Soluble CD40 ligand stimulates CD40-dependent activation of the β2 integrin Mac-1 and protein kinase C zeda (PKCζ in neutrophils: implications for neutrophil-platelet interactions and neutrophil oxidative burst.

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Rong Jin

Full Text Available Recent work has revealed an essential involvement of soluble CD40L (sCD40L in inflammation and vascular disease. Activated platelets are the major source of sCD40L, which has been implicated in platelet and leukocyte activation, although its exact functional impact on leukocyte-platelet interactions and the underlying mechanisms remain undefined. We aimed to determine the impact and the mechanisms of sCD40L on neutrophils. We studied neutrophil interactions with activated, surface-adherent platelets as a model for leukocyte recruitment to the sites of injury. Our data show that CD40L contributes to neutrophil firm adhesion to and transmigration across activated surface-adherent platelets, possibly through two potential mechanisms. One involves the direct interaction of ligand-receptor (CD40L-CD40, i.e., platelet surface CD40L interaction with neutrophil CD40; another involves an indirect mechanism, i.e. soluble CD40L stimulates activation of the leukocyte-specific β2 integrin Mac-1 in neutrophils and thereby further promotes neutrophil adhesion and migration. Activation of the integrin Mac-1 is known to be critical for mediating neutrophil adhesion and migration. sCD40L activated Mac-1 in neutrophils and enhanced neutrophil-platelet interactions in wild-type neutrophils, but failed to elicit such responses in CD40-deficient neutrophils. Furthermore, our data show that the protein kinase C zeta (PKCζ is critically required for sCD40L-induced Mac-1 activation and neutrophil adhesive function. sCD40L strongly stimulated the focal clustering of Mac-1 (CD11b and the colocalization of Mac-1 with PKCζ in wild-type neutrophils, but had minimal effect in CD40-deficient neutrophils. Blocking PKCζ completely inhibited sCD40L-induced neutrophil firm adhesion. Moreover, sCD40L strongly stimulates neutrophil oxidative burst via CD40-dependent activation of PI3K/NF-KB, but independent of Mac-1 and PKCζ. These findings may contribute to a better

Fetal Diagnosis of Abnormal Origin of the Left Pulmonary Artery.

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Tretter, Justin T; Tretter, Eric M; Rafii, Daniela Y; Anderson, Robert H; Bhatla, Puneet

2016-08-01

Isolated anomalies of the branch pulmonary arteries are rare, more often occurring in the setting of complex congenital heart disease. These isolated anomalies are often not identified in the prenatal period. We describe two cases of isolated anomalies of the left pulmonary artery which were identified on fetal echocardiography and confirmed postnatally, an anomalous left pulmonary artery arising from the base of the left-sided brachiocephalic artery in the setting of a right-sided aortic arch, and a left pulmonary artery sling. These two cases support our current understanding of normal and abnormal development of the extrapericardial arterial vessels and highlight the importance of meticulous attention when sweeping from the three-vessel tracheal view. © 2016, Wiley Periodicals, Inc.

Abnormal pulmonary function in adults with sickle cell anemia.

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Klings, Elizabeth S; Wyszynski, Diego F; Nolan, Vikki G; Steinberg, Martin H

2006-06-01

Pulmonary complications of sickle cell anemia (Hb-SS) commonly cause morbidity, yet few large studies of pulmonary function tests (PFTs) in this population have been reported. PFTs (spirometry, lung volumes, and diffusion capacity for carbon monoxide [DLCO]) from 310 adults with Hb-SS were analyzed to determine the pattern of pulmonary dysfunction and their association with other systemic complications of sickle cell disease. Raw PFT data were compared with predicted values. Each subject was subclassified into one of five groups: obstructive physiology, restrictive physiology, mixed obstructive/restrictive physiology, isolated low DLCO, or normal. The association between laboratory data of patients with decreased DLCO or restrictive physiology and those of normal subjects was assessed by multivariate linear regression. Normal PFTs were present in only 31 of 310 (10%) patients. Overall, adults with Hb-SS were characterized by decreased total lung capacities (70.2 +/- 14.7% predicted) and DLCO (64.5 +/- 19.9%). The most common PFT patterns were restrictive physiology (74%) and isolated low DLCO (13%). Decreased DLCO was associated with thrombocytosis (p = 0.05), with hepatic dysfunction (elevated alanine aminotransferase; p = 0.07), and a trend toward renal dysfunction (elevated blood urea nitrogen and creatinine; p = 0.05 and 0.07, respectively). Pulmonary function is abnormal in 90% of adult patients with Hb-SS. Common abnormalities include restrictive physiology and decreased DLCO. Decreased DLCO may indicate more severe sickle vasculopathy characterized by impaired hepatic and renal function.

