCC and adjacent normal lung tissues was detected by immunohistochemistry. PRC1 expression was assessed in association with clinicopathological features and clinical outcomes of lung SCC patients. Results In lung SCC tissues, PRC1 protein expression was significantly higher than those in paired normal lung tissues. The lung SCC patients with PRC1 overexpression had an advanced pathological stage (TNM stage), positive lymph node metastasis, and a shorter overall survival (OS) time more frequently than patients with low PRC1 expression. Additional, PRC1 expression was also shown to be poor as a prognostic factor for OS in patients with lung SCC. Conclusions Our study indicated that aberrant expression of PRC1 may point to biochemical recurrence in lung SCC. This highlights its potential as a valuable prognostic marker for lung SCC. PMID:28840006

Index of prolonged air leak score validation in case of video-assisted thoracoscopic surgery anatomical lung resection: results of a nationwide study based on the French national thoracic database, EPITHOR.

PubMed

Orsini, Bastien; Baste, Jean Marc; Gossot, Dominique; Berthet, Jean Philippe; Assouad, Jalal; Dahan, Marcel; Bernard, Alain; Thomas, Pascal Alexandre

2015-10-01

The incidence rate of prolonged air leak (PAL) after lobectomy, defined as any air leak prolonged beyond 7 days, can be estimated to be in between 6 and 15%. In 2011, the Epithor group elaborated an accurate predictive score for PAL after open lung resections, so-called IPAL (index of prolonged air leak), from a nation-based surgical cohort constituted between 2004 and 2008. Since 2008, video-assisted thoracic surgery (VATS) has become popular in France among the thoracic surgical community, reaching almost 14% of lobectomies performed with this method in 2012. This minimally invasive approach was reported as a means to reduce the duration of chest tube drainage. The aim of our study was thus to validate the IPAL scoring system in patients having received VATS anatomical lung resections. We collected all anatomical VATS lung resections (lobectomy and segmentectomy) registered in the French national general thoracic surgery database (EPITHOR) between 2009 and 2012. The area under the receiver operating characteristic (ROC) curve estimated the discriminating value of the IPAL score. The slope value described the relation between the predicted and observed incidences of PALs. The Hosmer-Lemeshow test was also used to estimate the quality of adequacy between predicted and observed values. A total of 1233 patients were included: 1037 (84%) lobectomies and 196 (16%) segmentectomies. In 1099 cases (89.1%), the resection was performed for a malignant disease. Ninety-six patients (7.7%) presented with a PAL. The IPAL score provided a satisfactory predictive value with an area under the ROC curve of 0.72 (0.67-0.77). The value of the slope, 1.25 (0.9-1.58), and the Hosmer-Lemeshow test (χ(2) = 11, P = 0.35) showed that predicted and observed values were adequate. The IPAL score is valid for the estimation of the predictive risk of PAL after VATS lung resections. It may thus a priori be used to characterize any surgical population submitted to potential preventive measures

Ascorbate attenuates pulmonary emphysema by inhibiting tobacco smoke and Rtp801-triggered lung protein modification and proteolysis.

PubMed

Gupta, Indranil; Ganguly, Souradipta; Rozanas, Christine R; Stuehr, Dennis J; Panda, Koustubh

2016-07-19

Cigarette smoking causes emphysema, a fatal disease involving extensive structural and functional damage of the lung. Using a guinea pig model and human lung cells, we show that oxidant(s) present in tobacco smoke not only cause direct oxidative damage of lung proteins, contributing to the major share of lung injury, but also activate Rtp801, a key proinflammatory cellular factor involved in tobacco smoke-induced lung damage. Rtp801 triggers nuclear factor κB and consequent inducible NOS (iNOS)-mediated overproduction of NO, which in combination with excess superoxide produced during Rtp801 activation, contribute to increased oxido-nitrosative stress and lung protein nitration. However, lung-specific inhibition of iNOS with a iNOS-specific inhibitor, N6-(1-iminoethyl)-L-lysine, dihydrochloride (L-NIL) solely restricts lung protein nitration but fails to prevent or reverse the major tobacco smoke-induced oxidative lung injury. In comparison, the dietary antioxidant, ascorbate or vitamin C, can substantially prevent such damage by inhibiting both tobacco smoke-induced lung protein oxidation as well as activation of pulmonary Rtp801 and consequent iNOS/NO-induced nitration of lung proteins, that otherwise lead to increased proteolysis of such oxidized or nitrated proteins by endogenous lung proteases, resulting in emphysematous lung damage. Vitamin C also restricts the up-regulation of matrix-metalloproteinase-9, the major lung protease involved in the proteolysis of such modified lung proteins during tobacco smoke-induced emphysema. Overall, our findings implicate tobacco-smoke oxidant(s) as the primary etiopathogenic factor behind both the noncellular and cellular damage mechanisms governing emphysematous lung injury and demonstrate the potential of vitamin C to accomplish holistic prevention of such damage.

Ascorbate attenuates pulmonary emphysema by inhibiting tobacco smoke and Rtp801-triggered lung protein modification and proteolysis

PubMed Central

Gupta, Indranil; Ganguly, Souradipta; Rozanas, Christine R.; Stuehr, Dennis J.

2016-01-01

Cigarette smoking causes emphysema, a fatal disease involving extensive structural and functional damage of the lung. Using a guinea pig model and human lung cells, we show that oxidant(s) present in tobacco smoke not only cause direct oxidative damage of lung proteins, contributing to the major share of lung injury, but also activate Rtp801, a key proinflammatory cellular factor involved in tobacco smoke-induced lung damage. Rtp801 triggers nuclear factor κB and consequent inducible NOS (iNOS)-mediated overproduction of NO, which in combination with excess superoxide produced during Rtp801 activation, contribute to increased oxido-nitrosative stress and lung protein nitration. However, lung-specific inhibition of iNOS with a iNOS-specific inhibitor, N6-(1-iminoethyl)-L-lysine, dihydrochloride (L-NIL) solely restricts lung protein nitration but fails to prevent or reverse the major tobacco smoke-induced oxidative lung injury. In comparison, the dietary antioxidant, ascorbate or vitamin C, can substantially prevent such damage by inhibiting both tobacco smoke-induced lung protein oxidation as well as activation of pulmonary Rtp801 and consequent iNOS/NO-induced nitration of lung proteins, that otherwise lead to increased proteolysis of such oxidized or nitrated proteins by endogenous lung proteases, resulting in emphysematous lung damage. Vitamin C also restricts the up-regulation of matrix-metalloproteinase-9, the major lung protease involved in the proteolysis of such modified lung proteins during tobacco smoke-induced emphysema. Overall, our findings implicate tobacco-smoke oxidant(s) as the primary etiopathogenic factor behind both the noncellular and cellular damage mechanisms governing emphysematous lung injury and demonstrate the potential of vitamin C to accomplish holistic prevention of such damage. PMID:27382160

Alveolar type II cell transplantation restores pulmonary surfactant protein levels in lung fibrosis.

PubMed

Guillamat-Prats, Raquel; Gay-Jordi, Gemma; Xaubet, Antoni; Peinado, Victor I; Serrano-Mollar, Anna

2014-07-01

Alveolar Type II cell transplantation has been proposed as a cell therapy for the treatment of idiopathic pulmonary fibrosis. Its long-term benefits include repair of lung fibrosis, but its success partly depends on the restoration of lung homeostasis. Our aim was to evaluate surfactant protein restoration after alveolar Type II cell transplantation in an experimental model of bleomycin-induced lung fibrosis in rats. Lung fibrosis was induced by intratracheal instillation of bleomycin. Alveolar Type II cells were obtained from healthy animals and transplanted 14 days after bleomycin was administered. Furthermore, one group transplanted with alveolar macrophages and another group treated with surfactant were established to evaluate the specificity of the alveolar Type II cell transplantation. The animals were euthanized at 21 days after bleomycin instillation. Lung fibrosis was confirmed by a histologic study and an evaluation of the hydroxyproline content. Changes in surfactant proteins were evaluated by mRNA expression, Western blot and immunofluorescence studies. The group with alveolar Type II cell transplantation was the only one to show a reduction in the degree of lung fibrosis and a complete recovery to normal levels of surfactant proteins. One of the mechanisms involved in the beneficial effect of alveolar Type II cell transplantation is restoration of lung surfactant protein levels, which is required for proper respiratory function. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

[Water-cooled laser sealing of lung tissue in an ex-vivo ventilated porcine lung model].

PubMed

Tonoyan, T; Prisadov, G; Menges, P; Herrmann, K; Bobrov, P; Linder, A

2014-06-01

Laser resections of lung metastases are followed by air leaks from the parenchymal defect. Large surfaces after metastasectomy are closed by sutures or sealants while smaller areas are frequently sealed thermally by cautery or laser. In this study two different techniques of thermal sealing of lung tissue with laser light are investigated. Carbonisation of lung tissue during thermal sealing appears at temperatures higher than 180 °C. Hypothetically this is contraproductive to haemo- as well as to pneumostasis. In this experimental study thermal laser sealing with and without carbonisation is investigated. In one series tissue temperatures higher than 100 °C are avoided by water dropping from the tip of the light guide onto the parenchymal leak. In the other series carbonisation appeared because the laser light was applied in the non-contact mode without tissue cooling. The characteristics of the laser were 40 W, 1350 nm continuous mode. Air leaks (Vt) were measured with a simple and fast technique with high precision. The sealing effect of either series was defined as S = (1-Vt/V0) and the difference of S was statistically examined. The basic values V0 before sealing were about the same in both series. The air leaks Vt after 15, 30 and 45 s of sealing varied significantly in both series (p = 0.03). During simultaneous cooling the sealing effect was increasing with the duration of laser application, while it became worse in the series without cooling. Histological examination of the sealing zone showed only coagulation of the tissue, while ruptured alveolae could be seen more often in the non-cooled sealing area. It could be shown in the ex-vivo lung model that laser sealing of parenchymal leaks is improved by simultaneous cooling during laser application. Non cooled laser sealing seems to heat up the tissue abruptly and create carbonisation followed by multiple ruptures of alveola and small airways. In accordance with our clinical experience this

Intraoperative leak testing has no correlation with leak after laparoscopic sleeve gastrectomy.

PubMed

Sethi, Monica; Zagzag, Jonathan; Patel, Karan; Magrath, Melissa; Somoza, Eduardo; Parikh, Manish S; Saunders, John K; Ude-Welcome, Aku; Schwack, Bradley F; Kurian, Marina S; Fielding, George A; Ren-Fielding, Christine J

2016-03-01

Staple line leak is a serious complication of sleeve gastrectomy. Intraoperative methylene blue and air leak tests are routinely used to evaluate for leak; however, the utility of these tests is controversial. We hypothesize that the practice of routine intraoperative leak testing is unnecessary during sleeve gastrectomy. A retrospective cohort study was designed using a prospectively collected database of seven bariatric surgeons from two institutions. All patients who underwent sleeve gastrectomy from March 2012 to November 2014 were included. The performance of intraoperative leak testing and the type of test (air or methylene blue) were based on surgeon preference. Data obtained included BMI, demographics, comorbidity, presence of intraoperative leak test, result of test, and type of test. The primary outcome was leak rate between the leak test (LT) and no leak test (NLT) groups. SAS version 9.4 was used for univariate and multivariate analyses. A total of 1550 sleeve gastrectomies were included; most were laparoscopic (99.8%), except for one converted and two open cases. Routine intraoperative leak tests were performed in 1329 (85.7%) cases, while 221 (14.3%) did not have LTs. Of the 1329 cases with LTs, there were no positive intraoperative results. Fifteen (1%) patients developed leaks, with no difference in leak rate between the LT and NLT groups (1 vs. 1%, p = 0.999). After adjusting for baseline differences between the groups with a propensity analysis, the observed lack of association between leak and intraoperative leak test remained. In this cohort, leaks presented at a mean of 17.3 days postoperatively (range 1-67 days). Two patients with staple line leaks underwent repeat intraoperative leak testing at leak presentation, and the tests remained negative. Intraoperative leak testing has no correlation with leak due to laparoscopic sleeve gastrectomy and is not predictive of the later development of staple line leak.

Transduced PEP-1-Heme Oxygenase-1 Fusion Protein Attenuates Lung Injury in Septic Shock Rats

PubMed Central

Yan, Xue-Tao; Wang, Yan-Lin; Zhang, Zong-Ze; Tang, Jun-Jiao

2018-01-01

Oxidative stress and inflammation have been identified to play a vital role in the pathogenesis of lung injury induced by septic shock. Heme oxygenase-1 (HO-1), an effective antioxidant and anti-inflammatory and antiapoptotic substance, has been used for the treatment of heart, lung, and liver diseases. Thus, we postulated that administration of exogenous HO-1 protein transduced by cell-penetrating peptide PEP-1 has a protective role against septic shock-induced lung injury. Septic shock produced by cecal ligation and puncture caused severe lung damage, manifested in the increase in the lung wet/dry ratio, oxidative stress, inflammation, and apoptosis. However, these changes were reversed by treatment with the PEP-1-HO-1 fusion protein, whereas lung injury in septic shock rats was alleviated. Furthermore, the septic shock upregulated the expression of Toll-like receptor 4 (TLR4) and transcription factor NF-κB, accompanied by the increase of lung injury. Administration of PEP-1-HO-1 fusion protein reversed septic shock-induced lung injury by downregulating the expression of TLR4 and NF-κB. Our study indicates that treatment with HO-1 protein transduced by PEP-1 confers protection against septic shock-induced lung injury by its antioxidant, anti-inflammatory, and antiapoptotic effects. PMID:29682161

[Arf6, RalA and BIRC5 protein expression in non small cell lung cancer].

PubMed

Knizhnik, A V; Kovaleva, O B; Laktionov, K K; Mochal'nikova, V V; Komel'kov, A V; Chevkina, E M; Zborovskaia, I B

2011-01-01

Evaluation of tumor markers expression pattern which determines individual progression parameters is one of the major topics in molecular oncopathology research. This work presents research on expression analysis of several Ras-Ral associated signal transduction pathway proteins (Arf6, RalA and BIRC5) in accordance with clinical criteria in non small cell lung cancer patients. Using Western-blot analysis and RT-PCR Arf6, RalA and BIRC5 expression has been analyzed in parallel in 53 non small cell lung cancer samples of different origin. Arf6 protein expression was elevated in 55% non small cell lung cancer tumor samples in comparison with normal tissue. In the group of squamous cell lung cancer Arf6 expression elevation was observed more often. RalA protein expression was decreased in comparison to normal tissue samples in 64% of non small cell lung cancer regardless to morphological structure. Correlation between RalA protein expression decrease and absence of regional metastases was revealed for squamous cell lung cancer. BIRC5 protein expression in tumor samples versus corresponding normal tissue was 1.3 times more often elevated in the squamous cell lung cancer group (in 76% tumor samples). At the same time elevation of BIRC5 expression was fixed only in 63% of adenocarcinoma tumor samples. A statistically significant decrease (p = 0.0158) of RalA protein expression and increase (p = 0.0498) of Arf6 protein expression in comparison with normal tissue was found for T1-2N0M0 and T1-2N1-2M0 groups of squamous cell lung cancer correspondingly.

Persistent air leaks: a review with an emphasis on bronchoscopic management

PubMed Central

Lazarus, Donald R.

2017-01-01

Persistent air leak (PAL) is a cause of significant morbidity in patients who have undergone lung surgery and those with significant parenchymal lung disease suffering from a pneumothorax. Its management can be complex and challenging. Although conservative treatment with chest drain and observation is usually effective, other invasive techniques are needed when conservative treatment fails. Surgical management and medical pleurodesis have long been the usual treatments for PAL. More recently numerous bronchoscopic procedures have been introduced to treat PAL in those patients who are poor candidates for surgery or who decline surgery. These techniques include bronchoscopic use of sealants, sclerosants, and various types of implanted devices. Recently, removable one-way valves have been developed that are able to be placed bronchoscopically in the affected airways, ameliorating air-leaks in patients who are not candidates for surgery. Future comparative trials are needed to refine our understanding of the indications, effectiveness, and complications of bronchoscopic techniques for treating PAL. The following article will review the basic principles of management of PAL particularly focusing on bronchoscopic techniques. PMID:29268535

Alterations in proton leak, oxidative status and uncoupling protein 3 content in skeletal muscle subsarcolemmal and intermyofibrillar mitochondria in old rats

PubMed Central

2014-01-01

Background We considered of interest to evaluate how aging affects mitochondrial function in skeletal muscle. Methods We measured mitochondrial oxidative capacity and proton leak, together with lipid oxidative damage, superoxide dismutase specific activity and uncoupling protein 3 content, in subsarcolemmal and intermyofibrillar mitochondria from adult (six months) and old (two years) rats. Body composition, resting metabolic rate and plasma non esterified fatty acid levels were also assessed. Results Old rats displayed significantly higher body energy and lipids, while body proteins were significantly lower, compared to adult rats. In addition, plasma non esterified fatty acid levels were significantly higher, while resting metabolic rates were found to be significantly lower, in old rats compared to adult ones. Significantly lower oxidative capacities in whole tissue homogenates and in intermyofibrillar and subsarcolemmal mitochondria were found in old rats compared to adult ones. Subsarcolemmal and intermyofibrillar mitochondria from old rats exhibited a significantly lower proton leak rate, while oxidative damage was found to be significantly higher only in subsarcolemmal mitochondria. Mitochondrial superoxide dismutase specific activity was not significantly affected in old rats, while significantly higher content of uncoupling protein 3 was found in both mitochondrial populations from old rats compared to adult ones, although the magnitude of the increase was lower in subsarcolemmal than in intermyofibrillar mitochondria. Conclusions The decrease in oxidative capacity and proton leak in intermyofibrillar and subsarcolemmal mitochondria could induce a decline in energy expenditure and thus contribute to the reduced resting metabolic rate found in old rats, while oxidative damage is present only in subsarcolemmal mitochondria. PMID:24950599

Mitochondrial Proton Leak Plays a Critical Role in Pathogenesis of Cardiovascular Diseases.

PubMed

Cheng, Jiali; Nanayakkara, Gayani; Shao, Ying; Cueto, Ramon; Wang, Luqiao; Yang, William Y; Tian, Ye; Wang, Hong; Yang, Xiaofeng

2017-01-01

Mitochondrial proton leak is the principal mechanism that incompletely couples substrate oxygen to ATP generation. This chapter briefly addresses the recent progress made in understanding the role of proton leak in the pathogenesis of cardiovascular diseases. Majority of the proton conductance is mediated by uncoupling proteins (UCPs) located in the mitochondrial inner membrane. It is evident that the proton leak and reactive oxygen species (ROS) generated from electron transport chain (ETC) in mitochondria are linked to each other. Increased ROS production has been shown to induce proton conductance, and in return, increased proton conductance suppresses ROS production, suggesting the existence of a positive feedback loop that protects the biological systems from detrimental effects of augmented oxidative stress. There is mounting evidence attributing to proton leak and uncoupling proteins a crucial role in the pathogenesis of cardiovascular disease. We can surmise the role of "uncoupling" in cardiovascular disorders as follows; First, the magnitude of the proton leak and the mechanism involved in mediating the proton leak determine whether there is a protective effect against ischemia-reperfusion (IR) injury. Second, uncoupling by UCP2 preserves vascular function in diet-induced obese mice as well as in diabetes. Third, etiology determines whether the proton conductance is altered or not during hypertension. And fourth, proton leak regulates ATP synthesis-uncoupled mitochondrial ROS generation, which determines pathological activation of endothelial cells for recruitment of inflammatory cells. Continue effort in improving our understanding in the role of proton leak in the pathogenesis of cardiovascular and metabolic diseases would lead to identification of novel therapeutic targets for treatment.

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

PubMed Central

2012-01-01

Background G-protein-coupled estrogen receptor (GPER/GPR30) was reported to bind 17β-estradiol (E2), tamoxifen, and ICI 182,780 (fulvestrant) and promotes activation of epidermal growth factor receptor (EGFR)-mediated signaling in breast, endometrial and thyroid cancer cells. Although lung adenocarcinomas express estrogen receptors α and β (ERα and ERβ), the expression of GPER in lung cancer has not been investigated. The purpose of this study was to examine the expression of GPER in lung cancer. Methods The expression patterns of GPER in various lung cancer lines and lung tumors were investigated using standard quantitative real time PCR (at mRNA levels), Western blot and immunohistochemistry (IHC) methods (at protein levels). The expression of GPER was scored and the pairwise comparisons (cancer vs adjacent tissues as well as cancer vs normal lung tissues) were performed. Results Analysis by real-time PCR and Western blotting revealed a significantly higher expression of GPER at both mRNA and protein levels in human non small cell lung cancer cell (NSCLC) lines relative to immortalized normal lung bronchial epithelial cells (HBECs). The virally immortalized human small airway epithelial cell line HPL1D showed higher expression than HBECs and similar expression to NSCLC cells. Immunohistochemical analysis of tissue sections of murine lung adenomas as well as human lung adenocarcinomas, squamous cell carcinomas and non-small cell lung carcinomas showed consistently higher expression of GPER in the tumor relative to the surrounding non-tumor tissue. Conclusion The results from this study demonstrate increased GPER expression in lung cancer cells and tumors compared to normal lung. Further evaluation of the function and regulation of GPER will be necessary to determine if GPER is a marker of lung cancer progression. PMID:23273253

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

PubMed

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

2012-12-28

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

Cigarette smoke induces an unfolded protein response in the human lung: a proteomic approach.

PubMed

Kelsen, Steven G; Duan, Xunbao; Ji, Rong; Perez, Oscar; Liu, Chunli; Merali, Salim

2008-05-01

Cigarette smoking, which exposes the lung to high concentrations of reactive oxidant species (ROS) is the major risk factor for chronic obstructive pulmonary disease (COPD). Recent studies indicate that ROS interfere with protein folding in the endoplasmic reticulum and elicit a compensatory response termed the "unfolded protein response" (UPR). The importance of the UPR lies in its ability to alter expression of a variety of genes involved in antioxidant defense, inflammation, energy metabolism, protein synthesis, apoptosis, and cell cycle regulation. The present study used comparative proteomic technology to test the hypothesis that chronic cigarette smoking induces a UPR in the human lung. Studies were performed on lung tissue samples obtained from three groups of human subjects: nonsmokers, chronic cigarette smokers, and ex-smokers. Proteomes of lung samples from chronic cigarette smokers demonstrated 26 differentially expressed proteins (20 were up-regulated, 5 were down-regulated, and 1 was detected only in the smoking group) compared with nonsmokers. Several UPR proteins were up-regulated in smokers compared with nonsmokers and ex-smokers, including the chaperones, glucose-regulated protein 78 (GRP78) and calreticulin; a foldase, protein disulfide isomerase (PDI); and enzymes involved in antioxidant defense. In cultured human airway epithelial cells, GRP78 and the UPR-regulated basic leucine zipper, transcription factors, ATF4 and Nrf2, which enhance expression of important anti-oxidant genes, increased rapidly (< 24 h) with cigarette smoke extract. These data indicate that cigarette smoke induces a UPR response in the human lung that is rapid in onset, concentration dependent, and at least partially reversible with smoking cessation. We speculate that activation of a UPR by cigarette smoke may protect the lung from oxidant injury and the development of COPD.

Neonatal air leak syndrome and the role of high-frequency ventilation in its prevention.

PubMed

Jeng, Mei-Jy; Lee, Yu-Sheng; Tsao, Pei-Chen; Soong, Wen-Jue

2012-11-01

Air leak syndrome includes pulmonary interstitial emphysema, pneumothorax, pneumomediastinum, pneumopericardium, pneumoperitoneum, subcutaneous emphysema, and systemic air embolism. The most common cause of air leak syndrome in neonates is inadequate mechanical ventilation of the fragile and immature lungs. The incidence of air leaks in newborns is inversely related to the birth weight of the infants, especially in very-low-birth-weight and meconium-aspirated infants. When the air leak is asymptomatic and the infant is not mechanically ventilated, there is usually no specific treatment. Emergent needle aspiration and/or tube drainage are necessary in managing tension pneumothorax or pneumopericardium with cardiac tamponade. To prevent air leak syndrome, gentle ventilation with low pressure, low tidal volume, low inspiratory time, high rate, and judicious use of positive end expiratory pressure are the keys to caring for mechanically ventilated infants. Both high-frequency oscillatory ventilation (HFOV) and high-frequency jet ventilation (HFJV) can provide adequate gas exchange using extremely low tidal volume and supraphysiologic rate in neonates with acute pulmonary dysfunction, and they are considered to have the potential to reduce the risks of air leak syndrome in neonates. However, there is still no conclusive evidence that HFOV or HFJV can help to reduce new air leaks in published neonatal clinical trials. In conclusion, neonatal air leaks may present as a thoracic emergency requiring emergent intervention. To prevent air leak syndrome, gentle ventilations are key to caring for ventilated infants. There is insufficient evidence showing the role of HFOV and HFJV in the prevention or reduction of new air leaks in newborn infants, so further investigation will be necessary for future applications. Copyright © 2012. Published by Elsevier B.V.

Differential protein-coding gene and long noncoding RNA expression in smoking-related lung squamous cell carcinoma.

PubMed

Li, Shicheng; Sun, Xiao; Miao, Shuncheng; Liu, Jia; Jiao, Wenjie

2017-11-01

Cigarette smoking is one of the greatest preventable risk factors for developing cancer, and most cases of lung squamous cell carcinoma (lung SCC) are associated with smoking. The pathogenesis mechanism of tumor progress is unclear. This study aimed to identify biomarkers in smoking-related lung cancer, including protein-coding gene, long noncoding RNA, and transcription factors. We selected and obtained messenger RNA microarray datasets and clinical data from the Gene Expression Omnibus database to identify gene expression altered by cigarette smoking. Integrated bioinformatic analysis was used to clarify biological functions of the identified genes, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, the construction of a protein-protein interaction network, transcription factor, and statistical analyses. Subsequent quantitative real-time PCR was utilized to verify these bioinformatic analyses. Five hundred and ninety-eight differentially expressed genes and 21 long noncoding RNA were identified in smoking-related lung SCC. GO and KEGG pathway analysis showed that identified genes were enriched in the cancer-related functions and pathways. The protein-protein interaction network revealed seven hub genes identified in lung SCC. Several transcription factors and their binding sites were predicted. The results of real-time quantitative PCR revealed that AURKA and BIRC5 were significantly upregulated and LINC00094 was downregulated in the tumor tissues of smoking patients. Further statistical analysis indicated that dysregulation of AURKA, BIRC5, and LINC00094 indicated poor prognosis in lung SCC. Protein-coding genes AURKA, BIRC5, and LINC00094 could be biomarkers or therapeutic targets for smoking-related lung SCC. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Occurrence of occult CSF leaks during standard FESS procedures.

PubMed

Bucher, S; Kugler, A; Probst, E; Epprecht, L; Stadler, R S; Holzmann, D; Soyka, M B

2018-03-18

To determine the incidence of occult cerebrospinal fluid leaks (CSF) after functional endoscopic sinus surgery (FESS) and to evaluate the diagnostic performance of beta2-transferrin in blood-contaminated conditions. Prospective cohort study. An analysis of 57 intraoperative samples using hydrogel 6 beta2-transferrin assay after FESS was undertaken. In case of CSF positive samples and continuing rhinorrhea, reanalysis after more than 1 year was conducted. In-vivo analysis of a primary spontaneous CSF leak sample took place to verify difficulties in detecting beta2-transferrin in blood-contaminated settings. Own titrations were performed to evaluate detection limits of CSF by beta2-transferrin and beta-trace protein assays in these settings. An incidence of 13% for occult CSF leaks after FESS was found. In blood-contaminated conditions, routine beta2-transferrin assays showed low sensitivity. In over 1 year follow-up, all samples were negative for CSF and none of them developed clinical relevant CSF leaks or meningitis. Occult and clinically irrelevant CSF leaks do occur in a significant proportion of patients during and shortly after FESS. Intra- and postoperatively, routine beta2-transferrin assays show low sensitivity. They should not be used in these settings. The clinical course of patients with occult CSF leaks indicated possibility of an uneventful follow-up.

Identification of urine protein biomarkers with the potential for early detection of lung cancer.

PubMed

Zhang, Hongjuan; Cao, Jing; Li, Lin; Liu, Yanbin; Zhao, Hong; Li, Nan; Li, Bo; Zhang, Aiqun; Huang, Huanwei; Chen, She; Dong, Mengqiu; Yu, Lei; Zhang, Jian; Chen, Liang

2015-07-02

Lung cancer is the leading cause of cancer-related deaths and has an overall 5-year survival rate lower than 15%. Large-scale clinical trials have demonstrated a significant relative reduction in mortality in high-risk individuals with low-dose computed tomography screening. However, biomarkers capable of identifying the most at-risk population and detecting lung cancer before it becomes clinically apparent are urgently needed in the clinic. Here, we report the identification of urine biomarkers capable of detecting lung cancer. Using the well-characterized inducible Kras (G12D) mouse model of lung cancer, we identified alterations in the urine proteome in tumor-bearing mice compared with sibling controls. Marked differences at the proteomic level were also detected between the urine of patients and that of healthy population controls. Importantly, we identified 7 proteins commonly found to be significantly up-regulated in both tumor-bearing mice and patients. In an independent cohort, we showed that 2 of the 7 proteins were up-regulated in urine samples from lung cancer patients but not in those from controls. The kinetics of these proteins correlated with the disease state in the mouse model. These tumor biomarkers could potentially aid in the early detection of lung cancer.

The use of a water seal to manage air leaks after a pulmonary lobectomy: a retrospective study.

PubMed

Okamoto, Junichi; Okamoto, Tatsuro; Fukuyama, Yasuro; Ushijima, Chie; Yamaguchi, Masafumi; Ichinose, Yukito

2006-08-01

The methods for managing chest drainage tubes during the postoperative period differ among thoracic surgeons and, as a result, the optimal method remains controversial. We reviewed 170 consecutive patients undergoing a pulmonary lobectomy for either primary lung cancer or metastatic lung cancer from January 1998 to December 2002. After the operation, the chest drainage tube was placed on a suction pump with a negative pressure of -10 cmH(2)O in 120 patients before 2001, while such drainage tubes were kept on water seal in 47 cases mainly since 2001. Regarding the preoperative and postoperative variables, postoperative air leak as well as the video-assisted thoracic surgery (VATS) procedure were more frequently observed in the water seal group than in the suction group (p=0.01580, p<0.001, respectively). In comparing these different populations, each Kaplan-Meier curve, which presented the duration of the postoperative air leak seemed to be similar between the two methods. These observations suggest that applying chest tubes on water seal seems to be an effective method for preventing postoperative air leak in clinical practice. However, a prospective randomized trial using a larger series of patients is warranted for this subject.

Fluid leak indicator

NASA Technical Reports Server (NTRS)

Anderson, G. E.; Loo, S. (Inventor)

1985-01-01

A fluid leak indicator for detecting and indicating leaks in visually inaccessible fluid tubing joints, such as those obstructed by insulation includes a bag system and a wicking system surrounding or wrapping the joints under the visual obstructing material. Leaking fluid is collected in the bag or on the wicking material where it is conducted along the wicking material to a visily accessible capturing transparent indicator bulb for providing a visual indication of the leak without requiring a chemical change in the capturing indicator bulb.

γδ T cells protect against LPS-induced lung injury

PubMed Central

Wehrmann, Fabian; Lavelle, James C.; Collins, Colm B.; Tinega, Alex N.; Thurman, Joshua M.; Burnham, Ellen L.; Simonian, Philip L.

2016-01-01

γδ T lymphocytes are a unique T cell population with important anti-inflammatory capabilities. Their role in acute lung injury, however, is poorly understood but may provide significant insight into lung-protective mechanisms occurring after injury. In a murine model of lung injury, wild-type C57BL/6 and TCRδ−/− mice were exposed to Escherichia coli LPS, followed by analysis of γδ T cell and macrophage subsets. In the absence of γδ T cells, TCRδ−/− mice developed increased inflammation and alveolar-capillary leak compared with wild-type C57BL/6 mice after LPS exposure that correlated with expansion of distinct macrophage populations. Classically activated M1 macrophages were increased in the lung of TCRδ−/− mice at d 1, 4, and 7 after LPS exposure that peaked at d 4 and persisted at d 7 compared with wild-type animals. In response to LPS, Vγ1 and Vγ7 γδ T cells were expanded in the lung and expressed IL-4. Coculture experiments showed decreased expression of TNF-α by resident alveolar macrophages in the presence of γδ T cells that was reversed in the presence of an anti-IL-4-blocking antibody. Treatment of mice with rIL4 resulted in reduced numbers of M1 macrophages, inflammation, and alveolar-capillary leak. Therefore, one mechanism by which Vγ1 and Vγ7 γδ T cells protect against LPS-induced lung injury is through IL-4 expression, which decreases TNF-α production by resident alveolar macrophages, thus reducing accumulation of M1 macrophages, inflammation, and alveolar-capillary leak. PMID:26428678

E3 ubiquitin ligase RFWD2 controls lung branching through protein-level regulation of ETV transcription factors.

PubMed

Zhang, Yan; Yokoyama, Shigetoshi; Herriges, John C; Zhang, Zhen; Young, Randee E; Verheyden, Jamie M; Sun, Xin

2016-07-05

The mammalian lung is an elaborate branching organ, and it forms following a highly stereotypical morphogenesis program. It is well established that precise control at the transcript level is a key genetic underpinning of lung branching. In comparison, little is known about how regulation at the protein level may play a role. Ring finger and WD domain 2 (RFWD2, also termed COP1) is an E3 ubiquitin ligase that modifies specific target proteins, priming their degradation via the ubiquitin proteasome system. RFWD2 is known to function in the adult in pathogenic processes such as tumorigenesis. Here, we show that prenatal inactivation of Rfwd2 gene in the lung epithelium led to a striking halt in branching morphogenesis shortly after secondary branch formation. This defect is accompanied by distalization of the lung epithelium while growth and cellular differentiation still occurred. In the mutant lung, two E26 transformation-specific (ETS) transcription factors essential for normal lung branching, ETS translocation variant 4 (ETV4) and ETV5, were up-regulated at the protein level, but not at the transcript level. Introduction of Etv loss-of-function alleles into the Rfwd2 mutant background attenuated the branching phenotype, suggesting that RFWD2 functions, at least in part, through degrading ETV proteins. Because a number of E3 ligases are known to target factors important for lung development, our findings provide a preview of protein-level regulatory network essential for lung branching morphogenesis.

Distribution of surfactant protein A in rat lung.

PubMed

Doyle, I R; Barr, H A; Nicholas, T E

1994-10-01

Although surfactant protein A (SP-A) is an integral component of alveolar surfactant, its relative abundance in lamellar bodies, regarded as the intracellular storage organelles for surfactant, remains contentious. We have previously shown that lamellar bodies, isolated from rat lung by upward flotation on a sucrose gradient, can be subfractionated into classic-appearing lamellar bodies (Lb-A) and a vesicular fraction (Lb-B), which we have speculated may be a second release form of surfactant. In the present study, we have used two-dimensional protein electrophoresis and immunochemical analysis to clarify the origin and the composition of these two subcellular fractions. In addition, we have examined the hypothesis that the secretion of SP-A and surfactant phospholipids occurs by independent pathways by examining the distribution of SP-A, total protein, and disaturated phospholipids (DSP) in the tubular myelin-rich (Alv-1) and tubular myelin-poor (Alv-2) fractions separated from lavaged material and in Lb-A and Lb-B isolated from both lung homogenate and purified alveolar type II cells. Our findings indicate that Lb-B is derived from type II cells, although they do not indicate whether it is a secretory form of surfactant, a reuptake vesicle, or a mixture of both. We found that the lung has a large tissue pool of immunoreactive SP-A. The %SP-A/DSP of total lamellar bodies isolated from type II cells was 0.96 +/- 0.1 (mean +/- SE), intermediate between that in Lb-A (1.67 +/- 0.13) and in Lb-B (0.65 +/- 0.04). In contrast, the %SP-A/DSP was 11.16 +/- 0.84 in whole lung homogenate and 13.14 +/- 1.71 in whole type II cells. In the alveolar compartment, the %SP-A/DSP was 17.38 +/- 3.40 in Alv-1, 6.34 +/- 0.31 in Alv-2, and 10.49 +/- 1.43 in macrophages, values an order of magnitude greater than found with the lamellar bodies. Our results indicate that only a relatively small portion of alveolar SP-A is derived from lamellar bodies, and we suggest that secretion of SP

β-Adrenergic induced SR Ca2+ leak is mediated by an Epac-NOS pathway.

PubMed

Pereira, Laëtitia; Bare, Dan J; Galice, Samuel; Shannon, Thomas R; Bers, Donald M

2017-07-01

Cardiac β-adrenergic receptors (β-AR) and Ca 2+ -Calmodulin dependent protein kinase (CaMKII) regulate both physiological and pathophysiological Ca 2+ signaling. Elevated diastolic Ca 2+ leak from the sarcoplasmic reticulum (SR) contributes to contractile dysfunction in heart failure and to arrhythmogenesis. β-AR activation is known to increase SR Ca 2+ leak via CaMKII-dependent phosphorylation of the ryanodine receptor. Two independent and reportedly parallel pathways have been implicated in this β-AR-CaMKII cascade, one involving exchange protein directly activated by cAMP (Epac2) and another involving nitric oxide synthase 1 (NOS1). Here we tested whether Epac and NOS function in a single series pathway to increase β-AR induced and CaMKII-dependent SR Ca 2+ leak. Leak was measured as both Ca 2+ spark frequency and tetracaine-induced shifts in SR Ca 2+ , in mouse and rabbit ventricular myocytes. Direct Epac activation by 8-CPT (8-(4-chlorophenylthio)-2'-O-methyl-cAMP) mimicked β-AR-induced SR Ca 2+ leak, and both were blocked by NOS inhibition. The same was true for myocyte CaMKII activation (assessed via a FRET-based reporter) and ryanodine receptor phosphorylation. Inhibitor and phosphorylation studies also implicated phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) downstream of Epac and above NOS activation in this pathway. We conclude that these two independently characterized parallel pathways function mainly via a single series arrangement (β-AR-cAMP-Epac-PI3K-Akt-NOS1-CaMKII) to mediate increased SR Ca 2+ leak. Thus, for β-AR activation the cAMP-PKA branch effects inotropy and lusitropy (by effects on Ca 2+ current and SR Ca 2+ -ATPase), this cAMP-Epac-NOS pathway increases pathological diastolic SR Ca 2+ leak. This pathway distinction may allow novel SR Ca 2+ leak therapeutic targeting in treatment of arrhythmias in heart failure that spare the inotropic and lusitropic effects of the PKA branch. Copyright © 2017 Elsevier Ltd. All

Fluid leak indicator

NASA Technical Reports Server (NTRS)

Anderson, George E. (Inventor); Loo, Shu (Inventor)

1989-01-01

A fluid leak indicator (30) for detecting and indicating leaks in visually inaccessible fluid tubing joints (20, 21), such as those obstructed by insulation (24), includes a bag system (25) and a wicking system (30) surrounding or wrapping the joints (20, 21) under the visual obstructing material (24). Leaking fluid is collected in the bag (25) or on the wicking material (34) where it is conducted along the wicking material (34) to a visibly accessible capturing transparent indicator bulb (35) for providing a visual indication of the leak without requiring a chemical change in the capturing indicator bulb (35).

Effects of Pharmacologic Intervention on Oxygenation, Lung Water and Protein Leak in the Pseudomonas ARDS Porcine Model

DTIC Science & Technology

1989-07-01

model indicate that Pseudomonas primes these cells to produce superoxide anion at a much higher rate post-injury than pre-injury, thus implicating...as oxygen free radicals, the neutrophils, platelets, monocytes and lymphocytes can release a number of other factors which have an affect on...mediator in the lung injury seen with endotoxin induced ARDS is the inappropriately named platelet activating factor (PAF). This phospholipid, which is

Detecting Methane Leaks

NASA Technical Reports Server (NTRS)

Grant, W. B.; Hinkley, E. D.

1984-01-01

Remote sensor uses laser radiation backscattered from natural targets. He/Ne Laser System for remote scanning of Methane leaks employs topographic target to scatter light to receiver near laser transmitter. Apparatus powered by 1.5kW generator transported to field sites and pointed at suspected methane leaks. Used for remote detection of natural-gas leaks and locating methane emissions in landfill sites.

Diagnostic value of protein chips constructed by lung-cancer-associated markers selected by the T7 phage display library.

PubMed

Li, Hong-Mei; Guo, Kang; Yu, Zhuang; Feng, Rui; Xu, Ping

2015-07-01

Traditional diagnostic technology with tumor biomarkers is inefficient, expensive and requires a large number of serum samples. The purpose of this study was to construct human lung cancer protein chips with new lung cancer biomarkers screened by the T7-phage display library, and improve the early diagnosis rate of lung cancer. A T7-phage cDNA display library was constructed of fresh samples from 30 lung cancer patients. With biopanning and high-throughput screening, we gained the immunogenic phage clones from the cDNA library. The insert of selected phage was blasted at GeneBank for alignment to find the exact or the most similar known genes. Protein chips were then constructed and used to assay their expression level in lung cancer serum from 217 cases of lung cancer groups:80 cases of benign lung disease and 220 healthy controls. After four rounds of Biopanning and two rounds of enzyme-linked immunosorbent assay, 12 phage monoclonal samples were selected from 2880 phage monoclonal samples. After blasting at GeneBank, six similar genes were used to construct diagnostic protein chips. The protein chips were then used to assay expression level in lung cancer serum. The expression level of six genes in lung cancer groups was significantly higher than those in the other two groups (P < 0.05). In this study, we successfully constructed diagnostic protein chips with biomarkers selected from the lung cancer T7-phage cDNA library, which can be used for the early screening of lung cancer patients.

Ontogeny and nutritional programming of mitochondrial proteins in the ovine kidney, liver and lung.

PubMed

Yakubu, D P; Mostyn, A; Hyatt, M A; Kurlak, L O; Budge, H; Stephenson, T; Symonds, M E

2007-12-01

This study investigated the developmental and nutritional programming of two important mitochondrial proteins, namely voltage-dependent anion channel (VDAC) and cytochrome c, in the sheep kidney, liver and lung. The effect of maternal nutrient restriction between early and mid-gestation (i.e. 28- to 80-day gestation, the period of maximal placental growth) on the abundance of these proteins was also examined in fetal and juvenile offspring. Fetuses were sampled at 80 and 140 days of gestation (term approximately 147 days), and postnatal animals at 1 and 30 days and 6 months of age. The abundance of VDAC peaked at 140 days of gestation in the lung, compared with 1 day after birth in the kidney and liver, whereas cytochrome c abundance was greatest at 140 days of gestation in the liver, 1 day after birth in the kidney and 6 months of age in lungs. This differential ontogeny in mitochondrial protein abundance between tissues was accompanied with very different tissue-specific responses to changes in maternal food intake. In the liver, maternal nutrient restriction only increased mitochondrial protein abundance at 80 days of gestation, compared with no effect in the kidney. In contrast, in the lung mitochondrial protein, abundance was raised near to term, whereas VDAC abundance was decreased by 6 months of age. These findings demonstrate the tissue-specific nature of mitochondrial protein development that reflects differences in functional adaptation after birth. The divergence in mitochondrial response between tissues to maternal nutrient restriction early in pregnancy further reflects these differential ontogenies.

Single-Shell Tanks Leak Integrity Elements/ SX Farm Leak Causes and Locations - 12127

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

Girardot, Crystal; Harlow, Don; Venetz, Theodore

2012-07-01

Washington River Protection Solutions, LLC (WRPS) developed an enhanced single-shell tank (SST) integrity project in 2009. An expert panel on SST integrity was created to provide recommendations supporting the development of the project. One primary recommendation was to expand the leak assessment reports (substitute report or LD-1) to include leak causes and locations. The recommendation has been included in the M-045-91F Hanford Federal Facility Agreement and Consent Order (Tri-Party Agreement) as one of four targets relating to SST leak integrity. The 241-SX Farm (SX Farm) tanks with leak losses were addressed on an individual tank basis as part of LD-1.more » Currently, 8 out of 23 SSTs that have been reported to having a liner leak are located in SX Farm. This percentage was the highest compared to other tank farms which is why SX Farm was analyzed first. The SX Farm is comprised of fifteen SSTs built 1953-1954. The tanks are arranged in rows of three tanks each, forming a cascade. Each of the SX Farm tanks has a nominal 1-million-gal storage capacity. Of the fifteen tanks in SX Farm, an assessment reported leak losses for the following tanks: 241-SX-107, 241-SX-108, 241-SX-109, 241-SX- 111, 241-SX-112, 241-SX-113, 241-SX-114 and 241-SX-115. The method used to identify leak location consisted of reviewing in-tank and ex-tank leak detection information. This provided the basic data identifying where and when the first leaks were detected. In-tank leak detection consisted of liquid level measurement that can be augmented with photographs which can provide an indication of the vertical leak location on the sidewall. Ex-tank leak detection for the leaking tanks consisted of soil radiation data from laterals and dry-wells near the tank. The in-tank and ex-tank leak detection can provide an indication of the possible leak location radially around and under the tank. Potential leak causes were determined using in-tank and ex-tank information that is not directly

SINGLE-SHELL TANKS LEAK INTEGRITY ELEMENTS/SX FARM LEAK CAUSES AND LOCATIONS - 12127

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

VENETZ TJ; WASHENFELDER D; JOHNSON J

2012-01-25

Washington River Protection Solutions, LLC (WRPS) developed an enhanced single-shell tank (SST) integrity project in 2009. An expert panel on SST integrity was created to provide recommendations supporting the development of the project. One primary recommendation was to expand the leak assessment reports (substitute report or LD-1) to include leak causes and locations. The recommendation has been included in the M-045-9IF Hanford Federal Facility Agreement and Consent Order (Tri-Party Agreement) as one of four targets relating to SST leak integrity. The 241-SX Farm (SX Farm) tanks with leak losses were addressed on an individual tank basis as part of LD-1.more » Currently, 8 out of 23 SSTs that have been reported to having a liner leak are located in SX Farm. This percentage was the highest compared to other tank farms which is why SX Farm was analyzed first. The SX Farm is comprised of fifteen SSTs built 1953-1954. The tanks are arranged in rows of three tanks each, forming a cascade. Each of the SX Farm tanks has a nominal I-million-gal storage capacity. Of the fifteen tanks in SX Farm, an assessment reported leak losses for the following tanks: 241-SX-107, 241-SX-108, 241-SX-109, 241-SX-111, 241-SX-112, 241-SX-113, 241-SX-114 and 241-SX-115. The method used to identify leak location consisted of reviewing in-tank and ex-tank leak detection information. This provided the basic data identifying where and when the first leaks were detected. In-tank leak detection consisted of liquid level measurement that can be augmented with photographs which can provide an indication of the vertical leak location on the sidewall. Ex-tank leak detection for the leaking tanks consisted of soil radiation data from laterals and drywells near the tank. The in-tank and ex-tank leak detection can provide an indication of the possible leak location radially around and under the tank. Potential leak causes were determined using in-tank and ex-tank information that is not directly

Mapping urban pipeline leaks: methane leaks across Boston.

PubMed

Phillips, Nathan G; Ackley, Robert; Crosson, Eric R; Down, Adrian; Hutyra, Lucy R; Brondfield, Max; Karr, Jonathan D; Zhao, Kaiguang; Jackson, Robert B

2013-02-01

Natural gas is the largest source of anthropogenic emissions of methane (CH(4)) in the United States. To assess pipeline emissions across a major city, we mapped CH(4) leaks across all 785 road miles in the city of Boston using a cavity-ring-down mobile CH(4) analyzer. We identified 3356 CH(4) leaks with concentrations exceeding up to 15 times the global background level. Separately, we measured δ(13)CH(4) isotopic signatures from a subset of these leaks. The δ(13)CH(4) signatures (mean = -42.8‰ ± 1.3‰ s.e.; n = 32) strongly indicate a fossil fuel source rather than a biogenic source for most of the leaks; natural gas sampled across the city had average δ(13)CH(4) values of -36.8‰ (± 0.7‰ s.e., n = 10), whereas CH(4) collected from landfill sites, wetlands, and sewer systems had δ(13)CH(4) signatures ~20‰ lighter (μ = -57.8‰, ± 1.6‰ s.e., n = 8). Repairing leaky natural gas distribution systems will reduce greenhouse gas emissions, increase consumer health and safety, and save money. Copyright © 2012 Elsevier Ltd. All rights reserved.

The bisphosphonate zoledronic acid effectively targets lung cancer cells by inhibition of protein prenylation

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

Xie, Fan; Li, Pengcheng; Gong, Jianhua

Aberrant activation of oncoproteins such as members of the Ras family is common in human lung cancers. The proper function of Ras largely depends on a post-translational modification termed prenylation. Bisphosphonates have been shown to inhibit prenylation in cancer cells. In this study, we show that zoledronic acid, a third generation bisphosphonate, is effective in targeting lung cancer cells. This is achieved by the induction of apoptosis and inhibition of proliferation, through suppressing the activation of downstream Ras and EGFR signalling by zoledronic acid. The combination of zoledronic acid and paclitaxel or cisplatin (commonly used chemotherapeutic drugs for lung cancer)more » augmented the activity of either drug alone in in vitro lung cancer cellular system and in vivo lung xenograft mouse model. Importantly, zoledronic acid inhibits protein prenylation as shown by the increased levels of unprenylated Ras and Rap1A. In addition, the effects of zoledronic acid were reversed in the presence of geranylgeraniol and farnesol, further confirming that mechanism of zoledroinc acid's action in lung cancer cells is through prenylation inhibition. Since zoledronic acid is already available for clinic use, these results suggest that it may be an effective addition to the armamentarium of drugs for the treatment of lung cancer. - Highlights: • Zoledronic acid (ZA) is effectively against lung cancer cells in vitro and in vivo. • ZA acts on lung cancer cells through inhibition of protein prenylation. • ZA suppresses global downstream phosphorylation of Ras signalling. • ZA enhances the effects of chemotherapeutic drugs in lung cancer cells.« less

Analysis of the Plasma Proteome in COPD: Novel Low Abundance Proteins Reflect the Severity of Lung Remodeling

PubMed Central

Merali, Salim; Barrero, Carlos A.; Bowler, Russell P.; Chen, Diane Er; Criner, Gerard; Braverman, Alan; Litwin, Samuel; Yeung, Anthony; Kelsen, Steven G.

2015-01-01

The search for COPD biomarkers has largely employed a targeted approach that focuses on plasma proteins involved in the systemic inflammatory response and in lung injury and repair. This proof of concept study was designed to test the idea that an open, unbiased, in-depth proteomics approach could identify novel, low abundance plasma proteins i.e., ng/mL concentration, which could serve as potential biomarkers. Differentially expressed proteins were identified in a discovery group with severe COPD (FEV1 <45% predicted; n = 10). Subjects with normal lung function matched for age, sex, ethnicity and smoking history served as controls (n = 10). Pooled plasma from each group was exhaustively immunodepleted of abundant proteins, d separated by 1-D gel electrophoresis and extensively fractionated prior to LC-tandem mass spectroscopy (GeLC-MS). Thirty one differentially expressed proteins were identified in the discovery group including markers of lung defense against oxidant stress, alveolar macrophage activation, and lung tissue injury and repair. Four of the 31 proteins (i.e., GRP78, soluble CD163, IL1AP and MSPT9) were measured in a separate verification group of 80 subjects with varying COPD severity by immunoassay. All 4 were significantly altered in COPD and 2 (GRP78 and soluble CD163) correlated with both FEV1 and the extent of emphysema. In-depth, plasma proteomic analysis identified a group of novel, differentially expressed, low abundance proteins that reflect known pathogenic mechanisms and the severity of lung remodeling in COPD. These proteins may also prove useful as COPD biomarkers. PMID:24111704

Analysis of the plasma proteome in COPD: Novel low abundance proteins reflect the severity of lung remodeling.