Pulmonary function abnormalities in long-term survivors of childhood cancer

International Nuclear Information System (INIS)

Miller, R.W.; Fusner, J.E.; Fink, R.J.; Murphy, T.M.; Getson, P.R.; Vojtova, J.A.; Reaman, G.H.

1986-01-01

Pulmonary function testing (PFT) was performed on 29 long-term survivors of childhood cancer. The patients, whose mean age was 11.7 years and whose mean age at diagnosis was 3.7 years, included 12 females and 17 males. Original diagnoses included 15 patients with leukemia and 14 individuals with solid tumors. Nine patients had received cyclophosphamide and 20 had received radiation therapy. Included in this latter group were five patients who had received radiation therapy to the thorax. Eight patients had acquired pneumonia during their treatment. Physical examination was normal in all the patients, and none had a history of acute or chronic pulmonary disease. PFT demonstrated an incidence of abnormalities in forced vital capacity (FVC) and/or total lung capacity (TLC) in 48% of the patients. Patients who were under 3 years of age at the time of diagnosis or who had received radiation to the thorax were more likely to demonstrate PFT abnormalities, but these differences did not reach statistical significance. The natural history of pulmonary function and subsequent respiratory disease in survivors of childhood cancer requires further definition

Patterns of pulmonary maturation in normal and abnormal pregnancy.

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Goldkrand, J W; Slattery, D S

1979-03-01

Fetal pulmonary maturation may be a variable event depending on various feto-maternal environmental and biochemical influences. The patterns of maturation were studied in 211 amniotic fluid samples from 123 patients (normal 55; diabetes 23; Rh sensitization 19; preeclampsia 26). The phenomenon of globule formation from the amniotic fluid lipid extract and is relation to pulmonary maturity was utilized for this analysis. Validation of this technique is presented. A normal curve was constructed from 22 to 42 weeks; gestation and compared to the abnormal pregnancies. Patients with class A, B, and C diabetes and Rh-sensitized pregnancies had delayed pulmonary maturation. Patients with class D diabetes and preclampsia paralleled the normal course of maturation. A discussion of these results and their possible cause is presented.

Neutrophils in critical illness.

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McDonald, Braedon

2018-03-01

During critical illness, dramatic alterations in neutrophil biology are observed including abnormalities of granulopoeisis and lifespan, cell trafficking and antimicrobial effector functions. As a result, neutrophils transition from powerful antimicrobial protectors into dangerous mediators of tissue injury and organ dysfunction. In this article, the role of neutrophils in the pathogenesis of critical illness (sepsis, trauma, burns and others) will be explored, including pathological changes to neutrophil function during critical illness and the utility of monitoring aspects of the neutrophil phenotype as biomarkers for diagnosis and prognostication. Lastly, we review findings from clinical trials of therapies that target the harmful effects of neutrophils, providing a bench-to-bedside perspective on neutrophils in critical illness.

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

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

2015-05-01

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

Tamoxifen induces apoptotic neutrophil efferocytosis in horses.

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Olave, C; Morales, N; Uberti, B; Henriquez, C; Sarmiento, J; Ortloff, A; Folch, H; Moran, G

2018-03-01

Macrophages and neutrophils are important cellular components in the process of acute inflammation and its subsequent resolution, and evidence increasingly suggests that they play important functions during the resolution of chronic, adaptive inflammatory processes. Exacerbated neutrophil activity can be harmful to surrounding tissues; this is important in a range of diseases, including allergic asthma and chronic obstructive pulmonary disease in humans, and equine asthma (also known as recurrent airway obstruction (RAO). Tamoxifen (TX) is a non-steroidal estrogen receptor modulator with effects on cell growth and survival. Previous studies showed that TX treatment in horses with induced acute pulmonary inflammation promoted early apoptosis of blood and BALF neutrophils, reduction of BALF neutrophils, and improvement in animals' clinical status. The aim of this study was to describe if TX induces in vitro efferocytosis of neutrophils by alveolar macrophages. Efferocytosis assay, myeloperoxidase (MPO) detection and translocation phosphatidylserine (PS) were performed on neutrophils isolated from peripheral blood samples from five healthy horses. In in vitro samples from heathy horses, TX treatment increases the phenomenon of efferocytosis of peripheral neutrophils by alveolar macrophages. Similar increases in supernatant MPO concentration and PS translocation were observed in TX-treated neutrophils, compared to control cells. In conclusion, these results confirm that tamoxifen has a direct effect on equine peripheral blood neutrophils, through stimulation of the engulfment of apoptotic neutrophils by alveolar macrophages.

Advanced Role of Neutrophils in Common Respiratory Diseases

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Jinping Liu

2017-01-01

Full Text Available Respiratory diseases, always being a threat towards the health of people all over the world, are most tightly associated with immune system. Neutrophils serve as an important component of immune defense barrier linking innate and adaptive immunity. They participate in the clearance of exogenous pathogens and endogenous cell debris and play an essential role in the pathogenesis of many respiratory diseases. However, the pathological mechanism of neutrophils remains complex and obscure. The traditional roles of neutrophils in severe asthma, chronic obstructive pulmonary diseases (COPD, pneumonia, lung cancer, pulmonary fibrosis, bronchitis, and bronchiolitis had already been reviewed. With the development of scientific research, the involvement of neutrophils in respiratory diseases is being brought to light with emerging data on neutrophil subsets, trafficking, and cell death mechanism (e.g., NETosis, apoptosis in diseases. We reviewed all these recent studies here to provide you with the latest advances about the role of neutrophils in respiratory diseases.

Abnormal Pulmonary Function in Adults with Sickle Cell Anemia

Science.gov (United States)

Klings, Elizabeth S.; Wyszynski, Diego F.; Nolan, Vikki G.; Steinberg, Martin H.

2006-01-01

Rationale: Pulmonary complications of sickle cell anemia (Hb-SS) commonly cause morbidity, yet few large studies of pulmonary function tests (PFTs) in this population have been reported. Objectives: PFTs (spirometry, lung volumes, and diffusion capacity for carbon monoxide [DLCO]) from 310 adults with Hb-SS were analyzed to determine the pattern of pulmonary dysfunction and their association with other systemic complications of sickle cell disease. Methods: Raw PFT data were compared with predicted values. Each subject was subclassified into one of five groups: obstructive physiology, restrictive physiology, mixed obstructive/restrictive physiology, isolated low DLCO, or normal. The association between laboratory data of patients with decreased DLCO or restrictive physiology and those of normal subjects was assessed by multivariate linear regression. Measurements and Main Results: Normal PFTs were present in only 31 of 310 (10%) patients. Overall, adults with Hb-SS were characterized by decreased total lung capacities (70.2 ± 14.7% predicted) and DlCO (64.5 ± 19.9%). The most common PFT patterns were restrictive physiology (74%) and isolated low DlCO (13%). Decreased DLCO was associated with thrombocytosis (p = 0.05), with hepatic dysfunction (elevated alanine aminotransferase; p = 0.07), and a trend toward renal dysfunction (elevated blood urea nitrogen and creatinine; p = 0.05 and 0.07, respectively). Conclusions: Pulmonary function is abnormal in 90% of adult patients with Hb-SS. Common abnormalities include restrictive physiology and decreased DLCO. Decreased DLCO may indicate more severe sickle vasculopathy characterized by impaired hepatic and renal function. PMID:16556694