PubMed

Merali, Salim; Barrero, Carlos A; Bowler, Russell P; Chen, Diane Er; Criner, Gerard; Braverman, Alan; Litwin, Samuel; Yeung, Anthony; Kelsen, Steven G

2014-04-01

The search for COPD biomarkers has largely employed a targeted approach that focuses on plasma proteins involved in the systemic inflammatory response and in lung injury and repair. This proof of concept study was designed to test the idea that an open, unbiased, in-depth proteomics approach could identify novel, low abundance plasma proteins i.e., ng/mL concentration, which could serve as potential biomarkers. Differentially expressed proteins were identified in a discovery group with severe COPD (FEV1 <45% predicted; n = 10). Subjects with normal lung function matched for age, sex, ethnicity and smoking history served as controls (n = 10). Pooled plasma from each group was exhaustively immunodepleted of abundant proteins, d separated by 1-D gel electrophoresis and extensively fractionated prior to LC-tandem mass spectroscopy (GeLC-MS). Thirty one differentially expressed proteins were identified in the discovery group including markers of lung defense against oxidant stress, alveolar macrophage activation, and lung tissue injury and repair. Four of the 31 proteins (i.e., GRP78, soluble CD163, IL1AP and MSPT9) were measured in a separate verification group of 80 subjects with varying COPD severity by immunoassay. All 4 were significantly altered in COPD and 2 (GRP78 and soluble CD163) correlated with both FEV1 and the extent of emphysema. In-depth, plasma proteomic analysis identified a group of novel, differentially expressed, low abundance proteins that reflect known pathogenic mechanisms and the severity of lung remodeling in COPD. These proteins may also prove useful as COPD biomarkers.

A multi-center evaluation of a powered surgical stapler in video-assisted thoracoscopic lung resection procedures in China.

PubMed

Qiu, Bin; Yan, Wanpu; Chen, Keneng; Fu, Xiangning; Hu, Jian; Gao, Shugeng; Knippenberg, Susan; Schwiers, Michael; Kassis, Edmund; Yang, Tengfei

2016-05-01

Lung cancer is one of the most prevalent malignancies worldwide. The number of anatomic lung cancer resections performed via video-assisted thoracoscopic surgery (VATS) is growing rapidly. Staplers are widely used in VATS procedures, but there is limited clinical data regarding how they might affect performance and postoperative outcomes, including air leak. This clinical trial assessed the use of a powered stapler in VATS lung resection, with a primary study endpoint being occurrence and duration of air leak and prolonged air leak (PAL). Data was collected from a single arm, multi-center study in Chinese patients receiving VATS wedge resection or lobectomy. Intra-operative data included surgery duration; cartridge selection for ligation/transection of bronchus, major vessels, and lung parenchyma; staple line interventions; blood loss; and device usage. Post-operative data included air leak assessments, chest tube duration, length of hospital stay, and adverse events (AEs). A total of 94 procedures across four institutions in China were included in the final analysis: 15 wedge resections, 74 lobectomies, and five wedge resections followed by lobectomies. Post-operative air leak occurred in five (5.3%) patients who had lobectomy procedures, with PAL in one (1.1%) patient. Sites were generally consistent relative to cartridge use by tissue type. The incidence of stapler firings requiring surgical interventions was seven out of 550 (1.3%). Surgeons participating in the study were satisfied with the articulation and overall usability of the stapler. The powered staplers make the VATS procedure easier for the surgeons and have achieved intra- and post-operative patient outcomes comparable to those previously reported.

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.

Mitigated Transfer Line Leaks that Result in Surface Pools and Spray Leaks into Pits

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

HEY, B.E.

This analysis provides radiological and toxicological consequence calculations for postulated mitigated leaks during transfers of six waste compositions. Leaks in Cleanout Boxes equipped with supplemental covers and leaks in pits are analyzed.

Leak testing in parenteral packaging: establishment of direct correlation between helium leak rate measurements and microbial ingress for two different leak types.

PubMed

Morrical, Bradley D; Goverde, Marcel; Grausse, Jean; Gerwig, Tanja; Vorgrimler, Lothar; Morgen, Rachel; Büttiker, Jean-Pierre

2007-01-01

A direct test method using helium leak detection was developed to determine microbial ingress in parenteral vial/rubber closure systems. The purpose of this study was to establish a direct correlation between the helium leak rate and the presence of ingress when vials were submersed under pressure in a broth of bacteria. Results were obtained for two different types of leaks: microholes that have been laser-drilled into thin metal plates, and thin copper wire that was placed between the rubber closure and the glass vial's sealing surface. The results from the microholes showed that the helium leak rate was a function of the square of the hole diameter and fit well with theoretical calculations. The relationship with the wire gave a far more complex dependence and was not modeled theoretically. Comparison with the microbial challenge showed that for microholes a lower size limit was found to be 2 microm with a corresponding leak rate of 1.4 x 10(-3) mbarl/s. For the fine wire experiment the lower limit was 15-microm wire and a corresponding leak rate of 1.3 x 10(-5) mbarl/s. From these tests a safe, lower limit, leak rate was established.

The potential of targeting Ras proteins in lung cancer.

PubMed

McCormick, Frank

2015-04-01

The Ras pathway is a major driver in lung adenocarcinoma: over 75% of all cases harbor mutations that activate this pathway. While spectacular clinical successes have been achieved by targeting activated receptor tyrosine kinases in this pathway, little, if any, significant progress has been achieved targeting Ras proteins themselves or cancers driven by oncogenic Ras mutants. New approaches to drug discovery, new insights into Ras function, new ways of attacking undruggable proteins through RNA interference and new ways of harnessing the immune system could change this landscape in the relatively near future.

Routine intraoperative leak testing for sleeve gastrectomy: is the leak test full of hot air?

PubMed

Bingham, Jason; Lallemand, Michael; Barron, Morgan; Kuckelman, John; Carter, Preston; Blair, Kelly; Martin, Matthew

2016-05-01

Staple line leak after sleeve gastrectomy (SG) is a rare but dreaded complication with a reported incidence of 0% to 8%. Many surgeons routinely test the staple line with an intraoperative leak test (IOLT), but there is little evidence to validate this practice. In fact, there is a theoretical concern that the leak test may weaken the staple line and increase the risk of a postop leak. Retrospective review of all SGs performed over a 7-year period was conducted. Cases were grouped by whether an IOLT was performed, and compared for the incidence of postop staple line leaks. The ability of the IOLT for identifying a staple line defect and for predicting a postoperative leak was analyzed. Five hundred forty-two SGs were performed between 2007 and 2014. Thirteen patients (2.4%) developed a postop staple line leak. The majority of patients (n = 494, 91%) received an IOLT, including all 13 patients (100%) who developed a subsequent clinical leak. There were no (0%) positive IOLTs and no additional interventions were performed based on the IOLT. The IOLT sensitivity and positive predictive value were both 0%. There was a trend, although not significant, to increase leak rates when a routine IOLT was performed vs no routine IOLT (2.6% vs 0%, P = .6). The performance of routine IOLT after SG provided no actionable information, and was negative in all patients who developed a postoperative leak. The routine use of an IOLT did not reduce the incidence of postop leak, and in fact was associated with a higher leak rate after SG. Published by Elsevier Inc.

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

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

Wang, Chaoyun; Huang, Qingxian; Wang, Chunhua

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

Integrating Structure to Protein-Protein Interaction Networks That Drive Metastasis to Brain and Lung in Breast Cancer

PubMed Central

Engin, H. Billur; Guney, Emre; Keskin, Ozlem; Oliva, Baldo; Gursoy, Attila

2013-01-01

Blocking specific protein interactions can lead to human diseases. Accordingly, protein interactions and the structural knowledge on interacting surfaces of proteins (interfaces) have an important role in predicting the genotype-phenotype relationship. We have built the phenotype specific sub-networks of protein-protein interactions (PPIs) involving the relevant genes responsible for lung and brain metastasis from primary tumor in breast cancer. First, we selected the PPIs most relevant to metastasis causing genes (seed genes), by using the “guilt-by-association” principle. Then, we modeled structures of the interactions whose complex forms are not available in Protein Databank (PDB). Finally, we mapped mutations to interface structures (real and modeled), in order to spot the interactions that might be manipulated by these mutations. Functional analyses performed on these sub-networks revealed the potential relationship between immune system-infectious diseases and lung metastasis progression, but this connection was not observed significantly in the brain metastasis. Besides, structural analyses showed that some PPI interfaces in both metastasis sub-networks are originating from microbial proteins, which in turn were mostly related with cell adhesion. Cell adhesion is a key mechanism in metastasis, therefore these PPIs may be involved in similar molecular pathways that are shared by infectious disease and metastasis. Finally, by mapping the mutations and amino acid variations on the interface regions of the proteins in the metastasis sub-networks we found evidence for some mutations to be involved in the mechanisms differentiating the type of the metastasis. PMID:24278371

Brachyury Protein: A Potential Target in Lung Cancer Therapy | Center for Cancer Research

Cancer.gov

Previous research has shown that Brachyury protein plays a role in initiating the processes that lead to the growth and spread of cancer. Now CCR scientists have for the first time demonstrated the expression of Brachyury protein in lung cancer tumors, as well as a correlation between the overexpression of Brachyury protein and drug resistance.

Leak detection aid

DOEpatents

Steeper, Timothy J.

1989-01-01

A leak detection apparatus and method for detecting leaks across an O-ring sealing a flanged surface to a mating surface is an improvement in a flanged surface comprising a shallow groove following O-ring in communication with an entrance and exit port intersecting the shallow groove for injecting and withdrawing, respectively, a leak detection fluid, such as helium. A small quantity of helium injected into the entrance port will flow to the shallow groove, past the O-ring and to the exit port.

Leak detection aid

DOEpatents

Steeper, T.J.

1989-12-26

A leak detection apparatus and method for detecting leaks across an O-ring sealing a flanged surface to a mating surface is an improvement in a flanged surface comprising a shallow groove following O-ring in communication with an entrance and exit port intersecting the shallow groove for injecting and withdrawing, respectively, a leak detection fluid, such as helium. A small quantity of helium injected into the entrance port will flow to the shallow groove, past the O-ring and to the exit port. 2 figs.

C-reactive protein for the early prediction of anastomotic leak after esophagectomy in both neoadjuvant and non-neoadjuvant therapy case: a propensity score matching analysis

PubMed Central

Park, Jae Kil; Moon, Seok Whan

2017-01-01

Background Anastomotic leak is one of most significant causes of mortality after esophagectomy. Therefore, it is clinically valuable to detect anastomotic leak early after esophagectomy in esophageal cancer. The purpose of this study is to investigate the associations between routine postoperative laboratory findings and anastomotic leak and to analyze the laboratory findings to find out an independent predictive marker for anastomotic leak. In addition, this study compares cases treated with neoadjuvant therapy (NT) and those without (non-NT). Methods We retrospectively assessed the medical records of 201 consecutive cases that met this study’s criteria from January 2009 to December 2016. All patients underwent curative and complete esophagectomy for intra-thoracic esophageal cancer. We compiled and analyzed routine laboratory findings from the day before surgery to the eighth postoperative day on a daily basis. Routine laboratory tests consisted of 26 separate tests, including complete blood cell counts, blood chemistries, as well as erythrocyte sedimentation rate and C-reactive protein (CRP). Barium esophagogram with chest computed tomography (CT) was performed on the seventh postoperative day to evaluate the presence of an anastomotic leak. Results A total of 45 of 201 patients underwent NT. Anastomotic leaks were found in 23 (11.4%) of 201 patients (8 patients in NT and 15 patients in non-NT). White blood cell (WBC) from the second postoperative day (P=0.031, P=0.006, P=0.007, P=0.007, P=0.041, and P=0.003, respectively) and CRP from the third postoperative day (P=0.012, P<0.001, P=0.014, P<0.001, P=0.001, and P=0.006, respectively) were associated with anastomotic leak in non-NT; however, only CRP on the third, fifth, sixth, and seventh postoperative days (P=0.041, P=0.037, P=0.002, and P=0.003, respectively) was associated with anastomotic leak in NT. The CRP level on the third postoperative day was a significant independent predictive marker of

C-reactive protein for the early prediction of anastomotic leak after esophagectomy in both neoadjuvant and non-neoadjuvant therapy case: a propensity score matching analysis.

PubMed

Park, Jae Kil; Kim, Jae Jun; Moon, Seok Whan

2017-10-01

Anastomotic leak is one of most significant causes of mortality after esophagectomy. Therefore, it is clinically valuable to detect anastomotic leak early after esophagectomy in esophageal cancer. The purpose of this study is to investigate the associations between routine postoperative laboratory findings and anastomotic leak and to analyze the laboratory findings to find out an independent predictive marker for anastomotic leak. In addition, this study compares cases treated with neoadjuvant therapy (NT) and those without (non-NT). We retrospectively assessed the medical records of 201 consecutive cases that met this study's criteria from January 2009 to December 2016. All patients underwent curative and complete esophagectomy for intra-thoracic esophageal cancer. We compiled and analyzed routine laboratory findings from the day before surgery to the eighth postoperative day on a daily basis. Routine laboratory tests consisted of 26 separate tests, including complete blood cell counts, blood chemistries, as well as erythrocyte sedimentation rate and C-reactive protein (CRP). Barium esophagogram with chest computed tomography (CT) was performed on the seventh postoperative day to evaluate the presence of an anastomotic leak. A total of 45 of 201 patients underwent NT. Anastomotic leaks were found in 23 (11.4%) of 201 patients (8 patients in NT and 15 patients in non-NT). White blood cell (WBC) from the second postoperative day (P=0.031, P=0.006, P=0.007, P=0.007, P=0.041, and P=0.003, respectively) and CRP from the third postoperative day (P=0.012, P<0.001, P=0.014, P<0.001, P=0.001, and P=0.006, respectively) were associated with anastomotic leak in non-NT; however, only CRP on the third, fifth, sixth, and seventh postoperative days (P=0.041, P=0.037, P=0.002, and P=0.003, respectively) was associated with anastomotic leak in NT. The CRP level on the third postoperative day was a significant independent predictive marker of anastomotic leak (P=0.041, odd ratio

A unique cell-surface protein phenotype distinguishes human small-cell from non-small-cell lung cancer

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

Baylin, S.B.; Gazdar, A.F.; Minna, J.D.

1982-08-01

Radioiodination (/sup 125/I) and two-dimensional polyacrylamide gel electrophoresis was used to determine that small-(oat) cell lung carcinoma (SCC)-a tumor with neuroedocrine features-possesses a surface protein pattern distinct from the other types of lung cancer cells (squamous, adeno-, and large-cell undifferentiated carcinoma). Twelve distinguishing proteins, 40 to 70 kilodaltons (kDal), characterized four separate lines of SCC; three of these, designated E (60 kDal; pI = 7.3), S (30 kDal; pI = 6.0), and U 57 kDal; pI = 5.6), may be unique SCC gene products and were identified only in (/sup 35/S)methionine labeling of SCC and not in non-SCC or humanmore » fibroblasts. Two lines of adeno-, one of squamous, and one of undifferentiated large-cell lung carcinoma exhibited similar surface protein patterns to one another. Nine distinguishing proteins (40 to 100 kDal) and at least five large proteins (>100 kDal) were unique to these lines. The surface protein phenotypes for SCC and non-SCC were distinct from those for human lymphoblastoid cells and fibroblasts. However, the neuroendocrine features of SCC were further substantiated because 6 of the 12 distinguishing SCC surface proteins, including E and U, were identified on human neuroblastoma cells. The proteins identified should (i) help define differentiation steps for normal and neoplastic bronchial epithelial cells, (ii) prove useful in better classifying lung cancers, and (iii) be instrumental in tracing formation of neuroendocrine cells.« less

Postoperative air leak grading is useful to predict prolonged air leak after pulmonary lobectomy.

PubMed

Oh, Sang Gi; Jung, Yochun; Jheon, Sanghoon; Choi, Yunhee; Yun, Ju Sik; Na, Kook Joo; Ahn, Byoung Hee

2017-01-23

Results of studies to predict prolonged air leak (PAL; air leak longer than 5 days) after pulmonary lobectomy have been inconsistent and are of limited use. We developed a new scale representing the amount of early postoperative air leak and determined its correlation with air leak duration and its potential as a predictor of PAL. We grade postoperative air leak using a 5-grade scale. All 779 lobectomies from January 2005 to December 2009 with available medical records were reviewed retrospectively. We devised six 'SUM' variables using air leak grades in the initial 72 h postoperatively. Excluding unrecorded cases and postoperative broncho-pleural fistulas, there were 720 lobectomies. PAL occurred in 135 cases (18.8%). Correlation analyses showed each SUM variable highly correlated with air leak duration, and the SUM 4to9 , which was the sum of six consecutive values of air leak grades for every 8 h record on postoperative days 2 and 3, was proved to be the most powerful predictor of PAL; PAL could be predicted with 75.7% and 77.7% positive and negative predictive value, respectively, when SUM 4to9  ≥ 16. When 4 predictors derived from multivariable logistic regression of perioperative variables were combined with SUM 4to9 , there was no significant increase in predictability compared with SUM 4to9 alone. This simple new method to predict PAL using SUM 4to9 showed that the amount of early postoperative air leak is the most powerful predictor of PAL, therefore, grading air leak after pulmonary lobectomy is a useful method to predict PAL.

Effect of protein leaking BK-F PMMA-based hemodialysis on plasma pentosidine levels.

PubMed

Tessitore, Nicola; Lapolla, Annunziata; Aricò, Nadia Concetta; Poli, Albino; Gammaro, Linda; Bassi, Antonella; Bedogna, Valeria; Corgnati, Angela; Reitano, Rachele; Fedele, Domenico; Lupo, Antonio

2004-01-01

Advanced glycation end-products (AGEs) are now considered to contribute to the middle molecule toxicity of uremia and, because they are not cleared by conventional low-flux hemodialysis, alternative strategies are needed to improve their removal. In a prospective cross-over trial involving 18 adult chronic hemodialysis subjects, we evaluated the intradialytic removal and the long-term effect on predialysis levels of Protein-bound (PBPe) and Free (FPe) pentosidine by high-pore, protein-leaking BK-F Polymethylmethacrylate-based hemodialysis (BK-F-HD), by comparing it to hemodialysis using low-flux dialyzers (LF-HD). A single BK-F-HD session removed more PBPe, but not FPe, than LF-HD. Long-term BK-F-HD was associated with a significant decrease in pre-dialysis PBPe, FPe, and albumin (17.7 +/- 20.8, 25.3 +/- 17.3 and 8.0 +/- 3.3%, p<0.01) and no change in body mass index and protein catabolic rate, compared to LF-HD. Multiple stepwise regression analysis identified C-reactive Protein (CRP) (standardized beta coefficient=-0.629), pre-dialysis levels in LF-HD (beta=0.452) and dialysis vintage (beta=0.428) as significant determinants of BK-F-induced changes in predialysis PBPe, and predialysis FPe and PBPe levels in LF-HD as significant determinants of BK-F-induced changes in predialysis FPe (beta=0.720 and 0.286, respectively). Our study shows that long-term standard diffusive hemodialysis with BK-F membrane reduces predialysis PBPe and FPe levels by comparison with LF-HD, largely due to a greater intradialytic clearance of PBPe. Serum albumin is also reduced without any associated changes in nutritional status markers. The study also suggests that the effect of BK-F-HD in lowering PBPe levels is modulated by the body burden of pentosidine and is blunted or even lost in the presence of elevated CRP levels.

Measuring Small Leak Holes

NASA Technical Reports Server (NTRS)

Koch, D. E.; Stephenson, J. G.

1983-01-01

Hole sizes deduced from pressure measurements. Measuring apparatus consists of pitot tube attached to water-filled manometer. Compartment tested is pressurized with air. Pitot probe placed at known distance from leak. Dynamic pressure of jet measured at that point and static pressure measured in compartment. Useful in situations in which small leaks are tolerable but large leaks are not.

The Leaking-Toilet Challenge

ERIC Educational Resources Information Center

Roman, Harry T.

2008-01-01

Leaking toilets can cost homeowners big dollars--often before it is even realized. Homeowners do not necessarily hear it leaking. It just does, and when the water bill comes due, it can be a most unpleasant surprise. This article presents a classroom challenge to try to develop leak-detection ideas that would be inexpensive and easily added to…

GM2-activator protein: a new biomarker for lung cancer.

PubMed

Potprommanee, Laddawan; Ma, Haou-Tzong; Shank, Lalida; Juan, Yi-Hsiu; Liao, Wei-Yu; Chen, Shui-Tein; Yu, Chong-Jen

2015-01-01

Effective biomarkers for early diagnosis of lung cancer are needed. A recent study demonstrated that urinary GM2-activator protein (GM2AP) level was increased in lung cancer patients. This study aims to validate the potential application of GM2AP as a biomarker for diagnosis of lung cancer. Serum and urine samples were obtained from 189 participants (133 patients for treatment naive lung cancer, 26 healthy volunteers for urine, and 30 healthy volunteers for serum). GM2AP level was detected by Western blotting and quantified using enzyme-linked immunosorbent assay (ELISA). The GM2AP expression in tumors and nontumor parts of lung tissues from 143 nonsmall cell lung cancers was detected by immunohistochemical stains. There was an 8.11 ± 1.36 folds increase in urine and a 5.41 ± 0.73 folds increase in serum level of GM2AP in lung cancer patients compared with healthy volunteers (p < 0.0001), achieving a 0.89 AUC value in urine and 0.90 AUC value in serum for the receiver-operating characteristic curves. Both serum and urine levels of GM2AP correlated significantly with pathology stages (urine, p = 0.009; serum, p < 0.0001). Using immunohistochemical, positive expression of GM2AP was found at 83.9% of nonsmall cell lung cancers patients and none in normal tissue. The GM2AP expression was significantly correlated with pathology stage (p = 0.0001). Patients with higher GM2AP expression had shorter overall survival (p = 0.045) and disease-free survival (p = 0.049) than lower GM2AP expression. Moreover, the multivariate analysis suggested GM2AP as an independent predictors of disease-free survival and overall survival. Our study demonstrates that GM2AP might serve as potential diagnostic and prognostic biomarkers in patients with lung cancer.

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

PubMed

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

2017-02-01

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

Vehicle-based Methane Mapping Helps Find Natural Gas Leaks and Prioritize Leak Repairs

NASA Astrophysics Data System (ADS)

von Fischer, J. C.; Weller, Z.; Roscioli, J. R.; Lamb, B. K.; Ferrara, T.

2017-12-01

Recently, mobile methane sensing platforms have been developed to detect and locate natural gas (NG) leaks in urban distribution systems and to estimate their size. Although this technology has already been used in targeted deployment for prioritization of NG pipeline infrastructure repair and replacement, one open question regarding this technology is how effective the resulting data are for prioritizing infrastructure repair and replacement. To answer this question we explore the accuracy and precision of the natural gas leak location and emission estimates provided by methane sensors placed on Google Street View (GSV) vehicles. We find that the vast majority (75%) of methane emitting sources detected by these mobile platforms are NG leaks and that the location estimates are effective at identifying the general location of leaks. We also show that the emission rate estimates from mobile detection platforms are able to effectively rank NG leaks for prioritizing leak repair. Our findings establish that mobile sensing platforms are an efficient and effective tool for improving the safety and reducing the environmental impacts of low-pressure NG distribution systems by reducing atmospheric methane emissions.

Identification and characterization of proteins isolated from microvesicles derived from human lung cancer pleural effusions.

PubMed

Park, Jung Ok; Choi, Do-Young; Choi, Dong-Sic; Kim, Hee Joung; Kang, Jeong Won; Jung, Jae Hun; Lee, Jeong Hwa; Kim, Jayoung; Freeman, Michael R; Lee, Kye Young; Gho, Yong Song; Kim, Kwang Pyo

2013-07-01

Microvesicles (MVs, also known as exosomes, ectosomes, microparticles) are released by various cancer cells, including lung, colorectal, and prostate carcinoma cells. MVs released from tumor cells and other sources accumulate in the circulation and in pleural effusion. Although recent studies have shown that MVs play multiple roles in tumor progression, the potential pathological roles of MV in pleural effusion, and their protein composition, are still unknown. In this study, we report the first global proteomic analysis of highly purified MVs derived from human nonsmall cell lung cancer (NSCLC) pleural effusion. Using nano-LC-MS/MS following 1D SDS-PAGE separation, we identified a total of 912 MV proteins with high confidence. Three independent experiments on three patients showed that MV proteins from PE were distinct from MV obtained from other malignancies. Bioinformatics analyses of the MS data identified pathologically relevant proteins and potential diagnostic makers for NSCLC, including lung-enriched surface antigens and proteins related to epidermal growth factor receptor signaling. These findings provide new insight into the diverse functions of MVs in cancer progression and will aid in the development of novel diagnostic tools for NSCLC. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Gelatin based on Power-gel.TM. as solders for Cr.sup.4+laser tissue welding and sealing of lung air leak and fistulas in organs

DOEpatents

Alfano, Robert R.; Tang, Jing; Evans, Jonathan M.; Ho, Peng Pei

2006-04-25

Laser tissue welding can be achieved using tunable Cr.sup.4+ lasers, semiconductor lasers and fiber lasers, where the weld strength follows the absorption spectrum of water. The use of gelatin and esterified gelatin as solders in conjunction with laser inducted tissue welding impart much stronger tensile and torque strengths than albumin solders. Selected NIR wavelength from the above lasers can improve welding and avoid thermal injury to tissue when used alone or with gelatin and esterified gelatin solders. These discoveries can be used to enhance laser tissue welding of tissues such as skin, mucous, bone, blood vessel, nerve, brain, liver, pancreas, spleen, kidney, lung, bronchus, respiratory track, urinary tract, gastrointestinal tract, or gynecologic tract and as a sealant for pulmonary air leaks and fistulas such as intestinal, rectal and urinary fistulas.

Long-life leak standard assembly

DOEpatents

Basford, James A.; Mathis, John E.; Wright, Harlan C.

1982-01-01

The present invention is directed to a portable leak standard assembly which is capable of providing a stream of high-purity reference gas at a virtually constant flow rate over an extensive period of time. The leak assembly comprises a high pressure reservoir coupled to a metal leak valve through a valve-controlled conduit. A reproducible leak valve useful in this assembly is provided by a metal tube crimped with a selected pressure loading for forming an orifice in the tube with this orifice being of a sufficient size to provide the selected flow rate. The leak valve assembly is formed of metal so that it can be "baked-out" in a vacuum furnace to rid the reservoir and attendent components of volatile impurities which reduce the efficiency of the leak standard.

Aerosol delivery of Akt controls protein translation in the lungs of dual luciferase reporter mice.

PubMed

Tehrani, A M; Hwang, S-K; Kim, T-H; Cho, C-S; Hua, J; Nah, W-S; Kwon, J-T; Kim, J-S; Chang, S-H; Yu, K-N; Park, S-J; Bhandari, D R; Lee, K-H; An, G-H; Beck, G R; Cho, M-H

2007-03-01

Lung cancer has emerged as a leading cause of cancer death in the world; however, most of the current conventional therapies are not sufficiently effective in altering the progression of disease. Therefore, development of novel treatment approaches is needed. Although several genes and methods have been used for cancer gene therapy, a number of problems such as specificity, efficacy and toxicity reduce their application. This has led to re-emergence of aerosol gene delivery as a noninvasive method for lung cancer treatment. In this study, nano-sized glucosylated polyethyleneimine (GPEI) was used as a gene delivery carrier to investigate the effects of Akt wild type (WT) and kinase deficient (KD) on Akt-related signaling pathways and protein translation in the lungs of CMV- LucR-cMyc-IRES-LucF dual reporter mice. These mice are a powerful tool for the discrimination between cap-dependent/-independent protein translation. Aerosols containing self-assembled nano-sized GPEI/Akt WT or GPEI/Akt KD were delivered into the lungs of reporter mice through nose-only-inhalation-chamber with the aid of nebulizer. Aerosol delivery of Akt WT caused the increase of protein expression levels of Akt-related signals, whereas aerosol delivery of Akt KD did not. Furthermore, dual luciferase activity assay showed that aerosol delivery of Akt WT enhanced cap-dependent protein translation, whereas a reduction in cap-dependent protein translation by Akt KD was observed. Our results clearly showed that targeting Akt may be a good strategy for prevention as well as treatment of lung cancer. These studies suggest that our aerosol delivery is compatible for in vivo gene delivery which could be used as a noninvasive gene therapy in the future.

Scintigraphy for Pulmonary Capillary Protein Leak

DTIC Science & Technology

1983-09-01

In previous canine oleic acid studies, we have found that the SI was proportional to the severity of injury and was more sensitive than either...compared favorably to wet to dry lung weight ratios, alveolar epithelial membrane permeability, canine lymph flow, standard radiography and light...following lymph duct cannulation to determine if the pulmonary injury will resolve with time. 2. Canine Studies Dogs weighing approximately 20 kg, were

The Validation of a No-Drain Policy After Thoracoscopic Major Lung Resection.

PubMed

Murakami, Junichi; Ueda, Kazuhiro; Tanaka, Toshiki; Kobayashi, Taiga; Kunihiro, Yoshie; Hamano, Kimikazu

2017-09-01

The omission of postoperative chest tube drainage may contribute to early recovery after thoracoscopic major lung resection; however, a validation study is necessary before the dissemination of a selective drain policy. A total of 162 patients who underwent thoracoscopic anatomical lung resection for lung tumors were enrolled in this study. Alveolar air leaks were sealed with a combination of bioabsorbable mesh and fibrin glue. The chest tube was removed just after the removal of the tracheal tube in selected patients in whom complete pneumostasis was obtained. Alveolar air leaks were identified in 112 (69%) of the 162 patients in an intraoperative water-seal test performed just after anatomical lung resection. The chest tube could be removed in the operating room in 102 (63%) of the 162 patients. There were no cases of 30-day postoperative mortality or in-hospital death. None of the 102 patients who did not undergo postoperative chest tube placement required redrainage for a subsequent air leak or subcutaneous emphysema. The mean length of postoperative hospitalization was shorter in patients who had not undergone postoperative chest tube placement than in those who had. The omission of chest tube placement was associated with a reduction in the visual analog scale for pain from postoperative day 0 until postoperative day 3, in comparison with patients who underwent chest tube placement. The outcome of our validation cohort revealed that a no-drain policy is safe in selected patients undergoing thoracoscopic major lung resection and that it may contribute to an early recovery. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Improved Portable Ultrasonic Leak Detectors

NASA Technical Reports Server (NTRS)

Youngquist, Robert C.; Moerk, John S.; Haskell, William D.; Cox, Robert B.; Polk, Jimmy D.; Strobel, James P.; Luaces, Frank

1995-01-01

Improved portable ultrasonic leak detector features three interchangeable ultrasonic-transducer modules, each suited for operation in unique noncontact or contact mode. One module equipped with ultrasound-collecting horn for use in scanning to detect leaks from distance; horn provides directional sensitivity pattern with sensitivity multiplied by factor of about 6 in forward direction. Another module similar, does not include horn; this module used for scanning close to suspected leak, where proximity of leak more than offsets loss of sensitivity occasioned by lack of horn. Third module designed to be pressed against leaking vessel; includes rugged stainless-steel shell. Improved detectors perform significantly better, smaller, more rugged, and greater sensitivity.

Integration of protein phosphorylation, acetylation, and methylation data sets to outline lung cancer signaling networks.

PubMed

Grimes, Mark; Hall, Benjamin; Foltz, Lauren; Levy, Tyler; Rikova, Klarisa; Gaiser, Jeremiah; Cook, William; Smirnova, Ekaterina; Wheeler, Travis; Clark, Neil R; Lachmann, Alexander; Zhang, Bin; Hornbeck, Peter; Ma'ayan, Avi; Comb, Michael

2018-05-22

Protein posttranslational modifications (PTMs) have typically been studied independently, yet many proteins are modified by more than one PTM type, and cell signaling pathways somehow integrate this information. We coupled immunoprecipitation using PTM-specific antibodies with tandem mass tag (TMT) mass spectrometry to simultaneously examine phosphorylation, methylation, and acetylation in 45 lung cancer cell lines compared to normal lung tissue and to cell lines treated with anticancer drugs. This simultaneous, large-scale, integrative analysis of these PTMs using a cluster-filtered network (CFN) approach revealed that cell signaling pathways were outlined by clustering patterns in PTMs. We used the t-distributed stochastic neighbor embedding (t-SNE) method to identify PTM clusters and then integrated each with known protein-protein interactions (PPIs) to elucidate functional cell signaling pathways. The CFN identified known and previously unknown cell signaling pathways in lung cancer cells that were not present in normal lung epithelial tissue. In various proteins modified by more than one type of PTM, the incidence of those PTMs exhibited inverse relationships, suggesting that molecular exclusive "OR" gates determine a large number of signal transduction events. We also showed that the acetyltransferase EP300 appears to be a hub in the network of pathways involving different PTMs. In addition, the data shed light on the mechanism of action of geldanamycin, an HSP90 inhibitor. Together, the findings reveal that cell signaling pathways mediated by acetylation, methylation, and phosphorylation regulate the cytoskeleton, membrane traffic, and RNA binding protein-mediated control of gene expression. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Epigallocatechin-3-gallate Ameliorates Seawater Aspiration-Induced Acute Lung Injury via Regulating Inflammatory Cytokines and Inhibiting JAK/STAT1 Pathway in Rats

PubMed Central

Liu, Wei; Dong, Mingqing; Bo, Liyan; Li, Congcong; Liu, Qingqing; Li, Yanyan; Ma, Lijie; Xie, Yonghong; Fu, Enqing; Mu, Deguang; Pan, Lei; Jin, Faguang; Li, Zhichao

2014-01-01

Signal transducers and activators of transcriptions 1 (STAT1) play an important role in the inflammation process of acute lung injury (ALI). Epigallocatechin-3-gallate (EGCG) exhibits a specific and strong anti-STAT1 activity. Therefore, our study is to explore whether EGCG pretreatment can ameliorate seawater aspiration-induced ALI and its possible mechanisms. We detected the arterial partial pressure of oxygen, lung wet/dry weight ratios, protein content in bronchoalveolar lavage fluid, and the histopathologic and ultrastructure staining of the lung. The levels of IL-1, TNF-α, and IL-10 and the total and the phosphorylated protein level of STAT1, JAK1, and JAK2 were assessed in vitro and in vivo. The results showed that EGCG pretreatment significantly improved hypoxemia and histopathologic changes, alleviated pulmonary edema and lung vascular leak, reduced the production of TNF-α and IL-1, and increased the production of IL-10 in seawater aspiration-induced ALI rats. EGCG also prevented the seawater aspiration-induced increase of TNF-α and IL-1 and decrease of IL-10 in NR8383 cell line. Moreover, EGCG pretreatment reduced the total and the phosphorylated protein level of STAT1 in vivo and in vitro and reduced the phosphorylated protein level of JAK1 and JAK2. The present study demonstrates that EGCG ameliorates seawater aspiration-induced ALI via regulating inflammatory cytokines and inhibiting JAK/STAT1 pathway in rats. PMID:24692852

Superfluid helium leak sealant study

NASA Technical Reports Server (NTRS)

Vorreiter, J. W.

1981-01-01

Twenty-one leak specimens were fabricated in the ends of stainless steel and aluminum tubes. Eighteen of these tubes were coated with a copolymer material to seal the leak. The other three specimens were left uncoated and served as control specimens. All 21 tubes were cold shocked in liquid helium 50 times and then the leak rate was measured while the tubes were submerged in superfluid helium at 1.7 K. During the cold shocks two of the coated specimens were mechanically damaged and eliminated from the test program. Of the remaining 16 coated specimens one suffered a total coating failure and resulting high leak rate. Another three of the coated specimens suffered partial coating failures. The leak rates of the uncoated specimens were also measured and reported. The significance of various leak rates is discussed in view of the infrared astronomical satellite (IRAS) Dewar performance.

Familial Alzheimer disease-linked mutations specifically disrupt Ca2+ leak function of presenilin 1.

PubMed

Nelson, Omar; Tu, Huiping; Lei, Tianhua; Bentahir, Mostafa; de Strooper, Bart; Bezprozvanny, Ilya

2007-05-01

Mutations in presenilins are responsible for approximately 40% of all early-onset familial Alzheimer disease (FAD) cases in which a genetic cause has been identified. In addition, a number of mutations in presenilin-1 (PS1) have been suggested to be associated with the occurrence of frontal temporal dementia (FTD). Presenilins are highly conserved transmembrane proteins that support cleavage of the amyloid precursor protein by gamma-secretase. Recently, we discovered that presenilins also function as passive ER Ca(2+) leak channels. Here we used planar lipid bilayer reconstitution assays and Ca(2+) imaging experiments with presenilin-null mouse embryonic fibroblasts to analyze ER Ca(2+) leak function of 6 FAD-linked PS1 mutants and 3 known FTD-associated PS1 mutants. We discovered that L166P, A246E, E273A, G384A, and P436Q FAD mutations in PS1 abolished ER Ca(2+) leak function of PS1. In contrast, A79V FAD mutation or FTD-associated mutations (L113P, G183V, and Rins352) did not appear to affect ER Ca(2+) leak function of PS1 in our experiments. We validated our findings in Ca(2+) imaging experiments with primary fibroblasts obtained from an FAD patient possessing mutant PS1-A246E. Our results indicate that many FAD mutations in presenilins are loss-of-function mutations affecting ER Ca(2+) leak activity. In contrast, none of the FTD-associated mutations affected ER Ca(2+) leak function of PS1, indicating that the observed effects are disease specific. Our observations are consistent with the potential role of disturbed Ca(2+) homeostasis in Alzheimer disease pathogenesis.

[Suppression of WIFI transcript and protein in non-small cell lung carcinomas].

PubMed

Korobko, E V; Kalinichenko, S V; Shepelev, M V; Zborovskaia, I B; Allakhverdiev, A K; Zinov'eva, M V; Vinogradova, T V; Sverdlov, E D; Korobko, I V

2007-01-01

Changes in WIFI expression, an extracellular inhibitor of Wnt pathway, in non-small cell lung carcinomas were analyzed. Frequent (67% cases) suppression of WIFI transcript in non-small cell lung carcinomas were found. Our results, together with previously published data, suggest that inhibition of WIFI expression often occurs in squamous cell carcinomas and is less typical of adenocarcinomas. It was also found that a decrease in the WIFI transcript in tumors is parallel to concomitant suppression of the WIFI protein level. Our results provide further evidence that the WIFI suppression is a frequent event in the lung carcinogenesis, which might lead to disregulation of Wnt signaling pathway and contribute to tumor progression.

Triple SILAC quantitative proteomic analysis reveals differential abundance of cell signaling proteins between normal and lung cancer-derived exosomes.

PubMed

Clark, David J; Fondrie, William E; Yang, Austin; Mao, Li

2016-02-05

Exosomes are 30-100 nm sized membrane vesicles released by cells into the extracellular space that mediate intercellular communication via transfer of proteins and other biological molecules. To better understand the role of these microvesicles in lung carcinogenesis, we employed a Triple SILAC quantitative proteomic strategy to examine the differential protein abundance between exosomes derived from an immortalized normal bronchial epithelial cell line and two non-small cell lung cancer (NSCLC) cell lines harboring distinct activating mutations in the cell signaling molecules: Kirsten rat sarcoma viral oncogene homolog (KRAS) or epidermal growth factor receptor (EGFR). In total, we were able to quantify 721 exosomal proteins derived from the three cell lines. Proteins associated with signal transduction, including EGFR, GRB2 and SRC, were enriched in NSCLC exosomes, and could actively regulate cell proliferation in recipient cells. This study's investigation of the NSCLC exosomal proteome has identified enriched protein cargo that can contribute to lung cancer progression, which may have potential clinical implications in biomarker development for patients with NSCLC. The high mortality associated with lung cancer is a result of late-stage diagnosis of the disease. Current screening techniques used for early detection of lung cancer lack the specificity for accurate diagnosis. Exosomes are nano-sized extracellular vesicles, and the increased abundance of select protein cargo in exosomes derived from cancer cells may be used for diagnostic purposes. In this paper, we applied quantitative proteomic analysis to elucidate abundance differences in exosomal protein cargo between two NSCLC cell lines with distinctive oncogene mutations and an immortalized normal bronchial epithelial cell line. This study revealed proteins associated with cell adhesion, the extracellular matrix, and a variety of signaling molecules were enriched in NSCLC exosomes. The present data reveals

Clinical usefulness of free subcutaneous fat pad for reduction of intraoperative air leakage during thoracoscopic pulmonary resection in lung cancer cases.

PubMed

Shintani, Yasushi; Inoue, Masayoshi; Funaki, Soichiro; Kawamura, Tomohiro; Minami, Masato; Okumura, Meinoshin

2015-10-01

Intraoperative alveolar air leaks remain a significant problem in thoracoscopic surgery (TS) cases. We examined the usefulness of covering damaged lung tissue with a subcutaneous fat pad for preventing postoperative air leakage in patients with non-small cell lung cancer (NSCLC). Patients with NSCLC underwent a thoracoscopic lobectomy or segmentectomy. When alveolar air leakage from the superficial pulmonary parenchyma was found, fibrin glue in combination with an absorbable mesh sheet was applied (S group; n = 100). When leakage originated from deep within the pulmonary parenchyma, a subcutaneous fat pad about 2 × 2 cm in size was harvested from the utility incision and placed on the damaged lung tissue with fibrin glue and sutures (F group; n = 66). Patient characteristics, air leak duration, and chest-tube removal time were analyzed. The homogeneity of each group was consistent, with no statistical differences for age, respiratory function, surgical procedures, pathologic stage, and histological type. The air leak duration was significantly shorter (p = 0.015), and the chest tube was removed significantly earlier (p = 0.002) in patients in the F group. Use of a free subcutaneous fat pad during pulmonary resection for TS patients with NSCLC reduced the duration of air leakage and chest tube drainage. The present method is easy, safe, and effective for repairing an air leak from remaining lung tissues in such cases.

A prospective randomized trial comparing homologous and autologous fibrin sealants for the control of alveolar air leak

PubMed Central

Erşen, Ezel; Demirkaya, Ahmet; Kara, H. Volkan; Alizade, Nurlan; İşcan, Mehlika; Kaynak, Kamil; Turna, Akif

2017-01-01

Background Postoperative air leak is a common complication seen after pulmonary resection. It is a significant reason of morbidity and also leads to greater hospital cost owing to prolonged length of stay. The purpose of this study is to compare homologous sealant with autologous one to prevent air leak following pulmonary resection. Methods A total of 57 patients aged between 20 and 79 (mean age: 54.36) who underwent pulmonary resection other than pneumonectomy (lobar or sublobar resections) were analyzed. There were 47 males (83%) and 10 females (17%). Patients who intraoperatively had air leaks were randomized to receive homologous (Tisseel; n=28) or autologous (Vivostat; n=29) fibrin sealant. Differences among groups in terms of air leak, prolonged air leak, hospital stay, amount of air leak were analyzed. Results Indications for surgery were primary lung cancer in 42 patients (71.9%), secondary malignancy in 5 patients (8.8%), and benign disease in 10 patients (17.5%). Lobectomy was performed in 40 patients (70.2%), whereas 17 patients (29.8%) had wedge resection. Thirteen (46.4%) patients developed complications in patients receiving homologous sealant while 11 (38.0%) patients had complication in autologous sealant group (P=0.711). Median duration of air leak was 3 days in two groups. Time to intercostal drain removal was 3.39 and 3.38 days in homologous and autologous sealant group respectively (P=0.978). Mean hospital stay was 5.5 days in patients receiving homologous sealant whereas it was 5.0 days in patients who had autologous agent (P=0.140). There were no significant differences between groups in terms of measured maximum air leak (P=0.823) and mean air leak (P=0.186). There was no significant difference in the incidence of complications between two groups (P=0.711). Conclusions Autologous and heterologous fibrin sealants are safe and acts similarly in terms of air leak and hospital stay in patients who had resectional surgery. PMID:29221263

A prospective randomized trial comparing homologous and autologous fibrin sealants for the control of alveolar air leak.

PubMed

Kılıç, Burcu; Erşen, Ezel; Demirkaya, Ahmet; Kara, H Volkan; Alizade, Nurlan; İşcan, Mehlika; Kaynak, Kamil; Turna, Akif

2017-09-01

Postoperative air leak is a common complication seen after pulmonary resection. It is a significant reason of morbidity and also leads to greater hospital cost owing to prolonged length of stay. The purpose of this study is to compare homologous sealant with autologous one to prevent air leak following pulmonary resection. A total of 57 patients aged between 20 and 79 (mean age: 54.36) who underwent pulmonary resection other than pneumonectomy (lobar or sublobar resections) were analyzed. There were 47 males (83%) and 10 females (17%). Patients who intraoperatively had air leaks were randomized to receive homologous (Tisseel; n=28) or autologous (Vivostat; n=29) fibrin sealant. Differences among groups in terms of air leak, prolonged air leak, hospital stay, amount of air leak were analyzed. Indications for surgery were primary lung cancer in 42 patients (71.9%), secondary malignancy in 5 patients (8.8%), and benign disease in 10 patients (17.5%). Lobectomy was performed in 40 patients (70.2%), whereas 17 patients (29.8%) had wedge resection. Thirteen (46.4%) patients developed complications in patients receiving homologous sealant while 11 (38.0%) patients had complication in autologous sealant group (P=0.711). Median duration of air leak was 3 days in two groups. Time to intercostal drain removal was 3.39 and 3.38 days in homologous and autologous sealant group respectively (P=0.978). Mean hospital stay was 5.5 days in patients receiving homologous sealant whereas it was 5.0 days in patients who had autologous agent (P=0.140). There were no significant differences between groups in terms of measured maximum air leak (P=0.823) and mean air leak (P=0.186). There was no significant difference in the incidence of complications between two groups (P=0.711). Autologous and heterologous fibrin sealants are safe and acts similarly in terms of air leak and hospital stay in patients who had resectional surgery.

Neonatal respiratory distress syndrome: Chest X-ray or lung ultrasound? A systematic review

PubMed Central

Culpan, Anne-Marie; Watts, Catriona; Munyombwe, Theresa; Wolstenhulme, Stephen

2017-01-01

Background and aim Neonatal respiratory distress syndrome is a leading cause of morbidity in preterm new-born babies (<37 weeks gestation age). The current diagnostic reference standard includes clinical testing and chest radiography with associated exposure to ionising radiation. The aim of this review was to compare the diagnostic accuracy of lung ultrasound against the reference standard in symptomatic neonates of ≤42 weeks gestation age. Methods A systematic search of literature published between 1990 and 2016 identified 803 potentially relevant studies. Six studies met the review inclusion criteria and were retrieved for analysis. Quality assessment was performed before data extraction and meta-analysis. Results Four prospective cohort studies and two case control studies included 480 neonates. All studies were of moderate methodological quality although heterogeneity was evident across the studies. The pooled sensitivity and specificity of lung ultrasound were 97% (95% confidence interval [CI] 94–99%) and 91% (CI: 86–95%) respectively. False positive diagnoses were made in 16 cases due to pneumonia (n = 8), transient tachypnoea (n = 3), pneumothorax (n = 1) and meconium aspiration syndrome (n = 1); the diagnoses of the remaining three false positive results were not specified. False negatives diagnoses occurred in nine cases, only two were specified as air-leak syndromes. Conclusions Lung ultrasound was highly sensitive for the detection of neonatal respiratory distress syndrome although there is potential to miss co-morbid air-leak syndromes. Further research into lung ultrasound diagnostic accuracy for neonatal air-leak syndrome and economic modelling for service integration is required before lung ultrasound can replace chest radiography as the imaging component of the reference standard. PMID:28567102

Osthole induces lung cancer cell apoptosis through inhibition of inhibitor of apoptosis family proteins

PubMed Central

Xu, Xiao-Man; Zhang, Man-Li; Zhang, Yi; Zhao, Li

2016-01-01

In the present study, we investigated the effects and mechanisms of Osthole on the apoptosis of non-small cell lung cancer (NSCLC) cells and its synergistic effect with Embelin. Our results revealed that treatment with both Osthole and Embelin inhibited cell proliferation. Notably, combination treatment of Osthole and Embelin inhibited cell proliferation more significantly compared with monotherapy. In addition, morphological analysis and Annexin V/propidium iodide analysis revealed that the combination of Osthole and Embelin enhanced their effect on cell apoptosis. We further examined the effect of Osthole on the expression of inhibitor of apoptosis protein (IAP) family proteins. That treatment of A549 lung cancer cells with various concentrations of Osthole was observed to decrease the protein expression of X-chromosome-encoded IAP, c-IAP1, c-IAP2 and Survivin, and increase Smac expression in a dose-dependent manner. Furthermore, it was noted that Osthole or Embelin alone increased the expression of BAX, caspase-3, caspase-9, cleaved caspase-3 and cleaved caspase-9, and decreased Bcl-2 levels following treatment. Osthole and Embelin combination treatment had a synergistic effect on the regulation of these proteins. In conclusion, our study demonstrated that Osthole inhibited proliferation and induced the apoptosis of lung cancer cells via IAP family proteins in a dose-dependent manner. Osthole enhances the antitumor effect of Embelin, indicating that combination of Osthole and Embelin has potential clinical significance in the treatment of NSCLC. PMID:27895730

Protein Phosphatase 2A Regulates Innate Immune and Proteolytic Responses to Cigarette Smoke Exposure in the Lung

PubMed Central

Wallace, Alison M.; Hardigan, Andrew; Geraghty, Patrick; Salim, Shaneeza; Gaffney, Adam; Thankachen, Jincy; Arellanos, Leo; D'Armiento, Jeanine M.; Foronjy, Robert F.

2012-01-01

Protein phosphatase 2A (PP2A) is the primary serine-threonine phosphatase of eukaryotic cells, and changes in its activity have been linked to neoplastic and neurodegenerative diseases. However, the role of PP2A in noncancerous lung diseases such as chronic obstructive pulmonary disease (COPD) has not been previously examined. This study determined that PP2A activity was significantly increased in the lungs of advanced emphysema subjects compared with age-matched controls. Furthermore, we found that cigarette smoke exposure increases PP2A activity in mouse lung in vivo and in primary human small airway epithelial (SAE) cells in vitro. In mice, intratracheal transfection of PP2A protein prior to cigarette smoke exposure prevented acute smoke–induced lung inflammation. Conversely, inhibiting PP2A activity during smoke exposure exacerbated inflammatory responses in the lung. To further determine how PP2A modulates the responses to cigarette smoke in the lung, enzyme levels were manipulated in SAE cells using protein transfection and short hairpin RNA (shRNA) techniques. Increasing PP2A activity in SAE cells via PP2A protein transfection downregulated cytokine expression and prevented the induction of proteases following cigarette smoke extract (CSE) treatment. Conversely, decreasing enzymatic activity by stably transfecting SAE cells with shRNA for the A subunit of PP2A exacerbated these smoke-mediated responses. This study establishes that PP2A induction by cigarette smoke modulates immune and proteolytic responses to cigarette smoke exposure. Together, these findings suggest that manipulation of PP2A activity may be a plausible means to treat COPD and other inflammatory diseases. PMID:22223484

Disturbance of parathyroid hormone-related protein signaling in the nitrofen-induced hypoplastic lung.

PubMed

Doi, Takashi; Lukosiūte, Ausra; Ruttenstock, Elke; Dingemann, Jens; Puri, Prem

2010-01-01

Despite remarkable progress in resuscitation and intensive care, the morbidity and mortality rates in congenital diaphragmatic hernia (CDH) remain high due to severe pulmonary hypoplasia. The pathogenesis of pulmonary hypoplasia associated with CDH is still not clearly understood. Pulmonary parathyroid hormone-related protein (PTHrP) is expressed in the type II epithelial cells and stimulates surfactant production by a paracrine feedback loop regulated by PTHrP receptor (PTHrP-R), which is expressed in the mesenchyme, during terminal airway differentiation. It has been reported that PTHrP knockout and PTHrP-R null mice both exhibit pulmonary hypoplasia, disrupting alveolar maturation before birth. We designed this study to test the hypothesis that gene expression of PTHrP and PTHrP-R is downregulated in the late stages of lung morphogenesis in the nitrofen-induced hypoplastic lung. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetal lungs were harvested on D15, 18, and 21 and divided into three groups: control, nitrofen without CDH [CDH(-)], and nitrofen with CDH [CDH(+)] (n = 8 at each time point for each group, respectively). Total mRNA was extracted from fetal lungs and mRNA expression of PTHrP and PTHrP-R was analyzed by real-time RT-PCR and the significant differences between the groups were accepted at P < 0.05 by statistical analysis. Immunohistochemical studies were also performed to evaluate PTHrP and PTHrP-R protein expression at each time point. Pulmonary mRNA expression of PTHrP-R was significantly decreased in both nitrofen groups [CDH(-) and CDH(+)] compared to controls at D18 and 21. The mRNA level of PTHrP was significantly decreased at D21 in both nitrofen groups compared to controls. Immunoreactivity of PTHrP and PTHrP-R at D18 and 21 was diminished in the distal epithelium and in the mesenchyme, respectively, in the nitrofen-induced hypoplastic lung compared to control lungs. There were no significant

Activation of the protein-tyrosine kinase associated with the bombesin receptor complex in small cell lung carcinomas

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

Gaudino, G.; Cirillo, D.; Naldini, L.