Pulmonary exposure to carbonaceous nanomaterials and sperm quality

DEFF Research Database (Denmark)

Skovmand, Astrid; Lauvas, Anna Jacobsen; Christensen, Preben

2018-01-01

. Pulmonary inflammation was determined by differential cell count in bronchoalveolar lavage fluid. Epididymal sperm concentration and motility were measured by computer-assisted sperm analysis. Epididymal sperm viability and morphological abnormalities were assessed manually using Hoechst 33,342/PI...... inflammation is a potential modulator of endocrine function. The aim of this study was to investigate the effects of pulmonary exposure to carbonaceous nanomaterials on sperm quality parameters in an experimental mouse model.Methods: Effects on sperm quality after pulmonary inflammation induced by carbonaceous...... flourescent and Spermac staining, respectively. Epididymal sperm were assessed with regard to sperm DNA integrity (damage). Daily sperm production was measured in the testis, and testosterone levels were measured in blood plasma by ELISA.Results: Neutrophil numbers in the bronchoalveolar fluid showed...

Significance of various pulmonary and extrapulmonary abnormalities on HRCT of the chest in scleroderma lung

International Nuclear Information System (INIS)

Pandey, Anoop Kumar; Wilcox, Pearce; O’ Brien, Julie; Ellis, Jennifer; Brown, Jacquie; Leipsic, Jonathon

2013-01-01

Patients with systemic sclerosis (SSc) are routinely investigated with high-resolution computed tomography (HRCT) chest for early detection and accurate characterization of complicating interstitial lung diseases. Though the primary aim of HRCT is to delineate the burden of pulmonary involvement and to characterize the nature of fibrosis to potentially help guide management, it provides an opportunity to evaluate extrapulmonary manifestations, particularly the dilated pulmonary artery, esophageal dilatation, and pericardial abnormalities which have their own clinical significance. The aim of this article is to discuss the significance of various pulmonary and extrapulmonary abnormalities that may be identified on HRCT chest of SSc patients

Transcatheter therapy in partially abnormal pulmonary venous return with additional drainage to the left atrium.

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Luciano, Debora; Laux, Daniela; Boudjemline, Younes; Hascoët, Sébastien; Lusson, Jean-René; Sorensen, Clio; Ovaert, Caroline; Kreitmann, Bernard; Van Praagh, Richard; Fraisse, Alain

2013-12-10

A persistent anastomosis between the pulmonary veins that connect with the left atrium and the systemic vein that drains into the right atrium has occasionally been reported. We report characteristics and transcatheter therapy in partially abnormal pulmonary venous return with additional drainage to the left atrium. We retrospectively studied such patients in 5 institutions. Ten patients (6 girls) presented at a median age of 8 (0.1 to 54) years with 2 anatomic types: 8 vertical vein types with drainage of the left upper lobe to the innominate vein via a large vertical vein (left superior cardinal vein) and to the left atrium via the left upper pulmonary vein; and 2 scimitar vein (SV) types with drainage of the right middle and lower pulmonary veins into the inferior vena cava and to the left atrium via an anomalous connecting vein. Associated malformations were aortic coarctation (n=2) and secundum atrial septal defects (n=3). Two patients of the vertical vein type were operated. Transcatheter occlusion of the abnormal pulmonary venous return was performed in 7 cases, associated with occlusion of systemic arterial supply (n=2), secundum atrial septal closure (n=2), left upper pulmonary vein stenosis stenting (n=1), and coarctation stenting (n=1). Including previously published cases, 18 patients (13 vertical veins and 5 scimitar veins) underwent transcatheter repair. Patients over 40 years of age tend to be symptomatic at presentation (p=0.056). In partially abnormal pulmonary venous return with dual drainage, transcatheter therapy can be offered in the majority of patients. © 2013.