1988-04-01

It has been hypothesized that bombesin-like peptides produced by small cell lung carcinomas may sustain deregulated proliferation through an autocrine mechanism. The authors have shown that the neuropeptide bombesin leads to the activation of a protein-tyrosine kinase that phosphorylates a 115-kDa protein (p115) associated with the bombesin receptor complex in mouse Swiss 3T3 fibroblasts. They now report that phosphotyrosine antibodies recognize a 115-kDa protein, phosphorylated on tyrosine, in four human small cell lung carcinoma cell lines producing bombesin but not in a nonproducer variant line. p115 from detergent-treated small cell lung carcinoma cells binds to bombesin-Sepharose and can be phosphorylatedmore » on tyrosine in the presence of radiolabeled ATP and Mn{sup 2+}. As for the p115 immunoprecipitated from mouse fibroblast, the small cell lung carcinoma p115 can be phosphorylated in an immunocomplex kinase assay. However, the latter does not require the presence of exogenous bombesin for activity. Binding data, obtained by using radiolabeled ligand, suggest receptor occupancy in the cell lines producing bombesin. These observations are consistent with the hypothesis that proliferation in some human small cell lung carcinoma lines is under autocrine control, regulated through activation of bombesin receptors.« less

Expression and arrangement of extracellular matrix proteins in the lungs of mice infected with Paracoccidioides brasiliensis conidia

PubMed Central

González, Angel; Lenzi, Henrique Leonel; Motta, Ester Maria; Caputo, Luzia; Restrepo, Angela; Cano, Luz Elena

2008-01-01

Extracellular matrix (ECM) proteins are important modulators of migration, differentiation and proliferation for the various cell types present in the lungs; they influence the immune response as well as participate in the adherence of several fungi including Paracoccidioides brasiliensis. The expression, deposition and arrangement of ECM proteins such as laminin, fibronectin, fibrinogen, collagen and proteoglycans in the lungs of mice infected with P. brasiliensis conidia has been evaluated in this study, together with the elastic fibre system. Lungs of BALB/c mice infected with P. brasiliensis conidia were analysed for the different ECM proteins by histological and immunohistochemical procedures at different times of infection. In addition, laser scanning confocal microscopy and scanning electron microscopy were used. During the early periods, the lungs of infected animals showed an inflammatory infiltrate composed mainly of polymorphonuclear neutrophils (PMNs) and macrophages, while during the later periods, mice presented a chronic inflammatory response with granuloma formation. Re-arrangement and increased expression of all ECM proteins tested were observed throughout all studied periods, especially during the occurrence of inflammatory infiltration and formation of the granuloma. The elastic fibre system showed an elastolysis process in all experiments. In conclusion, this study provides new details of pulmonary ECM distribution during the course of paracoccidioidomycosis. PMID:18336528

The histone demethylase PHF8 is an oncogenic protein in human non-small cell lung cancer

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

Shen, Yuzhou; Pan, Xufeng; Zhao, Heng, E-mail: hengzhao1966@sina.com

2014-08-15

Highlights: • PHF8 overexpresses in human NSCLC and predicts poor survival. • PHF8 regulates lung cancer cell growth and transformation. • PHF8 regulates apoptosis in human lung cancer cells. • PHF8 promotes miR-21 expression in human lung cancer. • MiR-21 is critically essential for PHF8 function in human lung cancer cells. - Abstract: PHF8 is a JmjC domain-containing protein and erases repressive histone marks including H4K20me1 and H3K9me1/2. It binds to H3K4me3, an active histone mark usually located at transcription start sites (TSSs), through its plant homeo-domain, and is thus recruited and enriched in gene promoters. PHF8 is involved inmore » the development of several types of cancer, including leukemia, prostate cancer, and esophageal squamous cell carcinoma. Herein we report that PHF8 is an oncogenic protein in human non-small cell lung cancer (NSCLC). PHF8 is up-regulated in human NSCLC tissues, and high PHF8 expression predicts poor survival. Our in vitro and in vivo evidence demonstrate that PHF8 regulates lung cancer cell proliferation and cellular transformation. We found that PHF8 knockdown induces DNA damage and apoptosis in lung cancer cells. PHF8 promotes miR-21 expression in human lung cancer, and miR-21 knockdown blocks the effects of PHF8 on proliferation and apoptosis of lung cancer cells. In summary, PHF8 promotes lung cancer cell growth and survival by regulating miR-21.« less

HIP1-ALK, a novel fusion protein identified in lung adenocarcinoma.

PubMed

Hong, Mineui; Kim, Ryong Nam; Song, Ji-Young; Choi, So-Jung; Oh, Ensel; Lira, Maruja E; Mao, Mao; Takeuchi, Kengo; Han, Joungho; Kim, Jhingook; Choi, Yoon-La

2014-03-01

The most common mechanism underlying overexpression and activation of anaplastic lymphoma kinase (ALK) in non-small-cell lung carcinoma could be attributed to the formation of a fusion protein. To date, five fusion partners of ALK have been reported, namely, echinoderm microtubule associated protein like 4, tropomyosin-related kinase-fused gene, kinesin family member 5B, kinesin light chain 1, and protein tyrosine phosphatase, nonreceptor type 3. In this article, we report a novel fusion gene huntingtin interacting protein 1 (HIP1)-ALK, which is conjoined between the huntingtin-interacting protein 1 gene HIP1 and ALK. Reverse-transcriptase polymerase chain reaction and immunohistochemical analysis were used to detect this fusion gene's transcript and protein expression, respectively. We had amplified the full-length cDNA sequence of this novel fusion gene by using 5'-rapid amplification of cDNA ends. The causative genomic translocation t(2;7)(p23;q11.23) for generating this novel fusion gene was verified by using genomic sequencing. The examined adenocarcinoma showed predominant acinar pattern, and ALK immunostaining was localized to the cytoplasm, with intense staining in the submembrane region. In break-apart, fluorescence in situ hybridization analysis for ALK, split of the 5' and 3' probe signals, and isolated 3' signals were observed. Reverse-transcriptase polymerase chain reaction revealed that the tumor harbored a novel fusion transcript in which exon 21 of HIP1 was fused to exon 20 of ALK in-frame. The novel fusion gene and its protein HIP1-ALK harboring epsin N-terminal homology, coiled-coil, juxtamembrane, and kinase domains, which could play a role in carcinogenesis, could become diagnostic and therapeutic target of the lung adenocarcinoma and deserve a further study in the future.

Fibroblast Activation Protein (FAP) Accelerates Collagen Degradation and Clearance from Lungs in Mice*

PubMed Central

Fan, Ming-Hui; Zhu, Qiang; Li, Hui-Hua; Ra, Hyun-Jeong; Majumdar, Sonali; Gulick, Dexter L.; Jerome, Jacob A.; Madsen, Daniel H.; Christofidou-Solomidou, Melpo; Speicher, David W.; Bachovchin, William W.; Feghali-Bostwick, Carol; Puré, Ellen

2016-01-01

Idiopathic pulmonary fibrosis is a disease characterized by progressive, unrelenting lung scarring, with death from respiratory failure within 2–4 years unless lung transplantation is performed. New effective therapies are clearly needed. Fibroblast activation protein (FAP) is a cell surface-associated serine protease up-regulated in the lungs of patients with idiopathic pulmonary fibrosis as well as in wound healing and cancer. We postulate that FAP is not only a marker of disease but influences the development of pulmonary fibrosis after lung injury. In two different models of pulmonary fibrosis, intratracheal bleomycin instillation and thoracic irradiation, we find increased mortality and increased lung fibrosis in FAP-deficient mice compared with wild-type mice. Lung extracellular matrix analysis reveals accumulation of intermediate-sized collagen fragments in FAP-deficient mouse lungs, consistent with in vitro studies showing that FAP mediates ordered proteolytic processing of matrix metalloproteinase (MMP)-derived collagen cleavage products. FAP-mediated collagen processing leads to increased collagen internalization without altering expression of the endocytic collagen receptor, Endo180. Pharmacologic FAP inhibition decreases collagen internalization as expected. Conversely, restoration of FAP expression in the lungs of FAP-deficient mice decreases lung hydroxyproline content after intratracheal bleomycin to levels comparable with that of wild-type controls. Our findings indicate that FAP participates directly, in concert with MMPs, in collagen catabolism and clearance and is an important factor in resolving scar after injury and restoring lung homeostasis. Our study identifies FAP as a novel endogenous regulator of fibrosis and is the first to show FAP's protective effects in the lung. PMID:26663085

Hermetic Seal Leak Detection Apparatus

NASA Technical Reports Server (NTRS)

Kelley, Anthony R. (Inventor)

2013-01-01

The present invention is a hermetic seal leak detection apparatus, which can be used to test for hermetic seal leaks in instruments and containers. A vacuum tight chamber is created around the unit being tested to minimize gas space outside of the hermetic seal. A vacuum inducing device is then used to increase the gas chamber volume inside the device, so that a slight vacuum is pulled on the unit being tested. The pressure in the unit being tested will stabilize. If the stabilized pressure reads close to a known good seal calibration, there is not a leak in the seal. If the stabilized pressure reads closer to a known bad seal calibration value, there is a leak in the seal. The speed of the plunger can be varied and by evaluating the resulting pressure change rates and final values, the leak rate/size can be accurately calculated.

Paravalvular Leak in Structural Heart Disease.

PubMed

Goel, Kashish; Eleid, Mackram F

2018-03-06

This review will summarize the growing importance of diagnosing and managing paravalvular leak associated with surgical and transcatheter valves. The burden of paravalvular leak is increasing; however, advanced imaging techniques and high degree of clinical suspicion are required for diagnosis and management. The latest data from pivotal clinical trials in the field of transcatheter aortic valve replacement suggest that any paravalvular leak greater than mild was associated with worse clinical outcomes. Percutaneous techniques for paravalvular leak closure are now the preferred approach, and surgical repair is reserved for contraindications and unsuccessful procedures. Recent data from studies evaluating paravalvular leak closure outcomes report a greater than 90% success rate with a significant improvement in patient symptoms. Paravalvular leak is a growing problem in the structural heart disease arena. Percutaneous closure is successful in more than 90% of the procedures with a low complication rate.

A novel PHD-finger protein 14/KIF4A complex overexpressed in lung cancer is involved in cell mitosis regulation and tumorigenesis.

PubMed

Zhang, Lin; Huang, Qin; Lou, Jiatao; Zou, Liangjian; Wang, Yiguo; Zhang, Peng; Yang, Guang; Zhang, Junyi; Yu, Lan; Yan, Dai; Zhang, Chenyi; Qiao, Jing; Wang, Shuting; Wang, Sai; Xu, Yongdong; Ji, Hongbin; Chen, Zhengjun; Zhang, Zhe

2017-03-21

The plant homeodomain (PHD) finger-containing proteins have been implicated in many human diseases including cancer. In this study, we found that PHF14, a newly identified PHD finger protein, is highly expressed in lung cancer. The high expression level of PHF14 was associated with adenocarcinoma and poor survival in lung cancer patients. Knocking down PHF14 suppressed cancer cell growth and carcinogenesis, while over-expressing PHF14 promoted cell proliferation. During cell division, PHF14 directly bound to and co-localized with KIF4A (a nuclear motor protein involved in lung carcinogenesis) to form a functional complex. Similarly to the effect of KIF4A depletion, silencing PHF14 in several cell lines caused cell mitotic defects, prolonged M phase, and inhibited cell proliferation. What's more, these two proteins had a synergistic effect on cell proliferation and were significantly co-overexpressed in lung cancer tissues. Our data provide new insights into the biological significance of PHD finger proteins and imply that PHF14 may be a potential biomarker for lung cancer.

Traumatic orbital CSF leak

PubMed Central

Borumandi, Farzad

2013-01-01

Compared to the cerebrospinalfluid (CSF) leak through the nose and ear, the orbital CSF leak is a rare and underreported condition following head trauma. We present the case of a 49-year-old woman with oedematous eyelid swelling and ecchymosis after a seemingly trivial fall onto the right orbit. Apart from the above, she was clinically unremarkable. The CT scan revealed a minimally displaced fracture of the orbital roof with no emphysema or intracranial bleeding. The fractured orbital roof in combination with the oedematous eyelid swelling raised the suspicion for orbital CSF leak. The MRI of the neurocranium demonstrated a small-sized CSF fistula extending from the anterior cranial fossa to the right orbit. The patient was treated conservatively and the lid swelling resolved completely after 5 days. Although rare, orbital CSF leak needs to be included in the differential diagnosis of periorbital swelling following orbital trauma. PMID:24323381

Blind Leak Detection for Closed Systems

NASA Technical Reports Server (NTRS)

Oelgoetz, Peter; Johnson, Ricky; Todd, Douglas; Russell, Samuel; Walker, James

2003-01-01

The current inspection technique for locating interstitial leaking in the Space Shuttle Main Engine nozzles is the application of a liquid leak check solution in the openings where the interstitials space between the tubing and the structural jacket vent out the aft end of the nozzle, while its cooling tubes are pressurized to 25 psig with Helium. When a leak is found, it is classified, and if the leak is severe enough the suspect tube is cut open so that a boroscope can be inserted to find the leak point. Since the boroscope can only cover a finite tube length and since it is impossible to identify which tube (to the right or left of the identified interstitial) is leaking, many extra and undesired repairs have been made to fix just one leak. In certain instances when the interstitials are interlinked by poor braze bonding, many interstitials will show indications of leaking from a single source. What is desired is a technique that can identify the leak source so that a single repair can be performed. Dr, Samuel Russell and James Walker, both with NASA/MSFC have developed a thermographic inspection system that addresses a single repair approach. They have teamed with Boeing/Rocketdyne to repackage the inspection processes to be suitable to address full scale Shuttle development and flight hardware and implement the process at NASA centers. The methods and results presented address the thermographic identification of interstitial leaks in the Space Shuttle Main Engine nozzles. A highly sensitive digital infrared camera (capable of detecting a delta temperature difference of 0.025 C) is used to record the cooling effects associated with a leak source, such as a crack or pinhole, hidden within the nozzle wall by observing the inner hot wall surface as the nozzle is pressurized, These images are enhanced by digitally subtracting a thermal reference image taken before pressurization. The method provides a non-intrusive way of locating the tube that is leaking and the

Association between protein C levels and mortality in patients with advanced prostate, lung and pancreatic cancer.

PubMed

Wilts, I T; Hutten, B A; Meijers, J C M; Spek, C A; Büller, H R; Kamphuisen, P W

2017-06-01

Procoagulant factors promote cancer progression and metastasis. Protein C is involved in hemostasis, inflammation and signal transduction, and has a protective effect on the endothelial barrier. In mice, administration of activated protein C reduced experimental metastasis. We assessed the association between protein C and mortality in patients with three types of cancer. The study population consisted of patients with advanced prostate, non-small cell lung or pancreatic cancer, who participated in the INPACT trial (NCT00312013). The trial evaluated the addition of nadroparin to chemotherapy in patients with advanced malignancy. Patients were divided into tertiles based on protein C at baseline. The association between protein C levels and mortality was evaluated with Cox proportional hazard models. We analysed 477 patients (protein C tertiles: <97, 97-121 and ≥121%). Mean age was 65±9years; 390 (82%) were male; 191 patients (40%) had prostate cancer, 161 (34%) had lung cancer, and 125 (26%) pancreatic cancer. During a median follow-up of 10.4months, 291 patients (61%) died. Median protein C level was 107% (IQR 92-129). In the lowest tertile, 75 patients per 100 patient-years died, as compared to 60 and 54 in the middle and high tertile, respectively. Lower levels of protein C were associated with increased mortality (in tertiles: HR for trend 1.18, 95%CI 1.02-1.36, adjusted for age, sex and nadroparin use; as a continuous variable: HR 1.004, 95%CI 1.00-1.008, p=0.07). Protein C seems inversely associated with mortality in patients with advanced prostate, lung and pancreatic cancer. Further research should validate protein C as a biomarker for mortality, and explore the effects of protein C on progression of cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reinforcement of high-risk anastomoses using laser-activated protein solders: a clinical study

NASA Astrophysics Data System (ADS)

Libutti, Steven K.; Bessler, Marc; Chabot, J.; Bass, Lawrence S.; Oz, Mehmet C.; Auteri, Joseph S.; Kirsch, Andrew J.; Nowygrod, Roman; Treat, Michael R.

1993-07-01

Anastomotic leakage or breakdown can result in catastrophic complications and significantly increased post-operative morbidity and mortality. Certain anastomoses are subject to a higher incidence of disruption and are therefore termed high risk. In an attempt to decrease the risk of anastomotic leaks, we reinforced sutured anastomoses with a laser activated protein solder in patients undergoing esophagojejunostomies (n equals 2), lung transplantation (n equals 2), and pancreaticojejunostomies (Whipple procedure, n equals 5). The protein solder was composed of 1.0 ml of a 25% human albumin solution, 1.0 ml of sodium hyaluronate, and 0.1 ml of Cardiogreen dye. This composition was applied to the sutured anastomosis and activated with an 860 nm pulsed diode laser. Drains were placed when appropriate and patients were followed for up to 10 months post-operatively and assessed for clinical signs of anastomotic leaks. Results to data demonstrated that there were no immediate complications as a result of the procedure. Operative time was not significantly lengthened. There were no cases of clinically significant leakage from any of the reinforced anastomoses. Laser activated protein solders may help to reduce the incidence of leakage in high risk anastomoses. Large numbers of patients and longer follow-up is needed however, to draw significant conclusions.

FLOW-i ventilator performance in the presence of a circle system leak.

PubMed

Lucangelo, Umberto; Ajčević, Miloš; Accardo, Agostino; Borelli, Massimo; Peratoner, Alberto; Comuzzi, Lucia; Zin, Walter A

2017-04-01

Recently, the FLOW-i anaesthesia ventilator was developed based on the SERVO-i intensive care ventilator. The aim of this study was to test the FLOW-i's tidal volume delivery in the presence of a leak in the breathing circuit. We ventilated a test lung model in volume-, pressure-, and pressure-regulated volume-controlled modes (VC, PC, and PRVC, respectively) with a FLOW-i. First, the circuit remained airtight and the ventilator was tested with fresh gas flows of 6, 1, and 0.3 L/min in VC, PC, and PRVC modes and facing 4 combinations of different resistive and elastic loads. Second, a fixed leak in the breathing circuit was introduced and the measurements repeated. In the airtight system, FLOW-i maintained tidal volume (VT) and circuit pressure at approximately the set values, independently of respiratory mode, load, or fresh gas flow. In the leaking circuit, set VT = 500 mL, FLOW-i delivered higher VTs in PC (about 460 mL) than in VC and PRVC, where VTs were substantially less than 500 mL. Interestingly, VT did not differ appreciably from 6 to 0.3 L/min of fresh air flow among the 3 ventilatory modes. In the absence of leakage, peak inspiratory pressures were similar, while they were 35-45 % smaller in PRVC and VC than in PC mode in the presence of leaks. In conclusion, FLOW-i maintained VT (down to fresh gas flows of 0.3 L/min) to 90 % of its preset value in PC mode, which was 4-5 times greater than in VC or PRVC modes.

Leak locating microphone, method and system for locating fluid leaks in pipes

DOEpatents

Kupperman, David S.; Spevak, Lev

1994-01-01

A leak detecting microphone inserted directly into fluid within a pipe includes a housing having a first end being inserted within the pipe and a second opposed end extending outside the pipe. A diaphragm is mounted within the first housing end and an acoustic transducer is coupled to the diaphragm for converting acoustical signals to electrical signals. A plurality of apertures are provided in the housing first end, the apertures located both above and below the diaphragm, whereby to equalize fluid pressure on either side of the diaphragm. A leak locating system and method are provided for locating fluid leaks within a pipe. A first microphone is installed within fluid in the pipe at a first selected location and sound is detected at the first location. A second microphone is installed within fluid in the pipe at a second selected location and sound is detected at the second location. A cross-correlation is identified between the detected sound at the first and second locations for identifying a leak location.

Ammonia Leak Locator Study

NASA Technical Reports Server (NTRS)

Dodge, Franklin T.; Wuest, Martin P.; Deffenbaugh, Danny M.

1995-01-01

The thermal control system of International Space Station Alpha will use liquid ammonia as the heat exchange fluid. It is expected that small leaks (of the order perhaps of one pound of ammonia per day) may develop in the lines transporting the ammonia to the various facilities as well as in the heat exchange equipment. Such leaks must be detected and located before the supply of ammonia becomes critically low. For that reason, NASA-JSC has a program underway to evaluate instruments that can detect and locate ultra-small concentrations of ammonia in a high vacuum environment. To be useful, the instrument must be portable and small enough that an astronaut can easily handle it during extravehicular activity. An additional complication in the design of the instrument is that the environment immediately surrounding ISSA will contain small concentrations of many other gases from venting of onboard experiments as well as from other kinds of leaks. These other vapors include water, cabin air, CO2, CO, argon, N2, and ethylene glycol. Altogether, this local environment might have a pressure of the order of 10(exp -7) to 10(exp -6) torr. Southwest Research Institute (SwRI) was contracted by NASA-JSC to provide support to NASA-JSC and its prime contractors in evaluating ammonia-location instruments and to make a preliminary trade study of the advantages and limitations of potential instruments. The present effort builds upon an earlier SwRI study to evaluate ammonia leak detection instruments [Jolly and Deffenbaugh]. The objectives of the present effort include: (1) Estimate the characteristics of representative ammonia leaks; (2) Evaluate the baseline instrument in the light of the estimated ammonia leak characteristics; (3) Propose alternative instrument concepts; and (4) Conduct a trade study of the proposed alternative concepts and recommend promising instruments. The baseline leak-location instrument selected by NASA-JSC was an ion gauge.

Imaging review of cerebrospinal fluid leaks

PubMed Central

Vemuri, Naga V; Karanam, Lakshmi S P; Manchikanti, Venkatesh; Dandamudi, Srinivas; Puvvada, Sampath K; Vemuri, Vineet K

2017-01-01

Cerebrospinal fluid (CSF) leak occurs due to a defect in the dura and skull base. Trauma remains the most common cause of CSF leak; however, a significant number of cases are iatrogenic, and result from a complication of functional endoscopic sinus surgery (FESS). Early diagnosis of CSF leak is of paramount importance to prevent life-threatening complications such as brain abscess and meningitis. Imaging plays a crucial role in the detection and characterization of CSF leaks. Three-dimensional, isotropic, high resolution computed tomography (HRCT) accurately detects the site and size of the bony defect. CT cisternography, though invasive, helps accurately identify the site of CSF leak, especially in the presence of multiple bony defects. Magnetic resonance imaging (MRI) accurately detects CSF leaks and associated complications such as the encephaloceles and meningoceles. In this review, we emphasize the importance and usefulness of 3D T2 DRIVE MR cisternography in localizing CSF leaks. This sequence has the advantages of effective bone and fat suppression, decreased artefacts, faster acquisition times, three-dimensional capability, y and high spatial resolution in addition to providing very bright signal from the CSF. PMID:29379240

Imaging review of cerebrospinal fluid leaks.

PubMed

Vemuri, Naga V; Karanam, Lakshmi S P; Manchikanti, Venkatesh; Dandamudi, Srinivas; Puvvada, Sampath K; Vemuri, Vineet K

2017-01-01

Cerebrospinal fluid (CSF) leak occurs due to a defect in the dura and skull base. Trauma remains the most common cause of CSF leak; however, a significant number of cases are iatrogenic, and result from a complication of functional endoscopic sinus surgery (FESS). Early diagnosis of CSF leak is of paramount importance to prevent life-threatening complications such as brain abscess and meningitis. Imaging plays a crucial role in the detection and characterization of CSF leaks. Three-dimensional, isotropic, high resolution computed tomography (HRCT) accurately detects the site and size of the bony defect. CT cisternography, though invasive, helps accurately identify the site of CSF leak, especially in the presence of multiple bony defects. Magnetic resonance imaging (MRI) accurately detects CSF leaks and associated complications such as the encephaloceles and meningoceles. In this review, we emphasize the importance and usefulness of 3D T2 DRIVE MR cisternography in localizing CSF leaks. This sequence has the advantages of effective bone and fat suppression, decreased artefacts, faster acquisition times, three-dimensional capability, y and high spatial resolution in addition to providing very bright signal from the CSF.

Fibroblast Activation Protein (FAP) Accelerates Collagen Degradation and Clearance from Lungs in Mice.

PubMed

Fan, Ming-Hui; Zhu, Qiang; Li, Hui-Hua; Ra, Hyun-Jeong; Majumdar, Sonali; Gulick, Dexter L; Jerome, Jacob A; Madsen, Daniel H; Christofidou-Solomidou, Melpo; Speicher, David W; Bachovchin, William W; Feghali-Bostwick, Carol; Puré, Ellen

2016-04-08

Idiopathic pulmonary fibrosis is a disease characterized by progressive, unrelenting lung scarring, with death from respiratory failure within 2-4 years unless lung transplantation is performed. New effective therapies are clearly needed. Fibroblast activation protein (FAP) is a cell surface-associated serine protease up-regulated in the lungs of patients with idiopathic pulmonary fibrosis as well as in wound healing and cancer. We postulate that FAP is not only a marker of disease but influences the development of pulmonary fibrosis after lung injury. In two different models of pulmonary fibrosis, intratracheal bleomycin instillation and thoracic irradiation, we find increased mortality and increased lung fibrosis in FAP-deficient mice compared with wild-type mice. Lung extracellular matrix analysis reveals accumulation of intermediate-sized collagen fragments in FAP-deficient mouse lungs, consistent within vitrostudies showing that FAP mediates ordered proteolytic processing of matrix metalloproteinase (MMP)-derived collagen cleavage products. FAP-mediated collagen processing leads to increased collagen internalization without altering expression of the endocytic collagen receptor, Endo180. Pharmacologic FAP inhibition decreases collagen internalization as expected. Conversely, restoration of FAP expression in the lungs of FAP-deficient mice decreases lung hydroxyproline content after intratracheal bleomycin to levels comparable with that of wild-type controls. Our findings indicate that FAP participates directly, in concert with MMPs, in collagen catabolism and clearance and is an important factor in resolving scar after injury and restoring lung homeostasis. Our study identifies FAP as a novel endogenous regulator of fibrosis and is the first to show FAP's protective effects in the lung. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Identification of Oxidative Stress Related Proteins as Biomarkers for Lung Cancer and Chronic Obstructive Pulmonary Disease in Bronchoalveolar Lavage

PubMed Central

Pastor, Maria Dolores; Nogal, Ana; Molina-Pinelo, Sonia; Meléndez, Ricardo; Romero-Romero, Beatriz; Mediano, Maria Dolores; López-Campos, Jose L.; García-Carbonero, Rocío; Sanchez-Gastaldo, Amparo; Carnero, Amancio; Paz-Ares, Luis

2013-01-01

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. Cigarette smoke causes oxidative stress and an inflammatory response in lung cells, which in turn may be involved in COPD and lung cancer development. The aim of this study was to identify differential proteomic profiles related to oxidative stress response that were potentially involved in these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL) of 60 patients classified in four groups: COPD, COPD and LC, LC, and control (neither COPD nor LC). Proteins were separated into spots by two dimensional polyacrylamide gel electrophoresis (2D-PAGE) and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF). A total of 16 oxidative stress regulatory proteins were differentially expressed in BAL samples from LC and/or COPD patients as compared with the control group. A distinct proteomic reactive oxygen species (ROS) protein signature emerged that characterized lung cancer and COPD. In conclusion, our findings highlight the role of the oxidative stress response proteins in the pathogenic pathways of both diseases, and provide new candidate biomarkers and predictive tools for LC and COPD diagnosis. PMID:23389041

Identification of oxidative stress related proteins as biomarkers for lung cancer and chronic obstructive pulmonary disease in bronchoalveolar lavage.

PubMed

Pastor, Maria Dolores; Nogal, Ana; Molina-Pinelo, Sonia; Meléndez, Ricardo; Romero-Romero, Beatriz; Mediano, Maria Dolores; López-Campos, Jose L; García-Carbonero, Rocío; Sanchez-Gastaldo, Amparo; Carnero, Amancio; Paz-Ares, Luis

2013-02-06

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. Cigarette smoke causes oxidative stress and an inflammatory response in lung cells, which in turn may be involved in COPD and lung cancer development. The aim of this study was to identify differential proteomic profiles related to oxidative stress response that were potentially involved in these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL) of 60 patients classified in four groups: COPD, COPD and LC, LC, and control (neither COPD nor LC). Proteins were separated into spots by two dimensional polyacrylamide gel electrophoresis (2D-PAGE) and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF). A total of 16 oxidative stress regulatory proteins were differentially expressed in BAL samples from LC and/or COPD patients as compared with the control group. A distinct proteomic reactive oxygen species (ROS) protein signature emerged that characterized lung cancer and COPD. In conclusion, our findings highlight the role of the oxidative stress response proteins in the pathogenic pathways of both diseases, and provide new candidate biomarkers and predictive tools for LC and COPD diagnosis.

Procalcitonin and C-reactive protein as early markers of anastomotic leak after laparoscopic colorectal surgery within an enhanced recovery after surgery (ERAS) program.

PubMed

Muñoz, José Luis; Alvarez, María Oliva; Cuquerella, Vicent; Miranda, Elena; Picó, Carlos; Flores, Raquel; Resalt-Pereira, Marta; Moya, Pedro; Pérez, Ana; Arroyo, Antonio

2018-03-08

C-reactive protein (CRP) and procalcitonin (PCT) have been described as good predictors of anastomotic leak after colorectal surgery, obtaining the highest diagnostic accuracy on the 5th postoperative day. However, if an enhanced recovery after surgery (ERAS) program is performed, early predictors are needed in order to ensure a safe and early discharge. The aim of this study was to investigate the efficacy of CRP, PCT, and white blood cell (WBC) count determined on first postoperative days, in predicting septic complications, especially anastomotic leak, after laparoscopic colorectal surgery performed within an ERAS program. We conducted a prospective study including 134 patients who underwent laparoscopic colorectal surgery within an ERAS program between 2015 and 2017. The primary endpoint investigated was anastomotic leak. CRP, PCT, and WBC count were determined in the blood sample extracted on postoperative day 1 (POD 1), POD 2 and POD 3. Anastomotic leak (AL) was detected in 6 patients (4.5%). Serum levels of CRP and PCT, but not WBC, determined on POD 1, POD 2, and POD 3 were significantly higher in patients who had AL in the postoperative course. Using ROC analysis, the best AUC of the CRP and PCT levels was on POD 3 (0.837 and 0.947, respectively). A CRP cutoff level at 163 mg/l yielded 85% sensitivity, 80% specificity, and 99% negative predictive value (NPV). A PCT cutoff level at 2.5 ng/ml achieved 85% sensitivity, 95% specificity, 44% positive predictive value, and 99% NPV. CRP and PCT are relevant markers for detecting postoperative AL after laparoscopic colorectal surgery. Furthermore, they can ensure an early discharge with a low probability of AL when an ERAS program is performed.

Apparatus for detecting leaks

DOEpatents

Booth, Eugene T.

1976-02-24

A method and apparatus for determining the position of and estimating the size of leaks in an evacuating apparatus comprising the use of a testing gas such as helium or hydrogen flowing around said apparatus whereby the testing gas will be drawn in at the site of any leaks.

Gaseous leak detector

DOEpatents

Juravic, Jr., Frank E.

1988-01-01

In a short path length mass-spectrometer type of helium leak detector wherein the helium trace gas is ionized, accelerated and deflected onto a particle counter, an arrangement is provided for converting the detector to neon leak detection. The magnetic field of the deflection system is lowered so as to bring the non linear fringe area of the magnetic field across the ion path, thereby increasing the amount of deflection of the heavier neon ions.

Leak detection with expandable coatings

NASA Technical Reports Server (NTRS)

1971-01-01

Developed and evaluated is a system for leak detection that can be easily applied over separable connectors and that expands into a bubble or balloon if a leak is present. This objective is accomplished by using thin films of Parafilm tape wrapped over connectors, which are then overcoated with a special formulation. The low yield strength and the high elongation of the envelope permit bubble formation if leakage occurs. This system is appropriate for welds and other hardware besides separable connectors. The practical limit of this system appears to be for leaks exceeding 0.000001 cc/sec. If this envelope is used to trap gases for mass spectrometer inspection, leaks in the range of ten to the minus 8th power cc/sec. may be detectable.

The effect of PKA-mediated phosphorylation of ryanodine receptor on SR Ca2+ leak in ventricular myocytes.

PubMed

Bovo, Elisa; Huke, Sabine; Blatter, Lothar A; Zima, Aleksey V

2017-03-01

Functional impact of cardiac ryanodine receptor (type 2 RyR or RyR2) phosphorylation by protein kinase A (PKA) remains highly controversial. In this study, we characterized a functional link between PKA-mediated RyR2 phosphorylation level and sarcoplasmic reticulum (SR) Ca 2+ release and leak in permeabilized rabbit ventricular myocytes. Changes in cytosolic [Ca 2+ ] and intra-SR [Ca 2+ ] SR were measured with Fluo-4 and Fluo-5N, respectively. Changes in RyR2 phosphorylation at two PKA sites, serine-2031 and -2809, were measured with phospho-specific antibodies. cAMP (10μM) increased Ca 2+ spark frequency approximately two-fold. This effect was associated with an increase in SR Ca 2+ load from 0.84 to 1.24mM. PKA inhibitory peptide (PKI; 10μM) abolished the cAMP-dependent increase of SR Ca 2+ load and spark frequency. When SERCA was completely blocked by thapsigargin, cAMP did not affect RyR2-mediated Ca 2+ leak. The lack of a cAMP effect on RyR2 function can be explained by almost maximal phosphorylation of RyR2 at serine-2809 after sarcolemma permeabilization. This high RyR2 phosphorylation level is likely the consequence of a balance shift between protein kinase and phosphatase activity after permeabilization. When RyR2 phosphorylation at serine-2809 was reduced to its "basal" level (i.e. RyR2 phosphorylation level in intact myocytes) using kinase inhibitor staurosporine, SR Ca 2+ leak was significantly reduced. Surprisingly, further dephosphorylation of RyR2 with protein phosphatase 1 (PP1) markedly increased SR Ca 2+ leak. At the same time, phosphorylation of RyR2 at serine 2031 did not significantly change under identical experimental conditions. These results suggest that RyR2 phosphorylation by PKA has a complex effect on SR Ca 2+ leak in ventricular myocytes. At an intermediate level of RyR2 phosphorylation SR Ca 2+ leak is minimal. However, complete dephosphorylation and maximal phosphorylation of RyR2 increases SR Ca 2+ leak. Copyright © 2017 Elsevier

Prenatal retinoic acid treatment upregulates late gestation lung protein 1 in the nitrofen-induced hypoplastic lung in late gestation.

PubMed

Ruttenstock, Elke Maria; Doi, Takashi; Dingemann, Jens; Puri, Prem

2011-02-01

Pulmonary hypoplasia (PH), the leading cause of mortality in congenital diaphragmatic hernia (CDH), is associated with arrested alveolarization. Late gestation lung protein 1 (LGL1) plays a crucial role in the regulation of alveolarization. Inhibition of LGL1 impairs alveolar maturation in fetal rat lungs. LGL1 heterozygotus knockout mice display delayed lung maturation. It is well known that prenatal administration of retinoic acid (RA) stimulates alveologenesis in nitrofen-induced PH. In vitro studies have reported that RA is a key modulator of LGL1 during alveologenesis. We hypothesized, that pulmonary gene expression of LGL1 is downregulated in the late stage of lung development, and that prenatal administration of RA upregulates pulmonary LGL1 expression in the nitrofen CDH model. Pregnant rats were exposed to nitrofen on day 9 (D9) of gestation. RA was given intraperitoneally on D18, D19 and D20. Fetal lungs were dissected on D21 and divided into control, control + RA, CDH and CDH + RA group. Expression levels of LGL1 were determined using RT-PCR and immunohistochemistry. On D21, LGL1 relative mRNA expression levels were significantly downregulated in CDH group compared to controls. After RA treatment, gene expression levels of LGL1 were significantly upregulated in CDH + RA and control + RA compared to CDH group. Immunohistochemical studies confirmed these results. Downregulation of pulmonary LGL1 gene expression in the late stage of lung development may interfere with normal alveologenesis. Upregulation of LGL1 pulmonary gene expression after RA treatment may promote lung growth by stimulating alveologenesis in the nitrofen CDH model.

Control of Lung Inflammation by Microbiome and Peptidoglycan Recognition Protein

DTIC Science & Technology

2017-07-01

AWARD NUMBER: W81XWH-16-1-0230 TITLE: Control of Lung Inflammation by Microbiome and Peptidoglycan Recognition Protein PRINCIPAL INVESTIGATOR...the Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704-0188...for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO

Pathogenesis of vascular leak in dengue virus infection.

PubMed

Malavige, Gathsaurie Neelika; Ogg, Graham S

2017-07-01

Endothelial dysfunction leading to vascular leak is the hallmark of severe dengue. Vascular leak typically becomes clinically evident 3-6 days after the onset of illness, which is known as the critical phase. This critical phase follows the period of peak viraemia, and lasts for 24-48 hr and usually shows rapid and complete reversal, suggesting that it is likely to occur as a result of inflammatory mediators, rather than infection of the endothelium. Cytokines such as tumour necrosis factor-α, which are known to be elevated in the critical phase of dengue, are likely to be contributing factors. Dengue NS1, a soluble viral protein, has also been shown to disrupt the endothelial glycocalyx and thus contribute to vascular leak, although there appears to be a discordance between the timing of NS1 antigenaemia and occurrence of vascular leak. In addition, many inflammatory lipid mediators are elevated in acute dengue viral infection such as platelet activating factor (PAF) and leukotrienes. Furthermore, many other inflammatory mediators such as vascular endothelial growth factor and angiopoietin-2 have been shown to be elevated in patients with dengue haemorrhagic fever, exerting their action in part by inducing the activity of phospholipases, which have diverse inflammatory effects including generation of PAF. Platelets have also been shown to significantly contribute to endothelial dysfunction by production of interleukin-1β through activation of the NLRP3 inflammasome and also by inducing production of inflammatory cytokines by monocytes. Drugs that block down-stream immunological mediator pathways such as PAF may also be beneficial in the treatment of severe disease. © 2017 John Wiley & Sons Ltd.

High Levels of S100A8/A9 Proteins Aggravate Ventilator-Induced Lung Injury via TLR4 Signaling

PubMed Central

Aslami, Hamid; Jongsma, Geartsje; van den Berg, Elske; Vlaar, Alexander P. J.; Roelofs, Joris J. T. H.; Juffermans, Nicole P.; Schultz, Marcus J.; van der Poll, Tom; Roth, Johannes; Wieland, Catharina W.

2013-01-01

Background Bacterial products add to mechanical ventilation in enhancing lung injury. The role of endogenous triggers of innate immunity herein is less well understood. S100A8/A9 proteins are released by phagocytes during inflammation. The present study investigates the role of S100A8/A9 proteins in ventilator-induced lung injury. Methods Pulmonary S100A8/A9 levels were measured in samples obtained from patients with and without lung injury. Furthermore, wild-type and S100A9 knock-out mice, naive and with lipopolysaccharide-induced injured lungs, were randomized to 5 hours of spontaneously breathing or mechanical ventilation with low or high tidal volume (VT). In addition, healthy spontaneously breathing and high VT ventilated mice received S100A8/A9, S100A8 or vehicle intratracheal. Furthermore, the role of Toll-like receptor 4 herein was investigated. Results S100A8/A9 protein levels were elevated in patients and mice with lung injury. S100A8/A9 levels synergistically increased upon the lipopolysaccharide/high VT MV double hit. Markers of alveolar barrier dysfunction, cytokine and chemokine levels, and histology scores were attenuated in S100A9 knockout mice undergoing the double-hit. Exogenous S100A8/A9 and S100A8 induced neutrophil influx in spontaneously breathing mice. In ventilated mice, these proteins clearly amplified inflammation: neutrophil influx, cytokine, and chemokine levels were increased compared to ventilated vehicle-treated mice. In contrast, administration of S100A8/A9 to ventilated Toll-like receptor 4 mutant mice did not augment inflammation. Conclusion S100A8/A9 proteins increase during lung injury and contribute to inflammation induced by HVT MV combined with lipopolysaccharide. In the absence of lipopolysaccharide, high levels of extracellular S100A8/A9 still amplify ventilator-induced lung injury via Toll-like receptor 4. PMID:23874727

Leak testing and repair of fusion devices

NASA Astrophysics Data System (ADS)

Kozman, T. A.

1983-06-01

The leak testing, reporting and vacuum leak repair techniques of the MPTF yin-yang number one magnet system, the world's largest superconducting magnet system, are discussed. Based on this experience, techniques are developed for testing and repairing leaks on the 42 MPTF-B magnets. The leak hunting techniques for the yin-yang magnet systems were applied to two helium circuits (the coil bundle and guard vacuum; both require helium flow for magnet cooldown). Additionally, during MPTF-B operation there are warm water plasma shields and piping that require leak checking.

Low Level Leaks

NASA Technical Reports Server (NTRS)

1998-01-01

NASA has transferred the improved portable leak detector technology to UE Systems, Inc.. This instrument was developed to detect leaks in fluid systems of critical launch and ground support equipment. This system incorporates innovative electronic circuitry, improved transducers, collecting horns, and contact sensors that provide a much higher degree of reliability, sensitivity and versatility over previously used systems. Potential commercial uses are pipelines, underground utilities, air-conditioning systems, petrochemical systems, aerospace, power transmission lines and medical devices.

40 CFR 63.1005 - Leak repair.

Code of Federal Regulations, 2013 CFR

2013-07-01

... lubricant into the lubricated packing. (b) Leak identification removal—(1) Valves in gas/vapor and light liquid service. The leak identification on a valve in gas/vapor or light liquid service may be removed... monitoring. The leak identification on a connector in gas/vapor or light liquid service may be removed after...

40 CFR 63.1005 - Leak repair.

Code of Federal Regulations, 2012 CFR

2012-07-01

... lubricant into the lubricated packing. (b) Leak identification removal—(1) Valves in gas/vapor and light liquid service. The leak identification on a valve in gas/vapor or light liquid service may be removed... monitoring. The leak identification on a connector in gas/vapor or light liquid service may be removed after...

40 CFR 63.1005 - Leak repair.

Code of Federal Regulations, 2011 CFR

2011-07-01

... lubricant into the lubricated packing. (b) Leak identification removal—(1) Valves in gas/vapor and light liquid service. The leak identification on a valve in gas/vapor or light liquid service may be removed... monitoring. The leak identification on a connector in gas/vapor or light liquid service may be removed after...

40 CFR 63.1005 - Leak repair.

Code of Federal Regulations, 2014 CFR

2014-07-01

... lubricant into the lubricated packing. (b) Leak identification removal—(1) Valves in gas/vapor and light liquid service. The leak identification on a valve in gas/vapor or light liquid service may be removed... monitoring. The leak identification on a connector in gas/vapor or light liquid service may be removed after...

40 CFR 265.196 - Response to leaks or spills and disposition of leaking or unfit-for-use tank systems.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Response to leaks or spills and... leaks or spills and disposition of leaking or unfit-for-use tank systems. A tank system or secondary containment system from which there has been a leak or spill, or which is un-fit for use, must be removed from...

USP7 promotes cell proliferation through the stabilization of Ki-67 protein in non-small cell lung cancer cells.

PubMed

Zhang, Chao; Lu, Jing; Zhang, Quan-Wu; Zhao, Wei; Guo, Jia-Hui; Liu, Shan-Ling; Wu, Ying-Li; Jiang, Bin; Gao, Feng-Hou

2016-10-01

The Ki-67 antigen (Ki-67) is the most reliable immunohistochemical marker for evaluation of cell proliferation in non-small cell lung cancer. However, the mechanisms underlying the regulation of protein levels of Ki-67 in non-small cell lung cancer have remained elusive. In this study, we found that Ki-67 and ubiquitin-specific processing protease 7 (USP7) protein were highly expressed in the nucleus of non-small cell lung cancer cells. Furthermore, statistical analysis uncovered the existence of a strong correlation between Ki-67 and USP7 levels. We could also show that the protein levels of Ki-67 in non-small cell lung cancer cells significantly decreased after treatment with P22077, a selective chemical inhibitor of USP7, while the Ki-67 mRNA levels were unperturbed. Similar results were obtained by knocking down USP7 using short hairpin RNA (shRNA) in lung cancer cells. Interestingly, we noticed that ubiquitination levels of Ki-67 increased dramatically in USP7-silenced cells. The tests in vitro and vivo showed a significant delay in tumor cell growth upon knockdown of USP7. Additionally, drug sensitivity tests indicated that USP7-silenced A549 cells had enhanced sensitivity to paclitaxel and docetaxel, while there was no significant change in sensitivity toward carboplatin and cisplatin. Taken together, these data strongly suggest that the overexpression of USP7 might promote cell proliferation by deubiquitinating Ki-67 protein, thereby maintaining its high levels in the non-small cell lung cancer. Our study also hints potential for the development of deubiquitinase-based therapies, especially those targeting USP7 to improve the condition of patients diagnosed with non-small cell lung cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comprehensive Quantitative Analysis on Privacy Leak Behavior

PubMed Central

Fan, Lejun; Wang, Yuanzhuo; Jin, Xiaolong; Li, Jingyuan; Cheng, Xueqi; Jin, Shuyuan

2013-01-01

Privacy information is prone to be leaked by illegal software providers with various motivations. Privacy leak behavior has thus become an important research issue of cyber security. However, existing approaches can only qualitatively analyze privacy leak behavior of software applications. No quantitative approach, to the best of our knowledge, has been developed in the open literature. To fill this gap, in this paper we propose for the first time four quantitative metrics, namely, possibility, severity, crypticity, and manipulability, for privacy leak behavior analysis based on Privacy Petri Net (PPN). In order to compare the privacy leak behavior among different software, we further propose a comprehensive metric, namely, overall leak degree, based on these four metrics. Finally, we validate the effectiveness of the proposed approach using real-world software applications. The experimental results demonstrate that our approach can quantitatively analyze the privacy leak behaviors of various software types and reveal their characteristics from different aspects. PMID:24066046

Comprehensive quantitative analysis on privacy leak behavior.

PubMed

Fan, Lejun; Wang, Yuanzhuo; Jin, Xiaolong; Li, Jingyuan; Cheng, Xueqi; Jin, Shuyuan

2013-01-01

Privacy information is prone to be leaked by illegal software providers with various motivations. Privacy leak behavior has thus become an important research issue of cyber security. However, existing approaches can only qualitatively analyze privacy leak behavior of software applications. No quantitative approach, to the best of our knowledge, has been developed in the open literature. To fill this gap, in this paper we propose for the first time four quantitative metrics, namely, possibility, severity, crypticity, and manipulability, for privacy leak behavior analysis based on Privacy Petri Net (PPN). In order to compare the privacy leak behavior among different software, we further propose a comprehensive metric, namely, overall leak degree, based on these four metrics. Finally, we validate the effectiveness of the proposed approach using real-world software applications. The experimental results demonstrate that our approach can quantitatively analyze the privacy leak behaviors of various software types and reveal their characteristics from different aspects.

Unique spatial and cellular expression patterns of Hoxa5, Hoxb4 and Hoxb6 proteins in normal developing murine lung are modified in pulmonary hypoplasia

PubMed Central

Volpe, MaryAnn Vitoria; Wang, Karen Ting Wai; Nielsen, Heber Carl; Chinoy, Mala Romeshchandra

2009-01-01

Background Hox transcription factors modulate signaling pathways controlling organ morphogenesis and maintain cell fate and differentiation in adults. Retinoid signaling, key in regulating Hox expression, is altered in pulmonary hypoplasia. Information on pattern-specific expression of Hox proteins in normal lung development and in pulmonary hypoplasia is minimal. Our objective was to determine how pulmonary hypoplasia alters temporal, spatial and cellular expression of Hoxa5, Hoxb4 and Hoxb6 proteins compared to normal lung development. Methods Temporal, spatial and cellular Hoxa5, Hoxb4 and Hoxb6 expression was studied in normal (untreated) and nitrofen-induced hypoplastic (NT-PH) lungs from gestational day 13.5, 16, 19 fetuses and neonates using western blot and immunohistochemistry. Results Modification of protein levels and spatial and cellular Hox expression patterns in NT-PH lungs was consistent with delayed lung development. Distinct protein isoforms were detected for each Hox protein. Expression levels of the Hoxa5 and Hoxb6 isoforms changed with development and further in NT-PH lungs. Compared to normal lungs, Gd19 and neonatal NT-PH lungs had decreased Hoxb6 and increased Hoxa5 and Hoxb4. Hoxa5 cellular localization changed from mesenchyme to epithelia earlier in normal lungs. Hoxb4 was expressed in mesenchyme and epithelial cells throughout development. Hoxb6 remained mainly in mesenchymal cells around distal airways. Conclusions Unique spatial and cellular expression of Hoxa5, Hoxb4 and Hoxb6 participates in branching morphogenesis and terminal sac formation. Altered Hox protein temporal and cellular balance of expression either contributes to pulmonary hypoplasia or functions as a compensatory mechanism attempting to correct abnormal lung development and maturation in this condition. PMID:18553509

Glycol leak detection system

NASA Astrophysics Data System (ADS)

Rabe, Paul; Browne, Keith; Brink, Janus; Coetzee, Christiaan J.

2016-07-01

MonoEthylene glycol coolant is used extensively on the Southern African Large Telescope to cool components inside the telescope chamber. To prevent coolant leaks from causing serious damage to electronics and optics, a Glycol Leak Detection System was designed to automatically shut off valves in affected areas. After two years of research and development the use of leaf wetness sensors proved to work best and is currently operational. These sensors are placed at various critical points within the instrument payload that would trigger the leak detector controller, which closes the valves, and alerts the building management system. In this paper we describe the research of an initial concept and the final accepted implementation and the test results thereof.

The role of chitin, chitinases, and chitinase-like proteins in pediatric lung diseases.

PubMed

Mack, Ines; Hector, Andreas; Ballbach, Marlene; Kohlhäufl, Julius; Fuchs, Katharina J; Weber, Alexander; Mall, Marcus A; Hartl, Dominik

2015-12-01

Chitin, after cellulose, the second most abundant biopolymer on earth, is a key component of insects, fungi, and house-dust mites. Lower life forms are endowed with chitinases to defend themselves against chitin-bearing pathogens. Unexpectedly, humans were also found to express chitinases as well as chitinase-like proteins that modulate immune responses. Particularly, increased levels of the chitinase-like protein YKL-40 have been associated with severe asthma, cystic fibrosis, and other inflammatory disease conditions. Here, we summarize and discuss the potential role of chitin, chitinases, and chitinase-like proteins in pediatric lung diseases.

Comparative proteomic analysis of lung tissue from patients with idiopathic pulmonary fibrosis (IPF) and lung transplant donor lungs.

PubMed

Korfei, Martina; Schmitt, Sigrid; Ruppert, Clemens; Henneke, Ingrid; Markart, Philipp; Loeh, Benjamin; Mahavadi, Poornima; Wygrecka, Malgorzata; Klepetko, Walter; Fink, Ludger; Bonniaud, Philippe; Preissner, Klaus T; Lochnit, Günter; Schaefer, Liliana; Seeger, Werner; Guenther, Andreas

2011-05-06

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease for which no effective therapy exists to date. To identify the molecular mechanisms underlying IPF, we performed comparative proteome analysis of lung tissue from patients with sporadic IPF (n = 14) and human donor lungs (controls, n = 10) using two-dimensional gel electrophoresis and MALDI-TOF-MS. Eighty-nine differentially expressed proteins were identified, from which 51 were up-regulated and 38 down-regulated in IPF. Increased expression of markers for the unfolded protein response (UPR), heat-shock proteins, and DNA damage stress markers indicated a chronic cell stress-response in IPF lungs. By means of immunohistochemistry, induction of UPR markers was encountered in type-II alveolar epithelial cells of IPF but not of control lungs. In contrast, up-regulation of heat-shock protein 27 (Hsp27) was exclusively observed in proliferating bronchiolar basal cells and associated with aberrant re-epithelialization at the bronchiolo-alveolar junctions. Among the down-regulated proteins in IPF were antioxidants, members of the annexin family, and structural epithelial proteins. In summary, our results indicate that IPF is characterized by epithelial cell injury, apoptosis, and aberrant epithelial proliferation.