Epithelial Cell-Neutrophil Interactions in the Alimentary Tract: A Complex Dialog in Mucosal Surveillance and Inflammation

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Sean P. Colgan

2002-01-01

Full Text Available Inflammatory diseases of mucosal organs as diverse as the lung, kidney, and intestine, inevitably require the intimate interactions of neutrophils with columnar epithelia. The physiologic consequences of such interactions often determine endpoint organ function, and for this reason, much recent interest has developed in identifying mechanisms and novel targets for the treatment of mucosal inflammation. Elegant in vitro model systems incorporating purified human neutrophils and human epithelial cells grown in physiologic orientations have aided in discovery of new and insightful pathways to define basic inflammatory pathways. Here, we will review the recent literature regarding the interactions between columnar epithelial cells and neutrophils, with an emphasis on intestinal epithelial cells, structural aspects of neutrophil transepithelial migration, molecular determinants of neutrophil-epithelial cell interactions, as well as modulation of these pathways. These recent studies highlight the dynamic nature of these pathways and lend insight into the complexity of treating mucosal inflammation.

Abnormalities by pulmonary regions studied with computer tomography following local or local-regional radiotherapy for breast cancer

International Nuclear Information System (INIS)

Lind, Pehr; Svane, Gunilla; Gagliardi, Giovanna; Svensson, Christer

1999-01-01

Purpose: To study pulmonary radiological abnormalities with computer tomography (CT) following different radiotherapy (RT) techniques for breast cancer with respect to regions and density, and their correlation to pulmonary complications and reduction in vital capacity (VC). Methods and Materials: CT scans of the lungs were performed prior to and 4 months following RT in 105 breast cancer patients treated with local or local-regional RT. The radiological abnormalities were analyzed with a CT-adapted modification of a classification system originally proposed by Arriagada, and scored according to increasing density (0-3) and affected lung regions (apical-lateral, central-parahilar, basal-lateral). The highest density grade in each region were added together to form scores ranging from 0-9. The patients were monitored for RT-induced pulmonary complications. VC was measured prior to and 5 months following RT. Results: Increasing CT scores were correlated with both local-regional RT and pulmonary complications (p < 0.001). The mean reduction of VC for patients scoring 4-9 (-202 ml) was larger than for patients scoring 0-3 (-2 ml) (p = 0.035). The effect of confounding factors on the radiological scoring was tested in the local-regional RT group. Scores of 4-9 were less frequently seen in the patients who had received adjuvant chemotherapy prior to RT. The importance of the respective lung regions on the outcome of pulmonary complications was tested. Only radiological abnormalities in the central-parahilar and apical-lateral regions were significantly correlated to pulmonary complications. Discussion: Radiological abnormalities detected on CT images and scored with a modification of Arriagada's classification system can be used as an objective endpoint for pulmonary side effects in breast cancer. The described model should, however, be expanded with information about the volume of lung affected in each region before definite conclusions can be drawn concerning each

Magnetic resonance imaging compared with echocardiography in the evaluation of pulmonary artery abnormalities in children with tetralogy of Fallot following palliative and corrective surgery

International Nuclear Information System (INIS)

Greenberg, S.B.; Crisci, K.L.; Koenig, P.; Robinson, B.; Anisman, P.; Russo, P.

1997-01-01

Background. Abnormalities of the pulmonary arteries following palliative or corrective surgery for tetralogy of Fallot (TOF) are common. Our purpose was to compare the usefulness of magnetic resonance imaging (MRI) and echocardiography in the post- operative evaluation of the pulmonary arteries in children with TOF. Objective. Our hypothesis was that MRI is more sensitive than echocardiography in the detection of branch pulmonary artery abnormalities in children with TOF. Materials and methods. Pulmonary artery MRI and echocardiography were performed in 20 children following palliative and/or corrective surgery for TOF. MRI and echocardiography were compared in their ability to detect abnormalities of the pulmonary arteries. Angiographic or surgical correlation was available in 15 children. A perfusion scan for confirmation of pulmonary artery patency was available in one additional child. Results. Abnormalities of the branch pulmonary arteries identified by MRI included: absence or occlusion (2), focal stenosis (15), hypoplasia (2), aneurysm (1), and non-confluence (1). Echocardiography could not adequately visualize the right and left branch pulmonary arteries in eight and ten children, respectively. Echocardiography missed stenosis in 13 branch pulmonary arteries, patency of hypoplastic pulmonary arteries in two children, non-confluence of the pulmonary arteries in one child, and a left pulmonary artery aneurysm in one child. Abnormalities identified by MRI were confirmed in 16 children by angiography, surgery or perfusion scan. Conclusion. MRI is more sensitive than echocardiography for the evaluation of branch pulmonary artery abnormalities in children following surgery for TOF. (orig.)