Long-life leak standard assembly. [Patent application

DOEpatents

Basford, J.A.; Mathis, J.E.; Wright, H.C.

1980-11-12

The present invention is directed to a portable leak standard assembly which is capable of providing a stream of high-purity reference gas at a virtually constant flow rate over an extensive period of time. The leak assembly comprises a high pressure reservoir coupled to a metal leak valve through a valve-controlled conduit. A reproducible leak valve useful in this assembly is provided by a metal tube crimped with a selected pressure loading for forming an orifice in the tube with this orifice being of a sufficient size to provide the selected flow rate. The leak valve assembly is formed of metal so that it can be baked-out in a vacuum furnace to rid the reservoir and attendent components of volatile impurities which reduce the efficiency of the leak standard.

[Effects of heat shock protein 70-2 gene polymorphisms on the transcription of HSP 70-2 mRNA and the translation of HSP 70 protein in lung cancer].

PubMed

Lu, Hao-quan; Wang, Yu-zhen; Sun, Peng-hui; Liang, Shou-pei; Li, Jie; Wang, Xiao-long; Xu, Dong; Yao, Wu; Wu, Yi-ming; Zhou, Fang

2012-05-01

This study aimed to investigate the effects of gene polymorphism of heat shock protein 70-2 (HSP 70-2) 1267A/G on the mRNA level HSP 70-2 mRNA and the protein level HSP 70 in human lung cancer. Forty six lung cancer patients diagnosed histopathologically between February and August 2008 from a hospital in zhengzhou were enrolled as the subjects in this study. Gene polymorphism of HSP 70-2 1276A/G in 46 patients with lung cancer was detected by PCR-RFLP. The mRNA levels of HSP 70-2 mRNA and the protein levels of HSP 70 in lung tissue and para-cancerous tissues of these subjects were determined by RT-PCR and Western blotting respectively. The expression levels of HSP 70-2 mRNA (1.02 ± 0.30) and HSP 70 protein (0.44 ± 0.12) in the lung cancer tissues was significantly higher than that in para-cancerous tissues (0.19 ± 0.04, 0.12 ± 0.02). The relative levels of HSP 70-2 mRNA in the subjects with AA genotype (1.32 ± 0.22) were significantly higher than the patients with AG genotype or GG genotype (0.95 ± 0.17, 0.70 ± 0.16) at the site of 1267 (A/G) (P < 0.01); however, the relative protein levels of HSP 70 were 0.47 ± 0.13 (AA genotype), 0.42 ± 0.11 (AG genotype), 0.45 ± 0.11 (GG genotype), respectively, which showed no statistically significant difference (P > 0.05). The polymorphism of HSP 70-2 1267 (A/G) is highly associated with the transcription level of HSP 70-2 mRNA, but not with the expression level of HSP 70 protein.

Postoperative chest tube management: measuring air leak using an electronic device decreases variability in the clinical practice.

PubMed

Varela, Gonzalo; Jiménez, Marcelo F; Novoa, Nuria Maria; Aranda, José Luis

2009-01-01

Since there are no data in the literature regarding variability in the management of postoperative pleural drainages, we have designed a prospective randomized study aimed at measuring inter-observer variability in deciding when to withdraw chest tubes after lung resection and to evaluate if the use of an electronic device to measure postoperative air leak decreases clinical practice variations. Sixty-one patients undergoing pulmonary resection were randomly assigned to one of the following groups: digital group (electronic measure of pleural air leak using Millicore AB DigiVent chest drainage system) or traditional group (standard water seal pleural chamber). Chest tube withdrawal criteria were established in advance. During morning rounds, two thoracic surgeons with comparable clinical experience and blinded to the decision of their counterpart, evaluated chest tube withdrawal criteria and noted whether the tube should be withdrawn or not. Inter-observer variability kappa index and global, positive, and negative agreement rates were calculated on 2 x 2 tables. Each observation episode was considered in the calculation. Fifty-four observations were recorded in the traditional group. Kappa coefficient was 0.37 (overall agreement rate: 0.58; positive agreement rate: 0.72; and negative agreement rate: 0.64). In the digital group, 67 observations were recorded. Kappa coefficient was 0.88 (overall agreement rate: 0.94; positive agreement rate 0.94; and negative agreement rate 0.94). We have demonstrated a high rate of disagreement related to the indication to remove chest tubes after lung resection and the improvement of the agreement rate with the use of an electronic device to measure postoperative air leak and pleural pressures.

The interplay of lung surfactant proteins and lipids assimilates the macrophage clearance of nanoparticles.

PubMed

Ruge, Christian A; Schaefer, Ulrich F; Herrmann, Jennifer; Kirch, Julian; Cañadas, Olga; Echaide, Mercedes; Pérez-Gil, Jesús; Casals, Cristina; Müller, Rolf; Lehr, Claus-Michael

2012-01-01

The peripheral lungs are a potential entrance portal for nanoparticles into the human body due to their large surface area. The fact that nanoparticles can be deposited in the alveolar region of the lungs is of interest for pulmonary drug delivery strategies and is of equal importance for toxicological considerations. Therefore, a detailed understanding of nanoparticle interaction with the structures of this largest and most sensitive part of the lungs is important for both nanomedicine and nanotoxicology. Astonishingly, there is still little known about the bio-nano interactions that occur after nanoparticle deposition in the alveoli. In this study, we compared the effects of surfactant-associated protein A (SP-A) and D (SP-D) on the clearance of magnetite nanoparticles (mNP) with either more hydrophilic (starch) or hydrophobic (phosphatidylcholine) surface modification by an alveolar macrophage (AM) cell line (MH-S) using flow cytometry and confocal microscopy. Both proteins enhanced the AM uptake of mNP compared with pristine nanoparticles; for the hydrophilic ST-mNP, this effect was strongest with SP-D, whereas for the hydrophobic PL-mNP it was most pronounced with SP-A. Using gel electrophoretic and dynamic light scattering methods, we were able to demonstrate that the observed cellular effects were related to protein adsorption and to protein-mediated interference with the colloidal stability. Next, we investigated the influence of various surfactant lipids on nanoparticle uptake by AM because lipids are the major surfactant component. Synthetic surfactant lipid and isolated native surfactant preparations significantly modulated the effects exerted by SP-A and SP-D, respectively, resulting in comparable levels of macrophage interaction for both hydrophilic and hydrophobic nanoparticles. Our findings suggest that because of the interplay of both surfactant lipids and proteins, the AM clearance of nanoparticles is essentially the same, regardless of different

Ultrasonic Detectors Safely Identify Dangerous, Costly Leaks

NASA Technical Reports Server (NTRS)

2013-01-01

In 1990, NASA grounded its space shuttle fleet. The reason: leaks detected in the hydrogen fuel systems of the Space Shuttles Atlantis and Columbia. Unless the sources of the leaks could be identified and fixed, the shuttles would not be safe to fly. To help locate the existing leaks and check for others, Kennedy Space Center engineers used portable ultrasonic detectors to scan the fuel systems. As a gas or liquid escapes from a leak, the resulting turbulence creates ultrasonic noise, explains Gary Mohr, president of Elmsford, New York-based UE Systems Inc., a long-time leader in ultrasonic detector technologies. "In lay terms, the leak is like a dog whistle, and the detector is like the dog ear." Because the ultrasound emissions from a leak are highly localized, they can be used not only to identify the presence of a leak but also to help pinpoint a leak s location. The NASA engineers employed UE s detectors to examine the shuttle fuel tanks and solid rocket boosters, but encountered difficulty with the devices limited range-certain areas of the shuttle proved difficult or unsafe to scan up close. To remedy the problem, the engineers created a long-range attachment for the detectors, similar to "a zoom lens on a camera," Mohr says. "If you are on the ground, and the leak is 50 feet away, the detector would now give you the same impression as if you were only 25 feet away." The enhancement also had the effect of reducing background noise, allowing for a clearer, more precise detection of a leak s location.

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.

ZrO2 nanoparticles labeled via a native protein corona: detection by fluorescence microscopy and Raman microspectroscopy in rat lungs.

PubMed

Silge, Anja; Bräutigam, Katharina; Bocklitz, Thomas; Rösch, Petra; Vennemann, Antje; Schmitz, Inge; Popp, Jürgen; Wiemann, Martin

2015-08-07

ZrO2 nanoparticles are frequently used in composite materials such as dental fillers from where they may be released and inhaled upon polishing and grinding. Since the overall distribution of ZrO2 NP inside the lung parenchyma can hardly be observed by routine histology, here a labeling with a fluorphore was used secondary to the adsorption of serum proteins. Particles were then intratracheally instilled into rat lungs. After 3 h fluorescent structures consisted of agglomerates scattered throughout the lung parenchyma, which were mainly concentrated in alveolar macrophages after 3 d. A detection method based on Raman microspectroscopy was established to investigate the chemical composition of those fluorescent structures in detail. Raman measurements were arranged such that no spectral interference with the protein-bound fluorescence label was evident. Applying chemometrical methods, Raman signals of the ZrO2 nanomaterial were co-localized with the fluorescence label, indicating the stability of the nanomaterial-protein-dye complex inside the rat lung. The combination of Raman microspectroscopy and adsorptive fluorescence labeling may, therefore, become a useful tool for studying the localization of protein-coated nanomaterials in cells and tissues.

Leak detection using structure-borne noise

NASA Technical Reports Server (NTRS)

Holland, Stephen D. (Inventor); Roberts, Ronald A. (Inventor); Chimenti, Dale E. (Inventor)

2010-01-01

A method for detection and location of air leaks in a pressure vessel, such as a spacecraft, includes sensing structure-borne ultrasound waveforms associated with turbulence caused by a leak from a plurality of sensors and cross correlating the waveforms to determine existence and location of the leak. Different configurations of sensors and corresponding methods can be used. An apparatus for performing the methods is also provided.

Case Report of a Hypobaric Chamber Fitness to Fly Test in a Child With Severe Cystic Lung Disease.

PubMed

Loo, Sarah; Campbell, Andrew; Vyas, Julian; Pillarisetti, Naveen

2017-07-01

Patients with severe cystic lung disease are considered to be at risk for cyst rupture during air travel because of the possibility of increase in cyst size and impaired equilibration of pressure between the cysts and other parts of the lung. This may have clinically devastating consequences for the patient but may also result in significant costs for emergency alteration of flight schedule. We report the use of a hypobaric chamber to simulate cabin pressure changes encountered on a commercial flight to assess the safety to fly of a child with severe cystic lung disease secondary to Langerhans cell histiocytosis. The test did not result in an air leak, and the child subsequently undertook air travel without mishap. This is the first reported use of a hypobaric chamber test in a child with severe cystic lung disease. This test has the potential to be used as a fitness to fly test in children at risk for air leak syndromes who are being considered for air travel. Copyright © 2017 by the American Academy of Pediatrics.

Air-Leak Effects on Ear-Canal Acoustic Absorbance

PubMed Central

Rasetshwane, Daniel M.; Kopun, Judy G.; Gorga, Michael P.; Neely, Stephen T.

2015-01-01

Objective: Accurate ear-canal acoustic measurements, such as wideband acoustic admittance, absorbance, and otoacoustic emissions, require that the measurement probe be tightly sealed in the ear canal. Air leaks can compromise the validity of the measurements, interfere with calibrations, and increase variability. There are no established procedures for determining the presence of air leaks or criteria for what size leak would affect the accuracy of ear-canal acoustic measurements. The purpose of this study was to determine ways to quantify the effects of air leaks and to develop objective criteria to detect their presence. Design: Air leaks were simulated by modifying the foam tips that are used with the measurement probe through insertion of thin plastic tubing. To analyze the effect of air leaks, acoustic measurements were taken with both modified and unmodified foam tips in brass-tube cavities and human ear canals. Measurements were initially made in cavities to determine the range of critical leaks. Subsequently, data were collected in ears of 21 adults with normal hearing and normal middle-ear function. Four acoustic metrics were used for predicting the presence of air leaks and for quantifying these leaks: (1) low-frequency admittance phase (averaged over 0.1–0.2 kHz), (2) low-frequency absorbance, (3) the ratio of compliance volume to physical volume (CV/PV), and (4) the air-leak resonance frequency. The outcome variable in this analysis was the absorbance change (Δabsorbance), which was calculated in eight frequency bands. Results: The trends were similar for both the brass cavities and the ear canals. ΔAbsorbance generally increased with air-leak size and was largest for the lower frequency bands (0.1–0.2 and 0.2–0.5 kHz). Air-leak effects were observed in frequencies up to 10 kHz, but their effects above 1 kHz were unpredictable. These high-frequency air leaks were larger in brass cavities than in ear canals. Each of the four predictor variables

Air-leak effects on ear-canal acoustic absorbance.

PubMed

Groon, Katherine A; Rasetshwane, Daniel M; Kopun, Judy G; Gorga, Michael P; Neely, Stephen T

2015-01-01

Accurate ear-canal acoustic measurements, such as wideband acoustic admittance, absorbance, and otoacoustic emissions, require that the measurement probe be tightly sealed in the ear canal. Air leaks can compromise the validity of the measurements, interfere with calibrations, and increase variability. There are no established procedures for determining the presence of air leaks or criteria for what size leak would affect the accuracy of ear-canal acoustic measurements. The purpose of this study was to determine ways to quantify the effects of air leaks and to develop objective criteria to detect their presence. Air leaks were simulated by modifying the foam tips that are used with the measurement probe through insertion of thin plastic tubing. To analyze the effect of air leaks, acoustic measurements were taken with both modified and unmodified foam tips in brass-tube cavities and human ear canals. Measurements were initially made in cavities to determine the range of critical leaks. Subsequently, data were collected in ears of 21 adults with normal hearing and normal middle-ear function. Four acoustic metrics were used for predicting the presence of air leaks and for quantifying these leaks: (1) low-frequency admittance phase (averaged over 0.1-0.2 kHz), (2) low-frequency absorbance, (3) the ratio of compliance volume to physical volume (CV/PV), and (4) the air-leak resonance frequency. The outcome variable in this analysis was the absorbance change (Δabsorbance), which was calculated in eight frequency bands. The trends were similar for both the brass cavities and the ear canals. ΔAbsorbance generally increased with air-leak size and was largest for the lower frequency bands (0.1-0.2 and 0.2-0.5 kHz). Air-leak effects were observed in frequencies up to 10 kHz, but their effects above 1 kHz were unpredictable. These high-frequency air leaks were larger in brass cavities than in ear canals. Each of the four predictor variables exhibited consistent dependence on

High sensitivity leak detection method and apparatus

DOEpatents

Myneni, Ganapatic R.

1994-01-01

An improved leak detection method is provided that utilizes the cyclic adsorption and desorption of accumulated helium on a non-porous metallic surface. The method provides reliable leak detection at superfluid helium temperatures. The zero drift that is associated with residual gas analyzers in common leak detectors is virtually eliminated by utilizing a time integration technique. The sensitivity of the apparatus of this disclosure is capable of detecting leaks as small as 1.times.10.sup.-18 atm cc sec.sup.-1.

Aerospace Payloads Leak Test Methodology

NASA Technical Reports Server (NTRS)

Lvovsky, Oleg; Grayson, Cynthia M.

2010-01-01

Pressurized and sealed aerospace payloads can leak on orbit. When dealing with toxic or hazardous materials, requirements for fluid and gas leakage rates have to be properly established, and most importantly, reliably verified using the best Nondestructive Test (NDT) method available. Such verification can be implemented through application of various leak test methods that will be the subject of this paper, with a purpose to show what approach to payload leakage rate requirement verification is taken by the National Aeronautics and Space Administration (NASA). The scope of this paper will be mostly a detailed description of 14 leak test methods recommended.

Distribution System Audits, Leak Detection, and Repair: Kirtland Air Force Base Leak Detection and Repair Program

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

None

Water Best Management Practice #3 Fact Seet: Outlines how a leak detection and repair program helped Kirtland Air Force Base perform distribution system audits, leak detection, and repair to conserve water site-wide.

49 CFR 195.444 - CPM leak detection.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 3 2010-10-01 2010-10-01 false CPM leak detection. 195.444 Section 195.444... PIPELINE Operation and Maintenance § 195.444 CPM leak detection. Each computational pipeline monitoring (CPM) leak detection system installed on a hazardous liquid pipeline transporting liquid in single...

Automated Hydrogen Gas Leak Detection System

NASA Technical Reports Server (NTRS)

1995-01-01

The Gencorp Aerojet Automated Hydrogen Gas Leak Detection System was developed through the cooperation of industry, academia, and the Government. Although the original purpose of the system was to detect leaks in the main engine of the space shuttle while on the launch pad, it also has significant commercial potential in applications for which there are no existing commercial systems. With high sensitivity, the system can detect hydrogen leaks at low concentrations in inert environments. The sensors are integrated with hardware and software to form a complete system. Several of these systems have already been purchased for use on the Ford Motor Company assembly line for natural gas vehicles. This system to detect trace hydrogen gas leaks from pressurized systems consists of a microprocessor-based control unit that operates a network of sensors. The sensors can be deployed around pipes, connectors, flanges, and tanks of pressurized systems where leaks may occur. The control unit monitors the sensors and provides the operator with a visual representation of the magnitude and locations of the leak as a function of time. The system can be customized to fit the user's needs; for example, it can monitor and display the condition of the flanges and fittings associated with the tank of a natural gas vehicle.

Protective effects of a bacterially expressed NIF-KGF fusion protein against bleomycin-induced acute lung injury in mice.

PubMed

Li, Xinping; Li, Shengli; Zhang, Miaotao; Li, Xiukun; Zhang, Xiaoming; Zhang, Wenlong; Li, Chuanghong

2010-08-01

Current evidence suggests that the keratinocyte growth factor (KGF) and the polymorphonuclear leukocyte may play key roles in the development of lung fibrosis. Here we describe the construction, expression, purification, and identification of a novel NIF (neutrophil inhibitory factor)-KGF mutant fusion protein (NKM). The fusion gene was ligated via a flexible octapeptide hinge and expressed as an insoluble protein in Escherichia coli BL21 (DE3). The fusion protein retained the activities of KGF and NIF, as it inhibited both fibroblast proliferation and leukocyte adhesion. Next, the effects of NKM on bleomycin-induced lung fibrosis in mice were examined. The mice were divided into the following four groups: (i) saline group; (ii) bleomycin group (instilled with 5 mg/kg bleomycin intratracheally); (iii) bleomycin plus dexamethasone (Dex) group (Dex was given intraperitoneally (i.p.) at 1 mg/kg/day 2 days prior to bleomycin instillation and daily after bleomycin instillation until the end of the treatment); and (iv) bleomycin plus NKM group (NKM was given i.p. at 2 mg/kg/day using the same protocol as the Dex group). NKM significantly improved the survival rates of mice exposed to bleomycin. The marked morphological changes and increased hydroxyproline levels resulted from the instillation of bleomycin (on Day 17) in the lungs were significantly inhibited by NKM. These results revealed that NKM can attenuate bleomycin-induced lung fibrosis, suggesting that NKM could be used to prevent bleomycin-induced lung damage or other interstitial pulmonary fibrosis.

Coexpression of actin-related protein 2 and Wiskott-Aldrich syndrome family verproline-homologous protein 2 in adenocarcinoma of the lung.

PubMed

Semba, Seitaro; Iwaya, Keiichi; Matsubayashi, Jun; Serizawa, Hiromi; Kataba, Hiroaki; Hirano, Takashi; Kato, Harubumi; Matsuoka, Takeshi; Mukai, Kiyoshi

2006-04-15

Highly invasive and metastatic cancer cells, such as adenocarcinoma of the lung cells, form irregular protrusions by assembling a branched network of actin filaments. In mammalian cells, the actin-related protein 2 and 3 (Arp2/3) complex initiates actin assembly to form lamellipodial protrusions by binding to Wiskott-Aldrich syndrome (WASP)/WASP family verproline-homologous protein 2 (WAVE2). In this study, colocalization of Arp2 and WAVE2 in adenocarcinoma of the lung was investigated to elucidate its prognostic value. Immunohistochemical staining of Arp2 and WAVE2 was done on mirror sections of 115 adenocarcinomas of the lung from pathologic stage IA to IIIA classes. Kaplan-Meier disease-free survival and overall survival curves were analyzed to determine the prognostic significance of the coexpression of Arp2 and WAVE2. Immunoreactivity for both Arp2 and WAVE2 was detected in the same cancer cells in 78 (67.8%) of the 115 lung cancer specimens. The proportion of cancer cells expressing both Arp2 and WAVE2 was significantly higher in cases with lymph-node metastasis (P = 0.0046), and significantly lower in bronchioloalveolar carcinomas (P < 0.0001). The patients whose cancer cells coexpressed them had a shorter disease-free survival time (P < 0.0001) and overall survival time (P < 0.0001). Multivariate Cox regression analysis revealed that coexpression of Arp2 and WAVE2 is an independent risk factor for tumor recurrence. Coexpression of Arp2 and WAVE2 is correlated with poorer patient outcome, and may be involved in the mechanism of cancer metastasis.

Late INa increases diastolic SR-Ca2+-leak in atrial myocardium by activating PKA and CaMKII

PubMed Central

Fischer, Thomas H.; Herting, Jonas; Mason, Fleur E.; Hartmann, Nico; Watanabe, Saera; Nikolaev, Viacheslav O.; Sprenger, Julia U.; Fan, Peidong; Yao, Lina; Popov, Aron-Frederik; Danner, Bernhard C.; Schöndube, Friedrich; Belardinelli, Luiz; Hasenfuss, Gerd; Maier, Lars S.; Sossalla, Samuel

2015-01-01

Aims Enhanced cardiac late Na current (late INa) and increased sarcoplasmic reticulum (SR)-Ca2+-leak are both highly arrhythmogenic. This study seeks to identify signalling pathways interconnecting late INa and SR-Ca2+-leak in atrial cardiomyocytes (CMs). Methods and results In murine atrial CMs, SR-Ca2+-leak was increased by the late INa enhancer Anemonia sulcata toxin II (ATX-II). An inhibition of Ca2+/calmodulin-dependent protein kinase II (Autocamide-2-related inhibitory peptide), protein kinase A (H89), or late INa (Ranolazine or Tetrodotoxin) all prevented ATX-II-dependent SR-Ca2+-leak. The SR-Ca2+-leak induction by ATX-II was not detected when either the Na+/Ca2+ exchanger was inhibited (KBR) or in CaMKIIδc-knockout mice. FRET measurements revealed increased cAMP levels upon ATX-II stimulation, which could be prevented by inhibition of adenylyl cyclases (ACs) 5 and 6 (NKY 80) but not by inhibition of phosphodiesterases (IBMX), suggesting PKA activation via an AC-dependent increase of cAMP levels. Western blots showed late INa-dependent hyperphosphorylation of CaMKII as well as PKA target sites at ryanodine receptor type-2 (-S2814 and -S2808) and phospholamban (-Thr17, -S16). Enhancement of late INa did not alter Ca2+-transient amplitude or SR-Ca2+-load. However, upon late INa activation and simultaneous CaMKII inhibition, Ca2+-transient amplitude and SR-Ca2+-load were increased, whereas PKA inhibition reduced Ca2+-transient amplitude and load and additionally slowed Ca2+ elimination. In atrial CMs from patients with atrial fibrillation, inhibition of late INa, CaMKII, or PKA reduced the SR-Ca2+-leak. Conclusion Late INa exerts distinct effects on Ca2+ homeostasis in atrial myocardium through activation of CaMKII and PKA. Inhibition of late INa represents a potential approach to attenuate CaMKII activation and decreases SR-Ca2+-leak in atrial rhythm disorders. The interconnection with the cAMP/PKA system further increases the antiarrhythmic potential of late

Protein corona of airborne nanoscale PM2.5 induces aberrant proliferation of human lung fibroblasts based on a 3D organotypic culture.

PubMed

Li, Yan; Wang, Pengcheng; Hu, Chuanlin; Wang, Kun; Chang, Qing; Liu, Lieju; Han, Zhenggang; Shao, Yang; Zhai, Ying; Zuo, Zhengyu; Mak, Michael; Gong, Zhiyong; Wu, Yang

2018-01-31

Exposure to PM2.5 has become one of the most important factors affecting public health in the world. Both clinical and research studies have suggested that PM2.5 inhalation is associated with impaired lung function. In this study, material characterization identified the existence of nanoscale particulate matter (NPM) in airborne PM2.5 samples. When coming into contact with protein-rich fluids, the NPM becomes covered by a protein layer that forms a "protein corona". Based on a 3D organotypic cell culture, the protein corona was shown to mitigate NPM cytotoxicity and further stimulate the proliferation of human lung fibroblasts (HLFs). ROS-activated alpha-smooth muscle actin (α-SMA) is considered to be one of the proliferation pathways. In this research, 3D cell cultures exhibited more tissue-like properties compared with the growth in 2D models. Animal models have been widely used in toxicological research. However, species differences make it impossible to directly translate discoveries from animals to humans. In this research, the 3D HLF model could partly simulate the biological responses of NPM-protein corona-induced aberrant HLF proliferation in the human lung. Our 3D cellular results provide auxiliary support for an animal model in research on PM2.5-induced impaired lung function, particularly in lung fibrosis.

Sensitivities of Soap Solutions in Leak Detection

NASA Technical Reports Server (NTRS)

Stuck, D.; Lam, D. Q.; Daniels, C.

1985-01-01

Document describes method for determining minimum leak rate to which soap-solution leak detectors sensitive. Bubbles formed at smaller leak rates than previously assumed. In addition to presenting test results, document discusses effects of joint-flange configurations, properties of soap solutions, and correlation of test results with earlier data.

High sensitivity leak detection method and apparatus

DOEpatents

Myneni, G.R.

1994-09-06

An improved leak detection method is provided that utilizes the cyclic adsorption and desorption of accumulated helium on a non-porous metallic surface. The method provides reliable leak detection at superfluid helium temperatures. The zero drift that is associated with residual gas analyzers in common leak detectors is virtually eliminated by utilizing a time integration technique. The sensitivity of the apparatus of this disclosure is capable of detecting leaks as small as 1 [times] 10[sup [minus]18] atm cc sec[sup [minus]1]. 2 figs.

Obesity-Induced Endoplasmic Reticulum Stress Causes Lung Endothelial Dysfunction and Promotes Acute Lung Injury.

PubMed

Shah, Dilip; Romero, Freddy; Guo, Zhi; Sun, Jianxin; Li, Jonathan; Kallen, Caleb B; Naik, Ulhas P; Summer, Ross

2017-08-01

Obesity is a significant risk factor for acute respiratory distress syndrome. The mechanisms underlying this association are unknown. We recently showed that diet-induced obese mice exhibit pulmonary vascular endothelial dysfunction, which is associated with enhanced susceptibility to LPS-induced acute lung injury. Here, we demonstrate that lung endothelial dysfunction in diet-induced obese mice coincides with increased endoplasmic reticulum (ER) stress. Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice. Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins. Similar changes were observed in lung endothelial cells and in whole-lung tissue after exposure to tunicamycin, a compound that causes ER stress by blocking N-linked glycosylation, indicating that ER stress causes endothelial dysfunction in the lung. Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice. Our work indicates that fatty acids in obese serum induce ER stress in the pulmonary endothelium, leading to pulmonary endothelial cell dysfunction. Our work suggests that reducing protein load in the ER of pulmonary endothelial cells might protect against acute respiratory distress syndrome in obese

40 CFR 63.424 - Standards: Equipment leaks.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 9 2010-07-01 2010-07-01 false Standards: Equipment leaks. 63.424....424 Standards: Equipment leaks. (a) Each owner or operator of a bulk gasoline terminal or pipeline breakout station subject to the provisions of this subpart shall perform a monthly leak inspection of all...

Fungal Allergen β-Glucans Trigger p38 Mitogen-Activated Protein Kinase–Mediated IL-6 Translation in Lung Epithelial Cells

PubMed Central

Neveu, Wendy A.; Bernardo, Edgar; Allard, Jenna L.; Nagaleekar, Viswas; Wargo, Matthew J.; Davis, Roger J.; Iwakura, Yoichiro; Whittaker, Laurie A.

2011-01-01

In addition to immune cells, airway epithelial cells can contribute to and shape the immune response in the lung by secreting specific cytokines. IL-6 is a key factor in determining the effector fate of CD4+ T cells. Here we show that under basal conditions, the IL-6 gene is already highly expressed in lung epithelial cells, but not in immune cells resident in the lung. However, upon exposure of the lungs to fungal allergens, the direct contact of β-glucans present in the fungus cell wall with lung epithelial cells is sufficient to trigger the rapid synthesis and secretion of IL-6 protein. This posttranscriptional regulation of IL-6 in response to fungal extracts is mediated by the p38 mitogen-activated protein kinase pathway. The inhalation of β-glucans with a nonallergenic antigen is sufficient to provide an adjuvant effect that leads to mucous hyperplasia in the airways. Thus, β-glucans may constitute a common determinant of the fungal and plant-derived allergens responsible for some of the pathological features in allergic asthma. PMID:21642586

Postoperative ascitic leaks: the ongoing challenge.

PubMed

Rosemurgy, A S; Statman, R C; Murphy, C G; Albrink, M H; McAllister, E W

1992-06-01

The leak of ascitic fluid from surgical incisions is thought to be associated with a very high mortality rate. There have been few reports, however, focusing on the clinical characteristics, management, or mortality rates of this condition. During a 10-year period, 18 patients with postoperative ascitic fluid leaks were treated. All patients had ascites before surgery and all had liver disease; in 13 of the 18 patients alcoholic liver disease was the cause of ascites. Ten of the 18 patients died (56%). Midline incisions were more often associated with recalcitrant leaks and fatal complications than were transverse incisions. Early consideration of fascial dehiscence and prompt repair is emphasized. The most effective predictor of survival was cessation of the leak.

Cost Analysis of Cerebrospinal Fluid Leaks and Cerebrospinal Fluid Leak Prevention in Patients Undergoing Cerebellopontine Angle Surgery.

PubMed

Chern, Alexander; Hunter, Jacob B; Bennett, Marc L

2017-01-01

To determine if cranioplasty techniques following translabyrinthine approaches to the cerebellopontine angle are cost-effective. Retrospective case series. One hundred eighty patients with available financial data who underwent translabyrinthine approaches at a single academic referral center between 2005 and 2015. Cranioplasty with a dural substitute, layered fat graft, and a resorbable mesh plate secured with screws Main Outcome Measures: billing data was obtained for each patient's hospital course for translabyrinthine approaches and postoperative cerebrospinal fluid (CSF) leaks. One hundred nineteen patients underwent translabyrinthine approaches with an abdominal fat graft closure, with a median cost of $25759.89 (range, $15885.65-$136433.07). Sixty-one patients underwent translabyrinthine approaches with a dural substitute, abdominal fat graft, and a resorbable mesh for closure, with a median cost of $29314.97 (range, $17674.28-$111404.55). The median cost of a CSF leak was $50401.25 (range, $0-$384761.71). The additional cost of a CSF leak when shared by all patients who underwent translabyrinthine approaches is $6048.15. The addition of a dural substitute and a resorbable mesh plate after translabyrinthine approaches reduced the CSF leak from 12 to 1.9%, an 84.2% reduction, and a median savings per patient of $2932.23. Applying our cohort's billing data to previously published cranioplasty techniques, costs, and leak rate improvements after translabyrinthine approaches, all techniques were found to be cost-effective. Resorbable mesh cranioplasty is cost-effective at reducing CSF leaks after translabyrinthine approaches. Per our billing data and achieving the same CSF leak rate, cranioplasty costs exceeding $5090.53 are not cost-effective.

Transcriptional mechanisms and protein kinase signaling mediate organic dust induction of IL-8 expression in lung epithelial and THP-1 cells

PubMed Central

Gottipati, Koteswara R.; Bandari, Shiva Kumar; Nonnenmann, Matthew W.; Levin, Jeffrey L.; Dooley, Gregory P.; Reynolds, Stephen J.

2014-01-01

Exposure to the agricultural work environment is a risk factor for the development of respiratory symptoms and chronic lung diseases. Inflammation is an important contributor to the pathogenesis of tissue injury and disease. Cellular and molecular mechanisms mediating lung inflammatory responses to agricultural dust are not yet fully understood. We studied the effects of poultry dust extract on molecular regulation of interleukin-8 (IL-8), a proinflammatory cytokine, in A549 and Beas2B lung epithelial and THP-1 monocytic cells. Our findings indicate that poultry dust extract potently induces IL-8 levels by increasing IL-8 gene transcription without altering IL-8 mRNA stability. Increase in IL-8 promoter activity was due to enhanced binding of activator protein 1 and NF-κB. IL-8 induction was associated with protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) activation and inhibited by PKC and MAPK inhibitors. IL-8 increase was not inhibited by polymyxin B or l-nitroarginine methyl ester, indicating lack of involvement of lipopolysaccharide and nitric oxide in the induction. Lung epithelial and THP-1 cells share common mechanisms for induction of IL-8 levels. Our findings identify key roles for transcriptional mechanisms and protein kinase signaling pathways for IL-8 induction and provide insights into the mechanisms regulating lung inflammatory responses to organic dust exposure. PMID:25398986

40 CFR 63.691 - Standards: Equipment leaks.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 10 2010-07-01 2010-07-01 false Standards: Equipment leaks. 63.691....691 Standards: Equipment leaks. (a) The provisions of this section apply to the control of air emissions from equipment leaks for which § 63.683(d) references the use of this section for such air...

A Leak Monitor for Industry

NASA Technical Reports Server (NTRS)

1996-01-01

GenCorp Aerojet Industrial Products, Lewis Research Center, Marshall Space Flight Center, and Case Western Reserve University developed a gas leak detection system, originally for use with the Space Shuttle propulsion system and reusable launch vehicles. The Model HG200 Automated Gas Leak Detection System has miniaturized sensors that can identify extremely low concentrations of hydrogen without requiring oxygen. A microprocessor-based hardware/software system monitors the sensors and displays the source and magnitude of hydrogen leaks in real time. The system detects trace hydrogen around pipes, connectors, flanges and pressure tanks, and has been used by Ford Motor Company in the production of a natural gas-powered car.

Improved gaseous leak detector

DOEpatents

Juravic, F.E. Jr.

1983-10-06

In a short path length mass-spectrometer type of helium leak detector wherein the helium trace gas is ionized, accelerated and deflected onto a particle counter, an arrangement is provided for converting the detector to neon leak detection. The magnetic field of the deflection system is lowered so as to bring the nonlinear fringe area of the magnetic field across the ion path, thereby increasing the amount of deflection of the heavier neon ions.

Nitrofen interferes with trophoblastic expression of retinol-binding protein and transthyretin during lung morphogenesis in the nitrofen-induced congenital diaphragmatic hernia model.

PubMed

Kutasy, Balazs; Gosemann, Jan H; Doi, Takashi; Fujiwara, Naho; Friedmacher, Florian; Puri, Prem

2012-02-01

Retinoids play a key role in lung development. Retinoid signaling pathway has been shown to be disrupted in the nitrofen model of congenital diaphragmatic hernia (CDH) but the exact mechanism is not clearly understood. Retinol-binding protein (RBP) and transthyretin (TTR) are transport proteins for delivery of retinol to the tissues via circulation. Previous studies have shown that pulmonary retinol levels are decreased during lung morphogenesis in the nitrofen CDH model. In human newborns with CDH, both retinol and RBP levels are decreased. It has been reported that maternal RBP does not cross the placenta and the fetus produces its own RBP by trophoblast. RBP and TTR synthesized in the fetus are essential for retinol transport to the developing organs including lung morphogenesis. We hypothesized that nitrofen interferes with the trophoblastic expression of RBP and TTR during lung morphogenesis and designed this study to examine the trophoblastic expression of RBP and TTR, and the total level of RBP and TTR in the lung in the nitrofen model of CDH. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetal lungs and placenta harvested on D21 and divided into two groups: control (n = 8) and nitrofen with CDH (n = 8). Total lung RBP and TTR levels using protein extraction were compared with enzyme linked immunoassay (ELISA). Immunohistochemistry was performed to evaluate trophoblastic RBP and TTR expression. Total protein levels of lung RBP and TTR were significantly lower in CDH (0.26 ± 0.003 and 6.4 ± 0.5 μg/mL) compared with controls (0.4 ± 0.001 and 9.9 ± 1.6 μg/mL, p < 0.05). In the control group, immunohistochemical staining showed strong immunoreactivity of RBP and TTR in the trophoblast compared to CDH group. Decreased trophoblast expression of retinol transport proteins suggest that nitrofen may interfere with the fetal retinol transport resulting in reduced pulmonary RBP and TTR levels and causing pulmonary

Factors impacting cerebrospinal fluid leak rates in endoscopic sellar surgery.

PubMed

Karnezis, Tom T; Baker, Andrew B; Soler, Zachary M; Wise, Sarah K; Rereddy, Shruthi K; Patel, Zara M; Oyesiku, Nelson M; DelGaudio, John M; Hadjipanayis, Constantinos G; Woodworth, Bradford A; Riley, Kristen O; Lee, John; Cusimano, Michael D; Govindaraj, Satish; Psaltis, Alkis; Wormald, Peter John; Santoreneos, Steve; Sindwani, Raj; Trosman, Samuel; Stokken, Janalee K; Woodard, Troy D; Recinos, Pablo F; Vandergrift, W Alexander; Schlosser, Rodney J

2016-11-01

In patients undergoing transnasal endoscopic sellar surgery, an analysis of risk factors and predictors of intraoperative and postoperative cerebrospinal fluid leak (CSF) would provide important prognostic information. A retrospective review of patients undergoing endoscopic sellar surgery for pituitary adenomas or craniopharyngiomas between 2002 and 2014 at 7 international centers was performed. Demographic, comorbidity, and tumor characteristics were evaluated to determine the associations between intraoperative and postoperative CSF leaks. Correlations between reconstructive and CSF diversion techniques were associated with postoperative CSF leak rates. Odds ratios (OR) were identified using a multivariate logistic regression model. Data were collected on 1108 pituitary adenomas and 53 craniopharyngiomas. Overall, 30.1% of patients had an intraoperative leak and 5.9% had a postoperative leak. Preoperative factors associated with increased intraoperative leaks were mild liver disease, craniopharyngioma, and extension into the anterior cranial fossa. In patients with intraoperative CSF leaks, postoperative leaks occurred in 10.3%, with a higher postoperative leak rate in craniopharyngiomas (20.8% vs 5.1% in pituitary adenomas). Once an intraoperative leak occurred, craniopharyngioma (OR = 4.255, p = 0.010) and higher body mass index (BMI) predicted postoperative leak (OR = 1.055, p = 0.010). In patients with an intraoperative leak, the use of septal flaps reduced the occurrence of postoperative leak (OR = 0.431, p = 0.027). Rigid reconstruction and CSF diversion techniques did not impact postoperative leak rates. Intraoperative CSF leaks can occur during endoscopic sellar surgery, especially in larger tumors or craniopharyngiomas. Once an intraoperative leak occurs, risk factors for postoperative leaks include craniopharyngiomas and higher BMI. Use of septal flaps decreases this risk. © 2016 ARS-AAOA, LLC.

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

PubMed Central

Jorgensen, Ellen; Stinson, Andy; Shan, Lin; Yang, Jin; Gietl, Diana; Albino, Anthony P

2008-01-01

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

Comprehensive leak detection survey and benefit/cost analysis

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

Scholze, R.J. Jr.; Maloney, S.W.

1995-06-01

Fort Carson, Colorado was the site of a comprehensive leak detection investigation of the potable water system with the express purpose of quantifying the benefits to be derived by a military installation from use of leak detection and repair technology. Military bases are often the size of a small city and one Directorate or Department has responsibility for all real estate (buildings, roads, grounds, etc.) unlike a municipal public works department. The investigation used state of the art noise correlation and computer correlation technology to survey the distribution system mains. This was complemented by a building to building survey coveringmore » office and commercial buildings along with family and barracks housing where investigators entered buildings and quantified visible leaks in faucets and water closets, etc. Following repairs and a year`s time, a follow-on survey is performed to again examine all aspects of the system. The result was a complete economic evaluation and benefit/cost analysis of the installation. Representative findings include: the majority of distribution system leaks were at hydrants or similar appurtenances; and family housing was found to be the other major concentration of leaks. However, where the first survey found 80 percent of housing units had leaks, findings from the second round on the order of 20 percent. Office buildings were found from the first survey to not merit follow-on attention due to limited numbers of leaks. Water-consciousness was raised for both the responsible directorate and individuals in family housing and leak repair was given a higher priority for repairs. This paper will outline the leak detection methodology used, characterize the types and patterns of leaks found, introduce an economic analysis for the entire leak detection process, and finally, provide lessons learned with practical results and implications.« less

Probabilistic pipe fracture evaluations for leak-rate-detection applications

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

Rahman, S.; Ghadiali, N.; Paul, D.

1995-04-01

Regulatory Guide 1.45, {open_quotes}Reactor Coolant Pressure Boundary Leakage Detection Systems,{close_quotes} was published by the U.S. Nuclear Regulatory Commission (NRC) in May 1973, and provides guidance on leak detection methods and system requirements for Light Water Reactors. Additionally, leak detection limits are specified in plant Technical Specifications and are different for Boiling Water Reactors (BWRs) and Pressurized Water Reactors (PWRs). These leak detection limits are also used in leak-before-break evaluations performed in accordance with Draft Standard Review Plan, Section 3.6.3, {open_quotes}Leak Before Break Evaluation Procedures{close_quotes} where a margin of 10 on the leak detection limit is used in determining the crackmore » size considered in subsequent fracture analyses. This study was requested by the NRC to: (1) evaluate the conditional failure probability for BWR and PWR piping for pipes that were leaking at the allowable leak detection limit, and (2) evaluate the margin of 10 to determine if it was unnecessarily large. A probabilistic approach was undertaken to conduct fracture evaluations of circumferentially cracked pipes for leak-rate-detection applications. Sixteen nuclear piping systems in BWR and PWR plants were analyzed to evaluate conditional failure probability and effects of crack-morphology variability on the current margins used in leak rate detection for leak-before-break.« less

Anastomotic leaks in stage IV colorectal cancer.

PubMed

Ng, Suat Chin; Stupart, Douglas; Bartolo, David; Watters, David

2018-06-12

The purpose of this study was to determine the anastomotic leak rate for colorectal cancer resections in patients with metastases (compared to those without), and to determine the impact of anastomotic leaks on survival. This is a retrospective analysis of all patients who underwent resection and primary anastomosis for colorectal adenocarcinoma at a single institution between January 2002 and December 2014. A total of 843 patients underwent a resection and primary anastomosis for colorectal adenocarcinoma (661 colon and 182 rectal). Of these, 135 (16%) had metastases and 708 (84%) did not. Anastomotic leaks occurred in 17 of 135 (13%) patients with metastases, and in 37 of 798 (5.2%) patients without metastases (P = 0.003). Peri-operative mortality occurred in 13 of 135 (9.6%) patients with metastases, compared with 19 of 708 (2.7%) patients without metastases (P = 0.0003). Anastomotic leak was associated with a reduction in overall survival (median survival 121 months without anastomotic leak versus 66 months in patients who had an anastomotic leak (P = 0.02)). If the patients who died peri-operatively are excluded from this analysis, however, long-term mortality was similar (125 months versus 101 months; P = 0.70). Metastatic disease was associated with an increased risk of anastomotic leak and a higher peri-operative mortality rate after colorectal resections for cancer. Patients with anastomotic leaks had a higher peri-operative mortality rate, but long-term survival was unaffected beyond the peri-operative phase. © 2018 Royal Australasian College of Surgeons.

[Clinical significance of levels of lung surfactant protein A in serum, in various lung diseases].

PubMed

Abe, S; Honda, Y; Ando, M; Saita, N; Kida, K; Jinno, S; Kondo, A; Kuroki, Y; Akino, T

1995-11-01

To assess the utility of measuring lung surfactant protein A (SP-A) in serum, a newly developed SP-A kit (Teijin TDR-30) was used at four facilities to measure serum SP-A levels in patients with various lung diseases. Serum SP-A levels in healthy volunteers were 24.6 +/- 9.6 ng/ml (mean +/- SD). serum SP-A levels did not differ significantly between different age groups (thirties through seventies). A cut-off level of 43.8 ng/ml was calculated, based on the values of the healthy volunteers. The serum SP-A levels in patients with idiopathic interstitial pneumonia (IIP: 67.9 +/- 42.5 ng/ml), pulmonary alveolar proteinosis (PAP: 7.0 +/- 45.7 ng/ml), and collagen disease with interstitial pneumonia (CDIP: 55.3 +/- 37.9 ng/ml) were significantly higher than those in healthy volunteers. When calculated with the cut-off value stated above, the positive rate of diagnosis for IIP was 71.4%. SP-A levels correlated closely with the clinical course; SP-A levels rose significantly during exacerbations of IIP. Measurement of SP-A in serum is useful for the diagnosis of IIP, PAP, and CDIP, and for monitoring exacerbations of IIP.

40 CFR 264.196 - Response to leaks or spills and disposition of leaking or unfit-for-use tank systems.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Response to leaks or spills and... HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL FACILITIES Tank Systems § 264.196 Response to leaks or... system from which there has been a leak or spill, or which is unfit for use, must be removed from service...

Plasma pro-surfactant protein B and lung function decline in smokers.

PubMed

Leung, Janice M; Mayo, John; Tan, Wan; Tammemagi, C Martin; Liu, Geoffrey; Peacock, Stuart; Shepherd, Frances A; Goffin, John; Goss, Glenwood; Nicholas, Garth; Tremblay, Alain; Johnston, Michael; Martel, Simon; Laberge, Francis; Bhatia, Rick; Roberts, Heidi; Burrowes, Paul; Manos, Daria; Stewart, Lori; Seely, Jean M; Gingras, Michel; Pasian, Sergio; Tsao, Ming-Sound; Lam, Stephen; Sin, Don D

2015-04-01

Plasma pro-surfactant protein B (pro-SFTPB) levels have recently been shown to predict the development of lung cancer in current and ex-smokers, but the ability of pro-SFTPB to predict measures of chronic obstructive pulmonary disease (COPD) severity is unknown. We evaluated the performance characteristics of pro-SFTPB as a biomarker of lung function decline in a population of current and ex-smokers. Plasma pro-SFTPB levels were measured in 2503 current and ex-smokers enrolled in the Pan-Canadian Early Detection of Lung Cancer Study. Linear regression was performed to determine the relationship of pro-SFTPB levels to changes in forced expiratory volume in 1 s (FEV1) over a 2-year period as well as to baseline FEV1 and the burden of emphysema observed in computed tomography (CT) scans. Plasma pro-SFTPB levels were inversely related to both FEV1 % predicted (p=0.024) and FEV1/forced vital capacity (FVC) (p<0.001), and were positively related to the burden of emphysema on CT scans (p<0.001). Higher plasma pro-SFTPB levels were also associated with a more rapid decline in FEV1 at 1 year (p=0.024) and over 2 years of follow-up (p=0.004). Higher plasma pro-SFTPB levels are associated with increased severity of airflow limitation and accelerated decline in lung function. Pro-SFTPB is a promising biomarker for COPD severity and progression. Copyright ©ERS 2015.

A Co-operative Regulation of Neuronal Excitability by UNC-7 Innexin and NCA/NALCN Leak Channel

PubMed Central

2011-01-01

Gap junctions mediate the electrical coupling and intercellular communication between neighboring cells. Some gap junction proteins, namely connexins and pannexins in vertebrates, and innexins in invertebrates, may also function as hemichannels. A conserved NCA/Dmα1U/NALCN family cation leak channel regulates the excitability and activity of vertebrate and invertebrate neurons. In the present study, we describe a genetic and functional interaction between the innexin UNC-7 and the cation leak channel NCA in Caenorhabditis elegans neurons. While the loss of the neuronal NCA channel function leads to a reduced evoked postsynaptic current at neuromuscular junctions, a simultaneous loss of the UNC-7 function restores the evoked response. The expression of UNC-7 in neurons reverts the effect of the unc-7 mutation; moreover, the expression of UNC-7 mutant proteins that are predicted to be unable to form gap junctions also reverts this effect, suggesting that UNC-7 innexin regulates neuronal activity, in part, through gap junction-independent functions. We propose that, in addition to gap junction-mediated functions, UNC-7 innexin may also form hemichannels to regulate C. elegans' neuronal activity cooperatively with the NCA family leak channels. PMID:21489288

Stochastic Consequence Analysis for Waste Leaks

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

HEY, B.E.

This analysis evaluates the radiological consequences of potential Hanford Tank Farm waste transfer leaks. These include ex-tank leaks into structures, underneath the soil, and exposed to the atmosphere. It also includes potential misroutes, tank overflow

Recent advances in the treatment of air leaks.

PubMed

Cerfolio, Robert James

2005-07-01

Alveolar-pleural fistulas (air leaks) are an extremely common clinical problem and remain the most common complication after elective pulmonary resection and video-assisted procedures. The decision making process used to manage air leaks and chest tubes that control them has been, until very recently, based on opinions and training preferences as opposed to facts derived from randomized clinical trials. Recently, several prospective randomized trials have studied air leaks. An objective, reproducible classification system has also been designed and clinically validated to help study air leaks. This system and these studies have shown that water seal is superior to wall suction to help stop most leaks. Even in patients with a pneumothorax and an air leak, water seal is safe and best; however, if a patient has a large leak (greater than an expiratory 3 on the classification system) or experiences subcutaneous emphysema or an expanding pneumothorax that causes hypoxia, then some suction (-10 cm of water) should be applied to the chest tubes. Air leaks were a poorly understood yet extremely common clinical problem that had never been scientifically studied. Over the past 5 years, prospective randomized studies have shown that water seal is the best setting for chest tubes and that a pneumothorax is not a contraindication to leaving tubes on seal. Further studies are needed to investigate the ideal management of alveolar-pleural fistulas (air leaks) in different clinical scenarios besides those that occur postoperatively.

Protein Secretion Is Required for Pregnancy-Associated Plasma Protein-A to Promote Lung Cancer Growth In Vivo

PubMed Central

Pan, Hong; Hanada, Sayaka; Zhao, Jun; Mao, Li; Ma, Mark Zhi-Qing

2012-01-01

Pregnancy-associated plasma protein-A (PAPPA) has been reported to regulate the activity of insulin-like growth factor (IGF) signal pathway through proteolytic degradation of IGF binding proteins (IGFBPs) thereby increasing the local concentration of free IGFs available to receptors. In this study we found that PAPPA is secreted from two out of seven lung cancer cell lines examined. None of immortalized normal bronchial epithelial cells (HBE) tested secrets PAPPA. There is no correlation between expression level and secretion of PAPPA in these cells. A cell line over-expressing PAPPA accompanied with secretion shows no notable changes in proliferation under cell culture conditions in vitro, but displays significantly augmentation of tumor growth in vivo in a xenograft model. In contrast, a cell line over-expressing PAPPA without secretion exhibits reduction of tumor growth both in vitro and in vivo. Down-regulation of PAPPA expression and secretion by RNAi knockdown decreases tumor growth after implanted in vivo. The tumor promoting activity of PAPPA appears to be mediated mainly through augmentation of the IGF signaling pathway as indicated by notable increases in downstream Akt kinase phosphorylation in tumor samples. Our results indicate that PAPPA secretion may play an important role in lung cancer growth and progression. PMID:23152806

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.

Alterations of peroxisome proliferator-activated receptor γ and monocyte chemoattractant protein 1 gene expression in the nitrofen-induced hypoplastic lung.

PubMed

Gosemann, Jan-Hendrik; Doi, Takashi; Kutasy, Balazs; Friedmacher, Florian; Dingemann, Jens; Puri, Prem

2012-05-01

Peroxisome proliferator-activated receptor γ (PPARγ) plays a key role in normal lung development. Peroxisome proliferator-activated receptor γ messenger RNA (mRNA) is detectable at 18 days of gestation in fetal rat lungs, and levels peak just before birth. Peroxisome proliferator-activated receptor γ agonists are reported to stimulate lung development, whereas inhibition of PPARγ disrupts postnatal lung maturation. Monocyte chemoattractant protein 1 (MCP-1), which is inhibited by PPARγ, is reported to disrupt late lung morphogenesis. This study was designed to investigate the hypothesis that PPARγ expression is downregulated and that MCP-1 expression is upregulated during the late stages of lung development in nitrofen-induced hypoplastic lungs. Pregnant rats were treated with nitrofen or vehicle on D9. RNA was extracted from fetal lungs (D18 and D21), and relative mRNA expression levels of PPARγ and MCP-1 were determined by reverse transcriptase-polymerase chain reaction. Immunohistochemistry was performed to evaluate protein expression/distribution of PPARγ and MCP-1. Relative mRNA expression levels of PPARγ were significantly downregulated in the nitrofen group compared with controls on D21, whereas MCP-1 levels were upregulated. Immunohistochemical study showed markedly decreased PPARγ and increased MCP-1 immunoreactivity in the nitrofen-induced hypoplastic lungs compared with controls on gestational day 21. Altered pulmonary gene expression of PPARγ and MCP-1 during late gestation may impair lung development and maturation, contributing to pulmonary hypoplasia in the nitrofen-induced congenital diaphragmatic hernia model. Copyright © 2012 Elsevier Inc. All rights reserved.

Ex vivo evaluation of canine lung biopsy techniques.

PubMed

Marvel, Sarah; Monnet, Eric

2013-05-01

An ex vivo comparison of thoracoscopic lung biopsy techniques in dogs. Experimental. Cadaveric canine lung lobes. Lungs were inflated to 10 cmH2 O. After collecting biopsies 3 cm from the edge of lung lobes, leak pressures were recorded as inflation pressure was increased to 40 cmH2 O. Pre-tied loop ligature, square knot (SQ), modified 4S Roeder knot (M4SR) with glycomer 631 and polyglactin 910 size 0 and 2-0 were used in addition to EndoGIA 45-2.5 mm (Covidien, Norwalk, CT) and a vessel sealant device (VSDS single and VSDD double seal). Six biopsies were performed with each of these modalities. Median airway pressure at which leakage occurred was 28 (20-34)cmH2 O for EndoGIA 45; 33 (14-40) for VSDD; and 33 (10-40) for VSDS while other groups reached a median pressure of 40 cmH2 O (P < .0001). Leakage occurred at 20 cmH2 O in 1 sample with the EndoGIA and the VSDS, and in 2 with the VSDD while leakage did not occur in any other group (P = .36). Leakage occurred at 30 cmH2 O in 1 specimen each of the 0-polyglactin SQ, 2-0 glycomer 631 M4SR, 2-0 polyglactin M4SR, and 2-0 Surgitie (Covidien, Norwalk, CT); 2 with the VSDS; and 3 with the EndoGIA and the VSDD while leakage did not occur in any other group (P = .26). All tested techniques seemed safe except the vessel sealant device since it did not consistently seal every biopsy and leaked at pressures <20 cmH2 O. © Copyright 2013 by The American College of Veterinary Surgeons.

Altered protein expression profile associated with phenotypic changes in lung fibroblasts co-cultured with gold nanoparticle-treated small airway epithelial cells.

PubMed

Ng, Cheng-Teng; Yung, Lin-Yue Lanry; Swa, Hannah Lee-Foon; Poh, Rebecca Wan-Yan; Gunaratne, Jayantha; Bay, Boon-Huat

2015-01-01

Despite the availability of toxicity studies on cellular exposure to gold nanoparticles (AuNPs), there is scarcity of information with regard to the bystander effects induced by AuNPs on neighboring cells not exposed to the NPs. In this study, we showed that exposure of small airway epithelial cells (SAECs) to AuNPs induced changes in protein expression associated with functional effects in neighboring MRC5 lung fibroblasts in a co-culture system. Uptake of 20 nm size AuNPs by SAECs was first verified by focused ion beam scanning electron microscopy. Subsequently, pretreated SAECs were co-cultured with unexposed MRC5 lung fibroblasts, which then underwent proteome profiling using a quantitative proteomic approach. Stable-isotope labeling by amino acids in cell culture (SILAC)-based mass spectrometry identified 109 proteins (which included 47 up-regulated and 62 down-regulated proteins) that were differentially expressed in the lung fibroblasts co-cultured with AuNP pretreated SAECs. There was altered expression of proteins such as Paxillin, breast cancer anti-estrogen resistance 1 and Caveolin-1, which are known to be involved in the cell adhesion process. Morphological studies revealed that there was a concomitant increase in cell adhesion and altered F-actin stress fiber arrangement involving vinculin in the lung fibroblasts. It is likely that phenotypic changes observed in the underlying lung fibroblasts were mediated by AuNP-induced downstream signals in the pretreated SAECs and cell-cell cross talk. Copyright © 2014 Elsevier Ltd. All rights reserved.

Endoplasmic reticulum-Golgi intermediate compartment protein 3 knockdown suppresses lung cancer through endoplasmic reticulum stress-induced autophagy.

PubMed

Hong, Seong-Ho; Chang, Seung-Hee; Cho, Kyung-Cho; Kim, Sanghwa; Park, Sungjin; Lee, Ah Young; Jiang, Hu-Lin; Kim, Hyeon-Jeong; Lee, Somin; Yu, Kyeong-Nam; Seo, Hwi Won; Chae, Chanhee; Kim, Kwang Pyo; Park, Jongsun; Cho, Myung-Haing

2016-10-04

Trafficking from the endoplasmic reticulum (ER) to the Golgi apparatus is elevated in cancer cells. Therefore, proteins of the ER-Golgi intermediate compartment (ERGIC) attract significant attention as targets for cancer treatment. Enhanced cancer cell growth and epithelial-mesenchymal transition by ERGICs correlates with poor-prognosis of lung cancer. This prompted us to assess whether knockdown of ERGIC3 may decrease lung cancer growth. To test the hypothesis, the effects of ERGIC3 short hairpin RNA (shERGIC3) on ER stress-induced cell death and lung tumorigenesis were investigated both in vitro and in vivo. Knockdown of ERGIC3 led to ER stress-induced autophagic cell death and suppression of proliferation in the A549 human lung cancer cell-line. Moreover, non-invasive aerosol-delivery of shERGIC3 using the biocompatible carrier glycerol propoxylate triacrylate and spermine (GPT-SPE) inhibited lung tumorigenesis in the K-rasLA1 murine model of lung cancer. Our data suggest that suppression of ERGIC3 could provide a framework for the development of effective lung cancer therapies.

Evidence for a G protein-coupled diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A) receptor binding site in lung membranes from rat.

PubMed

Laubinger, W; Reiser, G

1999-01-29

Nucleotide receptors are of considerable importance in the treatment of lung diseases, such as cystic fibrosis. Because diadenosine polyphosphates may also be of significance as signalling molecules in lung, as they are in a variety of tissues, in the present work we investigated the binding sites for [3H]diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A) in plasma membranes from rat lung and studied their possible coupling to G proteins. We present evidence for a single high-affinity binding site for [3H]Ap4A with similar affinity for other diadenosine polyphosphates ApnA (n = 2 to 6). Displacement studies with different nucleotides revealed that the [3H]Ap4A binding site was different from P2X and P2Y2 receptor binding sites. Pretreatment of lung membranes with GTPgammaS or GTP in the presence of Mg2+ increased the Ki for Ap4A from 91 nM to 5.1 microM, which is indicative of G protein coupling. The putative coupling to G proteins was further confirmed by the enhancement of [35S]GTPgammaS binding (to Galpha proteins) to lung membranes by Ap4A (63% increase over basal) in a concentration-dependent manner. Therefore, our data for the first time provide evidence of a G protein-coupled Ap4A binding site in lung membranes.

Transthoracic Anastomotic Leak After Esophagectomy: Current Trends.

PubMed

Ryan, Carrie E; Paniccia, Alessandro; Meguid, Robert A; McCarter, Martin D

2017-01-01

Leaks from intrathoracic esophagogastric anastomosis are thought to be associated with higher rates of morbidity and mortality than leaks from cervical anastomosis. We challenge this assumption and hypothesize that there is no significant difference in mortality based on the location of the esophagogastric anastomosis. A systematic literature search was conducted using PubMed and Embase databases on all studies published from January 2000 to June 2015, comparing transthoracic (TTE) and transhiatal (THE) esophagectomies. Studies using jejunal or colonic interposition were excluded. Outcomes analyzed were leak rate, leak-associated mortality, overall 30-day mortality, and overall morbidity. Meta-analyses were performed using Mantel-Haenszel statistical analyses on studies reporting leak rates of both approaches. Nominal data are presented as frequency and interquartile range (IQR); measures of the association between treatments and outcomes are presented as odds ratio (OR) with 95 % confidence interval. Twenty-one studies (3 randomized controlled trials) were analyzed comprising of 7167 patients (54 % TTE). TTE approach yields a lower anastomotic leak rate (9.8 %; IQR 6.0-12.2 %) than THE (12 %; IQR 11.6-22.1 %; OR 0.56 [0.34-0.92]), without any significant difference in leak associated mortality (7.1 % TTE vs. 4.6 % THE: OR 1.83 [0.39-8.52]). There was no difference in overall 30-day mortality (3.9 % TTE vs. 4.3 % THE; OR 0.86 [0.66-1.13]) and morbidity (59.0 % TTE vs. 66.6 % THE; OR 0.76 [0.37-1.59]). Based on meta-analysis, TTE is associated with a lower leak rate and does not result in higher morbidity or mortality than THE. The previously assumed higher rate of transthoracic anastomotic leak-associated mortality is overstated, thus supporting surgeon discretion and other factors to influence the choice of thoracic versus cervical anastomosis.

Effect of lung resection on pleuro-pulmonary mechanics and fluid balance.

PubMed

Salito, C; Bovio, D; Orsetti, G; Salati, M; Brunelli, A; Aliverti, A; Miserocchi, G

2016-01-15

The aim of the study was to determine in human patients the effect of lung resection on lung compliance and on pleuro-pulmonary fluid balance. Pre and post-operative values of compliance were measured in anesthetized patients undergoing resection for lung cancer (N=11) through double-lumen bronchial intubation. Lung compliance was measured for 10-12 cm H2O increase in alveolar pressure from 5 cm H2O PEEP in control and repeated after resection. No air leak was assessed and pleural fluid was collected during hospital stay. A significant negative correlation (r(2)=0.68) was found between compliance at 10 min and resected mass. Based on the pre-operative estimated lung weight, the decrease in compliance following lung resection exceeded by 10-15% that expected from resected mass. Significant negative relationships were found by relating pleural fluid drainage flow to the remaining lung mass and to post-operative lung compliance. Following lung re-expansion, data suggest a causative relationship between the decrease in compliance and the perturbation in pleuro-pulmonary fluid balance. Copyright © 2015 Elsevier B.V. All rights reserved.

Differential protein folding and chemical changes in lung tissues exposed to asbestos or particulates

PubMed Central

Pascolo, Lorella; Borelli, Violetta; Canzonieri, Vincenzo; Gianoncelli, Alessandra; Birarda, Giovanni; Bedolla, Diana E.; Salomé, Murielle; Vaccari, Lisa; Calligaro, Carla; Cotte, Marine; Hesse, Bernhard; Luisi, Fernando; Zabucchi, Giuliano; Melato, Mauro; Rizzardi, Clara

2015-01-01

Environmental and occupational inhalants may induce a large number of pulmonary diseases, with asbestos exposure being the most risky. The mechanisms are clearly related to chemical composition and physical and surface properties of materials. A combination of X-ray fluorescence (μXRF) and Fourier Transform InfraRed (μFTIR) microscopy was used to chemically characterize and compare asbestos bodies versus environmental particulates (anthracosis) in lung tissues from asbestos exposed and control patients. μXRF analyses revealed heterogeneously aggregated particles in the anthracotic structures, containing mainly Si, K, Al and Fe. Both asbestos and particulates alter lung iron homeostasis, with a more marked effect in asbestos exposure. μFTIR analyses revealed abundant proteins on asbestos bodies but not on anthracotic particles. Most importantly, the analyses demonstrated that the asbestos coating proteins contain high levels of β-sheet structures. The occurrence of conformational changes in the proteic component of the asbestos coating provides new insights into long-term asbestos effects. PMID:26159651

Postoperative esophageal leak management with the Polyflex esophageal stent.

PubMed

Freeman, Richard K; Ascioti, Anthony J; Wozniak, Thomas C

2007-02-01

Leak after esophageal anastomosis or perforation repair prolongs hospitalization, prevents oral hydration and nutrition, and can produce localized infection or sepsis. This investigation reviews our experience treating postoperative esophageal leaks with the Polyflex esophageal stent (Boston Scientific, Natick, Mass). Over a 30-month period, patients with a postoperative esophageal leak were treated with the Polyflex stent for leak occlusion. Leak occlusion was confirmed by means of esophagraphy. Patients were followed until their stent was removed and their esophageal leak had resolved. Twenty-one patients had 27 stents placed for leak occlusion after esophagectomy (n = 5), esophageal perforation (n = 5), surgical (n = 4) or endoscopic (n = 2) antireflux procedure, and esophageal diverticulectomy (n = 3) or myotomy (n = 2). The mean interval between surgical intervention and stent placement was 12 +/- 8 days (range, 3-31 days). Occlusion of the leak occurred in 20 patients. One patient experienced a dehiscence of the surgical esophageal perforation repair requiring esophageal diversion. Stent migration requiring repositioning (n = 3) or replacement (n = 4) occurred in 5 (24%) patients. Twenty (95%) stents were removed without residual leak (mean, 51 +/- 43 days; range, 15-175 days). One patient had a stricture after stent removal that required endoscopic dilatation. One patient in this series died. The Polyflex esophageal stent is an effective method for occluding a postoperative esophageal leak. It rapidly eliminates contamination of the mediastinum, pleura, and peritoneum; allows oral hydration and nutrition; and is easily removable. These stents also offer an appealing alternative to traditional esophageal diversion and subsequent reconstruction in patients with a persistent esophageal leak.

Successful endoscopic therapy of traumatic bile leaks.

PubMed

Spinn, Matthew P; Patel, Mihir K; Cotton, Bryan A; Lukens, Frank J

2013-01-01

Traumatic bile leaks often result in high morbidity and prolonged hospital stay that requires multimodality management. Data on endoscopic management of traumatic bile leaks are scarce. Our study objective was to evaluate the efficacy of the endoscopic management of a traumatic bile leak. We performed a retrospective case review of patients who were referred for endoscopic retrograde cholangiopancreatography (ERCP) after traumatic bile duct injury secondary to blunt (motor vehicle accident) or penetrating (gunshot) trauma for management of bile leaks at our tertiary academic referral center. Fourteen patients underwent ERCP for the management of a traumatic bile leak over a 5-year period. The etiology included blunt trauma from motor vehicle accident in 8 patients, motorcycle accident in 3 patients and penetrating injury from a gunshot wound in 3 patients. Liver injuries were grade III in 1 patient, grade IV in 10 patients, and grade V in 3 patients. All patients were treated by biliary stent placement, and the outcome was successful in 14 of 14 cases (100%). The mean duration of follow-up was 85.6 days (range 54-175 days). There were no ERCP-related complications. In our case review, endoscopic management with endobiliary stent placement was found to be successful and resulted in resolution of the bile leak in all 14 patients. Based on our study results, ERCP should be considered as first-line therapy in the management of traumatic bile leaks.

Interventional Vitamin C-A Strategy for Attenuation of Coagulopathy and Inflammation in Hemorrhagic Trauma and Shock

DTIC Science & Technology

2017-10-01

edema, protein leak and exuberant infiltration of inflammatory cells. Significant hemorrhage and cellular damage were also evident in liver and kidney ...Treatment with VitC also reduced the expression of pro-inflammatory mediators in lungs, liver and kidneys . Preliminary lipidomic analysis showed that VitC at...Histological changes to lung, liver and kidney f. Proteomic analysis of plasma for identification of novel circulating proteins, and g. Lipidomic

Locating air leaks in manned spacecraft using structure-borne noise.

PubMed

Holland, Stephen D; Chimenti, D E; Roberts, Ron; Strei, Michael

2007-06-01

All manned spacecraft are vulnerable to leaks generated by micrometeorite or debris impacts. Methods for locating such leaks using leak-generated, structure-borne ultrasonic noise are discussed and demonstrated. Cross-correlations of ultrasonic noise waveforms from a leak into vacuum are used to find the location of the leak. Four methods for sensing and processing leak noise have been developed and tested and each of these can be used to reveal the leak location. The methods, based on phased-array, distributed sensor, and dual sensor approaches, utilize the propagation patterns of guided ultrasonic Lamb waves in the spacecraft skin structure to find the source or direction of the leak noise. It is shown that each method can be used to successfully locate the leak to within a few millimeters on a 0.6-m2 aluminum plate. The relative merits of the four methods are discussed.

Mucosal immunization with PspA (Pneumococcal surface protein A)-adsorbed nanoparticles targeting the lungs for protection against pneumococcal infection

PubMed Central

Rodrigues, Tasson C.; Oliveira, Maria Leonor S.; Soares-Schanoski, Alessandra; Chavez-Rico, Stefanni L.; Figueiredo, Douglas B.; Gonçalves, Viviane M.; Ferreira, Daniela M.; Kunda, Nitesh K.; Saleem, Imran Y.

2018-01-01

Burden of pneumonia caused by Streptococcus pneumoniae remains high despite the availability of conjugate vaccines. Mucosal immunization targeting the lungs is an attractive alternative for the induction of local immune responses to improve protection against pneumonia. Our group had previously described the development of poly(glycerol adipate-co-ω-pentadecalactone) (PGA-co-PDL) polymeric nanoparticles (NPs) adsorbed with Pneumococcal surface protein A from clade 4 (PspA4Pro) within L-leucine microcarriers (nanocomposite microparticles—NCMPs) for mucosal delivery targeting the lungs (NP/NCMP PspA4Pro). NP/NCMP PspA4Pro was now used for immunization of mice. Inoculation of this formulation induced anti-PspA4Pro IgG antibodies in serum and lungs. Analysis of binding of serum IgG to intact bacteria showed efficient binding to bacteria expressing PspA from clades 3, 4 and 5 (family 2), but no binding to bacteria expressing PspA from clades 1 and 2 (family 1) was observed. Both mucosal immunization with NP/NCMP PspA4Pro and subcutaneous injection of the protein elicited partial protection against intranasal lethal pneumococcal challenge with a serotype 3 strain expressing PspA from clade 5 (PspA5). Although similar survival levels were observed for mucosal immunization with NP/NCMP PspA4Pro and subcutaneous immunization with purified protein, NP/NCMP PspA4Pro induced earlier control of the infection. Conversely, neither immunization with NP/NCMP PspA4Pro nor subcutaneous immunization with purified protein reduced bacterial burden in the lungs after challenge with a serotype 19F strain expressing PspA from clade 1 (PspA1). Mucosal immunization with NP/NCMP PspA4Pro targeting the lungs is thus able to induce local and systemic antibodies, conferring protection only against a strain expressing PspA from the homologous family 2. PMID:29360883

MicroRNA-490 regulates lung cancer metastasis by targeting poly r(C)-binding protein 1.

PubMed

Li, Jindong; Feng, Qingchuan; Wei, Xudong; Yu, Yongkui

2016-11-01

Lung cancer remains a leading cause of cancer-related mortality, with metastatic progression remaining the single largest cause of lung cancer mortality. Hence, it is imperative to determine reliable biomarkers of lung cancer prognosis. MicroRNA-490-3p has been previously reported to be a positive prognostic biomarker for hepatocellular cancer. However, its role in human lung cancer has not yet been elucidated. Here, we report that hsa-miR-490-3p expression is significantly higher in human lung cancer tissue specimens and cell line. Gain- and loss-of-function studies of hsa-miR-490-3p showed that it regulates cell proliferation and is required for induction of in vitro migration and invasion-the latter being a hallmark of epithelial to mesenchymal transition. In situ analysis revealed that hsa-miR-490-3p targets poly r(C)-binding protein 1 (PCBP1), which has been previously shown to be a negative regulator of lung cancer metastasis. Reporter assays confirmed PCBP1 as a bona fide target of miR-490-3p, and metagenomic analysis revealed an inverse relation between expression of miR-490-3p and PCBP1 in metastatic lung cancer patients. In fact, PCBP1 expression, as detected by immunohistochemistry, was undetectable in advanced stages of lung cancer patients' brain and lymph node tissues. Xenograft tail vein colonization assays proved that high expression of miR-490-3p is a prerequisite for metastatic progression of lung cancer. Our results suggest that hsa-miR-490-3p might be a potential biomarker for lung cancer prognosis. In addition, we can also conclude that the lung cancer cells have evolved refractory mechanisms to downregulate the expression of the metastatic inhibitor, PCBP1.

C-reactive protein, fibrinogen, and procalcitonin levels as early markers of staple line leak after laparoscopic sleeve gastrectomy in morbidly obese patients within an Enhanced Recovery After Surgery (ERAS) program.

PubMed

Ruiz-Tovar, Jaime; Muñoz, Jose Luis; Gonzalez, Juan; Garcia, Alejandro; Ferrigni, Carlos; Jimenez, Montiel; Duran, Manuel

2017-12-01

The performance of most bariatric procedures within an Enhanced Recovery After Surgery program has resulted in significant advantages, including a reduction in the length of hospital stay to 2-3 days. However, some postoperative complications may appear after the patient has been discharged. The aim of this study was to investigate the efficacy of various acute-phase parameters determined 24 h after a laparoscopic sleeve gastrectomy for predicting staple line leak in the postoperative course. A prospective study of 208 morbidly obese patients undergoing laparoscopic sleeve gastrectomy as bariatric procedure between 2012 and 2015 was performed. Blood analysis was performed 24 h after surgery. Acute-phase parameters (C-reactive protein, procalcitonin, fibrinogen, and White Blood Cell count) were investigated. Staple line leak appeared in eight patients (3.8%). Using receiver operating characteristic analysis at 24 h postoperatively, a cutoff level of CRP at 9 mg/dL achieved 85% sensitivity and 90% specificity for predicting staple line leak, a cutoff level of procalcitonin at 0.85 ng/mL achieved 70% sensitivity and 90% specificity, and a cutoff level of fibrinogen at 600 mg/dL achieved 80% sensitivity and 87.5% specificity. An elevation of CRP > 9 mg/dL, procalcitonin > 0.85 ng/mL and fibrinogen > 600 mg/dL should alert the surgeon the possibility of occurrence of postoperative staple line leak.

Distributed wireless sensing for methane leak detection technology

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

Klein, Levente; van Kesse, Theodor

Large scale environmental monitoring requires dynamic optimization of data transmission, power management, and distribution of the computational load. In this work, we demonstrate the use of a wireless sensor network for detection of chemical leaks on gas oil well pads. The sensor network consist of chemi-resistive and wind sensors and aggregates all the data and transmits it to the cloud for further analytics processing. The sensor network data is integrated with an inversion model to identify leak location and quantify leak rates. We characterize the sensitivity and accuracy of such system under multiple well controlled methane release experiments. It ismore » demonstrated that even 1 hour measurement with 10 sensors localizes leaks within 1 m and determines leak rate with an accuracy of 40%. This integrated sensing and analytics solution is currently refined to be a robust system for long term remote monitoring of methane leaks, generation of alarms, and tracking regulatory compliance.« less

Distributed wireless sensing for fugitive methane leak detection

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

Klein, Levente J.; van Kessel, Theodore; Nair, Dhruv

Large scale environmental monitoring requires dynamic optimization of data transmission, power management, and distribution of the computational load. In this work, we demonstrate the use of a wireless sensor network for detection of chemical leaks on gas oil well pads. The sensor network consist of chemi-resistive and wind sensors and aggregates all the data and transmits it to the cloud for further analytics processing. The sensor network data is integrated with an inversion model to identify leak location and quantify leak rates. We characterize the sensitivity and accuracy of such system under multiple well controlled methane release experiments. It ismore » demonstrated that even 1 hour measurement with 10 sensors localizes leaks within 1 m and determines leak rate with an accuracy of 40%. This integrated sensing and analytics solution is currently refined to be a robust system for long term remote monitoring of methane leaks, generation of alarms, and tracking regulatory compliance.« less

Distributed wireless sensing for fugitive methane leak detection

DOE PAGES

Klein, Levente J.; van Kessel, Theodore; Nair, Dhruv; ...

2017-12-11

Large scale environmental monitoring requires dynamic optimization of data transmission, power management, and distribution of the computational load. In this work, we demonstrate the use of a wireless sensor network for detection of chemical leaks on gas oil well pads. The sensor network consist of chemi-resistive and wind sensors and aggregates all the data and transmits it to the cloud for further analytics processing. The sensor network data is integrated with an inversion model to identify leak location and quantify leak rates. We characterize the sensitivity and accuracy of such system under multiple well controlled methane release experiments. It ismore » demonstrated that even 1 hour measurement with 10 sensors localizes leaks within 1 m and determines leak rate with an accuracy of 40%. This integrated sensing and analytics solution is currently refined to be a robust system for long term remote monitoring of methane leaks, generation of alarms, and tracking regulatory compliance.« less

Drain amylase aids detection of anastomotic leak after esophagectomy.

PubMed

Baker, Erin H; Hill, Joshua S; Reames, Mark K; Symanowski, James; Hurley, Susie C; Salo, Jonathan C

2016-04-01

Anastomotic leak following esophagectomy is associated with significant morbidity and mortality. As hospital length of stay decreases, the timely diagnosis of leak becomes more important. We evaluated CT esophagram, white blood count (WBC), and drain amylase levels in the early detection of anastomotic leak. The diagnostic performance of CT esophagram, drain amylase >800 IU/L, and WBC >12,000/µL within the first 10 days after surgery in predicting leak at any time after esophagectomy was calculated. Anastomotic leak occurred in 13 patients (13%). CT esophagram performed within 10 days of surgery diagnosed six of these leaks with a sensitivity of 0.54. Elevation in drain amylase level within 10 days of surgery diagnosed anastomotic leak with a sensitivity of 0.38. When the CT esophagram and drain amylase were combined, the sensitivity rose to 0.69 with a specificity of 0.98. WBC elevation had a sensitivity of 0.92, with a specificity of 0.34. Among 30 patients with normal drain amylase and a normal WBC, one developed an anastomotic leak. Drain amylase adds to the sensitivity of CT esophagram in the early detection of anastomotic leak. Selected patients with normal drain amylase levels and normal WBC may be able to safely forgo CT esophagram.

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

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

Seki, Yasuhiro; Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology; Yoshida, Yukihiro

2014-01-24

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

[A comparison of leak compensation in six acute care ventilators during non-invasive ventilation].

PubMed

Hu, X S; Wang, Y; Wang, Z T; Yan, P; Zhang, X G; Zhao, S F; Xie, F; Gu, H J; Xie, L X

2017-02-12

Objective: To compare the ability of leak compensation in 6 medical ventilators during non-invasive ventilation. Methods: Six medical ventilators were selected, including 3 non-invasive ventilators (V60, Flexo and Stellar150), and 3 invasive ventilators(Avea, Servo I and BellaVist). Using a lung simulator, the ability of leak compensation was evaluated during triggering and cycling in 2 respiratory mechanics conditions (high airway resistance condition and high elastance resistance condition), and each condition was performed under 2 PEEP levels (4, and 8 cmH(2)O, 1 mmHg=0.098 kPa) at 4 air leak level conditions (L0: 2-3 L/min, L1: 8-10 L/min, L2: 22-27 L/min, L3: 35-40 L/min). Results: In the high elastance resistance condition (L2, L3)with different leak levels, the number of auto-triggering and miss-triggering of the non-invasive ventilator Flexo was significantly less than those of the others (L2: 1, 1; L3: 1.67, 1.33, P <0.01), and had better synchronization (L2: 2.33, 2.33; L3: 3.33, 3.33, P <0.01). In the high airway resistance condition with PEEP 4 cmH(2)O, V60 had less number of auto-triggering than other ventilators ( P <0.01), while in the high airway resistance condition with PEEP 8 cmH(2)O, Stellar150 had less number of miss-triggering than other ventilators (1, 0.67, 0, P <0.01). Flexo had a shorter trigger delay time than other ventilators in both high airway resistance and high elastance resistance conditions with L0 and L1 leak levels and PEEP levels [ARDS, PEEP=4: (109.8±1.8) ms, (112.0±0.6) ms; ARDS, PEEP=8: (103.1±0.7) ms, (109.7±0.7) ms; COPD, PEEP=4: (207.3±1.1) ms, (220.8±1.1) ms; COPD, PEEP=8: (195.6±6.7) ms, (200.0±1.2) ms , P <0.01]. Stellar150 had the shortest trigger delay time in high airway resistance condition with PEEP 4 cmH(2)O and high leak level L3[(262.8±0.8) ms , P <0.01]. V60 had a good performance on trigger delay time in high elastance resistance condition with PEEP 4 and 8 cmH(2)O, and also was most stable in

Proteomic analysis of ubiquitination-associated proteins in a cisplatin-resistant human lung adenocarcinoma cell line.

PubMed

Qin, Xia; Chen, Shizhi; Qiu, Zongyin; Zhang, Yuan; Qiu, Feng

2012-05-01

The objective of this study was to screen for ubiquitination-associated proteins involved in cisplatin resistance in a human lung adenocarcinoma cell strain using a comparative proteomic strategy. We employed 1D SDS-PAGE to separate ubiquitinated proteins isolated and enriched from A549 and A549/CDDP lysates via affinity chromatography. The differentially expressed bands between 45-85 kDa were subsequently hydrolyzed by trypsin and subjected to HPLC-CHIP-MS/MS analysis. Of the 11 proteins identified, 7 proteins were monoubiquitinated or polyubiquitinated substrates and 4 proteins were E3 ubiquitin ligase-associated proteins. The results of western blotting and confocal laser scanning microscopy indicated that the expression levels of the E3 ubiquitin ligases RNF6, LRSAM1 and TRIM25 in A549 cells were significantly lower than those in the A549/CDDP cell line. The expression levels of the above three ubiquitin ligases in both cell lines were significantly decreased upon treatment with cis-diamminedichloroplatinum (CDDP), and the expression in the A549/CDDP cell after the treatment with CDDP decreased to a lesser extent. The expression of the substrate PKM2 in the A549 cell was higher than that in the A549/CDDP cells. Moreover, the expression of PKM2 increased in the A549 cell line and decreased in the A549/CDDP cell line upon CDDP treatment. This study suggests that drug resistance is closely correlated with changes in the ubiquitination process at the protein level in a human lung adenocarcinoma cell line.

Study of Residual Gas Analyser (RGA) Response towards Known Leaks

NASA Astrophysics Data System (ADS)

Pathan, Firozkhan S.; Khan, Ziauddin; Semwal, Pratibha; George, Siju; Raval, Dilip C.; Thankey, Prashant L.; Manthena, Himabindu; Yuvakiran, Paravastu; Dhanani, Kalpesh R.

2012-11-01

Helium leak testing is the most versatile form of weld qualification test for any vacuum application. Almost every ultra-high vacuum (UHV) system utilizes this technique for insuring leak tightness for the weld joints as well as demountable joints. During UHV system under operational condition with many other integrated components, in-situ developed leaks identification becomes one of the prime aspect for maintaining the health of such system and for continuing the experiments onwards. Since online utilization of leak detector (LD) has many practical limitations, residual gas analyser (RGA) can be used as a potential instrument for online leak detection. For this purpose, a co-relation for a given leak rate between Leak Detector and RGA is experimentally established. This paper describes the experimental aspect and the relationship between leak detector and RGA.

A Comparative Study of Rat Lung Decellularization by Chemical Detergents for Lung Tissue Engineering

PubMed Central

Tebyanian, Hamid; Karami, Ali; Motavallian, Ebrahim; Aslani, Jafar; Samadikuchaksaraei, Ali; Arjmand, Babak; Nourani, Mohammad Reza

2017-01-01

BACKGROUND: Lung disease is the most common cause of death in the world. The last stage of pulmonary diseases is lung transplantation. Limitation and shortage of donor organs cause to appear tissue engineering field. Decellularization is a hope for producing intact ECM in the development of engineered organs. AIM: The goal of the decellularization process is to remove cellular and nuclear material while retaining lung three-dimensional and molecular proteins. Different concentration of detergents was used for finding the best approach in lung decellularization. MATERIAL AND METHODS: In this study, three-time approaches (24, 48 and 96 h) with four detergents (CHAPS, SDS, SDC and Triton X-100) were used for decellularizing rat lungs for maintaining of three-dimensional lung architecture and ECM protein composition which have significant roles in differentiation and migration of stem cells. This comparative study determined that variable decellularization approaches can cause significantly different effects on decellularized lungs. RESULTS: Results showed that destruction was increased with increasing the detergent concentration. Single detergent showed a significant reduction in maintaining of three-dimensional of lung and ECM proteins (Collagen and Elastin). But, the best methods were mixed detergents of SDC and CHAPS in low concentration in 48 and 96 h decellularization. CONCLUSION: Decellularized lung tissue can be used in the laboratory to study various aspects of pulmonary biology and physiology and also, these results can be used in the continued improvement of engineered lung tissue. PMID:29362610

Conceptual apparatus for detecting leaks of nonconductive liquids

NASA Technical Reports Server (NTRS)

Walsh, G. D.

1968-01-01

Apparatus detects leaks at joints in lines carrying electrically nonconductive liquids. The proposed apparatus could include a panel that would give a visual or audible indication of a leak /to permit manual shutdown/ and/or an electromechanical actuator that would automatically cut off the flow when a leak occurs.

ISS Ammonia Leak Detection Through X-Ray Fluorescence

NASA Technical Reports Server (NTRS)

Camp, Jordan; Barthelmy, Scott; Skinner, Gerry

2013-01-01

Ammonia leaks are a significant concern for the International Space Station (ISS). The ISS has external transport lines that direct liquid ammonia to radiator panels where the ammonia is cooled and then brought back to thermal control units. These transport lines and radiator panels are subject to stress from micrometeorites and temperature variations, and have developed small leaks. The ISS can accommodate these leaks at their present rate, but if the rate increased by a factor of ten, it could potentially deplete the ammonia supply and impact the proper functioning of the ISS thermal control system, causing a serious safety risk. A proposed ISS astrophysics instrument, the Lobster X-Ray Monitor, can be used to detect and localize ISS ammonia leaks. Based on the optical design of the eye of its namesake crustacean, the Lobster detector gives simultaneously large field of view and good position resolution. The leak detection principle is that the nitrogen in the leaking ammonia will be ionized by X-rays from the Sun, and then emit its own characteristic Xray signal. The Lobster instrument, nominally facing zenith for its astrophysics observations, can be periodically pointed towards the ISS radiator panels and some sections of the transport lines to detect and localize the characteristic X-rays from the ammonia leaks. Another possibility is to use the ISS robot arm to grab the Lobster instrument and scan it across the transport lines and radiator panels. In this case the leak detection can be made more sensitive by including a focused 100-microampere electron beam to stimulate X-ray emission from the leaking nitrogen. Laboratory studies have shown that either approach can be used to locate ammonia leaks at the level of 0.1 kg/day, a threshold rate of concern for the ISS. The Lobster instrument uses two main components: (1) a microchannel plate optic (also known as a Lobster optic) that focuses the X-rays and directs them to the focal plane, and (2) a CCD (charge

Prospective randomized trial compares suction versus water seal for air leaks.

PubMed

Cerfolio, R J; Bass, C; Katholi, C R

2001-05-01

Surgeons treat air leaks differently. Our goal was to evaluate whether it is better to place chest tubes on suction or water seal for stopping air leaks after pulmonary surgery. A second goal was to evaluate a new classification system for air leaks that we developed. Patients were prospectively randomized before surgery to receive suction or water seal to their chest tubes on postoperative day (POD) #2. Air leaks were described and quantified daily by a classification system and a leak meter. The air-leak meter scored leaks from 1 (least) to 7 (greatest). The group randomized to water seal stayed on water seal unless a pneumothorax developed. On POD #2, 33 of 140 patients had an air leak. Eighteen patients had been preoperatively randomized to water seal and 15 to suction. Air leaks resolved in 12 (67%) of the water seal patients by the morning of POD #3. All 6 patients whose air leak did not stop had a leak that was 4/7 or greater (p < 0.0001) on the leak meter. Of the 15 patients randomized to suction, only 1 patient's air leak (7%) resolved by the morning of POD #3. The randomization aspect of the trial was ended and statistical analysis showed water seal was superior (p = 0.001). The remaining 14 patients were then placed to water seal and by the morning of POD #4, 13 patients' leaks had stopped. Of the 32 total patients placed to seal, 7 (22%) developed a pneumothorax and 6 of these 7 patients had leaks that were 4/7 or greater (p = 0.001). Placing chest tubes on water seal seems superior to wall suction for stopping air leaks after pulmonary resection. However, water seal does not stop expiratory leaks that are 4/7 or greater. Pneumothorax may occur when chest tubes are placed on seal with leaks this large.

Lung cancer incidence and survival in chromium exposed individuals with respect to expression of anti-apoptotic protein survivin and tumor suppressor P53 protein

PubMed Central

2010-01-01

Objective Workers chronically exposed to hexavalent chromium have elevated risk of lung cancer. Our study investigates the incidence of lung cancer types, age at onset of the disease, and survival time among chromium exposed workers with respect to the expression of anti-apoptotic p53 and pro-apoptotic survivin proteins. Materials and methods 67 chromium exposed workers and 104 male controls diagnosed with lung cancer were analyzed. The mean exposure time among workers was 16.7 ± 10.0(SD) years (range 1- 41 years). To investigate the possible regulation of survivin by p53 we examined the expression of both proteins using immohistochemical visualization. Results Chromium exposure significantly decreases the age of onset of the disease by 3.5 years (62.2 ± 9.1 in the exposed group vs. 65.7 ± 10.5 years in controls; P = 0.018). Small cell lung carcinoma (SCLC) amounted for 25.4% of all cases in chromium exposed workers and for 16.3% in non-exposed individuals. The mean survival time in the exposed group was 9.0 ± 12.7 vs. 12.1 ± 21.9 months in controls, but this difference was not significant. Survivin was predominantly expressed in both cell nucleus and cytoplasm, whereas p53 was expressed in the nucleus. There was a negative correlation between survivin and p53 expression. A decreased intensity of expression and fewer cells positive for survivin was detected in SCLC compared with other types of lung cancer. P53 was expressed in 94.1% and survivin in 79.6% of the samples analyzed. Conclusion The study calls attention to decreased expression of survivin, as opposed to p53, in small cell lung carcinoma. PMID:21147621

The effect of sodium hyaluronate-carboxymethyl cellulose membrane in the prevention of parenchymal air leaks: an experimental and manometric study in rats.

PubMed

Büyükkale, Songül; Çıtak, Necati; İşgörücü, Özgür; Sayar, Adnan

2017-12-01

We aimed to examine effectiveness of sodium hyaluronate-carboxymethly cellulose (NaH/CMC) for sealing pulmonary air leaks during postoperative period. The study was conducted in 16 male Sprague-Dawley rats. A linear insicion (length= 0.2 cm, depth= 0.1 cm) to the lung parenchyma on the inflated by a cutter was made. The animals were randomly divided; the control group (n= 8) and NaH/CMC-treated group (the study group, n= 8). Control group was left for physiologic healing while a NaH/CMC membrane was applied over the the incisional area in the study group. Then the pressure point where the air leakage observed was noted. No polymorphonucleer leucocytes (PMNL) infiltration was detected in control group, whereas PMNL infiltration was 0.38 ± 0.5 cell per 100 high field in study group (p= 0.234). The degree of macrophage, lymphocyte infiltration and the mean fibroblast count were found to be higher in study group compared with control group (p= 0.007, p= 0.02, p= 0.05, respectively). The mean pressure value for air leak to occur in the control group was 43.50 ± 9.55 mmHg whereas it was 73.75 ± 16.68 mmHg in the study group (p< 0.001). The data revealed that bioabsorbable NaH/CMC membrane accelerates healing with preserving the expansile character of lung parenchyma even in high ventilation pressures. However, further studies are required to assess the prevent impact of the pulmonary air-leak for NaH/CMC membrane.

Critical role for CCAAT/Enhancer-binding protein beta in immune complex-induced acute lung injury

USDA-ARS?s Scientific Manuscript database

Although inflammation plays a central role in the pathogenesis of acute lung injury (ALI), the molecular mechanisms underlying inflammatory responses in ALI are poorly understood, and therapeutic options remain limited. The CCAAT/enhancer-binding protein (C/EBP) gamma and -gamma have been implicated...

The matricellular protein CYR61 promotes breast cancer lung metastasis by facilitating tumor cell extravasation and suppressing anoikis.

PubMed

Huang, Yu-Ting; Lan, Qiang; Lorusso, Girieca; Duffey, Nathalie; Rüegg, Curzio

2017-02-07

Matricellular proteins play multiple roles in primary tumor growth, local invasion and tumor angiogenesis. However, their contribution to metastasis and the putative mechanisms involved are less well characterized. In ER-negative human breast cancer, elevated expression levels of the matricellular protein Cysteine-rich angiogenic inducer 61 (CYR61) are associated with more aggressive progression. Here, we investigated the role of CYR61 in breast cancer lung metastasis using the triple negative human breast cancer cell lines MDA-MB-231 and SUM159. Silencing of CYR61 significantly decreased lung metastasis from tumors orthotopically implanted in pre-irradiated or naive mammary tissue and upon tail vein injection. Constitutive CYR61 silencing impaired cancer cell extravasation to the lung during the first 24 hours after tail vein injection. In contrast, CYR61 inducible silencing starting 24 hours after cancer cell injection had no impact on lung metastasis formation. In vitro experiments revealed that CYR61 silencing decreased cancer cell transendothelial migration and motility, reduced CYR61 levels present at the cell surface and sensitized cancer cells to anoikis. Furthermore, we demonstrate that CYR61-dependent cell survival under non-adhesive conditions relied, at least partially, on β1 integrin ligation and AMPKα signaling while it was independent of AKT, FAK and ERK1/2 activation. Our data provide the first evidence that CYR61 promotes breast cancer lung metastasis by facilitating tumor cell extravasation and protecting from anoikis during initial seeding to the lung. The uncovered CYR61-β1 integrin-AMPKα axis may serve as a potential therapeutic target to prevent breast cancer metastasis to the lung.

Thermal acclimation mitigates cold-induced paracellular leak from the Drosophila gut.

PubMed

MacMillan, Heath A; Yerushalmi, Gil Y; Jonusaite, Sima; Kelly, Scott P; Donini, Andrew

2017-08-18

Chill susceptible insects suffer tissue damage and die at low temperatures. The mechanisms that cause chilling injury are not well understood but a growing body of evidence suggests that a cold-induced loss of ion and water homeostasis leads to hemolymph hyperkalemia that depolarizes cells, leading to cell death. The apparent root of this cascade is the net leak of osmolytes down their concentration gradients in the cold. Many insects, however, are capable of adjusting their thermal physiology, and cold-acclimated Drosophila can maintain homeostasis and avoid injury better than warm-acclimated flies. Here, we test whether chilling causes a loss of epithelial barrier function in female adult Drosophila, and provide the first evidence of cold-induced epithelial barrier failure in an invertebrate. Flies had increased rates of paracellular leak through the gut epithelia at 0 °C, but cold acclimation reduced paracellular permeability and improved cold tolerance. Improved barrier function was associated with changes in the abundance of select septate junction proteins and the appearance of a tortuous ultrastructure in subapical intercellular regions of contact between adjacent midgut epithelial cells. Thus, cold causes paracellular leak in a chill susceptible insect and cold acclimation can mitigate this effect through changes in the composition and structure of transepithelial barriers.

Discovery of potential protein biomarkers of lung adenocarcinoma in bronchoalveolar lavage fluid by SWATH MS data-independent acquisition and targeted data extraction.

PubMed

Ortea, I; Rodríguez-Ariza, A; Chicano-Gálvez, E; Arenas Vacas, M S; Jurado Gámez, B

2016-04-14

Lung cancer currently ranks as the neoplasia with the highest global mortality rate. Although some improvements have been introduced in recent years, new advances in diagnosis are required in order to increase survival rates. New mildly invasive endoscopy-based diagnostic techniques include the collection of bronchoalveolar lavage fluid (BALF), which is discarded after using a portion of the fluid for standard pathological procedures. BALF proteomic analysis can contribute to clinical practice with more sensitive biomarkers, and can complement cytohistological studies by aiding in the diagnosis, prognosis, and subtyping of lung cancer, as well as the monitoring of treatment response. The range of quantitative proteomics methodologies used for biomarker discovery is currently being broadened with the introduction of data-independent acquisition (DIA) analysis-related approaches that address the massive quantitation of the components of a proteome. Here we report for the first time a DIA-based quantitative proteomics study using BALF as the source for the discovery of potential lung cancer biomarkers. The results have been encouraging in terms of the number of identified and quantified proteins. A panel of candidate protein biomarkers for adenocarcinoma in BALF is reported; this points to the activation of the complement network as being strongly over-represented and suggests this pathway as a potential target for lung cancer research. In addition, the results reported for haptoglobin, complement C4-A, and glutathione S-transferase pi are consistent with previous studies, which indicates that these proteins deserve further consideration as potential lung cancer biomarkers in BALF. Our study demonstrates that the analysis of BALF proteins by liquid chromatography-tandem mass spectrometry (LC-MS/MS), combining a simple sample pre-treatment and SWATH DIA MS, is a useful method for the discovery of potential lung cancer biomarkers. Bronchoalveolar lavage fluid (BALF

Non-Canonical Thinking for Targeting ALK-Fusion Onco-Proteins in Lung Cancer

PubMed Central

Wu, Wei; Haderk, Franziska; Bivona, Trever G.

2017-01-01

Anaplastic lymphoma kinase (ALK) gene rearrangements have been identified in lung cancer at 3–7% frequency, thus representing an important subset of genetic lesions that drive oncogenesis in this disease. Despite the availability of multiple FDA-approved small molecule inhibitors targeting ALK fusion proteins, drug resistance to ALK kinase inhibitors is a common problem in clinic. Thus, there is an unmet need to deepen the current understanding of genomic characteristics of ALK rearrangements and to develop novel therapeutic strategies that can overcome ALK inhibitor resistance. In this review, we present the genomic landscape of ALK fusions in the context of co-occurring mutations with other cancer-related genes, pointing to the central role of genetic epistasis (gene-gene interactions) in ALK-driven advanced-stage lung cancer. We discuss the possibility of targeting druggable domains within ALK fusion partners in addition to available strategies inhibiting the ALK kinase domain directly. Finally, we examine the potential of targeting ALK fusion-specific neoantigens in combination with other treatments, a strategy that could open a new avenue for the improved treatment of ALK positive lung cancer patients. PMID:29189709

49 CFR 230.64 - Leaks under lagging.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS Boilers and Appurtenances Steam Leaks § 230.64 Leaks under lagging. The steam locomotive owner and/or operator shall take out of...

Anastomotic leaks: what is the best diagnostic imaging study?

PubMed

Nicksa, G A; Dring, R V; Johnson, K H; Sardella, W V; Vignati, P V; Cohen, J L

2007-02-01

Postoperative anastomotic leaks are one of the most devastating consequences of colorectal surgery. Diagnostic imaging for upper gastrointestinal anastomotic leaks has been evaluated and reported on extensively. No study has compared the utility and effectiveness of CT scans and water-soluble enemas for the identification of postoperative lower gastrointestinal anastomotic leaks. The present study was designed to evaluate and compare these two common radiographic imaging modalities in detecting lower gastrointestinal anastomotic leaks. A retrospective chart review was performed that identified 36 patients during a seven-year period who underwent reoperative surgery for a lower gastrointestinal anastomotic leak. Patient's imaging studies were classified as positive if extravasation of contrast material was demonstrated. When negative, a study was retrospectively reviewed in an attempt to identify findings suggestive of an anastomotic leak. There were 36 patients identified with a postoperative lower gastrointestinal leak requiring surgical intervention. There were 28 of 36 patients (78 percent) re-explored on the basis of a radiologic study demonstrating an anastomotic leak. A total of 27 CT scans were performed, of which 4 (14.8 percent) were considered positive for an anastomotic leak. On review of the remaining negative CT scans, nine (33.3 percent) were considered descriptive positive with a large amount of fluid or air in the peritoneal cavity but without obvious extravasation of contrast. Eighteen patients were evaluated with a water-soluble enema and 15 (83.3 percent) demonstrated extravasation of contrast material. In the 26 patients with a distal anastomotic leak, 17 water-soluble enemas were performed, with 15 (88 percent) demonstrating a leak. In contrast, only 2 of 17 (12 percent) CT scans were positive in this group of patients (P < 0.001). There were ten patients who initially had a CT scan followed by a water-soluble enema. Of these patients, eight of

Leak and Pipe Detection Method and System

NASA Technical Reports Server (NTRS)

Youngquist, Robert C. (Inventor)

2003-01-01

A method and system for locating leaks of conductive fluids from non-conductive pipes and other structures or for locat- ing non-conductive pipes or structures having conductive fluid contained therein, employ a charge generator to apply a time varying charge to the conductive fluid, and a capaci- tive type detector that can detect the variable charge that is induced in the fluid. The capacitive detector, which prefer- ably includes a handheld housing, employs a large conduc- tive pickup plate that is used to locate the pipe or leak by scanning the plate over the ground and detecting the induced charge that is generated when the plate comes in close proximity to the pipe or leak. If a leak is encountered, the resulting signal will appear over an area larger than expected for a buried pipe, assuming the leak provides an electrically conductive path between the flow and the wet surrounding ground. The detector uses any suitable type of indicator device, such as a pair of headphones that enable an operator to hear the detected signal as a chirping sound, for example.

Evaluation of a new chest tube removal protocol using digital air leak monitoring after lobectomy: a prospective randomised trial.

PubMed

Brunelli, Alessandro; Salati, Michele; Refai, Majed; Di Nunzio, Luca; Xiumé, Francesco; Sabbatini, Armando

2010-01-01

The objective of this randomised trial was to assess the effectiveness of a new fast-track chest tube removal protocol taking advantage of digital monitoring of air leak compared to a traditional protocol using visual and subjective assessment of air leak (bubbles). One hundred and sixty-six patients submitted to pulmonary lobectomy for lung cancer were randomised in two groups with different chest tube removal protocols: (1) in the new protocol, chest tube was removed based on digitally recorded measurements of air leak flow; (2) in the traditional protocol, the chest tube removal was based on an instantaneous assessment of air leak during daily rounds. The two groups were compared in terms of chest tube duration, hospital stay and costs. The two groups were well matched for several preoperative and operative variables. Compared to the traditional protocol, the new digital recording protocol showed mean reductions in chest tube duration (p=0.0007), hospital stay (p=0.007) of 0.9 day, and a mean cost saving of euro 476 per patient (p=0.008). In the new chest tube removal protocol, 51% of patients had their chest tube removed by the second postoperative day versus only 12% of those in the traditional protocol. The application of a chest tube removal protocol using a digital drainage unit featuring a continuous recording of air leak was safe and cost effective. Although future studies are warranted to confirm these results in other settings, the use of this new protocol is now routinely applied in our practice. Copyright 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

40 CFR 63.1023 - Instrument and sensory monitoring for leaks.

Code of Federal Regulations, 2010 CFR

2010-07-01

... leaks. 63.1023 Section 63.1023 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... (CONTINUED) National Emission Standards for Equipment Leaks-Control Level 2 Standards § 63.1023 Instrument and sensory monitoring for leaks. (a) Monitoring for leaks. The owner or operator of a regulated...

Leak detection by mass balance effective for Norman Wells line

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

Liou, J.C.P.

Mass-balance calculations for leak detection have been shown as effective as a leading software system, in a comparison based on a major Canadian crude-oil pipeline. The calculations and NovaCorp`s Leakstop software each detected 4% (approximately) or greater leaks on Interprovincial Pipe Line (IPL) Inc.`s Norman Wells pipeline. Insufficient data exist to assess performances of the two methods for leaks smaller than 4%. Pipeline leak detection using such software-based systems are common. Their effectiveness is measured by how small and how quickly a leak can be detected. Algorithms used and measurement uncertainties determine leak detectability.

10 CFR 36.59 - Detection of leaking sources.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Detection of leaking sources. 36.59 Section 36.59 Energy... Irradiators § 36.59 Detection of leaking sources. (a) Each dry-source-storage sealed source must be tested for leakage at intervals not to exceed 6 months using a leak test kit or method approved by the Commission or...

40 CFR 65.104 - Instrument and sensory monitoring for leaks.

Code of Federal Regulations, 2010 CFR

2010-07-01

... leaks. 65.104 Section 65.104 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONSOLIDATED FEDERAL AIR RULE Equipment Leaks § 65.104 Instrument and sensory monitoring for leaks. (a) Monitoring for leaks. The owner or operator of a regulated source subject to this...

Leak rates in sealed cells.

NASA Technical Reports Server (NTRS)

Frank, H. A.; Uchiyama, A. A.

1973-01-01

Water vapor loss rates were determined from simulated and imperfectly sealed alkaline cells in the vacuum environment. The observed rates were found to be in agreement with a semi-empirical equation employed in vacuum technology. Results thereby give support for using this equation for the prediction of loss rates of battery gases and vapors to the aerospace environment. On this basis it was shown how the equation can be applied to the solution of many heretofore unresolved questions regarding leaks in batteries. Among these are the maximum permissible leak size consistent with a given cell life or conversely the maximum life consistent with a given leak size. It was also shown that loss rates of these cells in the terrestrial environment are several orders of magnitude less than the corresponding loss rates in the aerospace environment.

Detection of lung cancer using plasma protein profiling by matrix-assisted laser desorption/ionization mass spectrometry.

PubMed

Shevchenko, Valeriy E; Arnotskaya, Natalia E; Zaridze, David G

2010-01-01

There are no satisfactory plasma biomarkers which are available for the early detection and monitoring of lung cancer, one of the most frequent cancers worldwide. The aim of this study is to explore the application of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS) to plasma proteomic patterns to distinguish lung cancer patients from healthy individuals. The EDTA plasma samples have been pre-fractionated using magnetic bead kits functionalized with weak cation exchange coatings. We compiled MS protein profiles for 90 patients with squamous cell carcinomas (SCC) and compared them with profiles from 187 healthy controls. The MALDI-ToF spectra were analyzed statistically using ClinProTools bioinformatics software. Depending on the sample used, up to 441 peaks/spectrum could be detected in a mass range of 1000-20,000 Da; 33 of these proteins had statistically differential expression levels between SCC and control plasma (P < 0.001). The series of the peaks were automatically chosen as potential biomarker patterns in the training set. They allowed the discrimination of plasma samples from healthy control and samples from SCC patients (sensitivity and specificity >90%) in external validation test. These results suggest that plasma MALDI-ToF MS protein profiling can distinguish patients with SCC and also from healthy individuals with relatively high sensitivity and specificity and that MALDI- ToF MS is a potential tool for the screening of lung cancer.

A risk score to predict the incidence of prolonged air leak after video-assisted thoracoscopic lobectomy: An analysis from the European Society of Thoracic Surgeons database.

PubMed

Pompili, Cecilia; Falcoz, Pierre Emmanuel; Salati, Michele; Szanto, Zalan; Brunelli, Alessandro

2017-04-01

The study objective was to develop an aggregate risk score for predicting the occurrence of prolonged air leak after video-assisted thoracoscopic lobectomy from patients registered in the European Society of Thoracic Surgeons database. A total of 5069 patients who underwent video-assisted thoracoscopic lobectomy (July 2007 to August 2015) were analyzed. Exclusion criteria included sublobar resections or pneumonectomies, lung resection associated with chest wall or diaphragm resections, sleeve resections, and need for postoperative assisted mechanical ventilation. Prolonged air leak was defined as an air leak more than 5 days. Several baseline and surgical variables were tested for a possible association with prolonged air leak using univariable and logistic regression analyses, determined by bootstrap resampling. Predictors were proportionally weighed according to their regression estimates (assigning 1 point to the smallest coefficient). Prolonged air leak was observed in 504 patients (9.9%). Three variables were found associated with prolonged air leak after logistic regression: male gender (P < .0001, score = 1), forced expiratory volume in 1 second less than 80% (P < .0001, score = 1), and body mass index less than 18.5 kg/m 2 (P < .0001, score = 2). The aggregate prolonged air leak risk score was calculated for each patient by summing the individual scores assigned to each variable (range, 0-4). Patients were then grouped into 4 classes with an incremental risk of prolonged air leak (P < .0001): class A (score 0 points, 1493 patients) 6.3% with prolonged air leak, class B (score 1 point, 2240 patients) 10% with prolonged air leak, class C (score 2 points, 1219 patients) 13% with prolonged air leak, and class D (score >2 points, 117 patients) 25% with prolonged air leak. An aggregate risk score was created to stratify the incidence of prolonged air leak after video-assisted thoracoscopic lobectomy. The score can be used for patient counseling

Proteomic study of differential protein expression in mouse lung tissues after aerosolized ricin poisoning.

PubMed

Guo, Zhendong; Han, Chao; Du, Jiajun; Zhao, Siyan; Fu, Yingying; Zheng, Guanyu; Sun, Yucheng; Zhang, Yi; Liu, Wensen; Wan, Jiayu; Qian, Jun; Liu, Linna

2014-04-28

Ricin is one of the most poisonous natural toxins from plants and is classified as a Class B biological threat pathogen by the Centers for Disease Control and Prevention (CDC) of U.S.A. Ricin exposure can occur through oral or aerosol routes. Ricin poisoning has a rapid onset and a short incubation period. There is no effective treatment for ricin poisoning. In this study, an aerosolized ricin-exposed mouse model was developed and the pathology was investigated. The protein expression profile in the ricin-poisoned mouse lung tissue was analyzed using proteomic techniques to determine the proteins that were closely related to the toxicity of ricin. 2D gel electrophoresis, mass spectrometry and subsequent biological functional analysis revealed that six proteins including Apoa1 apolipoprotein, Ywhaz 14-3-3 protein, Prdx6 Uncharacterized Protein, Selenium-binding protein 1, HMGB1, and DPYL-2, were highly related to ricin poisoning.

Leak test adapter for containers

DOEpatents

Hallett, Brian H.; Hartley, Michael S.

1996-01-01

An adapter is provided for facilitating the charging of containers and leak testing penetration areas. The adapter comprises an adapter body and stem which are secured to the container's penetration areas. The container is then pressurized with a tracer gas. Manipulating the adapter stem installs a penetration plug allowing the adapter to be removed and the penetration to be leak tested with a mass spectrometer. Additionally, a method is provided for using the adapter.

40 CFR 63.1004 - Instrument and sensory monitoring for leaks.

Code of Federal Regulations, 2010 CFR

2010-07-01

... leaks. 63.1004 Section 63.1004 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... (CONTINUED) National Emission Standards for Equipment Leaks-Control Level 1 § 63.1004 Instrument and sensory monitoring for leaks. (a) Monitoring for leaks. The owner or operator of a regulated source subject to this...

[Comparative study of protein markers in serum and bronchoalveolar lavage fluid from patients with lung cancer by surface-enhanced laser desorption ionization time of flight mass spectrometry].

PubMed

Zhou, Ji-hong; Liu, Guang-nan; Huang, Si-ming; Zhong, Xiao-ning; Su, Hong; Zhou, Yi

2011-04-01

To detect the protein markers in serum and bronchoalveolar lavage fluid (BALF) of the patients with lung cancer by surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS) technology, and to explore if they can be used as markers for the diagnosis of lung cancer. SELDI-TOF-MS technology and protein chips weak cation exchange (WCX-2 chip) were used to detect the protein mass spectrum in serum and BALF of 35 patients with lung cancer and 18 cases of benign pulmonary diseases. The different protein markers were analyzed by Biomarker Pattern Software and the initial diagnosis models were set up. The diagnosis models were verified further by blind screen to confirm the efficacy of diagnosis. Five protein peaks in the sera of the patients with lung cancer were significantly higher (P < 0.05). The protein peak with a mass/charge ratio (M/Z) of 5639 was selected to establish the classification tree model. The sensitivity of diagnosis was 80% (28/35) and the specificity was 78% (14/18). The results verified by blind screen showed a sensitivity of 85% (17/20), a specificity of 90% (9/10), a crude accuracy (CA) of 87% (26/30) and Youden's index (γ) of 0.7. Eight protein peaks in the BALF of the patients with lung cancer were significantly higher (P < 0.05). The different protein peaks with M/Z of 7976 and 11 809 respectively were selected to establish the classification tree model. The sensitivity of diagnosis was 86% (30/35) and the specificity was 72% (13/18). The results verified by blind screen showed a sensitivity of 90% (18/20), a specificity of 90% (9/10), a CA of 90% (27/30) and γ of 0.8. There was a complementary role in combination of differential proteins in serum and BALF and the sensitivity, specificity and accuracy of diagnosis for lung cancer were 100% by parallel test. The SELDI-TOF-MS technology can screen out the differential protein markers in serum and BALF of the patients with lung cancer, which show high sensitivity

Double Shell Tank AY-102 Radioactive Waste Leak Investigation

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

Washenfelder, Dennis J.

2014-04-10

PowerPoint. The objectives of this presentation are to: Describe Effort to Determine Whether Tank AY-102 Leaked; Review Probable Causes of the Tank AY-102 Leak; and, Discuss Influence of Leak on Hanford’s Double-Shell Tank Integrity Program.

Tanshinone IIA suppresses lung injury and apoptosis, and modulates protein kinase B and extracellular signal-regulated protein kinase pathways in rats challenged with seawater exposure.

PubMed

Li, Jia-Huan; Xu, Min; Xie, Xiao-Yan; Fan, Qi-Xin; Mu, De-Guang; Zhang, Yong; Cao, Fa-Le; Wang, Yan-Xia; Zhao, Peng-Tao; Zhang, Bo; Jin, Fa-Guang; Li, Zhi-Chao

2011-04-01

1. Tanshinone IIA (TIIA) is one of the main active components of the Chinese herb, Danshen. In the present study, we investigated the role of apoptosis in seawater exposure-induced acute lung injury (ALI), and explored the effects of TIIA on lung injury, apoptosis, and protein kinase B (Akt) and extracellular signal-regulated protein kinase (ERK) pathways in seawater-challenged rats. The rats were randomly divided into four groups: (i) naive group, no drug was given; (ii) TIIA control group, TIIA (50 mg/kg) was given intraperitoneally; (iii) seawater (SW) group, seawater (4 mL/kg) was given; and (iv) TIIA/SW group, TIIA (50 mg/kg) was injected intraperitoneally 10 min after seawater instillation. 2. The results showed that TIIA treatment significantly improved seawater exposure-induced lung histopathological changes, alleviated the decrease in PaO(2) , and reduced lung oedema, vascular leakage and cell infiltration. As shown by terminal deoxynucleotidyl transferase-mediated nick end labelling (TUNEL) assay, seawater exposure induced apoptosis in lung tissue cells. Furthermore, seawater exposure also changed apoptosis-related factors Bcl-2 and caspase-3, and caused a reduction in the activation of Akt and ERK1/2 pathways. Furthermore, TIIA treatment decreased the number of apoptotic cells, reversed changes in Bcl-2 and caspase-3, and upregulated the activation of Akt and ERK1/2 in seawater-challenged rats. 3. In conclusion, the data suggest that apoptosis might play an important role in seawater exposure-induced lung injury and that TIIA could significantly attenuate the severity of ALI and apoptosis in seawater-challenged rats, which is possibly through modulation of Akt and ERK1/2 pathways. © 2011 The Authors. Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.

40 CFR 63.1024 - Leak repair.

Code of Federal Regulations, 2012 CFR

2012-07-01

... light liquid service. The leak identification on a valve in gas/vapor or light liquid service may be... that monitoring. The leak identification on a connector in gas/vapor or light liquid service may be... or light liquid service that is subject to the provisions of § 63.1027(b)(3)(iv), may be removed...

40 CFR 63.1024 - Leak repair.

Code of Federal Regulations, 2011 CFR

2011-07-01

... light liquid service. The leak identification on a valve in gas/vapor or light liquid service may be... that monitoring. The leak identification on a connector in gas/vapor or light liquid service may be... or light liquid service that is subject to the provisions of § 63.1027(b)(3)(iv), may be removed...

40 CFR 63.1024 - Leak repair.

Code of Federal Regulations, 2013 CFR

2013-07-01

... light liquid service. The leak identification on a valve in gas/vapor or light liquid service may be... that monitoring. The leak identification on a connector in gas/vapor or light liquid service may be... or light liquid service that is subject to the provisions of § 63.1027(b)(3)(iv), may be removed...

40 CFR 63.1024 - Leak repair.

Code of Federal Regulations, 2014 CFR

2014-07-01

... light liquid service. The leak identification on a valve in gas/vapor or light liquid service may be... that monitoring. The leak identification on a connector in gas/vapor or light liquid service may be... or light liquid service that is subject to the provisions of § 63.1027(b)(3)(iv), may be removed...

Experiences with leak rate calculations methods for LBB application

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

Grebner, H.; Kastner, W.; Hoefler, A.

1997-04-01

In this paper, three leak rate computer programs for the application of leak before break analysis are described and compared. The programs are compared to each other and to results of an HDR Reactor experiment and two real crack cases. The programs analyzed are PIPELEAK, FLORA, and PICEP. Generally, the different leak rate models are in agreement. To obtain reasonable agreement between measured and calculated leak rates, it was necessary to also use data from detailed crack investigations.

Hazardous Gas Leak Analysis in the Space Shuttle

NASA Technical Reports Server (NTRS)

Barile, Ronald G.

1991-01-01

Helium tests of the main propulsion system in the Space Shuttle and on hydrogen leaks are examined. The hazardous gas detection system (HGDS) in the mobile launch pad uses mass spectrometers (MS) to monitor the shuttle environment for leaks. The mass spectrometers are fed by long tubes to sample gas from the payload bay, mid-body, aft engine compartment, and external tank. The purpose is to improve the HGDS, especially in its potential for locating cryogen leaks. Pre-existing leak data was analyzed for transient information to determine if the leak location could be pinpointed from test data. A rapid response leak detection experiment was designed, built, and tested. Large eddies and vortices were visually seen with Schlieren imaging, and they were detected in the time plots of the various instruments. The response time of the MS was found in the range of 0.05 to 0.1 sec. Pulsed concentration waves were clearly detected at 25 cycles per sec by spectral analysis of MS data. One conclusion is that the backup HGDS sampling frequency should be increased above the present rate of 1 sample per second.

Leak test fixture and method for using same

DOEpatents

Hawk, Lawrence S.

1976-01-01

A method and apparatus are provided which are especially useful for leak testing seams such as an end closure or joint in an article. The test does not require an enclosed pressurized volume within the article or joint section to be leak checked. A flexible impervious membrane is disposed over an area of the seamed surfaces to be leak checked and sealed around the outer edges. A preselected vacuum is applied through an opening in the membrane to evacuate the area between the membrane and the surface being leak checked to essentially collapse the membrane to conform to the article surface or joined adjacent surfaces. A pressure differential is concentrated at the seam bounded by the membrane and only the seam experiences a pressure differential as air or helium molecules are drawn into the vacuum system through a leak in the seam. A helium detector may be placed in a vacuum exhaust line from the membrane to detect the helium. Alternatively, the vacuum system may be isolated at a preselected pressure and leaks may be detected by a subsequent pressure increase in the vacuum system.

Operational Philosophy Concerning Manned Spacecraft Cabin Leaks

NASA Technical Reports Server (NTRS)

DeSimpelaere, Edward

2011-01-01

The last thirty years have seen the Space Shuttle as the prime United States spacecraft for manned spaceflight missions. Many lessons have been learned about spacecraft design and operation throughout these years. Over the next few decades, a large increase of manned spaceflight in the commercial sector is expected. This will result in the exposure of commercial crews and passengers to many of the same risks crews of the Space Shuttle have encountered. One of the more dire situations that can be encountered is the loss of pressure in the habitable volume of the spacecraft during on orbit operations. This is referred to as a cabin leak. This paper seeks to establish a general cabin leak response philosophy with the intent of educating future spacecraft designers and operators. After establishing a relative definition for a cabin leak, the paper covers general descriptions of detection equipment, detection methods, and general operational methods for management of a cabin leak. Subsequently, all these items are addressed from the perspective of the Space Shuttle Program, as this will be of the most value to future spacecraft due to similar operating profiles. Emphasis here is placed upon why and how these methods and philosophies have evolved to meet the Space Shuttle s needs. This includes the core ideas of: considerations of maintaining higher cabin pressures vs. lower cabin pressures, the pros and cons of a system designed to feed the leak with gas from pressurized tanks vs. using pressure suits to protect against lower cabin pressures, timeline and consumables constraints, re-entry considerations with leaks of unknown origin, and the impact the International Space Station (ISS) has had to the standard Space Shuttle cabin leak response philosophy. This last item in itself includes: procedural management differences, hardware considerations, additional capabilities due to the presence of the ISS and its resource, and ISS docking/undocking considerations with a

The effects of drugs, other foreign compounds, and cigarette smoke on the synthesis of protein by lung slices

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

Hellstern, K.; Curtis, C.G.; Powell, G.M.

1990-04-01

The incorporation of {sup 14}C-leucine into rabbit lung slices was monitored in the absence and presence of selected drugs and chemicals relevant to the perturbation of lung function and the development of lung disease. Known inhibitors of protein synthesis (cycloheximide and ricin) inhibited the incorporation of {sup 14}C-leucine. Marked inhibition was also recorded with the lung toxins paraquat and 4-ipomeanol. By contrast, orciprenaline, salbutamol, and terbutaline were without effect although some response was recorded with isoprenaline. The filtered gas phase of cigarette smoke and acrolein, one of its components, were inhibitory but protection was afforded by N-acetylcysteine. It is suggestedmore » that the inhibitory effects of cigarette smoke may be due to its acrolein content. It is further suggested that the use of lung slices and measurements of {sup 14}C-leucine incorporation provide valuable means for monitoring potential pulmonary toxins.« less

Fibrin glue as agent for sealing corneal and conjunctival wound leaks.

PubMed

Scalcione, C; Ortiz-Vaquerizas, D; Said, D G; Dua, H S

2018-02-01

PurposeTo describe a novel use of fibrin glue in managing leaking blebs and leaking wounds following trauma or surgery.MethodsInterventional case series.ResultsWe report eight patients, including three where intra-operative or immediate post-penetrating keratoplasty recalcitrant leaks from the graft-host junction and/or openings created by the needle pass, were noted. All three had thin recipient beds in the sector of leak. This was managed by intra-cameral injection of fibrin glue in the affected quadrant. This stopped the leak and allowed the defect to heal. One patient of Descemets-stripping-endothelial-keratoplasty had leak from the surgical wound, which was also sealed with fibrin glue. Two patients with leaking glaucoma-surgery-related blebs were treated with intra-bleb injection of fibrin glue to stop the leak. One patient with a penetrating corneal injury with a metal wire had a brisk leak upon removal of the wire. This was sealed with fibrin glue. Another patient of chemical burn with spontaneous leaks was managed by glue injection in the perforations. Transient rise of intraocular pressure in one patient with a leaking bleb was the only adverse event recorded.ConclusionThis novel adaptation of the application of fibrin glue can help to deal with persistent intra-operative, post-operative and traumatic aqueous and air leaks.

Presidential Leaks: Rhetoric and Mediated Political Knowledge.

ERIC Educational Resources Information Center

Erickson, Keith V.

1989-01-01

Argues that presidential leaks constitute rhetorical acts, enabling administrations to exercise a variety of rhetorically potent options not afforded by the public forum. Proposes a typology of presidential leaks and analyzes their rhetorical functions, benefits, and liabilities. (MM)

Treatment of air leak in polytrauma patients with blunt chest injury.

PubMed

Halat, Gabriel; Negrin, Lukas L; Chrysou, Konstantina; Hoksch, Beatrix; Schmid, Ralph A; Kocher, Gregor J

2017-09-01

Precise diagnostics and an adequate therapeutic approach are mandatory in the treatment of air leak in polytrauma patients with blunt chest trauma. The aim of this study was to evaluate the incidence, characteristics, and management of air leak following this injury pattern. Data from 110 polytrauma patients was collected retrospectively. Fifty-four patients received initial treatment by chest tube placement for pneumothorax. These patients were classified into two groups, one with severe air leak and one with minor air leak. An evaluation of injury pattern, chest wall injuries in particular, duration of air leak, reason for drainage maintenance in place, hospital length of stay, ICU stay, ventilator duration, type of treatment, and the delay to surgical intervention was performed. Whereas 4 patients showed severe air leak and were subsequently scheduled for timely surgical intervention, the remaining 50 patients only showed minor air leak. Only 7 patients with minor air leak suffered from prolonged air leak (>5days), which spontaneously resolved in all of them after a mean duration of 7.7days (range 6-12days). Absence of a prolonged air leak resulted in a shorter length of stay and a shorter duration of mechanical ventilation, although no statistical significance was observed. Early spontaneous cessation of most minor air leaks as well as early surgical intervention for severe air leak lead to very satisfactory patient outcomes with a relatively short hospital stay in our patients. We therefore advocate early surgery for lacerations of the pulmonary parenchyma resulting in severe air leak, whereas minor air leaks can usually be treated conservatively. Copyright © 2017 Elsevier Ltd. All rights reserved.

Endotracheal tube leak pressure and tracheal lumen size in swine.

PubMed

Finholt, D A; Audenaert, S M; Stirt, J A; Marcella, K L; Frierson, H F; Suddarth, L T; Raphaely, R C

1986-06-01

Endotracheal tube "leak" is often estimated in children to judge the fit of uncuffed endotracheal tubes within the trachea. Twenty-five swine were intubated with uncuffed tracheal tubes to determine whether a more sensitive measurement of leaks could be devised and whether leak pressure estimates fit between tracheal tube and trachea. We compared leak pressure measurement using a stethoscope and aneroid manometer with a technique using a microphone, pressure transducer, and recorder, and found no differences between the two methods. The tracheas were then removed and slides prepared of tracheal cross-sectional specimens. Regression analysis revealed a linear relationship between tracheal lumen size and tracheal tube size for both low leak pressure (y = -0.4 + 0.79x, r = 0.88, P less than 0.05) and high leak pressure (y = -2.9 + 0.71x, r = 0.92, P less than 0.05) groups. We conclude that leak testing with a stethoscope and aneroid manometer is sensitive and accurate, and that tracheal tube leak pressure accurately portrays fit between tube and trachea.

The receptor protein tyrosine phosphatase PTPRJ negatively modulates the CD98hc oncoprotein in lung cancer cells

PubMed Central

D’Agostino, Sabrina; Lanzillotta, Delia; Varano, Mariaconcetta; Botta, Cirino; Baldrini, Antonio; Bilotta, Anna; Scalise, Stefania; Dattilo, Vincenzo; Amato, Rosario; Gaudio, Eugenio; Paduano, Francesco; Palmieri, Camillo; Iuliano, Rodolfo; Perrotti, Nicola; Indiveri, Cesare; Fusco, Alfredo; Gaspari, Marco; Trapasso, Francesco

2018-01-01

PTPRJ, a receptor protein tyrosine phosphatase strongly downregulated in human cancer, displays tumor suppressor activity by negatively modulating several proteins involved in proliferating signals. Here, through a proteomic-based approach, we identified a list of potential PTPRJ-interacting proteins and among them we focused on CD98hc, a type II glycosylated integral membrane protein encoded by SLC3A2, corresponding to the heavy chain of a heterodimeric transmembrane amino-acid transporter, including LAT1. CD98hc is widely overexpressed in several types of cancers and contributes to the process of tumorigenesis by interfering with cell proliferation, adhesion, and migration. We first validated PTPRJ-CD98hc interaction, then demonstrated that PTPRJ overexpression dramatically reduces CD98hc protein levels in A549 lung cancer cells. In addition, following to the treatment of PTPRJ-transduced cells with MG132, a proteasome inhibitor, CD98hc levels did not decrease compared to controls, indicating that PTPRJ is involved in the regulation of CD98hc proteasomal degradation. Moreover, PTPRJ overexpression combined with CD98hc silencing consistently reduced cell proliferation and triggered apoptosis of lung cancer cells. Interestingly, by interrogating the can Evolve database, we observed an inverse correlation between PTPRJ and SLC3A2 gene expression. Indeed, the non-small cell lung cancers (NSCLCs) of patients showing a short survival rate express the lowest and the highest levels of PTPRJ and SLC3A2, respectively. Therefore, the results reported here contribute to shed lights on PTPRJ signaling in cancer cells: moreover, our findings also support the development of a novel anticancer therapeutic approach by targeting the pathway of PTPRJ that is usually downregulated in highly malignant human neoplasias.

A Low-Protein Diet Enhances Angiotensin II Production in the Lung of Pregnant Rats but Not Nonpregnant Rats

PubMed Central

Gao, Haijun; Tanchico, Daren Tubianosa; Yallampalli, Uma; Yallampalli, Chandrasekhar

2016-01-01

Pulmonary angiotensin II production is enhanced in pregnant rats fed a low-protein (LP) diet. Here we assessed if LP diet induces elevations in angiotensin II production in nonpregnant rats and whether Ace expression and ACE activity in lungs are increased. Nonpregnant rats were fed a normal (CT) or LP diet for 8, 12, or 17 days and timed pregnant rats fed for 17 days from Day 3 of pregnancy. Plasma angiotensin II, expressions of Ace and Ace2, and activities of these proteins in lungs, kidneys, and plasma were measured. These parameters were compared among nonpregnant rats or between nonpregnant and pregnant rats fed different diets. Major findings are as follows: (1) plasma angiotensin II levels were slightly higher in the LP than CT group on Days 8 and 12 in nonpregnant rats; (2) expression of Ace and Ace2 and abundance and activities of ACE and ACE2 in lungs, kidneys, and plasma of nonpregnant rats were unchanged by LP diet except for minor changes; (3) the abundance and activities of ACE in lungs of pregnant rats fed LP diet were greater than nonpregnant rats, while those of ACE2 were decreased. These results indicate that LP diet-induced increase in pulmonary angiotensin II production depends on pregnancy. PMID:27195150

A case of ulcerative colitis complicated with bronchiolitis obliterans organizing pneumonia (BOOP) and air leak syndrome.

PubMed

Aydoğdu, Müge; Gürsel, Gül; Özyilmaz, Ezgi; Akyürek, Nalan; Memış, Leyla

2012-01-01

Extraintestinal manifestations of inflammatory bowel diseases are well recognized and mainly affect the joints, skin, liver, and eyes; however, clinically significant pulmonary involvement is very rare. Early identification of pulmonary involvement is important and will be life-saving. We report herein a case of an ulcerative colitis patient, presenting with acute respiratory distress syndrome and bilateral recurring pneumothorax, pneumomediastinum and subcutaneous emphysema, i.e., air leak syndrome. He was diagnosed with open lung biopsy as bronchiolitis obliterans organizing pneumonia most probably due to viral etiology and responded well to steroid therapy, with almost complete resolution of radiographic and clinical findings. In inflammatory bowel disease patients, bronchiolitis obliterans organizing pneumonia developing due to viral or fungal infectious etiology or due to the inflammatory bowel disease itself may progress to acute respiratory distress syndrome and may present with air leak syndrome. Early detection is important and life-saving, since bronchiolitis obliterans organizing pneumonia often responds well to steroid treatment provided an infectious etiology has been excluded or adequate antimicrobial therapy has already been initiated.

Follistatin-like 1 (Fstl1) is a bone morphogenetic protein (BMP) 4 signaling antagonist in controlling mouse lung development

PubMed Central

Geng, Yan; Dong, Yingying; Yu, Mingyan; Zhang, Long; Yan, Xiaohua; Sun, Jingxia; Qiao, Long; Geng, Huixia; Nakajima, Masahiro; Furuichi, Tatsuya; Ikegawa, Shiro; Gao, Xiang; Chen, Ye-Guang; Jiang, Dianhua; Ning, Wen

2011-01-01

Lung morphogenesis is a well orchestrated, tightly regulated process through several molecular pathways, including TGF-β/bone morphogenetic protein (BMP) signaling. Alteration of these signaling pathways leads to lung malformation. We investigated the role of Follistatin-like 1 (Fstl1), a secreted follistatin-module–containing glycoprotein, in lung development. Deletion of Fstl1 in mice led to postnatal lethality as a result of respiratory failure. Analysis of the mutant phenotype showed that Fstl1 is essential for tracheal cartilage formation and alveolar maturation. Deletion of the Fstl1 gene resulted in malformed tracheal rings manifested as discontinued rings and reduced ring number. Fstl1-deficient mice displayed septal hypercellularity and end-expiratory atelectasis, which were associated with impaired differentiation of distal alveolar epithelial cells and insufficient production of mature surfactant proteins. Mechanistically, Fstl1 interacted directly with BMP4, negatively regulated BMP4/Smad1/5/8 signaling, and inhibited BMP4-induced surfactant gene expression. Reducing BMP signaling activity by Noggin rescued pulmonary atelectasis of Fstl1-deficient mice. Therefore, we provide in vivo and in vitro evidence to demonstrate that Fstl1 modulates lung development and alveolar maturation, in part, through BMP4 signaling. PMID:21482757

40 CFR 86.328-79 - Leak checks.

Code of Federal Regulations, 2013 CFR

2013-07-01

... flows may be used to estimate the in-use flow rates. (3) The sample probe and the connection between the sample probe and valve V2 (Figure D79-1) may be excluded from the leak check. (b) Pressure side leak...

40 CFR 86.328-79 - Leak checks.

Code of Federal Regulations, 2012 CFR

2012-07-01

... flows may be used to estimate the in-use flow rates. (3) The sample probe and the connection between the sample probe and valve V2 (Figure D79-1) may be excluded from the leak check. (b) Pressure side leak...

40 CFR 86.328-79 - Leak checks.

Code of Federal Regulations, 2010 CFR

2010-07-01

... flows may be used to estimate the in-use flow rates. (3) The sample probe and the connection between the sample probe and valve V2 (Figure D79-1) may be excluded from the leak check. (b) Pressure side leak...

40 CFR 86.328-79 - Leak checks.

Code of Federal Regulations, 2011 CFR

2011-07-01

... flows may be used to estimate the in-use flow rates. (3) The sample probe and the connection between the sample probe and valve V2 (Figure D79-1) may be excluded from the leak check. (b) Pressure side leak...

Vaccination of calves using the BRSV nucleocapsid protein in a DNA prime-protein boost strategy stimulates cell-mediated immunity and protects the lungs against BRSV replication and pathology.

PubMed

Letellier, Carine; Boxus, Mathieu; Rosar, Laurent; Toussaint, Jean-François; Walravens, Karl; Roels, Stefan; Meyer, Gilles; Letesson, Jean-Jacques; Kerkhofs, Pierre

2008-09-02

Respiratory syncytial virus (RSV) is a major cause of respiratory disease in both cattle and young children. Despite the development of vaccines against bovine (B)RSV, incomplete protection and exacerbation of subsequent RSV disease have occurred. In order to circumvent these problems, calves were vaccinated with the nucleocapsid protein, known to be a major target of CD8(+) T cells in cattle. This was performed according to a DNA prime-protein boost strategy. The results showed that DNA vaccination primed a specific T-cell-mediated response, as indicated by both a lymphoproliferative response and IFN-gamma production. These responses were enhanced after protein boost. After challenge, mock-vaccinated calves displayed gross pneumonic lesions and viral replication in the lungs. In contrast, calves vaccinated by successive administrations of plasmid DNA and protein exhibited protection against the development of pneumonic lesions and the viral replication in the BAL fluids and the lungs. The protection correlated to the cell-mediated immunity and not to the antibody response.

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

PubMed

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

2005-06-01

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

Fluid pipeline leak detection and location with miniature RF tags

DOEpatents

McIntyre, Timothy J.

2017-05-16

Sensors locate troublesome leaks in pipes or conduits that carry a flowing medium. These sensors, through tailored physical and geometric properties, preferentially seek conduit leaks or breaches due to flow streaming. The sensors can be queried via transceivers outside the conduit or located and interrogated inside by submersible unmanned vehicle to identify and characterize the nature of a leak. The sensors can be functionalized with other capabilities for additional leak and pipeline characterization if needed. Sensors can be recovered from a conduit flow stream and reused for future leak detection activities.

Identification of new candidate drugs for lung cancer using chemical-chemical interactions, chemical-protein interactions and a K-means clustering algorithm.

PubMed

Lu, Jing; Chen, Lei; Yin, Jun; Huang, Tao; Bi, Yi; Kong, Xiangyin; Zheng, Mingyue; Cai, Yu-Dong

2016-01-01

Lung cancer, characterized by uncontrolled cell growth in the lung tissue, is the leading cause of global cancer deaths. Until now, effective treatment of this disease is limited. Many synthetic compounds have emerged with the advancement of combinatorial chemistry. Identification of effective lung cancer candidate drug compounds among them is a great challenge. Thus, it is necessary to build effective computational methods that can assist us in selecting for potential lung cancer drug compounds. In this study, a computational method was proposed to tackle this problem. The chemical-chemical interactions and chemical-protein interactions were utilized to select candidate drug compounds that have close associations with approved lung cancer drugs and lung cancer-related genes. A permutation test and K-means clustering algorithm were employed to exclude candidate drugs with low possibilities to treat lung cancer. The final analysis suggests that the remaining drug compounds have potential anti-lung cancer activities and most of them have structural dissimilarity with approved drugs for lung cancer.

Respiratory syncytial virus infection accelerates lung fibrosis through the unfolded protein response in a bleomycin-induced pulmonary fibrosis animal model.

PubMed

Wang, Lina; Cheng, Wei; Zhang, Zhimin

2017-07-01

Emerging evidence has demonstrated that endoplasmic reticulum stress (ER) is involved in the pathogenesis of idiopathic pulmonary fibrosis, however, the underlying mechanism remains unclear. Viral infection often triggers a hyperinflammatory response by an expansion of the ER. The present study was designed to observe the role of respiratory syncytial virus infection (RSV)‑induced ER stress on lung fibrosis. In order to determine the role of ER stress on the onset and progression of pulmonary fibrosis, mice received an intratracheal combined injection of RSV and bleomycin on day 0. At day 7, 14 and 21 following combined injection, RSV in the lung tissues was assayed by immunohistochemistry, cellular classification was assayed by direct microscopic observation after Wright staining and the secretion of cytokines in the broncho‑alveolar lavage fluid (BALF) was assayed by ELISA. The expression of collagen type I was assayed by immunofluorescence and western blot analysis. The expression of ER stress related proteins was analyzed by western blot. In addition, the correlations of ER‑stress related proteins with collagen type‑1 were examined. RSV administration resulted in increased inflammation, as demonstrated by increased levels of leukocytes and pro‑inflammatory cytokines in the BALF, and increased collagen type‑1 deposition in the lung tissues of bleomycin-induced pulmonary fibrosis animal model at 7, 14 and 21 days. RSV promoted the expression of phosphorylated protein kinase R‑like endoplasmic reticulum kinase (p‑PERK), 78 kDa glucose‑regulated protein (GRP78) and activating transcription factor 6α (ATF6α), which accelerated the severity and process of fibrosis in bleomycin‑induced animal models. The present study provides evidence that RSV infection accelerated the unfolded protein response and bleomycin‑induced lung fibrosis, which may improve our understanding of the pathogenesis of pulmonary fibrosis.

Capacitive system detects and locates fluid leaks

NASA Technical Reports Server (NTRS)

1966-01-01

Electronic monitoring system automatically detects and locates minute leaks in seams of large fluid storage tanks and pipelines covered with thermal insulation. The system uses a capacitive tape-sensing element that is adhesively bonded over seams where fluid leaks are likely to occur.

Measuring Pinhole Leaks - A Novel Method

NASA Technical Reports Server (NTRS)

Dunn, Carol Anne

2009-01-01

Both of the shuttle pads have one of these large liquid hydrogen tanks and the Shuttle program is currently using both pads. However, just recently, there has been increasing concerns over possible air leaks from the outside into the evacuated region. A method to detect leaks involving measuring the change in the boil-off rate of the liquid hydrogen in the tank.

INNOVATIVE ACOUSTIC SENSOR TECHNOLOGIES FOR LEAK DETECTION IN CHALLENGING PIPE TYPES

DTIC Science & Technology

2016-12-30

through focused acoustic surveys that are typically conducted at the correlated location prior to marking the leak location. All three technologies were...shift” survey with cross- correlation Echologics LeakFinderRTT M Field survey of leak signatures. Recommended every 3-5 years Contractor...cross- correlation features to detect and pinpoint leaks in challenging pipe types, as well as metallic pipes. 15. SUBJECT TERMS Leak detection

ATF3 Protects Pulmonary Resident Cells from Acute and Ventilator-Induced Lung Injury by Preventing Nrf2 Degradation

PubMed Central

Shan, Yuexin; Akram, Ali; Amatullah, Hajera; Zhou, Dun Yuan; Gali, Patricia L.; Maron-Gutierrez, Tatiana; González-López, Adrian; Zhou, Louis; Rocco, Patricia R.M.; Hwang, David; Albaiceta, Guillermo M.; Haitsma, Jack J.

2015-01-01

Abstract Aims: Ventilator-induced lung injury (VILI) contributes to mortality in patients with acute respiratory distress syndrome, the most severe form of acute lung injury (ALI). Absence of activating transcription factor 3 (ATF3) confers susceptibility to ALI/VILI. To identify cell-specific ATF3-dependent mechanisms of susceptibility to ALI/VILI, we generated ATF3 chimera by adoptive bone marrow (BM) transfer and randomized to inhaled saline or lipopolysacharide (LPS) in the presence of mechanical ventilation (MV). Adenovirus vectors to silence or overexpress ATF3 were used in primary human bronchial epithelial cells and murine BM-derived macrophages from wild-type or ATF3-deficient mice. Results: Absence of ATF3 in myeloid-derived cells caused increased pulmonary cellular infiltration. In contrast, absence of ATF3 in parenchymal cells resulted in loss of alveolar-capillary membrane integrity and increased exudative edema. ATF3-deficient macrophages were unable to limit the expression of pro-inflammatory mediators. Knockdown of ATF3 in resident cells resulted in decreased junctional protein expression and increased paracellular leak. ATF3 overexpression abrogated LPS induced membrane permeability. Despite release of ATF3-dependent Nrf2 transcriptional inhibition, mice that lacked ATF3 expression in resident cells had increased Nrf2 protein degradation. Innovation: In our model, in the absence of ATF3 in parenchymal cells increased Nrf2 degradation is the result of increased Keap-1 expression and loss of DJ-1 (Parkinson disease [autosomal recessive, early onset] 7), previously not known to play a role in lung injury. Conclusion: Results suggest that ATF3 confers protection to lung injury by preventing inflammatory cell recruitment and barrier disruption in a cell-specific manner, opening novel opportunities for cell specific therapy for ALI/VILI. Antioxid. Redox Signal. 22, 651–668. PMID:25401197

Remote Leak Detection: Indirect Thermal Technique

NASA Technical Reports Server (NTRS)

Clements, Sandra

2002-01-01

Remote sensing technologies are being considered for efficient, low cost gas leak detection. Eleven specific techniques have been identified for further study and evaluation of several of these is underway. The Indirect Thermal Technique is one of the techniques that is being explored. For this technique, an infrared camera is used to detect the temperature change of a pipe or fitting at the site of a gas leak. This temperature change is caused by the change in temperature of the gas expanding from the leak site. During the 10-week NFFP program, the theory behind the technique was further developed, experiments were performed to determine the conditions for which the technique might be viable, and a proof-of-concept system was developed and tested in the laboratory.

1999 Leak Detection and Monitoring and Mitigation Strategy Update

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

OHL, P.C.

This document is a complete revision of WHC-SD-WM-ES-378, Rev 1. This update includes recent developments in Leak Detection, Leak Monitoring, and Leak Mitigation technologies, as well as, recent developments in single-shell tank retrieval technologies. In addition, a single-shell tank retrieval release protection strategy is presented.

Leak Detection and Location Technology Assessment for Aerospace Applications

NASA Technical Reports Server (NTRS)

Wilson, William C.; Coffey, Neil C.; Madaras, Eric I.

2008-01-01

Micro Meteoroid and Orbital Debris (MMOD) and other impacts can cause leaks in the International Space Station and other aerospace vehicles. The early detection and location of leaks is paramount to astronaut safety. Therefore this document surveys the state of the art in leak detection and location technology for aerospace vehicles.

Scanning, standoff TDLAS leak imaging and quantification

NASA Astrophysics Data System (ADS)

Wainner, Richard T.; Aubut, Nicholas F.; Laderer, Matthew C.; Frish, Michael B.

2017-05-01

This paper reports a novel quantitative gas plume imaging tool, based on active near-infrared Backscatter Tunable Diode Laser Absorption Spectroscopy (b-TDLAS) technology, designed for upstream natural gas leak applications. The new tool integrates low-cost laser sensors with video cameras to create a highly sensitive gas plume imager that also quantifies emission rate, all in a lightweight handheld ergonomic package. It is intended to serve as a lower-cost, higherperformance, enhanced functionality replacement for traditional passive non-quantitative mid-infrared Optical Gas Imagers (OGI) which are utilized by industry to comply with natural gas infrastructure Leak Detection and Repair (LDAR) requirements. It addresses the need for reliable, robust, low-cost sensors to detect and image methane leaks, and to quantify leak emission rates, focusing on inspections of upstream oil and gas operations, such as well pads, compressors, and gas plants. It provides: 1) Colorized quantified images of path-integrated methane concentration. The images depict methane plumes (otherwise invisible to the eye) actively interrogated by the laser beam overlaid on a visible camera image of the background. The detection sensitivity exceeds passive OGI, thus simplifying the manual task of leak detection and location; and 2) Data and algorithms for using the quantitative information gathered by the active detection technique to deduce plume flux (i.e. methane emission rate). This key capability will enable operators to prioritize leak repairs and thereby minimize the value of lost product, as well as to quantify and minimize greenhouse gas emissions, using a tool that meets EPA LDAR imaging equipment requirements.

Real-time Non-invasive Spectral Imaging of Orthotopic Red Fluorescent Protein-expressing Lung Tumor Growth in Nude Mice.

PubMed

Zhang, Yong; Zhang, Nan; Zhao, Ming; Hoffman, Robert M

2015-07-01

Orthotopic implantation of cancer allows metastasis to occur. The most patient-like metastatic orthotopic models are developed with surgical orthotopic implantation using intact tissue in order to preserve the natural tissue structure of the tumor which contains both cancer cells and stroma. In the present study, we performed a simple thoracotomy by making an intercostal incision between the fourth and fifth ribs on the left side of the chest of nude mice. Lung tumor fragments expressing red fluorescent protein were then implanted on the left lung. It was possible to monitor tumor formation in the lung non-invasively by spectral imaging using the Maestro system with a liquid tunable filter. The model described here has high tumorigenicity in the lung (100%) and a low mortality rate (5%). This imageable nude mouse model using surgical orthotopic implantation of lung cancer will be useful for all types of longitudinal studies. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Lymphangiography in the Diagnosis and Localization of Various Chyle Leaks

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

Deso, Steve; Ludwig, Benjamin; Kabutey, Nii-Kabu

2012-02-15

Purpose: Chyle leaks are rare entities infrequently encountered by most physicians. However, large centers providing advanced surgical care are inevitably confronted with chyle leaks as a complication of surgery, an extension of disease, or as a primary disorder. Regardless of the etiology, proper diagnosis and localization are paramount in the management of any chyle leak. Materials and Methods: Here we present 16 patients with 17 chyle leaks (5 chyluria, 8 chylothorax, and 4 chylous ascites) who underwent bipedal lymphangiography (LAG) and postprocedure computed tomography (CT) imaging. Results: In each case, the source of the chyle leak was identified and properlymore » localized to guide further treatment. Of the 16 patients who underwent LAG and postprocedure CT imaging, the initial LAG alone provided the diagnosis and localized the chyle leak in 4 patients (25%); the postprocedure CT imaging provided the diagnosis and localized the chyle leak in 6 patients (37.5%); and the two modalities were equal in the diagnosing and localizing the chyle leak in the remaining 6 patients (37.5%)ConclusionThese cases highlight the unparalleled abilities of LAG and the added benefit of post-LAG CT imaging in the diagnosis and fine anatomic localization of chyle leaks. In addition, these cases demonstrate the retained utility of LAG in these investigations despite the development of alternative tests involving CT, magnetic resonance imaging, and nuclear medicine imaging.« less

Identification of protein expression alterations in gefitinib-resistant human lung adenocarcinoma: PCNT and mPR play key roles in the development of gefitinib-associated resistance

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

Lin, Chi-Chen; Institute of Biomedical Science, and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taiwan; Department of Medical Research and Education, Taichung Veterans General Hospital, Taichung, Taiwan

2015-11-01

Gefitinib is the first-line chemotherapeutic drug for treating non-small cell lung cancer (NSCLC), which comprises nearly 85% of all lung cancer cases worldwide. However, most patients eventually develop drug resistance after 12–18 months of treatment. Hence, investigating the drug resistance mechanism and resistance-associated biomarkers is necessary. Two lung adenocarcinoma cell lines, PC9 and gefitinib-resistant PC9/Gef, were established for examining resistance mechanisms and identifying potential therapeutic targets. Two-dimensional differential gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry were used for examining global protein expression changes between PC9 and PC9/Gef. The results revealed that 164 identified proteins were associated withmore » the formation of gefitinib resistance in PC9 cells. Additional studies using RNA interference showed that progesterone receptor membrane component 1 and pericentrin proteins have major roles in gefitinib resistance. In conclusion, the proteomic approach enabled identifying of numerous proteins involved in gefitinib resistance. The results provide useful diagnostic markers and therapeutic candidates for treating gefitinib-resistant NSCLC. - Highlights: • 164 proteins associated with gefitinib resistance were identified through proteomic analysis. • In this study, a lung adenocarcinoma and its gefitinib resistant partner were established. • mPR and PCNT proteins have evidenced to play important roles in gefitinib resistance.« less

A Hydrogen Leak Detection System for Aerospace and Commercial Applications

NASA Technical Reports Server (NTRS)

Hunter, Gary W.; Makel, D. B.; Jansa, E. D.; Patterson, G.; Cova, P. J.; Liu, C. C.; Wu, Q. H.; Powers, W. T.

1995-01-01

Leaks on the space shuttle while on the launch pad have generated interest in hydrogen leak monitoring technology. Microfabricated hydrogen sensors are being fabricated at Case Western Reserve University (CWRU) and tested at NASA Lewis Research Center (LeRC). These sensors have been integrated into hardware and software designed by Aerojet. This complete system allows for multipoint leak monitoring designed to provide leak source and magnitude information in real time. The monitoring system processes data from the hydrogen sensors and presents the operator with a visual indication of the leak location and magnitude. Although the leak monitoring system was designed for hydrogen propulsion systems, the possible applications of this monitoring system are wide ranged. This system is in operation in an automotive application which requires high sensitivity to hydrogen.

Protein kinase C-α and arginase I mediate pneumolysin-induced pulmonary endothelial hyperpermeability.

PubMed

Lucas, Rudolf; Yang, Guang; Gorshkov, Boris A; Zemskov, Evgeny A; Sridhar, Supriya; Umapathy, Nagavedi S; Jezierska-Drutel, Agnieszka; Alieva, Irina B; Leustik, Martin; Hossain, Hamid; Fischer, Bernhard; Catravas, John D; Verin, Alexander D; Pittet, Jean-François; Caldwell, Ruth B; Mitchell, Timothy J; Cederbaum, Stephen D; Fulton, David J; Matthay, Michael A; Caldwell, Robert W; Romero, Maritza J; Chakraborty, Trinad

2012-10-01

Antibiotics-induced release of the pore-forming virulence factor pneumolysin (PLY) in patients with pneumococcal pneumonia results in its presence days after lungs are sterile and is a major factor responsible for the induction of permeability edema. Here we sought to identify major mechanisms mediating PLY-induced endothelial dysfunction. We evaluated PLY-induced endothelial hyperpermeability in human lung microvascular endothelial cells (HL-MVECs) and human lung pulmonary artery endothelial cells in vitro and in mice instilled intratracheally with PLY. PLY increases permeability in endothelial monolayers by reducing stable and dynamic microtubule content and modulating VE-cadherin expression. These events, dependent upon an increased calcium influx, are preceded by protein kinase C (PKC)-α activation, perturbation of the RhoA/Rac1 balance, and an increase in myosin light chain phosphorylation. At later time points, PLY treatment increases the expression and activity of arginase in HL-MVECs. Arginase inhibition abrogates and suppresses PLY-induced endothelial barrier dysfunction by restoring NO generation. Consequently, a specific PKC-α inhibitor and the TNF-derived tonoplast intrinsic protein peptide, which blunts PLY-induced PKC-α activation, are able to prevent activation of arginase in HL-MVECs and to reduce PLY-induced endothelial hyperpermeability in mice. Arginase I (AI)(+/-)/arginase II (AII)(-/-) C57BL/6 mice, displaying a significantly reduced arginase I expression in the lungs, are significantly less sensitive to PLY-induced capillary leak than their wild-type or AI(+/+)/AII(-/-) counterparts, indicating an important role for arginase I in PLY-induced endothelial hyperpermeability. These results identify PKC-α and arginase I as potential upstream and downstream therapeutic targets in PLY-induced pulmonary endothelial dysfunction.

Protein Kinase C-α and Arginase I Mediate Pneumolysin-Induced Pulmonary Endothelial Hyperpermeability

PubMed Central

Yang, Guang; Gorshkov, Boris A.; Zemskov, Evgeny A.; Sridhar, Supriya; Umapathy, Nagavedi S.; Jezierska-Drutel, Agnieszka; Alieva, Irina B.; Leustik, Martin; Hossain, Hamid; Fischer, Bernhard; Catravas, John D.; Verin, Alexander D.; Pittet, Jean-François; Caldwell, Ruth B.; Mitchell, Timothy J.; Cederbaum, Stephen D.; Fulton, David J.; Matthay, Michael A.; Caldwell, Robert W.; Romero, Maritza J.; Chakraborty, Trinad

2012-01-01

Antibiotics-induced release of the pore-forming virulence factor pneumolysin (PLY) in patients with pneumococcal pneumonia results in its presence days after lungs are sterile and is a major factor responsible for the induction of permeability edema. Here we sought to identify major mechanisms mediating PLY-induced endothelial dysfunction. We evaluated PLY-induced endothelial hyperpermeability in human lung microvascular endothelial cells (HL-MVECs) and human lung pulmonary artery endothelial cells in vitro and in mice instilled intratracheally with PLY. PLY increases permeability in endothelial monolayers by reducing stable and dynamic microtubule content and modulating VE-cadherin expression. These events, dependent upon an increased calcium influx, are preceded by protein kinase C (PKC)-α activation, perturbation of the RhoA/Rac1 balance, and an increase in myosin light chain phosphorylation. At later time points, PLY treatment increases the expression and activity of arginase in HL-MVECs. Arginase inhibition abrogates and suppresses PLY-induced endothelial barrier dysfunction by restoring NO generation. Consequently, a specific PKC-α inhibitor and the TNF-derived tonoplast intrinsic protein peptide, which blunts PLY-induced PKC-α activation, are able to prevent activation of arginase in HL-MVECs and to reduce PLY-induced endothelial hyperpermeability in mice. Arginase I (AI)+/−/arginase II (AII)−/− C57BL/6 mice, displaying a significantly reduced arginase I expression in the lungs, are significantly less sensitive to PLY-induced capillary leak than their wild-type or AI+/+/AII−/− counterparts, indicating an important role for arginase I in PLY-induced endothelial hyperpermeability. These results identify PKC-α and arginase I as potential upstream and downstream therapeutic targets in PLY-induced pulmonary endothelial dysfunction. PMID:22582175

Risk of anastomotic leak after laparoscopic versus open colectomy.

PubMed

Murray, Alice C A; Chiuzan, Cody; Kiran, Ravi P

2016-12-01

Anastomotic leak following colorectal surgery is associated with significant morbidity and mortality. With the widespread adoption of laparoscopy, data from initial clinical trials evaluating the efficacy of laparoscopic when compared to open surgery may not currently be generalizable. We assess the risk of anastomotic leak after laparoscopic versus open colorectal resection using a nationwide database with standardized definitions. The 2012-2013 ACS-NSQIP targeted colectomy data were queried for all elective colorectal resections. Characteristics were compared for those patients undergoing laparoscopic versus open operations. Univariable and multivariable analyses, followed by a propensity score-matched analysis, were performed to assess the impact of laparoscopy on the development of an anastomotic leak. Of 23,568 patients, 3.4 % developed an anastomotic leak. Laparoscopic surgery was associated with a leak rate of 2.8 % (n = 425) and open surgery, 4.5 % (n = 378, p < 0.0001). Patients who developed a leak were more likely to die within 30 days of surgery (5.7 vs. 0.6 %, p < 0.0001). Patients who underwent laparoscopic surgery compared to open were younger (61 vs. 63 years, p = 0, p = 0.045) and with fewer comorbidities. On univariable analysis laparoscopic surgery was associated with reduced odds of developing an anastomotic leak (OR 0.60, p < 0.0001), and this remained after adjusting for all significant preoperative and disease-related confounders (OR 0.69, 95 % CI 0.58-0.82). A propensity score-matched analysis confirmed benefit of laparoscopic surgery over open surgery for anastomotic leak. Laparoscopic colectomy is safe and associated with reduced odds of developing an anastomotic leak following colectomy when controlling for patient-, disease- and procedure-related factors.

Extra corporeal membrane oxygenation to facilitate lung protective ventilation and prevent ventilator-induced lung injury in severe Pneumocystis pneumonia with pneumomediastinum: a case report and short literature review.

PubMed

Ali, Husain Shabbir; Hassan, Ibrahim Fawzy; George, Saibu

2016-04-14

Pulmonary infections caused by Pneumocystis jirovecii in immunocompromised host can be associated with cysts, pneumatoceles and air leaks that can progress to pneumomediastinum and pneumothoraxes. In such cases, it can be challenging to maintain adequate gas exchange by conventional mechanical ventilation and at the same time prevent further ventilator-induced lung injury. We report a young HIV positive male with poorly compliant lungs and pneumomediastinum secondary to severe Pneumocystis infection, rescued with veno-venous extra corporeal membrane oxygenation (V-V ECMO). A 26 year old male with no significant past medical history was admitted with fever, cough and shortness of breath. He initially required non-invasive ventilation for respiratory failure. However, his respiratory function progressively deteriorated due to increasing pulmonary infiltrates and development of pneumomediastinum, eventually requiring endotracheal intubation and invasive ventilation. Despite attempts at optimizing gas exchange by ventilatory maneuvers, patients' pulmonary parameters worsened necessitating rescue ECMO therapy. The introduction of V-V ECMO facilitated the use of ultra-protective lung ventilation and prevented progression of pneumomediastinum, maintaining optimal gas exchange. It allowed time for the antibiotics to show effect and pulmonary parenchyma to heal. Further diagnostic workup revealed Pneumocystis jirovecii as the causative organism for pneumonia and serology confirmed Human Immunodeficiency Virus infection. Patient was successfully treated with appropriate antimicrobials and de-cannulated after six days of ECMO support. ECMO was an effective salvage therapy in HIV positive patient with an otherwise fatal respiratory failure due to Pneumocystis pneumonia and air leak syndrome.

Meta-markers for the differential diagnosis of lung cancer and lung disease.

PubMed

Kim, Yong-In; Ahn, Jung-Mo; Sung, Hye-Jin; Na, Sang-Su; Hwang, Jaesung; Kim, Yongdai; Cho, Je-Yoel

2016-10-04

Misdiagnosis of lung cancer remains a serious problem due to the difficulty of distinguishing lung cancer from other respiratory lung diseases. As a result, the development of serum-based differential diagnostic biomarkers is in high demand. In this study, 198 clinical serum samples from non-cancer lung disease and lung cancer patients were analyzed using nLC-MRM-MS for the levels of seven lung cancer biomarker candidates. When the candidates were assessed individually, only SERPINEA4 showed statistically significant changes in the serum levels. The MRM results and clinical information were analyzed using a logistic regression analysis to select model for the best 'meta-marker', or combination of biomarkers for differential diagnosis. Also, under consideration of statistical interaction, variables having low significance as a single factor but statistically influencing on meta-marker model were selected. Using this probabilistic classification, the best meta-marker was determined to be made up of two proteins SERPINA4 and PON1 with age factor. This meta-marker showed an enhanced differential diagnostic capability (AUC=0.915) for distinguishing the two patient groups. Our results suggest that a statistical model can determine optimal meta-markers, which may have better specificity and sensitivity than a single biomarker and thus improve the differential diagnosis of lung cancer and lung disease patients. Diagnosing lung cancer commonly involves the use of radiographic methods. However, an imaging-based diagnosis may fail to differentiate lung cancer from non-cancerous lung disease. In this study, we examined several serum proteins in the sera of 198 lung cancer and non-cancerous lung disease patients by multiple-reaction monitoring. We then used a combination of variables to generate a meta-marker model that is useful as a differential diagnostic biomarker. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Assessing Surgeon Behavior Change after Anastomotic Leak in Colorectal Surgery

PubMed Central

Simianu, Vlad V.; Basu, Anirban; Alfonso-Cristancho, Rafael; Thirlby, Richard C.; Flaxman, Abraham D.; Flum, David R.

2016-01-01

Background Recency effect suggests that people disproportionately value events from the immediate past when making decisions, but the extent of this impact on surgeons’ decisions is unknown. This study evaluates for recency effect in surgeons by examining use of preventative leak testing before and after colorectal operations with anastomotic leaks. Materials and Methods Prospective cohort of adult patients (≥18 years) undergoing elective colorectal operations at Washington State hospitals participating in the Surgical Care and Outcomes Assessment Program (2006–2013). The main outcome measure was surgeons’ change in leak testing from 6 months before to 6 months after an anastomotic leak occurred. Results Across 4,854 elective colorectal operations performed by 282 surgeons at 44 hospitals, there was a leak rate of 2.6% (n=124). The 40 leaks (32%) in which the anastomosis was not tested occurred across 25 surgeons. While the ability to detect an overall difference in use of leak testing was limited by small sample size, 9 (36%) of 25 surgeons increased their leak testing by 5 percent points or more after leaks in cases where the anastomosis was not tested. Surgeons who increased their leak testing more frequently performed operations for diverticulitis (45% vs 33%), more frequently began their cases laparoscopically (65% vs 37%), and had longer mean operative times (195±99 vs 148±87 minutes), all p<0.001. Conclusions Recency effect was demonstrated by only one-third of eligible surgeons. Understanding the extent to which clinical decisions may be influenced by recency effect may be important in crafting quality improvement initiatives that require clinician behavior change. PMID:27664886

Assessing surgeon behavior change after anastomotic leak in colorectal surgery.

PubMed

Simianu, Vlad V; Basu, Anirban; Alfonso-Cristancho, Rafael; Thirlby, Richard C; Flaxman, Abraham D; Flum, David R

2016-10-01

Recency effect suggests that people disproportionately value events from the immediate past when making decisions, but the extent of this impact on surgeons' decisions is unknown. This study evaluates for recency effect in surgeons by examining use of preventative leak testing before and after colorectal operations with anastomotic leaks. Prospective cohort of adult patients (≥18 y) undergoing elective colorectal operations at Washington State hospitals participating in the Surgical Care and Outcomes Assessment Program (2006-2013). The main outcome measure was surgeons' change in leak testing from 6 mo before to 6 mo after an anastomotic leak occurred. Across 4854 elective colorectal operations performed by 282 surgeons at 44 hospitals, there was a leak rate of 2.6% (n = 124). The 40 leaks (32%) in which the anastomosis was not tested occurred across 25 surgeons. While the ability to detect an overall difference in use of leak testing was limited by small sample size, nine (36%) of 25 surgeons increased their leak testing by 5% points or more after leaks in cases where the anastomosis was not tested. Surgeons who increased their leak testing more frequently performed operations for diverticulitis (45% versus 33%), more frequently began their cases laparoscopically (65% versus 37%), and had longer mean operative times (195 ± 99 versus 148 ± 87 min), all P < 0.001. Recency effect was demonstrated by only one-third of eligible surgeons. Understanding the extent to which clinical decisions may be influenced by recency effect may be important in crafting quality improvement initiatives that require clinician behavior change. Copyright © 2016 Elsevier Inc. All rights reserved.

Host DNA repair proteins in response to Pseudomonas aeruginosa in lung epitehlial cells and in mice

USDA-ARS?s Scientific Manuscript database

Host DNA damage and DNA repair response to bacterial infections and its significance are not fully understood. Here, we demonstrate that infection by Gram-negative bacterium P. aeruginosa significantly altered the expression and enzymatic activity of base excision DNA repair protein OGG1 in lung epi...

Clinical Factors and Postoperative Impact of Bile Leak After Liver Resection.

PubMed

Martin, Allison N; Narayanan, Sowmya; Turrentine, Florence E; Bauer, Todd W; Adams, Reid B; Stukenborg, George J; Zaydfudim, Victor M

2018-04-01

Despite technical advances, bile leak remains a significant complication after hepatectomy. The current study uses a targeted multi-institutional dataset to characterize perioperative factors that are associated with bile leakage after hepatectomy to better understand the impact of bile leak on morbidity and mortality. Adult patients in the 2014-2015 ACS NSQIP targeted hepatectomy dataset were linked to the ACS NSQIP PUF dataset. Bivariable and multivariable regression analyses were used to assess the associations between clinical factors and post-hepatectomy bile leak. Of 6859 patients, 530 (7.7%) had a postoperative bile leak. Proportion of bile leaks was significantly greater in patients after major compared to minor hepatectomy (12.6 vs. 5.1%, p < 0.001). The proportion of patients with bile leak was significantly greater in patients after major hepatectomy who had concomitant enterohepatic reconstruction (31.8 vs. 10.1%, p < 0.001). Postoperative mortality was significantly greater in patients with bile leaks (6.0 vs. 1.7%, p < 0.001). After adjusting for significant covariates, bile leak was independently associated with increased risk of postoperative morbidity (OR = 4.55; 95% CI 3.72-5.56; p < 0.001). After adjusting for significant effects of postoperative complications, liver failure, and reoperation (all p<0.001), bile leak was not independently associated with increased risk of postoperative mortality (p = 0.262). Major hepatectomy and enterohepatic biliary reconstruction are associated with significantly greater rates of bile leak after liver resection. Bile leak is independently associated with significant postoperative morbidity. Mitigation of bile leak is critical in reducing morbidity and mortality after liver resection.

Fighting the Epidemic of Nuclear Plant Leaks.

ERIC Educational Resources Information Center

Udell, Richard A.

1983-01-01

The current epidemic of steam generator tube leaks alone should put to rest the rosy future once envisioned for nuclear power. It is impossible to regulate quality into a nuclear plant; it must be built and designed that way. The economic impact of the leaks is discussed. (RM)

Chemseal 3808-A2 penetration into small leak path

NASA Technical Reports Server (NTRS)

Carruth, M. R., Jr.; Dehaye, R. F.

1988-01-01

A possible fix to a leak in the oxidizer system of the Space Shuttle Discovery's attitude control system was proposed by MSFC. This fix involved the passing of a shuttlecock past the leaking Dynaflow fitting and sealing the vent tube containing the fitting with Chemseal 3808-A2. The question of whether the Chemseal 3808-A2 can flow into the leak path and provide a better seal was addressed analytically and by experiment to verify the analytical formula used. The results show that the equations are applicable and that the Chemseal will flow into the expected leak path and seal.

Resilience to leaking--dynamic systems modeling of information security.

PubMed

Hamacher, Kay

2012-01-01

Leaking of confidential material is a major threat to information security within organizations and to society as a whole. This insight has gained traction in the political realm since the activities of Wikileaks, which hopes to attack 'unjust' systems or 'conspiracies'. Eventually, such threats to information security rely on a biologistic argument on the benefits and drawbacks that uncontrolled leaking might pose for 'just' and 'unjust' entities. Such biological metaphors are almost exclusively based on the economic advantage of participants. Here, I introduce a mathematical model of the complex dynamics implied by leaking. The complex interactions of adversaries are modeled by coupled logistic equations including network effects of econo-communication networks. The modeling shows, that there might arise situations where the leaking envisioned and encouraged by Wikileaks and the like can strengthen the defending entity (the 'conspiracy'). In particular, the only severe impact leaking can have on an organization seems to originate in the exploitation of leaks by another entity the organization competes with. Therefore, the model suggests that leaks can be used as a `tactical mean' in direct adversary relations, but do not necessarily increase public benefit and societal immunization to 'conspiracies'. Furthermore, within the model the exploitation of the (open) competition between entities seems to be a more promising approach to control malicious organizations : divide-et-impera policies triumph here.

Autogenous Metallic Pipe Leak Repair in Potable Water Systems.

PubMed

Tang, Min; Triantafyllidou, Simoni; Edwards, Marc A

2015-07-21

Copper and iron pipes have a remarkable capability for autogenous repair (self-repair) of leaks in potable water systems. Field studies revealed exemplars that metallic pipe leaks caused by nails, rocks, and erosion corrosion autogenously repaired, as confirmed in the laboratory experiments. This work demonstrated that 100% (N = 26) of 150 μm leaks contacting representative bulk potable water in copper pipes sealed autogenously via formation of corrosion precipitates at 20-40 psi, pH 3.0-11.0, and with upward and downward leak orientations. Similar leaks in carbon steel pipes at 20 psi self-repaired at pH 5.5 and 8.5, but two leaks did not self-repair permanently at pH 11.0 suggesting that water chemistry may control the durability of materials that seal the leaks and therefore the permanence of repair. Larger 400 μm holes in copper pipes had much lower (0-33%) success of self-repair at pH 3.0-11.0, whereas all 400 μm holes in carbon steel pipes at 20 psi self-repaired at pH 4.0-11.0. Pressure tests indicated that some of the repairs created at 20-40 psi ambient pressure could withstand more than 100 psi without failure. Autogenous repair has implications for understanding patterns of pipe failures, extending the lifetime of decaying infrastructure, and developing new plumbing materials.

Fluorescence, polarized fluorescence, and Brewster angle microscopy of palmitic acid and lung surfactant protein B monolayers.

PubMed Central

Lipp, M M; Lee, K Y; Waring, A; Zasadzinski, J A

1997-01-01

Fluorescence, polarized fluorescence, and Brewster angle microscopy reveal that human lung surfactant protein SP-B and its amino terminus (SP-B[1-25]) alter the phase behavior of palmitic acid monolayers by inhibiting the formation of condensed phases and creating a new fluid protein-rich phase. This fluid phase forms a network that separates condensed phase domains at coexistence and persists to high surface pressures. The network changes the monolayer collapse mechanism from heterogeneous nucleation/growth and fracturing processes to a more homogeneous process through isolating individual condensed phase domains. This results in higher surface pressures at collapse, and monolayers easier to respread on expansion, factors essential to the in vivo function of lung surfactant. The network is stabilized by a low-line tension between the coexisting phases, as confirmed by the observation of extended linear domains, or "stripe" phases, and a Gouy-Chapman analysis of protein-containing monolayers. Comparison of isotherm data and observed morphologies of monolayers containing SP-B(1-25) with those containing the full SP-B sequence show that the shortened peptide retains most of the native activity of the full-length protein, which may lead to cheaper and more effective synthetic replacement formulations. Images FIGURE 1 FIGURE 3 FIGURE 4 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 FIGURE 10 PMID:9168053

Fugitive methane emissions from leak-prone natural gas distribution infrastructure in urban environments.

PubMed

Hendrick, Margaret F; Ackley, Robert; Sanaie-Movahed, Bahare; Tang, Xiaojing; Phillips, Nathan G

2016-06-01

Fugitive emissions from natural gas systems are the largest anthropogenic source of the greenhouse gas methane (CH4) in the U.S. and contribute to the risk of explosions in urban environments. Here, we report on a survey of CH4 emissions from 100 natural gas leaks in cast iron distribution mains in Metro Boston, MA. Direct measures of CH4 flux from individual leaks ranged from 4.0 - 2.3 × 10(4) g CH4•day(-1). The distribution of leak size is positively skewed, with 7% of leaks contributing 50% of total CH4 emissions measured. We identify parallels in the skewed distribution of leak size found in downstream systems with midstream and upstream stages of the gas process chain. Fixing 'superemitter' leaks will disproportionately stem greenhouse gas emissions. Fifteen percent of leaks surveyed qualified as potentially explosive (Grade 1), and we found no difference in CH4 flux between Grade 1 leaks and all remaining leaks surveyed (p = 0.24). All leaks must be addressed, as even small leaks cannot be disregarded as 'safely leaking.' Key methodological impediments to quantifying and addressing the impacts of leaking natural gas distribution infrastructure involve inconsistencies in the manner in which gas leaks are defined, detected, and classified. To address this need, we propose a two-part leak classification system that reflects both the safety and climatic impacts of natural gas leaks. Copyright © 2016 Elsevier Ltd. All rights reserved.

Immunohistochemical quantification of expression of a tight junction protein, claudin-7, in human lung cancer samples using digital image analysis method.

PubMed

Lu, Zhe; Liu, Yi; Xu, Junfeng; Yin, Hongping; Yuan, Haiying; Gu, Jinjing; Chen, Yan-Hua; Shi, Liyun; Chen, Dan; Xie, Bin

2018-03-01

Tight junction proteins are correlated with cancer development. As the pivotal proteins in epithelial cells, altered expression and distribution of different claudins have been reported in a wide variety of human malignancies. We have previously reported that claudin-7 was strongly expressed in benign bronchial epithelial cells at the cell-cell junction while expression of claudin-7 was either altered with discontinued weak expression or completely absent in lung cancers. Based on these results, we continued working on the expression pattern of claudin-7 and its relationship with lung cancer development. We herein proposed a new Digital Image Classification, Fragmentation index, Morphological analysis (DICFM) method for differentiating the normal lung tissues and lung cancer tissues based on the claudin-7 immunohistochemical staining. Seventy-seven lung cancer samples were obtained from the Second Affiliated Hospital of Zhejiang University and claudin-7 immunohistochemical staining was performed. Based on C++ and Open Source Computer Vision Library (OpenCV, version 2.4.4), the DICFM processing module was developed. Intensity and fragmentation of claudin-7 expression, as well as the morphological parameters of nuclei were calculated. Evaluation of results was performed using Receiver Operator Characteristic (ROC) analysis. Agreement between these computational results and the results obtained by two pathologists was demonstrated. The intensity of claudin-7 expression was significantly decreased while the fragmentation was significantly increased in the lung cancer tissues compared to the normal lung tissues and the intensity was strongly positively associated with the differentiation of lung cancer cells. Moreover, the perimeters of the nuclei of lung cancer cells were significantly greater than that of the normal lung cells, while the parameters of area and circularity revealed no statistical significance. Taken together, our DICFM approach may be applied as an

40 CFR 61.135 - Standard: Equipment leaks.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Emissions from Coke By-Product Recovery Plants § 61.135 Standard: Equipment leaks. (a) Each owner or... benzene service. (d) Each exhauster shall be monitored quarterly to detect leaks by the methods specified... stuffing box pressure; or (ii) Equipped with a barrier fluid system that is connected by a closed vent...

The Predictive Value of Coefficient of PCT × BG for Anastomotic Leak in Esophageal Carcinoma Patients With ARDS After Esophagectomy.

PubMed

Li, Huan; Wang, Daofeng; Wei, Wenxiao; Ouyang, Lamei; Lou, Ning

2017-01-01

Anastomotic leak was a potentially severe life-threatening complication of esophagectomy, which drew attention in consequence of progressive dyspnea until acute respiratory distress syndrome (ARDS) due to the early asymptomatic presentation. Respiratory failure, caused by ARDS as the severe presentation of anastomotic leak, is the most common organ failure. CRP (C-reactive protein), procalcitonin (PCT), and Blood G (BG) test are the sensitivity markers for inflammatory, sepsis, and fungemia, respectively. Early recognition and intervention treatment of anastomotic leak may alleviate complication and improve outcome. We retrospectively analyzed 71 patients, accepting mechanical ventilation support because of ARDS as the complication after radical resection of esophagus cancer. Clinical data were collected from the patients' electronic medical records, including their clinically hematological examination, drainage fluid cultures, and sputum culture. Accord to appearance of anastomotic leak or not, all patients were divided into 2 groups, leak group and no-leak group. Inflammatory markers, such as CRP, PCT, and the coefficient of BG and PCT, were significantly different between the 2 groups. Respiratory index, white blood cell, hemoglobin (HBG), platelet (PLT), and other clinical factors were not significantly different between the 2 groups. Receiver operating characteristic curves were constructed to calculate the sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve for various cutoff levels of several factors. Blood G tests presented the better predicting value for anastomotic leak. Blood G tests and PCT should be tested after esophagectomy. The coefficient of PCT and BG (>260) is of great significance, and clinical value to predict anastomotic leak for patients with postesophagectomy ARDS, early PCT and BG test, and especially, dynamic variation may alleviate complication and improve outcome.

Risk Factors for Gastrointestinal Leak after Bariatric Surgery: MBASQIP Analysis.

PubMed

Alizadeh, Reza Fazl; Li, Shiri; Inaba, Colette; Penalosa, Patrick; Hinojosa, Marcelo W; Smith, Brian R; Stamos, Michael J; Nguyen, Ninh T

2018-03-30

Gastrointestinal leak remains one of the most dreaded complications in bariatric surgery. We aimed to evaluate risk factors and the impact of common perioperative interventions on the development of leak in patients who underwent laparoscopic bariatric surgery. Using the 2015 database of accredited centers, data were analyzed for patients who underwent laparoscopic sleeve gastrectomy or Roux-en-Y gastric bypass (LRYGB). Emergent, revisional, and converted cases were excluded. Multivariate logistic regression was used to analyze risk factors for leak, including provocative testing of anastomosis, surgical drain placement, and use of postoperative swallow study. Data from 133,478 patients who underwent laparoscopic sleeve gastrectomy (n = 92,495 [69.3%]) and LRYGB (n = 40,983 [30.7%]) were analyzed. Overall leak rate was 0.7% (938 of 133,478). Factors associated with increased risk for leak were oxygen dependency (adjusted odds ratio [AOR] 1.97), hypoalbuminemia (AOR 1.66), sleep apnea (AOR 1.52), hypertension (AOR 1.36), and diabetes (AOR 1.18). Compared with LRYGB, laparoscopic sleeve gastrectomy was associated with a lower risk of leak (AOR 0.52; 95% CI 0.44 to 0.61; p < 0.01). Intraoperative provocative test was performed in 81.9% of cases and the leak rate was higher in patients with vs without a provocative test (0.8% vs 0.4%, respectively; p < 0.01). A surgical drain was placed in 24.5% of cases and the leak rate was higher in patients with vs without a surgical drain placed (1.6% vs 0.4%, respectively; p < 0.01). A swallow study was performed in 41% of cases and the leak rate was similar between patients with vs without swallow study (0.7% vs 0.7%; p = 0.50). The overall rate of gastrointestinal leak in bariatric surgery is low. Certain preoperative factors, procedural type (LRYGB), and interventions (intraoperative provocative test and surgical drain placement) were associated with a higher risk for leaks. Copyright © 2018 American College of Surgeons

Dengue virus NS1 cytokine-independent vascular leak is dependent on endothelial glycocalyx components

PubMed Central

Beatty, P. Robert

2017-01-01

Dengue virus (DENV) is the most prevalent, medically important mosquito-borne virus. Disease ranges from uncomplicated dengue to life-threatening disease, characterized by endothelial dysfunction and vascular leakage. Previously, we demonstrated that DENV nonstructural protein 1 (NS1) induces endothelial hyperpermeability in a systemic mouse model and human pulmonary endothelial cells, where NS1 disrupts the endothelial glycocalyx-like layer. NS1 also triggers release of inflammatory cytokines from PBMCs via TLR4. Here, we examined the relative contributions of inflammatory mediators and endothelial cell-intrinsic pathways. In vivo, we demonstrated that DENV NS1 but not the closely-related West Nile virus NS1 triggers localized vascular leak in the dorsal dermis of wild-type C57BL/6 mice. In vitro, we showed that human dermal endothelial cells exposed to DENV NS1 do not produce inflammatory cytokines (TNF-α, IL-6, IL-8) and that blocking these cytokines does not affect DENV NS1-induced endothelial hyperpermeability. Further, we demonstrated that DENV NS1 induces vascular leak in TLR4- or TNF-α receptor-deficient mice at similar levels to wild-type animals. Finally, we blocked DENV NS1-induced vascular leak in vivo using inhibitors targeting molecules involved in glycocalyx disruption. Taken together, these data indicate that DENV NS1-induced endothelial cell-intrinsic vascular leak is independent of inflammatory cytokines but dependent on endothelial glycocalyx components. PMID:29121099

Targeting Heat Shock Protein 90 Overrides the Resistance of Lung Cancer Cells by Blocking Radiation-induced Stabilization of Hypoxia-inducible Factor 1α

PubMed Central

Kim, Woo-Young; Oh, Seung Hyun; Woo, Jong-Kyu; Hong, Waun Ki; Lee, Ho-Young

2008-01-01

Hypoxia-inducible factor-1 (HIF-1) has been suggested to play a major role in tumor radioresistance. However, the mechanisms through which irradiation regulates HIF-1α expression remain unclear. The purpose of this study was to investigate the mechanisms that mediate HIF-1 activation and thus radioresistance. Here we show that irradiation induces survival and angiogenic activity in a subset of radioresistant lung cancer cell lines by elevating HIF-1α protein expression. Radiation induced HIF-1α protein expression mainly through two distinct pathways, including an increase in de novo protein synthesis via activation of PI3K/Akt/mTOR and stabilization of HIF-1α protein via augmenting the interaction between heat shock protein 90 (Hsp90) and HIF-1α protein. While the PI3K/Akt/mTOR pathway was activated by irradiation in all the lung cancer cells examined, the HSP90-HIF-1α interaction was enhanced in the resistant cells only. Inhibition of Hsp90 function by 17-AAG or deguelin, a novel natural inhibitor of HSP90, suppressed increases in HIF-1α/Hsp90 interaction and HIF-1α expression in radioresistant cells. Furthermore, combined treatment of radiation with deguelin significantly decreased the survival and angiogenic potential of radioresistant lung cancer cells in vitro. We finally determined in vivo that systemic administration of deguelin resulted in profound inhibition of tumor growth and angiogenesis when combined with radiation. These results provide a strong rationale to target Hsp90 as a means to block radiation-induced HIF-1α and thus to circumvent radioresistance in lung cancer cells. PMID:19176399

Environmental Pollutant Ozone Causes Damage to Lung Surfactant Protein B (SP-B)

PubMed Central

2015-01-01

Lung surfactant protein B (SP-B) is an essential protein found in the surfactant fluid at the air–water interface of the lung. Exposure to the air pollutant ozone could potentially damage SP-B and lead to respiratory distress. We have studied two peptides, one consisting of the N-terminus of SP-B [SP-B(1–25)] and the other a construct of the N- and C-termini of SP-B [SP-B(1–25,63–78)], called SMB. Exposure to dilute levels of ozone (∼2 ppm) of monolayers of each peptide at the air–water interface leads to a rapid reaction, which is evident from an increase in the surface tension. Fluorescence experiments revealed that this increase in surface tension is accompanied by a loss of fluorescence from the tryptophan residue at the interface. Neutron and X-ray reflectivity experiments show that, in contrast to suggestions in the literature, the peptides are not solubilized upon oxidation but rather remain at the interface with little change in their hydration. Analysis of the product material reveals that no cleavage of the peptides occurs, but a more hydrophobic product is slowly formed together with an increased level of oligomerization. We attributed this to partial unfolding of the peptides. Experiments conducted in the presence of phospholipids reveal that the presence of the lipids does not prevent oxidation of the peptides. Our results strongly suggest that exposure to low levels of ozone gas will damage SP-B, leading to a change in its structure. The implication is that the oxidized protein will be impaired in its ability to interact at the air–water interface with negatively charged phosphoglycerol lipids, thus compromising what is thought to be its main biological function. PMID:26270023

Schlieren optics for leak detection

NASA Technical Reports Server (NTRS)

Peale, Robert E.; Ruffin, Alranzo B.

1995-01-01

The purpose of this research was to develop an optical method of leak detection. Various modifications of schlieren optics were explored with initial emphasis on leak detection of the plumbing within the orbital maneuvering system of the space shuttle (OMS pod). The schlieren scheme envisioned for OMS pod leak detection was that of a high contrast pattern on flexible reflecting material imaged onto a negative of the same pattern. We find that the OMS pod geometry constrains the characteristic length scale of the pattern to the order of 0.001 inch. Our experiments suggest that optical modulation transfer efficiency will be very low for such patterns, which will limit the sensitivity of the technique. Optical elements which allow a negative of the scene to be reversibly recorded using light from the scene itself were explored for their potential in adaptive single-ended schlieren systems. Elements studied include photochromic glass, bacteriorhodopsin, and a transmissive liquid crystal display. The dynamics of writing and reading patterns were studied using intensity profiles from recorded images. Schlieren detection of index gradients in air was demonstrated.

Effect of compound Maqin decoction on TGF-β1/Smad proteins and IL-10 and IL-17 content in lung tissue of asthmatic rats.

PubMed

Xie, Y H; Li, X P; Xu, Z X; Qian, P; Li, X L; Wang, Y Q

2016-09-02

In this research, compound Maqin decoction (CMD) has been shown to positively affect in airway inflammation of asthma models. We evaluated the effects of CMD on the expression of transforming growth factor (TGF)-β1/Smad proteins, interleukin (IL)-17, and IL-10 in lung tissue of asthmatic rats. Asthma was induced in a rat model using ovalbumin. After a 4-week treatment with CMD, rats were killed to evaluate the expression of TGF-β1 and Smad proteins in lung tissue. IL-10 and IL-17 levels in lung tissue homogenates were determined by ELISA. The expression of TGF-β1 and Smad3 protein increased, whereas expression of Smad7 protein decreased upon high-dose or low-dose treatment with CMD or by intervention with dexamethasone, compared to the control. There was a significant difference between treatment with a high dose CMD and the control treatment, but no significant difference was found between high-dose CMD treatment and dexamethasone intervention. The expression of TGF-β1 and Smad7 protein increased, whereas the expression of Smad3 protein decreased in the model group compared to other groups. In the CMD high-dose group, low-dose group, and dexamethasone intervention group, the IL-17 concentrations in lung tissue homogenates were decreased, while IL-10 levels were increased. Again, there was a significant difference between CMD high-dose and control treatment, but not between CMD high-dose treatment and dexamethasone intervention. Thus, positive effects of CMD against asthmatic airway remodeling may be due to its regulatory effect on TGF-β1, Smad3, and Smad7 protein levels and on cytokines such as IL-10 and IL-17.

Measurement of Submerged Oil/Gas Leaks using ROV Video

NASA Astrophysics Data System (ADS)

Shaffer, Franklin; de Vera, Giorgio; Lee, Kenneth; Savas, Ömer

2013-11-01

Drilling for oil or gas in the Gulf of Mexico is increasing rapidly at depths up to three miles. The National Commission on the Deepwater Horizon Oil Leak concluded that inaccurate estimates of the leak rate from the Deepwater Horizon caused an inadequate response and attempts to cap the leak to fail. The first response to a submerged oil/gas leak will be to send a Remotely Operated Vehicle (ROV) down to view the leak. During the response to the Deepwater Horizon crisis, the authors Savas and Shaffer were members of the Flow Rate Technical Group's Plume Team who used ROV video to develop the FRTG's first official estimates of the oil leak rate. Savas and Shaffer developed an approach using the larger, faster jet features (e.g., turbulent eddies, vortices, entrained particles) in the near-field developing zone to measure discharge rates. The authors have since used the Berkeley Tow Tank to test this approach on submerged dye-colored water jets and compressed air jets. Image Correlation Velocimetry has been applied to measure the velocity of visible features. Results from tests in the Berkeley Tow Tank and submerged oil jets in the OHMSETT facility will be presented.

Local Leak Detection and Health Monitoring of Pressurized Tanks

NASA Technical Reports Server (NTRS)

Polzin, Kurt; Witherow, William; Korman, Valentin; Sinko, John; Hendrickson, Adam

2011-01-01

An optical gas-detection sensor safely monitors pressurized systems (such as cryogenic tanks) and distribution systems for leaks. This sensor system is a fiber-coupled, solid optical body interferometer that allows for the miniaturized sensing element of the device to be placed in the smallest of recesses, and measures a wide range of gas species and densities (leaks). The deflection of the fringe pattern is detected and recorded to yield the time-varying gas density in the gap. This technology can be used by manufacturers or storage facilities with toxic, hazardous, or explosive gases. The approach is to monitor the change in the index of refraction associated with low-level gas leaks into a vacuum environment. The completion of this work will provide NASA with an enabling capability to detect gas system leaks in space, and to verify that pressurized systems are in a safe (i.e. non-leaking) condition during manned docking and transit operations. By recording the output of the sensor, a time-history of the leak can be constructed to indicate its severity. Project risk is mitigated by having several interferometric geometries and detection techniques available, each potentially leveraging hardware and lessons learned to enhance detectability.

The anti-apoptotic BAG3 protein is expressed in lung carcinomas and regulates small cell lung carcinoma (SCLC) tumor growth.

PubMed

Chiappetta, Gennaro; Basile, Anna; Barbieri, Antonio; Falco, Antonia; Rosati, Alessandra; Festa, Michelina; Pasquinelli, Rosa; Califano, Daniela; Palma, Giuseppe; Costanzo, Raffaele; Barcaroli, Daniela; Capunzo, Mario; Franco, Renato; Rocco, Gaetano; Pascale, Maria; Turco, Maria Caterina; De Laurenzi, Vincenzo; Arra, Claudio

2014-08-30

BAG3, member the HSP70 co-chaperones family, has been shown to play a relevant role in the survival, growth and invasiveness of different tumor types. In this study, we investigate the expression of BAG3 in 66 specimens from different lung tumors and the role of this protein in small cell lung cancer (SCLC) tumor growth. Normal lung tissue did not express BAG3 while we detected the expression of BAG3 by immunohistochemistry in all the 13 squamous cell carcinomas, 13 adenocarcinomas and 4 large cell carcinomas. Furthermore, we detected BAG3 expression in 22 of the 36 SCLCs analyzed. The role on SCLC cell survival was determined by down-regulating BAG3 levels in two human SCLC cell lines, i.e. H69 and H446, in vitro and measuring cisplatin induced apoptosis. Indeed down-regulation of BAG3 determines increased cell death and sensitizes cells to cisplatin treatment. The effect of BAG3 down-regulation on tumor growth was also investigated in an in vivo xenograft model by treating mice with an adenovirus expressing a specific bag3 siRNA. Treatment with bag3 siRNA-Ad significantly reduced tumor growth and improved animal survival. In conclusion we show that a subset of SCLCs over express BAG3 that exerts an anti-apoptotic effect resulting in resistance to chemotherapy.

Detection of Leaks in Water Distribution System using Non-Destructive Techniques

NASA Astrophysics Data System (ADS)

Aslam, H.; Kaur, M.; Sasi, S.; Mortula, Md M.; Yehia, S.; Ali, T.

2018-05-01

Water is scarce and needs to be conserved. A considerable amount of water which flows in the water distribution systems was found to be lost due to pipe leaks. Consequently, innovations in methods of pipe leakage detections for early recognition and repair of these leaks is vital to ensure minimum wastage of water in distribution systems. A major component of detection of pipe leaks is the ability to accurately locate the leak location in pipes through minimum invasion. Therefore, this paper studies the leak detection abilities of the three NDT’s: Ground Penetration Radar (GPR) and spectrometer and aims at determining whether these instruments are effective in identifying the leak. An experimental setup was constructed to simulate the underground conditions of water distribution systems. After analysing the experimental data, it was concluded that both the GPR and the spectrometer were effective in detecting leaks in the pipes. However, the results obtained from the spectrometer were not very differentiating in terms of observing the leaks in comparison to the results obtained from the GPR. In addition to this, it was concluded that both instruments could not be used if the water from the leaks had reached on the surface, resulting in surface ponding.

Endoscopic dilation for treatment of anastomotic leaks following transhiatal esophagectomy.

PubMed

Bhasin, D K; Sharma, B C; Gupta, N M; Sinha, S K; Singh, K

2000-06-01

Anastomotic leak is a known complication after transhiatal esophagectomy (THE) and cervical esophagogastric anastomosis. Conservative management takes a long time to heal such leaks. We assessed the role of endoscopic dilation in patients with anastomotic leak following THE. Eight consecutive patients (seven men, one woman; mean age 51) with anastomotic leak following THE were subjected to endoscopic dilation using Savary Gilliard dilators of 7-15 mm diameter. The mean interval between surgery and detection of leak was 9 days (range 5-22 days) and dilation was performed at a mean interval of 11.4 days (range 1-20 days) after detection of the leak. Drainage from fistulas stopped completely after 1-8 days (mean 3 days). X-ray with water soluble contrast showed closure of the fistula in all cases. Duration of follow-up ranged from 2 to 12 months. Anastomotic strictures developed in three patients. These patients required three sessions each of repeat dilation, and were alive at follow-up periods of 2, 4, and 12 months, respectively. One patient developed recurrence of growth at an anastomotic site. Four patients died because of distant metastasis. Bougie dilation of anastomotic sites is a safe and effective technique for the healing of anastomotic leaks following THE. However there is a need for a prospective randomized trial comparing endoscopic dilation with no dilation in patients with anastomotic leaks following THE.

Refrigerant leak detector

NASA Technical Reports Server (NTRS)

Byrne, E. J.

1979-01-01

Quantitative leak detector visually demonstrates refrigerant loss from precision volume of large refrigeration system over established period of time from single test point. Mechanical unit is less costly than electronic "sniffers" and is more reliable due to absence of electronic circuits that are susceptible to drift.

40 CFR 63.1255 - Standards: Equipment leaks.

Code of Federal Regulations, 2013 CFR

2013-07-01

... requirements of this section. (9) Equipment that is in organic HAP service, but is in such service less than... required in paragraph (g)(9) of this section. (10) When each leak is detected by visual, audible, or... paragraphs (c)(5) through (9) of this section. (ii) Leak definition. The instrument reading, as determined by...

Gas Leak Detection by Dilution of Atmospheric Oxygen

PubMed Central

Lambrecht, Armin; Maier, Eric; Strahl, Thomas; Herbst, Johannes

2017-01-01

Gas leak detection is an important issue in infrastructure monitoring and industrial production. In this context, infrared (IR) absorption spectroscopy is a major measurement method. It can be applied in an extractive or remote detection scheme. Tunable laser spectroscopy (TLS) instruments are able to detect CH4 leaks with column densities below 10 ppm·m from a distance of 30 m in less than a second. However, leak detection of non-IR absorbing gases such as N2 is not possible in this manner. Due to the fact that any leaking gas displaces or dilutes the surrounding background gas, an indirect detection is still possible. It is shown by sensitive TLS measurements of the ambient background concentration of O2 that N2 leaks can be localized with extractive and standoff methods for distances below 1 m. Minimum leak rates of 0.1 mbar·L/s were determined. Flow simulations confirm that the leakage gas typically effuses in a narrow jet. The sensitivity is mainly determined by ambient flow conditions. Compared to TLS detection of CH4 at 1651 nm, the indirect method using O2 at 761 nm is experimentally found to be less sensitive by a factor of 100. However, the well-established TLS of O2 may become a universal tool for rapid leakage screening of vessels that contain unknown or inexpensive gases, such as N2. PMID:29206133

Apoptosis of Lewis Lung Carcinoma Cells Induced by Microwave via p53 and Proapoptotic Proteins In vivo

PubMed Central

Zhang, Kou-Dong; Tong, Lin-Rong; Wang, Shui-Ming; Peng, Rui-Yun; Huang, Hai-Dong; Dong, Yu-Chao; Zhang, Xing-Xing; Li, Qiang; Bai, Chong

2017-01-01

Background: Microwave therapy is a minimal invasive procedure and has been employed in clinical practice for the treatment of various types of cancers. However, its therapeutic application in non-small-cell lung cancer and the underlying mechanism remains to be investigated. This study aimed to investigate its effect on Lewis lung carcinoma (LLC) tumor in vivo. Methods: Fifty LLC tumor-bearing C57BL/6 mice were adopted to assess the effect of microwave radiation on the growth and apoptosis of LLC tumor in vivo. These mice were randomly assigned to 10 groups with 5 mice in each group. Five groups were treated by single pulse microwave at different doses for different time, and the other five groups were radiated by multiple-pulse treatment of a single dose. Apoptosis of cancer cells was determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Western blotting was applied to detect the expression of proteins. Results: Single pulse of microwave radiation for 5 min had little effect on the mice. Only 15-min microwave radiation at 30 mW/cm2 significantly increased the mice body temperature (2.20 ± 0.82)°C as compared with the other groups (0.78 ± 0.29 °C, 1.24 ± 0.52 °C, 0.78 ± 0.42 °C, respectively), but it did not affect the apoptosis of LLC tumor cells significantly. Continous microwave radiation exposure, single dose microwave radiation once per day for up to seven days, inhibited cell division and induced apoptosis of LLC tumor cells in a dose- and duration-dependent manner. It upregulated the protein levels of p53, Caspase 3, Bax and downregulated Bcl-2 protein. Conclusions: Multiple exposures of LLC-bearing mice to microwave radiation effectively induced tumor cell apoptosis at least partly by upregulating proapoptotic proteins and downregulating antiapoptotic proteins. Continuous radiation at low microwave intensity for a short time per day is promising in treating non-small-cell lung cancer. PMID:28051018

Apoptosis of Lewis Lung Carcinoma Cells Induced by Microwave via p53 and Proapoptotic Proteins In vivo.

PubMed

Zhang, Kou-Dong; Tong, Lin-Rong; Wang, Shui-Ming; Peng, Rui-Yun; Huang, Hai-Dong; Dong, Yu-Chao; Zhang, Xing-Xing; Li, Qiang; Bai, Chong

Microwave therapy is a minimal invasive procedure and has been employed in clinical practice for the treatment of various types of cancers. However, its therapeutic application in non-small-cell lung cancer and the underlying mechanism remains to be investigated. This study aimed to investigate its effect on Lewis lung carcinoma (LLC) tumor in vivo. Fifty LLC tumor-bearing C57BL/6 mice were adopted to assess the effect of microwave radiation on the growth and apoptosis of LLC tumor in vivo. These mice were randomly assigned to 10 groups with 5 mice in each group. Five groups were treated by single pulse microwave at different doses for different time, and the other five groups were radiated by multiple-pulse treatment of a single dose. Apoptosis of cancer cells was determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Western blotting was applied to detect the expression of proteins. Single pulse of microwave radiation for 5 min had little effect on the mice. Only 15-min microwave radiation at 30 mW/cm2 significantly increased the mice body temperature (2.20 ± 0.82)°C as compared with the other groups (0.78 ± 0.29 °C, 1.24 ± 0.52 °C, 0.78 ± 0.42 °C, respectively), but it did not affect the apoptosis of LLC tumor cells significantly. Continous microwave radiation exposure, single dose microwave radiation once per day for up to seven days, inhibited cell division and induced apoptosis of LLC tumor cells in a dose- and duration-dependent manner. It upregulated the protein levels of p53, Caspase 3, Bax and downregulated Bcl-2 protein. Multiple exposures of LLC-bearing mice to microwave radiation effectively induced tumor cell apoptosis at least partly by upregulating proapoptotic proteins and downregulating antiapoptotic proteins. Continuous radiation at low microwave intensity for a short time per day is promising in treating non-small-cell lung cancer.

Analysis of acute-phase proteins, AHSG, C3, CLI, HP and SAA, reveals distinctive expression patterns associated with breast, colorectal and lung cancer.

PubMed

Dowling, Paul; Clarke, Colin; Hennessy, Kim; Torralbo-Lopez, Beatriz; Ballot, Jo; Crown, John; Kiernan, Ingrid; O'Byrne, Kenneth J; Kennedy, M John; Lynch, Vincent; Clynes, Martin

2012-08-15

Early detection, clinical management and disease recurrence monitoring are critical areas in cancer treatment in which specific biomarker panels are likely to be very important in each of these key areas. We have previously demonstrated that levels of alpha-2-heremans-schmid-glycoprotein (AHSG), complement component C3 (C3), clusterin (CLI), haptoglobin (HP) and serum amyloid A (SAA) are significantly altered in serum from patients with squamous cell carcinoma of the lung. Here, we report the abundance levels for these proteins in serum samples from patients with advanced breast cancer, colorectal cancer (CRC) and lung cancer compared to healthy controls (age and gender matched) using commercially available enzyme-linked immunosorbent assay kits. Logistic regression (LR) models were fitted to the resulting data, and the classification ability of the proteins was evaluated using receiver-operating characteristic curve and leave-one-out cross-validation (LOOCV). The most accurate individual candidate biomarkers were C3 for breast cancer [area under the curve (AUC) = 0.89, LOOCV = 73%], CLI for CRC (AUC = 0.98, LOOCV = 90%), HP for small cell lung carcinoma (AUC = 0.97, LOOCV = 88%), C3 for lung adenocarcinoma (AUC = 0.94, LOOCV = 89%) and HP for squamous cell carcinoma of the lung (AUC = 0.94, LOOCV = 87%). The best dual combination of biomarkers using LR analysis were found to be AHSG + C3 (AUC = 0.91, LOOCV = 83%) for breast cancer, CLI + HP (AUC = 0.98, LOOCV = 92%) for CRC, C3 + SAA (AUC = 0.97, LOOCV = 91%) for small cell lung carcinoma and HP + SAA for both adenocarcinoma (AUC = 0.98, LOOCV = 96%) and squamous cell carcinoma of the lung (AUC = 0.98, LOOCV = 84%). The high AUC values reported here indicated that these candidate biomarkers have the potential to discriminate accurately between control and cancer groups both individually and in combination with other proteins. Copyright © 2011 UICC.

Leak detectability of the Norman Wells pipeline by mass balance

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

Liou, J.C.P.

Pipeline leak detection using software-based systems is becoming common practice. The detectability of such systems is measured by how small and how quickly a leak can be detected. Algorithms used and measurement uncertainties determine leak detectability. This paper addresses leak detectability using mass balance, establishes leak detectability for Norman Wells pipelines, and compares it with field leak test results. The pipeline is operated by the Interprovincial Pipe Line (IPL) Inc., of Edmonton, Canada. It is a 12.75-inch outside diameter steel pipe with variable wall thickness. The length of the pipe is approximately 550 miles (868.9 km). The pipeline transports lightmore » crude oil at a constant flow rate of about 250 m{sup 3}/hr. The crude oil can enter the pipeline at two locations. Besides the Norman Wells inlet, there is a side line near Zama terminal that can inject crude oil into the pipeline.« less

Hollow-core fiber sensing technique for pipeline leak detection

NASA Astrophysics Data System (ADS)

Challener, W. A.; Kasten, Matthias A.; Karp, Jason; Choudhury, Niloy

2018-02-01

Recently there has been increased interest on the part of federal and state regulators to detect and quantify emissions of methane, an important greenhouse gas, from various parts of the oil and gas infrastructure including well pads and pipelines. Pressure and/or flow anomalies are typically used to detect leaks along natural gas pipelines, but are generally very insensitive and subject to false alarms. We have developed a system to detect and localize methane leaks along gas pipelines that is an order of magnitude more sensitive by combining tunable diode laser spectroscopy (TDLAS) with conventional sensor tube technology. This technique can potentially localize leaks along pipelines up to 100 km lengths with an accuracy of +/-50 m or less. A sensor tube buried along the pipeline with a gas-permeable membrane collects leaking gas during a soak period. The leak plume within the tube is then carried to the nearest sensor node along the tube in a purge cycle. The time-to-detection is used to determine leak location. Multiple sensor nodes are situated along the pipeline to minimize the time to detection, and each node is composed of a short segment of hollow core fiber (HCF) into which leaking gas is transported quickly through a small pressure differential. The HCF sensing node is spliced to standard telecom solid core fiber which transports the laser light for spectroscopy to a remote interrogator. The interrogator is multiplexed across the sensor nodes to minimize equipment cost and complexity.

Low levels of the AhR in chronic obstructive pulmonary disease (COPD)-derived lung cells increases COX-2 protein by altering mRNA stability

PubMed Central

Zago, Michela; Sheridan, Jared A.; Traboulsi, Hussein; Hecht, Emelia; Zhang, Yelu; Guerrina, Necola; Matthews, Jason; Nair, Parameswaran; Eidelman, David H.; Hamid, Qutayba

2017-01-01

Heightened inflammation, including expression of COX-2, is associated with chronic obstructive pulmonary disease (COPD) pathogenesis. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is reduced in COPD-derived lung fibroblasts. The AhR also suppresses COX-2 in response to cigarette smoke, the main risk factor for COPD, by destabilizing the Cox-2 transcript by mechanisms that may involve the regulation of microRNA (miRNA). Whether reduced AhR expression is responsible for heightened COX-2 in COPD is not known. Here, we investigated the expression of COX-2 as well as the expression of miR-146a, a miRNA known to regulate COX-2 levels, in primary lung fibroblasts derived from non-smokers (Normal) and smokers (At Risk) with and without COPD. To confirm the involvement of the AhR, AhR knock-down via siRNA in Normal lung fibroblasts and MLE-12 cells was employed as were A549-AhRko cells. Basal expression of COX-2 protein was higher in COPD lung fibroblasts compared to Normal or Smoker fibroblasts but there was no difference in Cox-2 mRNA. Knockdown of AhR in lung structural cells increased COX-2 protein by stabilizing the Cox-2 transcript. There was less induction of miR-146a in COPD-derived lung fibroblasts but this was not due to the AhR. Instead, we found that RelB, an NF-κB protein, was required for transcriptional induction of both Cox-2 and miR-146a. Therefore, we conclude that the AhR controls COX-2 protein via mRNA stability by a mechanism independent of miR-146a. Low levels of the AhR may therefore contribute to the heightened inflammation common in COPD patients. PMID:28749959

Low levels of the AhR in chronic obstructive pulmonary disease (COPD)-derived lung cells increases COX-2 protein by altering mRNA stability.

PubMed

Zago, Michela; Sheridan, Jared A; Traboulsi, Hussein; Hecht, Emelia; Zhang, Yelu; Guerrina, Necola; Matthews, Jason; Nair, Parameswaran; Eidelman, David H; Hamid, Qutayba; Baglole, Carolyn J

2017-01-01

Heightened inflammation, including expression of COX-2, is associated with chronic obstructive pulmonary disease (COPD) pathogenesis. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is reduced in COPD-derived lung fibroblasts. The AhR also suppresses COX-2 in response to cigarette smoke, the main risk factor for COPD, by destabilizing the Cox-2 transcript by mechanisms that may involve the regulation of microRNA (miRNA). Whether reduced AhR expression is responsible for heightened COX-2 in COPD is not known. Here, we investigated the expression of COX-2 as well as the expression of miR-146a, a miRNA known to regulate COX-2 levels, in primary lung fibroblasts derived from non-smokers (Normal) and smokers (At Risk) with and without COPD. To confirm the involvement of the AhR, AhR knock-down via siRNA in Normal lung fibroblasts and MLE-12 cells was employed as were A549-AhRko cells. Basal expression of COX-2 protein was higher in COPD lung fibroblasts compared to Normal or Smoker fibroblasts but there was no difference in Cox-2 mRNA. Knockdown of AhR in lung structural cells increased COX-2 protein by stabilizing the Cox-2 transcript. There was less induction of miR-146a in COPD-derived lung fibroblasts but this was not due to the AhR. Instead, we found that RelB, an NF-κB protein, was required for transcriptional induction of both Cox-2 and miR-146a. Therefore, we conclude that the AhR controls COX-2 protein via mRNA stability by a mechanism independent of miR-146a. Low levels of the AhR may therefore contribute to the heightened inflammation common in COPD patients.

Malondialdehyde-Acetaldehyde (MAA) Protein Adducts Are Found Exclusively in the Lungs of Smokers with Alcohol Use Disorders and Are Associated with Systemic Anti-MAA Antibodies.

PubMed

Sapkota, Muna; Burnham, Ellen L; DeVasure, Jane M; Sweeter, Jenea M; Hunter, Carlos D; Duryee, Michael J; Klassen, Lynell W; Kharbanda, Kusum K; Sisson, Joseph H; Thiele, Geoffrey M; Wyatt, Todd A

2017-12-01

Malondialdehyde (MDA) and acetaldehyde (AA) exist following ethanol metabolism and tobacco pyrolysis. As such, lungs of individuals with alcohol use disorders (AUDs) are a target for the effects of combined alcohol and cigarette smoke metabolites. MDA and AA form a stable protein adduct, malondialdehyde-acetaldehyde (MAA) adduct, known to be immunogenic, profibrotic, and proinflammatory. MAA adduct is the dominant epitope in anti-MAA antibody formation. We hypothesized that MAA-adducted protein forms in lungs of those who both abuse alcohol and smoke cigarettes, and that this would be associated with systemically elevated anti-MAA antibodies. Four groups were established: AUD subjects who smoked cigarettes (+AUD/+smoke), smokers without AUD (-AUD/+smoke), AUD without smoke (+AUD/-smoke), and non-AUD/nonsmokers (-AUD/-smoke). We observed a significant increase in MAA adducts in lung cells of +AUD/+smoke versus -AUD/-smoke. No significant increase in MAA adducts was observed in -AUD/+smoke or in +AUD/-smoke compared to -AUD/-smoke. Serum from +AUD/+smoke had significantly increased levels of circulating anti-MAA IgA antibodies. After 1 week of alcohol that MAA-adducted protein is formed in the lungs of those who smoke cigarettes and abuse alcohol, leading to a subsequent increase in serum IgA antibodies. MAA-adducted proteins could play a role in pneumonia and other diseases of the lung in the setting of AUD and smoking. Copyright © 2017 by the Research Society on Alcoholism.

Assessing copper pinhole leaks in residential plumbing.

PubMed

Edwards, M; Rushing, J C; Kvech, S; Reiber, S

2004-01-01

Pinhole leaks in copper tubes are a major problem for homeowners, and an aggressive conscientious effort by utilities is recommended to diagnose the problem and identify potential solutions. In a case study at one utility, pinhole leak frequency data was compiled and a methodology was followed that might prove to be a useful guide for those facing similar problems.

40 CFR 53.52 - Leak check test.

Code of Federal Regulations, 2013 CFR

2013-07-01

... be verified at the highest and lowest pressures and temperatures used in the tests and shall be... 40 Protection of Environment 6 2013-07-01 2013-07-01 false Leak check test. 53.52 Section 53.52... Leak check test. (a) Overview. In section 7.4.6 of 40 CFR part 50, appendix L, the sampler is required...

Identification of sewage leaks by active remote-sensing methods

NASA Astrophysics Data System (ADS)

Goldshleger, Naftaly; Basson, Uri

2016-04-01

The increasing length of sewage pipelines, and concomitant risk of leaks due to urban and industrial growth and development is exposing the surrounding land to contamination risk and environmental harm. It is therefore important to locate such leaks in a timely manner, to minimize the damage. Advances in active remote sensing Ground Penetrating Radar (GPR) and Frequency Domain Electromagnetic (FDEM) technologies was used to identify leaking potentially responsible for pollution and to identify minor spills before they cause widespread damage. This study focused on the development of these electromagnetic methods to replace conventional acoustic methods for the identification of leaks along sewage pipes. Electromagnetic methods provide an additional advantage in that they allow mapping of the fluid-transport system in the subsurface. Leak-detection systems using GPR and FDEM are not limited to large amounts of water, but enable detecting leaks of tens of liters per hour, because they can locate increases in environmental moisture content of only a few percentage along the pipes. The importance and uniqueness of this research lies in the development of practical tools to provide a snapshot and monitoring of the spatial changes in soil moisture content up to depths of about 3-4 m, in open and paved areas, at relatively low cost, in real time or close to real time. Spatial measurements performed using GPR and FDEM systems allow monitoring many tens of thousands of measurement points per hectare, thus providing a picture of the spatial situation along pipelines and the surrounding. The main purpose of this study was to develop a method for detecting sewage leaks using the above-proposed geophysical methods, since their contaminants can severely affect public health. We focused on identifying, locating and characterizing such leaks in sewage pipes in residential and industrial areas.

Surfactant protein DNA methylation: A new entrant in the field of lung cancer diagnostics? (Review)

PubMed Central

Vaid, Mudit; Floros, Joanna

2010-01-01

Lung cancer is a major cause of cancer-related mortality in both men and women. A 5-year survival of lung cancer patients is only 15% with a negative correlation between progressively advanced lung cancer stage and a 5-year survival period. The only chance for cure is surgical resection if done at the early stage of the disease. Therefore, an early diagnosis and a better prediction of prognosis could decrease mortality. An early diagnosis could provide the opportunity for a therapeutic intervention early in the course of the disease. Genetic alterations in the cancer genome include aneuploidy, deletions and amplifications of chromosomal regions, loss of heterozygosity (LOH), microsatellite alterations, point mutations and aberrant promoter methylation. Of the various types of genetic alterations (i.e. gene amplifications, allele deletions, point mutations or deletions and methylation) reported in different tumor types, aberrant promoter methylation of genes is recent and is the focus of the present review. Specifically, we will briefly review the role of promoter methylation in various malignancies and then focus on lung cancer diagnosis and promoter gene methylation with emphasis on the methylation status of genes of the innate host defense, namely the surfactant proteins A and D. PMID:19082436

Novel Indole-based Tambjamine-Analogues Induce Apoptotic Lung Cancer Cell Death through p38 Mitogen-Activated Protein Kinase Activation.

PubMed

Manuel-Manresa, Pilar; Korrodi-Gregório, Luís; Hernando, Elsa; Villanueva, Alberto; Martínez-García, David; Rodilla, Ananda M; Ramos, Ricard; Fardilha, Margarida; Moya, Juan; Quesada, Roberto; Soto-Cerrato, Vanessa; Pérez-Tomás, Ricardo

2017-07-01

Lung cancer has become the leading killer cancer worldwide, due to late diagnosis and lack of efficient anticancer drugs. We have recently described novel natural-derived tambjamine analogues that are potent anion transporters capable of disrupting cellular ion balance, inducing acidification of the cytosol and hyperpolarization of cellular plasma membranes. Although these tambjamine analogues were able to compromise cell survival, their molecular mechanism of action remains largely unknown. Herein we characterize the molecular cell responses induced by highly active indole-based tambjamine analogues treatment in lung cancer cells. Expression changes produced after compounds treatment comprised genes related to apoptosis, cell cycle, growth factors and its receptors, protein kinases and topoisomerases, among others. Dysregulation of BCL2 and BIRC5 /survivin genes suggested the apoptotic pathway as the induced molecular cell death mechanism. In fact, activation of several proapoptotic markers (caspase-9, caspase-3, and PARP) and reversion of the cytotoxic effect upon treatment with an apoptosis inhibitor (Z-VAD-FMK) were observed. Moreover, members of the Bcl-2 protein family suffered changes after tambjamine analogues treatment, with a concomitant protein decrease towards the prosurvival members. Besides this, it was observed cellular accumulation of ROS upon compound treatment and an activation of the stress-kinase p38 MAPK route that, when inhibited, reverted the cytotoxic effect of the tambjamine analogues. Finally, a significant therapeutic effect of these compounds was observed in subcutaneous and orthotopic lung cancer mice models. Taken together, these results shed light on the mechanism of action of novel cytotoxic anionophores and demonstrate the therapeutic effects against lung cancer. Mol Cancer Ther; 16(7); 1224-35. ©2017 AACR . ©2017 American Association for Cancer Research.

Improved techniques reduce face mask leak during simulated neonatal resuscitation: study 2.

PubMed

Wood, Fiona E; Morley, Colin J; Dawson, Jennifer A; Kamlin, C Omar F; Owen, Louise S; Donath, Susan; Davis, Peter G

2008-05-01

Techniques of positioning and holding neonatal face masks vary. Studies have shown that leak at the face mask is common and often substantial irrespective of operator experience. (1) To identify a technique for face mask placement and hold which will minimise mask leak. (2) To investigate the effect of written instruction and demonstration of the identified technique on mask leak for two round face masks. Three experienced neonatologists compared methods of placing and holding face masks to minimise the leak for Fisher & Paykel 60 mm and Laerdal size 0/1 masks. 50 clinical staff gave positive pressure ventilation to a modified manikin designed to measure leak at the face mask. They were provided with written instructions on how to position and hold each mask and then received a demonstration. Face mask leak was measured after each teaching intervention. A technique of positioning and holding the face masks was identified which minimised leak. The mean (SD) mask leaks before instruction, after instruction and after demonstration were 55% (31), 49% (30), 33% (26) for the Laerdal mask and 57% (25), 47% (28), 32% (30) for the Fisher & Paykel mask. There was no significant difference in mask leak between the two masks. Written instruction alone reduced leak by 8.8% (CI 1.4% to 16.2%) for either mask; when combined with a demonstration mask leak was reduced by 24.1% (CI 16.4% to 31.8%). Written instruction and demonstration of the identified optimal technique resulted in significantly reduced face mask leak.

Development problem analysis of correlation leak detector’s software

NASA Astrophysics Data System (ADS)

Faerman, V. A.; Avramchuk, V. S.; Marukyan, V. M.

2018-05-01

In the article, the practical application and the structure of the correlation leak detectors’ software is studied and the task of its designing is analyzed. In the first part of the research paper, the expediency of the facilities development of correlation leak detectors for the following operating efficiency of public utilities exploitation is shown. The analysis of the functional structure of correlation leak detectors is conducted and its program software tasks are defined. In the second part of the research paper some development steps of the software package – requirement forming, program structure definition and software concept creation – are examined in the context of the usage experience of the hardware-software prototype of correlation leak detector.

Surgical risk factors associated with lung transplantation.

PubMed

Paradela, M; González, D; Parente, I; Fernández, R; De La Torre, M M; Delgado, M; García, J A; Fieira, E; Bonhome, C; Maté, J M B

2009-01-01

Despite years of experience with lung transplantation, perioperative morbidity rates remain high. The objective of this study was to analyze our series of lung transplant recipients, seeking to identify possible intra- and postoperative risk factors associated with mortality. We performed a descriptive, retrospective study of 224 consecutive patients undergoing lung transplantation over a period of 112 months; we excluded retransplant procedures. We gathered details of the surgical procedure and postoperative period in the recovery unit. Univariate analysis using the chi-square test identified variables associated with the incidence of mortality. From 1999 to 2008, we performed 224 lung transplants, including 66% in men and 34% in women. Their overall mean age was 49.9 +/- 13.5 years. The conditions that led to transplantation were pulmonary fibrosis (38.4%); chronic obstructive pulmonary disease emphysema (29%); cystic fibrosis (10.7%); bronchiectasis (8.9%); pulmonary hypertension (3.1%); and other diseases (9.9%). A total of 124 (55.4%) patients underwent single and 100 (44.6%) received sequential bilateral lung transplantations. Surgical risk factors were identified in 51.3% of the cases, the most frequent being hemorrhage (25.3%), followed by severe pulmonary hypertension (14.7%) and cardiopulmonary bypass (12.1%). Greater perioperative mortality was detected among patients with surgical risk factors, namely, significantly related to cardiopulmonary bypass, pulmonary hypertension, and air leak. A higher frequency of surgical risk factors was observed among patients with bilateral lung transplantations and longer procedures, but they were not associated with greater perioperative mortality. Reoperation was necessary in 16 patients (7.2%), mainly owing to bleeding, it was not significantly related to mortality risk. The incidence of surgical risk factors in lung transplantation was high, especially in bilateral lung transplantations and prolonged procedures

Wnt5a Is Associated with Cigarette Smoke-Related Lung Carcinogenesis via Protein Kinase C

PubMed Central

Sung, Jae Sook; Ju, Hyun Jung; Kim, Hyun Kyung; Park, Kyong Hwa; Lee, Jong Won; Koh, In Song; Kim, Yeul Hong

2013-01-01

Wnt5a is overexpressed during the progression of human non-small cell lung cancer. However, the roles of Wnt5a during smoking-related lung carcinogenesis have not been clearly elucidated. We investigated the associations between Wnt5a and the early development of cigarette smoke related lung cancer using human bronchial epithelial (HBE) cells (NHBE, BEAS-2B, 1799, 1198 and 1170I) at different malignant stages established by exposure to cigarette smoke condensate (CSC). Abnormal up-regulation of Wnt5a mRNA and proteins was detected in CSC-exposed transformed 1198 and tumorigenic 1170I cells as compared with other non-CSC exposed HBE cells. Tumor tissues obtained from smokers showed higher Wnt5a expressions than matched normal tissues. In non-CSC exposed 1799 cells, treatment of recombinant Wnt5a caused the activations of PKC and Akt, and the blockage of Wnt5a and PKC significantly decreased the viabilities of CSC-transformed 1198 cells expressing high levels of Wnt5a. This reduced cell survival rate was associated with increased apoptosis via the down-regulation of Bcl2 and the induction of cleaved poly ADP-ribose polymerase. Moreover, CSC-treated 1799 cells showed induction of Wnt5a expression and enhanced colony-forming capacity. The CSC-induced colony forming efficiency was suppressed by the co-incubation with a PKC inhibitor. In conclusion, these results suggest that cigarette smoke induces Wnt5a-coupled PKC activity during lung carcinogenesis, which causes Akt activity and anti-apoptosis in lung cancer. Therefore, current study provides novel clues for the crucial role of Wnt5a in the smoking-related lung carcinogenesis. PMID:23349696

Wnt5a is associated with cigarette smoke-related lung carcinogenesis via protein kinase C.

PubMed

Whang, Young Mi; Jo, Ukhyun; Sung, Jae Sook; Ju, Hyun Jung; Kim, Hyun Kyung; Park, Kyong Hwa; Lee, Jong Won; Koh, In Song; Kim, Yeul Hong

2013-01-01

Wnt5a is overexpressed during the progression of human non-small cell lung cancer. However, the roles of Wnt5a during smoking-related lung carcinogenesis have not been clearly elucidated. We investigated the associations between Wnt5a and the early development of cigarette smoke related lung cancer using human bronchial epithelial (HBE) cells (NHBE, BEAS-2B, 1799, 1198 and 1170I) at different malignant stages established by exposure to cigarette smoke condensate (CSC). Abnormal up-regulation of Wnt5a mRNA and proteins was detected in CSC-exposed transformed 1198 and tumorigenic 1170I cells as compared with other non-CSC exposed HBE cells. Tumor tissues obtained from smokers showed higher Wnt5a expressions than matched normal tissues. In non-CSC exposed 1799 cells, treatment of recombinant Wnt5a caused the activations of PKC and Akt, and the blockage of Wnt5a and PKC significantly decreased the viabilities of CSC-transformed 1198 cells expressing high levels of Wnt5a. This reduced cell survival rate was associated with increased apoptosis via the down-regulation of Bcl2 and the induction of cleaved poly ADP-ribose polymerase. Moreover, CSC-treated 1799 cells showed induction of Wnt5a expression and enhanced colony-forming capacity. The CSC-induced colony forming efficiency was suppressed by the co-incubation with a PKC inhibitor. In conclusion, these results suggest that cigarette smoke induces Wnt5a-coupled PKC activity during lung carcinogenesis, which causes Akt activity and anti-apoptosis in lung cancer. Therefore, current study provides novel clues for the crucial role of Wnt5a in the smoking-related lung carcinogenesis.

Method and means of passive detection of leaks in buried pipes

DOEpatents

Claytor, T.

1979-10-30

A method and means for passive detection of a leak in a buried pipe containing fluid under pressure includes a plurality of acoustic detectors that are placed in contact with the pipe. Noise produced by the leak is detected by the detectors, and the detected signals are correlated to locate the leak. In one embodiment of the invention two detectors are placed at different locations to locate a leak between them. In an alternate embodiment two detectors of different waves are placed at substantially the same location to determine the distance of the leak from the location.

Method and means of passive detection of leaks in buried pipes

DOEpatents

Claytor, Thomas N.

1981-01-01

A method and means for passive detection of a leak in a buried pipe containing fluid under pressure includes a plurality of acoustic detectors that are placed in contact with the pipe. Noise produced by the leak is detected by the detectors, and the detected signals are correlated to locate the leak. In one embodiment of the invention two detectors are placed at different locations to locate a leak between them. In an alternate embodiment two detectors of different waves are placed at substantially the same location to determine the distance of the leak from the location.

Incidence, risk factors and clinical implications of chyle leak after pancreatic surgery.

PubMed

Strobel, O; Brangs, S; Hinz, U; Pausch, T; Hüttner, F J; Diener, M K; Schneider, L; Hackert, T; Büchler, M W

2017-01-01

Chyle leak is a well known but poorly characterized complication after pancreatic surgery. Available data on incidence, risk factors and clinical significance of chyle leak are highly heterogeneous. For this cohort study all patients who underwent pancreatic surgery between January 2008 and December 2012 were identified from a prospective database. Chyle leak was defined as any drainage output with triglyceride content of 110 mg/dl or more. Risk factors for chyle leak were assessed by univariable and multivariable analyses. The clinical relevance of chyle leak was evaluated using hospital stay and resolution by 14 days for short-term outcome and overall survival for long-term outcome. Chyle leak developed in 346 (10·4 per cent) of 3324 patients. Pre-existing diabetes, resection for malignancy, distal pancreatectomy, duration of surgery 180 min or longer, and concomitant pancreatic fistula or abscess were independent risk factors for chyle leak. Both isolated chyle leak and coincidental chyle leak (with other intra-abdominal complications) were associated with prolonged hospital stay. Some 178 (87·7 per cent) of 203 isolated chyle leaks and 90 (70·3 per cent) of 128 coincidental chyle leaks resolved with conservative management within 14 days. Initial and maximum drainage volumes were associated with duration of hospital stay and success of therapy by 14 days. Impact on survival was restricted to chyle leaks that persisted at 14 days in patients with cancer undergoing palliative surgery. Chyle leak is a relevant complication, with an incidence of more than 10 per cent after pancreatic surgery, and has a major impact on hospital stay. Drainage volume is associated with hospital stay and success of therapy. © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

Clinical and subclinical leaks after low colorectal anastomosis: a clinical and radiologic study.

PubMed

Lim, Michael; Akhtar, Saleem; Sasapu, Kishore; Harris, Keith; Burke, Dermot; Sagar, Peter; Finan, Paul

2006-10-01

This study was designed to examine the natural history of subclinical leaks and their effect on bowel function and quality of life and to evaluate water-soluble contrast enema features that predict anastomotic healing after leaks. Consecutive patients who underwent low rectal anastomosis were followed up postoperatively for leaks. All leaks were confirmed radiologically with CT scanning and water-soluble contrast enema imaging. Water-soluble contrast enemas were serially repeated to identify healing. Characteristics on initial water-soluble contrast enema were correlated with observed healing. Postoperatively, patients were required to fill in a quality of life and a bowel function questionnaire. A total of 138 patients underwent low rectal anastomosis procedures with a median follow-up period of 26 (interquartile range, 19-37) months. There were 23 documented leaks of which 13 (9 percent) presented clinically and 10 (8 percent) presented subclinically. Ileostomy closure was possible in 4 of 13 (30 percent) patients with a clinical leak and all 10 (100 percent) patients with a subclinical leak. Median quality of life scores were lower for patients with clinical leaks and no ileostomy closure (P = 0.03). Bowel function for subclinical leak patients and clinical leak patients with ileostomy closure were similarly impaired. The presence of a cavity (P = 0.01) and a stricture (P = 0.01) at the anastomotic site were unfavorable radiologic features associated with nonhealing. Subclinical leaks are more benign in their natural history compared with clinical leaks. Quality of life and bowel function is no better in patients with a subclinical leak compared with patients with a clinical leak who have ileostomy closure. Anastomotic leaks may resolve if favorable radiologic features are present.

40 CFR 1066.985 - Fuel storage system leak test procedure.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 33 2014-07-01 2014-07-01 false Fuel storage system leak test... Refueling Emission Test Procedures for Motor Vehicles § 1066.985 Fuel storage system leak test procedure. (a... conditions. (3) Leak test equipment must have the ability to pressurize fuel storage systems to at least 4.1...

[Ryanodine receptor, calcium leak and arrhythmias].

PubMed

Rueda, Angélica; de Alba-Aguayo, David R; Valdivia, Héctor H

2014-01-01

The participation of the ionic Ca(2+) release channel/ryanodine receptor in cardiac excitation-contraction coupling is well known since the late '80s, when various seminal papers communicated its purification for the first time and its identity with the "foot" structures located at the terminal cisternae of the sarcoplasmic reticulum. In addition to its main role as the Ca(2+) channel responsible for the transient Ca(2+) increase that activates the contractile machinery of the cardiomyocytes, the ryanodine receptor releases Ca(2+) during the relaxation phase of the cardiac cycle, giving rise to a diastolic Ca(2+) leak. In normal physiological conditions, diastolic Ca(2+) leak regulates the proper level of luminal Ca(2+), but in pathological conditions it participates in the generation of both, acquired and hereditary arrhythmias. Very recently, several groups have focused their efforts into the development of pharmacological tools to control the altered diastolic Ca(2+) leak via ryanodine receptors. In this review, we focus our interest on describing the participation of cardiac ryanodine receptor in the diastolic Ca(2+) leak under physiological or pathological conditions and also on the therapeutic approaches to control its undesired exacerbated activity during diastole. Copyright © 2013 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Fatal Primary Capillary Leak Syndrome in a Late Preterm Newborn.

PubMed

Kulihova, Katarina; Prochazkova, Martina; Semberova, Jana; Janota, Jan

2016-10-01

Primary capillary leak syndrome is a rare disease of unknown etiology, characterized by episodes of vascular collapse and plasma extravasation, which may lead to multiple organ failure. Primary capillary leak is extremely rare in children. The authors report a case of a late preterm newborn with fatal capillary leak syndrome of unknown etiology, manifesting as hypotension unresponsive to treatment, extravasation leading to generalised edema, disseminated intravascular coagulation and finally, multiple organ dysfunction syndrome. Aggressive volumotherapy and a combination of inotropes and high doses of terlipressin did not influence systemic vascular collapse and plasma extravasation. The newborn developed multiple organ failure and died on day 27 of life. Investigations performed failed to reveal any specific cause of capillary leak. This is the first report of a fatal primary capillary leak syndrome in a newborn.

Livermore study says oil leaks not severe

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

Patrick, L.

The Petroleum Marketers Association of America (PMAA), which is working to reform the federal Leaking Underground Storage Tank program, got some strong ammunition last month. A study that the Lawrence Livermore National Laboratory performed for the California State Water Resources Control Board has found that the environmental threat of leaks is not as severe as formerly thought. The study said: such leaks rarely jeopardize drinking water; fuel hydrocarbons have limited impacts on health, the environment, and groundwater; and cleanups often are done contrary to the knowledge and experience gained from prior remediations. As a result of the study, Gov. Petemore » Wilson ordered California cleanups halted at sites more than 250 feet from drinking water supplies.« less

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

MicroRNA networks in mouse lung organogenesis.

PubMed

Dong, Jie; Jiang, Guoqian; Asmann, Yan W; Tomaszek, Sandra; Jen, Jin; Kislinger, Thomas; Wigle, Dennis A

2010-05-26

MicroRNAs (miRNAs) are known to be important regulators of both organ development and tumorigenesis. MiRNA networks and their regulation of messenger RNA (mRNA) translation and protein expression in specific biological processes are poorly understood. We explored the dynamic regulation of miRNAs in mouse lung organogenesis. Comprehensive miRNA and mRNA profiling was performed encompassing all recognized stages of lung development beginning at embryonic day 12 and continuing to adulthood. We analyzed the expression patterns of dynamically regulated miRNAs and mRNAs using a number of statistical and computational approaches, and in an integrated manner with protein levels from an existing mass-spectrometry derived protein database for lung development. In total, 117 statistically significant miRNAs were dynamically regulated during mouse lung organogenesis and clustered into distinct temporal expression patterns. 11,220 mRNA probes were also shown to be dynamically regulated and clustered into distinct temporal expression patterns, with 3 major patterns accounting for 75% of all probes. 3,067 direct miRNA-mRNA correlation pairs were identified involving 37 miRNAs. Two defined correlation patterns were observed upon integration with protein data: 1) increased levels of specific miRNAs directly correlating with downregulation of predicted mRNA targets; and 2) increased levels of specific miRNAs directly correlating with downregulation of translated target proteins without detectable changes in mRNA levels. Of 1345 proteins analyzed, 55% appeared to be regulated in this manner with a direct correlation between miRNA and protein level, but without detectable change in mRNA levels. Systematic analysis of microRNA, mRNA, and protein levels over the time course of lung organogenesis demonstrates dynamic regulation and reveals 2 distinct patterns of miRNA-mRNA interaction. The translation of target proteins affected by miRNAs independent of changes in mRNA level appears to

Quantitative proteomics of bronchoalveolar lavage fluid in lung adenocarcinoma.

PubMed

Almatroodi, Saleh A; McDonald, Christine F; Collins, Allison L; Darby, Ian A; Pouniotis, Dodie S

2015-01-01

The most commonly reported primary lung cancer subtype is adenocarcinoma, which is associated with a poor prognosis and short survival. Proteomic studies on human body fluids such as bronchoalveolar lavage fluid (BALF) have become essential methods for biomarker discovery, examination of tumor pathways and investigation of potential treatments. This study used quantitative proteomics to investigate the up-regulation of novel proteins in BALF from patients with primary lung adenocarcinoma in order to identify potential biomarkers. BALF samples from individuals with and without primary lung adenocarcinoma were analyzed using liquid chromatography-mass spectrometry. One thousand and one hundred proteins were identified, 33 of which were found to be consistently overexpressed in all lung adenocarcinoma samples compared to non-cancer controls. A number of overexpressed proteins have been previously shown to be related to lung cancer progression including S100-A8, annexin A1, annexin A2, thymidine phosphorylase and transglutaminase 2. The overexpression of a number of specific proteins in BALF from patients with primary lung adenocarcinoma may be used as a potential biomarker for lung adenocarcinoma. Copyright© 2015, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

40 CFR 1065.644 - Vacuum-decay leak rate.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 33 2011-07-01 2011-07-01 false Vacuum-decay leak rate. 1065.644 Section 1065.644 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS ENGINE-TESTING PROCEDURES Calculations and Data Requirements § 1065.644 Vacuum-decay leak rate...

40 CFR 1065.644 - Vacuum-decay leak rate.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Vacuum-decay leak rate. 1065.644 Section 1065.644 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS ENGINE-TESTING PROCEDURES Calculations and Data Requirements § 1065.644 Vacuum-decay leak rate...

40 CFR 1065.644 - Vacuum-decay leak rate.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 33 2014-07-01 2014-07-01 false Vacuum-decay leak rate. 1065.644 Section 1065.644 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS ENGINE-TESTING PROCEDURES Calculations and Data Requirements § 1065.644 Vacuum-decay leak rate...

40 CFR 1065.644 - Vacuum-decay leak rate.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 34 2012-07-01 2012-07-01 false Vacuum-decay leak rate. 1065.644 Section 1065.644 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS ENGINE-TESTING PROCEDURES Calculations and Data Requirements § 1065.644 Vacuum-decay leak rate...

40 CFR 1065.644 - Vacuum-decay leak rate.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 34 2013-07-01 2013-07-01 false Vacuum-decay leak rate. 1065.644 Section 1065.644 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS ENGINE-TESTING PROCEDURES Calculations and Data Requirements § 1065.644 Vacuum-decay leak rate...

Accuracy improvement in the TDR-based localization of water leaks

NASA Astrophysics Data System (ADS)

Cataldo, Andrea; De Benedetto, Egidio; Cannazza, Giuseppe; Monti, Giuseppina; Demitri, Christian

A time domain reflectometry (TDR)-based system for the localization of water leaks has been recently developed by the authors. This system, which employs wire-like sensing elements to be installed along the underground pipes, has proven immune to the limitations that affect the traditional, acoustic leak-detection systems. Starting from the positive results obtained thus far, in this work, an improvement of this TDR-based system is proposed. More specifically, the possibility of employing a low-cost, water-absorbing sponge to be placed around the sensing element for enhancing the accuracy in the localization of the leak is addressed. To this purpose, laboratory experiments were carried out mimicking a water leakage condition, and two sensing elements (one embedded in a sponge and one without sponge) were comparatively used to identify the position of the leak through TDR measurements. Results showed that, thanks to the water retention capability of the sponge (which maintains the leaked water more localized), the sensing element embedded in the sponge leads to a higher accuracy in the evaluation of the position of the leak.

Assessing the Rayleigh Intensity Remote Leak Detection Technique

NASA Technical Reports Server (NTRS)

Clements, Sandra

2001-01-01

Remote sensing technologies are being considered for efficient, low cost gas leak detection. An exploratory project to identify and evaluate remote sensing technologies for application to gas leak detection is underway. During Phase 1 of the project, completed last year, eleven specific techniques were identified for further study. One of these, the Rayleigh Intensity technique, would make use of changes in the light scattered off of gas molecules to detect and locate a leak. During the 10-week Summer Faculty Fellowship Program, the scatter of light off of gas molecules was investigated. The influence of light scattered off of aerosols suspended in the atmosphere was also examined to determine if this would adversely affect leak detection. Results of this study indicate that in unconditioned air, it will be difficult, though perhaps not impossible, to distinguish between a gas leak and natural variations in the aerosol content of the air. Because information about the particle size distribution in clean room environments is incomplete, the applicability in clean rooms is uncertain though more promising than in unconditioned environments. It is suggested that problems caused by aerosols may be overcome by using the Rayleigh Intensity technique in combination with another remote sensing technique, the Rayleigh Doppler technique.

REFLEAK: NIST Leak/Recharge Simulation Program for Refrigerant Mixtures

National Institute of Standards and Technology Data Gateway

SRD 73 NIST REFLEAK: NIST Leak/Recharge Simulation Program for Refrigerant Mixtures (PC database for purchase)   REFLEAK estimates composition changes of zeotropic mixtures in leak and recharge processes.

Vanishing calcification associated with a spontaneous ventral spinal cerebrospinal fluid leak.

PubMed

Schievink, Wouter I; Ross, Lindsey; Prasad, Ravi S; Maya, M Marcel

2016-12-01

Some patients with spontaneous intracranial hypotension have a ventral spinal cerebrospinal fluid (CSF) leak and these CSF leaks may be associated with calcified disk herniations. Identifying these calcifications is helpful in directing treatment. We report here the unusual case of a patient with a ventral CSF leak in whom the associated calcification absorbed over a five-month period. A 42-year-old woman developed orthostatic headaches and bilateral abducens nerve palsies. Magnetic resonance imaging of her brain showed typical findings of spontaneous intracranial hypotension. Magnetic resonance imaging of her spine showed an extensive cervicothoracic CSF leak. Computed tomographic myelography showed calcification at the Th1-2 disk space. Three epidural blood patches were performed, but her symptoms persisted. Digital subtraction myelography performed five months later showed an upper thoracic ventral CSF, but the calcification was no longer present. A dural tear, found at surgery at the Th1-2 level, was repaired and the patient made an uneventful recovery. The resorption of calcifications at the level of a ventral spinal CSF leak could explain the absence of any calcifications in at least some patients with such leaks and demonstrates the usefulness of reviewing previous imaging in patients with ventral CSF leaks if the exact site of the leak remains unknown. © International Headache Society 2016.

Effect of Single vs Bilateral Lung Transplantation on Plasma Surfactant Protein D Levels in Idiopathic Pulmonary Fibrosis

PubMed Central

Beers, Michael F.; Ahya, Vivek N.; Kawut, Steven M.; Sims, Karen D.; Lederer, David J.; Palmer, Scott M.; Wille, Keith; Lama, Vibha N.; Shah, Pali D.; Orens, Jonathan B.; Bhorade, Sangeeta; Crespo, Maria; Weinacker, Ann; Demissie, Ejigayehu; Bellamy, Scarlett; Christie, Jason D.; Ware, Lorraine B.

2011-01-01

Background: Serum levels of surfactant protein D (SP-D) have been suggested as reflecting epithelial damage in acute lung injury, COPD, and idiopathic pulmonary fibrosis (IPF). However, little is known about SP-D levels in the setting of lung transplantation. Methods: We examined plasma SP-D levels in 104 subjects from a prospective, multicenter cohort study of lung allograft recipients. Plasma SP-D was measured by enzyme-linked immunosorbent assay prior to transplant and daily for 3 days after transplant. Results: Subjects undergoing transplant for IPF had higher baseline SP-D levels (median, 325 ng/mL) compared with subjects with cystic fibrosis, COPD, and pulmonary hypertension (median, 100, 80, and 82 ng/mL, respectively; P = .0001). Among subjects with IPF undergoing bilateral transplant, SP-D levels declined rapidly postoperatively. In contrast, SP-D levels in subjects undergoing single lung transplant for IPF remained significantly higher than those of bilateral allograft recipients. Among subjects undergoing single lung transplant for IPF, the development of primary graft dysfunction (PGD) was associated with a subsequent rise in SP-D levels, whereas SP-D levels in IPF subjects undergoing bilateral transplant declined, even in the presence of grade 3 PGD. Importantly, single lung allograft recipients without PGD had higher postoperative SP-D levels than bilateral allograft recipients with PGD. Conclusions: Subjects undergoing lung transplant for IPF have significantly higher baseline plasma SP-D levels compared with those with other diagnoses. Plasma SP-D is likely a biomarker of the air-blood barrier integrity in the native IPF lung, but may be less useful as a biomarker of PGD after transplant. PMID:21349925

[Capillary leak syndrome disclosing Ofuji's papuloerythroderma].

PubMed

Carsuzaa, F; Pierre, C; Morand, J J; Farnarier, C; Marrot, F; Kaplanski, G

1996-01-01

Capillary leak syndrome is a specific entity among syndromes with capillary hyperpermeability. Endothelial cell activation is related to the higt level of adhesion molecules (sICAM-1, sVCAM-&, sCD62E) possibly due to several cytokines (IL-2, TNF ...). An 84-year-old woman was hospitalized for erythroderma. Ofujui papuloerythroderma was diagnosed and edema was attributed to capillary leak. A kinetic study of several cytokines and adhesion molecules sCD62E, sVCAM-1 and sICAM-1 was done. Outcome was favorable with corticopuvatherapy. The capillary leak syndrome reported here is simlar to that described in other erythrodermas with or without lymphoma. The keratinocyte would be activated by the CD4 T lymphocyte via the gamma-interferon mediator. The T cell secretes cytokines (interleukin-1, tumor necrosis factor ...) which activates the endothelium and increases vascular permeability. The level of adhesion molecules and changes observed during the episode of edema demonstrated the endothelial activation.

Hemodynamic resuscitation with arginine vasopressin reduces lung injury after brain death in the transplant donor.

PubMed

Rostron, Anthony J; Avlonitis, Vassilios S; Cork, David M W; Grenade, Danielle S; Kirby, John A; Dark, John H

2008-02-27

The autonomic storm accompanying brain death leads to neurogenic pulmonary edema and triggers development of systemic and pulmonary inflammatory responses. Neurogenic vasoplegia exacerbates the pulmonary injury caused by brain death and primes the lung for ischemia reperfusion injury and primary graft dysfunction in the recipient. Donor resuscitation with norepinephrine ameliorates the inflammatory response to brain death, however norepinephrine has deleterious effects, particularly on the heart. We tested the hypothesis that arginine vasopressin is a suitable alternative to norepinephrine in managing the hypotensive brain dead donor. Brain death was induced in Wistar rats by intracranial balloon inflation. Pulmonary capillary leak was estimated using radioiodinated albumin. Development of pulmonary edema was assessed by measurement of wet and dry lung weights. Cell surface expression of CD11b/CD18 by neutrophils was determined using flow cytometry. Enzyme-linked immunosorbent assays were used to measure the levels of TNFalpha, IL-1beta, CINC-1, and CINC-3 in serum and bronchoalveolar lavage. Quantitative reverse-transcription polymerase chain reaction was used to determine the expression of cytokine mRNA (IL-1beta, CINC-1 and CINC-3) in lung tissue. There was a significant increase in pulmonary capillary permeability, wet/dry lung weight ratios, neutrophil integrin expression and pro-inflammatory cytokines in serum (TNFalpha, IL-1beta, CINC-1 and CINC-3), bronchoalveolar lavage (TNFalpha and IL-1beta) and lung tissue (IL-1beta and CINC-1) in braindead animals compared to controls. Correction of neurogenic hypotension with either arginine vasopressin or norepinephrine limits edema, reduces pulmonary capillary leak, and modulates systemic and pulmonary inflammatory responses to brain death. Arginine vasopressin and norepinephrine are equally effective in treating the hypotensive pulmonary donor in this rodent model.

Lewis lung carcinoma regulation of mechanical stretch-induced protein synthesis in cultured myotubes.

PubMed

Gao, Song; Carson, James A

2016-01-01

Mechanical stretch can activate muscle and myotube protein synthesis through mammalian target of rapamycin complex 1 (mTORC1) signaling. While it has been established that tumor-derived cachectic factors can induce myotube wasting, the effect of this catabolic environment on myotube mechanical signaling has not been determined. We investigated whether media containing cachectic factors derived from Lewis lung carcinoma (LLC) can regulate the stretch induction of myotube protein synthesis. C2C12 myotubes preincubated in control or LLC-derived media were chronically stretched. Protein synthesis regulation by anabolic and catabolic signaling was then examined. In the control condition, stretch increased mTORC1 activity and protein synthesis. The LLC treatment decreased basal mTORC1 activity and protein synthesis and attenuated the stretch induction of protein synthesis. LLC media increased STAT3 and AMP-activated protein kinase phosphorylation in myotubes, independent of stretch. Both stretch and LLC independently increased ERK1/2, p38, and NF-κB phosphorylation. In LLC-treated myotubes, the inhibition of ERK1/2 and p38 rescued the stretch induction of protein synthesis. Interestingly, either leukemia inhibitory factor or glycoprotein 130 antibody administration caused further inhibition of mTORC1 signaling and protein synthesis in stretched myotubes. AMP-activated protein kinase inhibition increased basal mTORC1 signaling activity and protein synthesis in LLC-treated myotubes, but did not restore the stretch induction of protein synthesis. These results demonstrate that LLC-derived cachectic factors can dissociate stretch-induced signaling from protein synthesis through ERK1/2 and p38 signaling, and that glycoprotein 130 signaling is associated with the basal stretch response in myotubes. Copyright © 2016 the American Physiological Society.

Pulmonary atelectasis during low stretch ventilation: "open lung" versus "lung rest" strategy.

PubMed

Fanelli, Vito; Mascia, Luciana; Puntorieri, Valeria; Assenzio, Barbara; Elia, Vincenzo; Fornaro, Giancarlo; Martin, Erica L; Bosco, Martino; Delsedime, Luisa; Fiore, Tommaso; Grasso, Salvatore; Ranieri, V Marco

2009-03-01

Limiting tidal volume (VT) may minimize ventilator-induced lung injury (VILI). However, atelectasis induced by low VT ventilation may cause ultrastructural evidence of cell disruption. Apoptosis seems to be involved as protective mechanisms from VILI through the involvement of mitogen-activated protein kinases (MAPKs). We examined the hypothesis that atelectasis may influence the response to protective ventilation through MAPKs. Prospective randomized study. University animal laboratory. Adult male 129/Sv mice. Isolated, nonperfused lungs were randomized to VILI: VT of 20 mL/kg and positive end-expiratory pressure (PEEP) zero; low stretch/lung rest: VT of 6 mL/kg and 8-10 cm H2O of PEEP; low stretch/open lung: VT of 6 mL/kg, two recruitment maneuvers and 14-16 cm H2O of PEEP. Ventilator settings were adjusted using the stress index. Both low stretch strategies equally blunted the VILI-induced derangement of respiratory mechanics (static volume-pressure curve), lung histology (hematoxylin and eosin), and inflammatory mediators (interleukin-6, macrophage inflammatory protein-2 [enzyme-linked immunosorbent assay], and inhibitor of nuclear factor-kB[Western blot]). VILI caused nuclear swelling and membrane disruption of pulmonary cells (electron microscopy). Few pulmonary cells with chromatin condensation and fragmentation were seen during both low stretch strategies. However, although cell thickness during low stretch/open lung was uniform, low stretch/lung rest demonstrated thickening of epithelial cells and plasma membrane bleb formation. Compared with the low stretch/open lung, low stretch/lung rest caused a significant decrease in apoptotic cells (terminal deoxynucleotidyl transferase mediated deoxyuridine-triphosphatase nick end-labeling) and tissue expression of caspase-3 (Western blot). Both low stretch strategies attenuated the activation of MAPKs. Such reduction was larger during low stretch/open lung than during low stretch/lung rest (p < 0.001). Low stretch

Treatment of cerebrospinal fluid leak after spine surgery.

PubMed

Fang, Zhao; Tian, Rong; Jia, Yu-Tao; Xu, Tian-Tong; Liu, Yang

2017-04-01

Owing to the complexity of spinal surgery, there is a great prevalence of dural tear causing cerebrospinal fluid (CSF) leakage. Many studies focused on suture repair for dural tear to stop CSF leak. Now some new treatment strategies have shown a promising effect that is listed as follows: 1) creating watertight dural closure to stop CSF leak with the help of dural substitute material; and 2) retarding CSF leak by changing pressure difference, including reducing the subarachnoid fluid pressure, increasing the epidural space pressure and both. In fact several methods mentioned above are usually combined to treat CSF leak. However, no update review summarized the relevant studies implemented in recent years. In this review, the authors would compare the effects of different dural closure techniques, and introduce the latest treatment methods and mechanisms. Copyright © 2017 Daping Hospital and the Research Institute of Surgery of the Third Military Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Prediction of failure pressure and leak rate of stress corrosion.

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

Majumdar, S.; Kasza, K.; Park, J. Y.

2002-06-24

An ''equivalent rectangular crack'' approach was employed to predict rupture pressures and leak rates through laboratory generated stress corrosion cracks and steam generator tubes removed from the McGuire Nuclear Station. Specimen flaws were sized by post-test fractography in addition to a pre-test advanced eddy current technique. The predicted and observed test data on rupture and leak rate are compared. In general, the test failure pressures and leak rates are closer to those predicted on the basis of fractography than on nondestructive evaluation (NDE). However, the predictions based on NDE results are encouraging, particularly because they have the potential to determinemore » a more detailed geometry of ligamented cracks, from which failure pressure and leak rate can be more accurately predicted. One test specimen displayed a time-dependent increase of leak rate under constant pressure.« less

Apparatus for Leak Testing Pressurized Hoses

NASA Technical Reports Server (NTRS)

Underwood, Steve D. (Inventor); Garrison, Steve G. (Inventor); Gant, Bobby D. (Inventor); Palmer, John R. (Inventor)

2015-01-01

A hose-attaching apparatus for leak-testing a pressurized hose may include a hose-attaching member. A bore may extend through the hose-attaching member. An internal annular cavity may extend coaxially around the bore. At least one of a detector probe hole and a detector probe may be connected to the internal annular cavity. At least a portion of the bore may have a diameter which is at least one of substantially equal to and less than a diameter of a hose to be leak-tested.

Methane Leaks from Natural Gas Systems Follow Extreme Distributions.

PubMed

Brandt, Adam R; Heath, Garvin A; Cooley, Daniel

2016-11-15

Future energy systems may rely on natural gas as a low-cost fuel to support variable renewable power. However, leaking natural gas causes climate damage because methane (CH 4 ) has a high global warming potential. In this study, we use extreme-value theory to explore the distribution of natural gas leak sizes. By analyzing ∼15 000 measurements from 18 prior studies, we show that all available natural gas leakage data sets are statistically heavy-tailed, and that gas leaks are more extremely distributed than other natural and social phenomena. A unifying result is that the largest 5% of leaks typically contribute over 50% of the total leakage volume. While prior studies used log-normal model distributions, we show that log-normal functions poorly represent tail behavior. Our results suggest that published uncertainty ranges of CH 4 emissions are too narrow, and that larger sample sizes are required in future studies to achieve targeted confidence intervals. Additionally, we find that cross-study aggregation of data sets to increase sample size is not recommended due to apparent deviation between sampled populations. Understanding the nature of leak distributions can improve emission estimates, better illustrate their uncertainty, allow prioritization of source categories, and improve sampling design. Also, these data can be used for more effective design of leak detection technologies.

Methane Leaks from Natural Gas Systems Follow Extreme Distributions

DOE PAGES

Brandt, Adam R.; Heath, Garvin A.; Cooley, Daniel

2016-10-14

Future energy systems may rely on natural gas as a low-cost fuel to support variable renewable power. However, leaking natural gas causes climate damage because methane (CH 4) has a high global warming potential. In this study, we use extreme-value theory to explore the distribution of natural gas leak sizes. By analyzing ~15,000 measurements from 18 prior studies, we show that all available natural gas leakage datasets are statistically heavy-tailed, and that gas leaks are more extremely distributed than other natural and social phenomena. A unifying result is that the largest 5% of leaks typically contribute over 50% of themore » total leakage volume. While prior studies used lognormal model distributions, we show that lognormal functions poorly represent tail behavior. Our results suggest that published uncertainty ranges of CH 4 emissions are too narrow, and that larger sample sizes are required in future studies to achieve targeted confidence intervals. Additionally, we find that cross-study aggregation of datasets to increase sample size is not recommended due to apparent deviation between sampled populations. Finally, understanding the nature of leak distributions can improve emission estimates, better illustrate their uncertainty, allow prioritization of source categories, and improve sampling design. Also, these data can be used for more effective design of leak detection technologies.« less

Methane Leaks from Natural Gas Systems Follow Extreme Distributions

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

Brandt, Adam R.; Heath, Garvin A.; Cooley, Daniel

Future energy systems may rely on natural gas as a low-cost fuel to support variable renewable power. However, leaking natural gas causes climate damage because methane (CH 4) has a high global warming potential. In this study, we use extreme-value theory to explore the distribution of natural gas leak sizes. By analyzing ~15,000 measurements from 18 prior studies, we show that all available natural gas leakage datasets are statistically heavy-tailed, and that gas leaks are more extremely distributed than other natural and social phenomena. A unifying result is that the largest 5% of leaks typically contribute over 50% of themore » total leakage volume. While prior studies used lognormal model distributions, we show that lognormal functions poorly represent tail behavior. Our results suggest that published uncertainty ranges of CH 4 emissions are too narrow, and that larger sample sizes are required in future studies to achieve targeted confidence intervals. Additionally, we find that cross-study aggregation of datasets to increase sample size is not recommended due to apparent deviation between sampled populations. Finally, understanding the nature of leak distributions can improve emission estimates, better illustrate their uncertainty, allow prioritization of source categories, and improve sampling design. Also, these data can be used for more effective design of leak detection technologies.« less

Resilience to Leaking — Dynamic Systems Modeling of Information Security

PubMed Central

Hamacher, Kay

2012-01-01

Leaking of confidential material is a major threat to information security within organizations and to society as a whole. This insight has gained traction in the political realm since the activities of Wikileaks, which hopes to attack ‘unjust’ systems or ‘conspiracies’. Eventually, such threats to information security rely on a biologistic argument on the benefits and drawbacks that uncontrolled leaking might pose for ‘just’ and ‘unjust’ entities. Such biological metaphors are almost exclusively based on the economic advantage of participants. Here, I introduce a mathematical model of the complex dynamics implied by leaking. The complex interactions of adversaries are modeled by coupled logistic equations including network effects of econo-communication networks. The modeling shows, that there might arise situations where the leaking envisioned and encouraged by Wikileaks and the like can strengthen the defending entity (the ‘conspiracy’). In particular, the only severe impact leaking can have on an organization seems to originate in the exploitation of leaks by another entity the organization competes with. Therefore, the model suggests that leaks can be used as a `tactical mean’ in direct adversary relations, but do not necessarily increase public benefit and societal immunization to ‘conspiracies’. Furthermore, within the model the exploitation of the (open) competition between entities seems to be a more promising approach to control malicious organizations : divide-et-impera policies triumph here. PMID:23227151

DO ACUTE PHASE PROTEINS REFLECT SEVERITY OF INFLAMMATION IN RAT MODELS OF POLLUTANT-INDUCED LUNG INJURY?

EPA Science Inventory

Title: DO ACUTE PHASE PROTEINS REFLECT THE SEVERITY OF INFLAMMATION IN RAT MODELS OF POLLUTANT-INDUCED LUNG INJURY?

M. C. Schladweiler, BS 1, P. S. Gilmour, PhD 2, D. L. Andrews, BS 1, D. L. Costa, ScD 1, A. D. Ledbetter, BS 1, K. E. Pinkerton, PhD 3 and U. P. Kodavanti, ...

Clinical impact of leak compensation during non-invasive ventilation.

PubMed

Storre, Jan Hendrik; Bohm, Philipp; Dreher, Michael; Windisch, Wolfram

2009-10-01

This study aimed to assess the impact of leak compensation capabilities during pressure- and volume-limited non-invasive positive-pressure ventilation (NPPV) in COPD patients. Fourteen patients with stable hypercapnic COPD who were receiving long-term NPPV were included in the study. For both modes of NPPV, a full face mask and an artificial leak in the ventilatory circuit were used at three different settings, and applied during daytime NPPV, either without leakage (setting I), with leakage during inspiration only (setting II), and with leakage during inspiration and expiration (setting III). Ventilation pattern was pneumotachy-graphically recorded. NPPV was feasible with negligible leak volumes, indicating optimal mask fitting during the daytime (setting I). In the presence of leakage (settings II and III), the attempt to compensate for leak was only evident during pressure-limited NPPV, since inspiratory volumes delivered by the ventilator increased from 726+/-129 (setting I) to 1104+/-164 (setting II), and to 1257+/-166 (setting III) ml during pressure-limited NPPV, respectively (all p<0.001); however, they remained stable during volume-limited NPPV. Leak compensation resulted in a decrease in leakage-induced dyspnea. However, 83%/87% (setting II/III) of the additionally-delivered inspiratory volume during pressure-limited NPPV was also lost via leakage. Expiratory volume was higher in setting II compared to setting III (both p<0.001), indicating the presence of significant expiratory leakage. The attempt at leak compensation largely feeds the leakage itself and only results in a marginal increase of tidal volume. However, pressure-limited--but not volume-limited--NPPV results in a clinically-important leak compensation in vivo. www.uniklinik-freiburg.de/zks/live/uklregister/Oeffentlich.html Identifier: UKF001272.

The ISS 2B PVTCS Ammonia Leak: An Operational History

NASA Technical Reports Server (NTRS)

Vareha, Anthony

2014-01-01

In 2006, the Photovoltaic Thermal Control System (PVTCS) for the International Space Station's 2B power channel began leaking ammonia at a rate of approximately 1.5lbm/year (out of a starting approximately 53lbm system ammonia mass). Initially, the operations strategy was "feed the leak," a strategy successfully put into action via Extra Vehicular Activity during the STS-134 mission. During this mission the system was topped off with ammonia piped over from a separate thermal control system. This recharge was to have allowed for continued power channel operation into 2014 or 2015, at which point another EVA would have been required. Without these periodic EVAs to refill the 2B coolant system, the channel would eventually leak enough fluid as to risk pump cavitation and system failure, resulting in the loss of the 2B power channel - the most critical of the Space Station's 8 power channels. In mid-2012, the leak rate increased to approximately 5lbm/year. Once discovered, an EVA was planned and executed within a 5 week timeframe to drastically alter the architecture of the PVTCS via connection to a dormant thermal control system not intended to be utilized as anything other than spare components. The purpose of this rerouting of the TCS was to increase system volume and to isolate the photovoltaic radiator, thought to be the likely leak source. This EVA was successfully executed on November 1st, 2012 and left the 2B PVTCS in a configuration where the system was now being adequately cooled via a totally different radiator than what the system was designed to utilize. Unfortunately, data monitoring over the next several months showed that the isolated radiator was not leaking, and the system itself continued to leak steadily until May 9th, 2013. It was on this day that the ISS crew noticed the visible presence of ammonia crystals escaping from the 2B channel's truss segment, signifying a rapid acceleration of the leak from 5lbm/year to 5lbm/day. Within 48 hours of the

Space Shuttle RCS Oxidizer Leak Repair for STS-26

NASA Technical Reports Server (NTRS)

Delventhal, R. A.; Faget, N. M.

1989-01-01

Following propellant loading of the Space Shuttle's reaction control system (RCS) for mission STS 26, an oxidizer leak was detected in the left orbital maneuvering system (OMS) pod, where the RCS is located. Subsequent investigation determined that the leak was isolated at a mechanical Dynatube fitting near the RCS nitrogen tetroxide tank. An intense effort was initiated to design, fabricate, and qualify a sealing device to stop the oxidizer leak externally so that the Space Shuttle launch could proceed. It was discovered that sealing devices called clamshells were widely used throughout the petrochemical and power generation industries to stop leaks developed in large diameter pipes which carry steam or other hazardous fluids. These clamshells are available in different diameters and strengths and are placed around the pipe at the location of the leak. A sealing compound is then injected under high pressure into the clamshell to stop the leak. This technology was scaled down and applied to the problem of stopping the leak on the Orbiter, which was on a half-inch diameter line in a nearly inaccessible location. Many obstacles had to be overcome such as determining that the sealing material would be compatible with the nitrogen tetroxide and ensuring that the clamshell would actually fit around the Dynatube fitting without interfering with other lines which were in close proximity. The effort at the NASA Johnson Space Center included materials compatibility testing of several sealants, design of a clamshell to fit in the confined compartment, and manufacture and qualification of the flight hardware. A clamshell was successfully placed around the Dynatube fitting on the Orbiter and the oxidizer leak was terminated. Then it was decided to apply this technology further and design clamshells for other mechanical fittings onboard the Orbiter and develop sealing compounds which will be compatible with fuels such as monomethyl hydrazine (MMH). The potential exists for

Transepithelial leak in Barrett's esophagus patients: The role of proton pump inhibitors