Abnormal shortened diastolic time length at increasing heart rates in patients with abnormal exercise-induced increase in pulmonary artery pressure

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Bombardini Tonino

2011-11-01

Full Text Available Abstract Background The degree of pulmonary hypertension is not independently related to the severity of left ventricular systolic dysfunction but is frequently associated with diastolic filling abnormalities. The aim of this study was to assess diastolic times at increasing heart rates in normal and in patients with and without abnormal exercise-induced increase in pulmonary artery pressure (PASP. Methods. We enrolled 109 patients (78 males, age 62 ± 13 years referred for exercise stress echocardiography and 16 controls. The PASP was derived from the tricuspid Doppler tracing. A cut-off value of PASP ≥ 50 mmHg at peak stress was considered as indicative of abnormal increase in PASP. Diastolic times and the diastolic/systolic time ratio were recorded by a precordial cutaneous force sensor based on a linear accelerometer. Results At baseline, PASP was 30 ± 5 mmHg in patients and 25 ± 4 in controls. At peak stress the PASP was normal in 95 patients (Group 1; 14 patients (Group 2 showed an abnormal increase in PASP (from 35 ± 4 to 62 ± 12 mmHg; P Conclusion The first and second heart sound vibrations non-invasively monitored by a force sensor are useful for continuously assessing diastolic time during exercise. Exercise-induced abnormal PASP was associated with reduced diastolic time at heart rates beyond 100 beats per minute.

Magnetic resonance imaging compared with echocardiography in the evaluation of pulmonary artery abnormalities in children with tetralogy of Fallot following palliative and corrective surgery

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Greenberg, S.B.; Crisci, K.L.; Koenig, P.; Robinson, B.; Anisman, P.; Russo, P. [St. Christopher`s Hospital for Children, Front Street at Erie Avenue, Philadelphia, PA 19134 (United States)

1997-12-01

Background. Abnormalities of the pulmonary arteries following palliative or corrective surgery for tetralogy of Fallot (TOF) are common. Our purpose was to compare the usefulness of magnetic resonance imaging (MRI) and echocardiography in the post- operative evaluation of the pulmonary arteries in children with TOF. Objective. Our hypothesis was that MRI is more sensitive than echocardiography in the detection of branch pulmonary artery abnormalities in children with TOF. Materials and methods. Pulmonary artery MRI and echocardiography were performed in 20 children following palliative and/or corrective surgery for TOF. MRI and echocardiography were compared in their ability to detect abnormalities of the pulmonary arteries. Angiographic or surgical correlation was available in 15 children. A perfusion scan for confirmation of pulmonary artery patency was available in one additional child. Results. Abnormalities of the branch pulmonary arteries identified by MRI included: absence or occlusion (2), focal stenosis (15), hypoplasia (2), aneurysm (1), and non-confluence (1). Echocardiography could not adequately visualize the right and left branch pulmonary arteries in eight and ten children, respectively. Echocardiography missed stenosis in 13 branch pulmonary arteries, patency of hypoplastic pulmonary arteries in two children, non-confluence of the pulmonary arteries in one child, and a left pulmonary artery aneurysm in one child. Abnormalities identified by MRI were confirmed in 16 children by angiography, surgery or perfusion scan. Conclusion. MRI is more sensitive than echocardiography for the evaluation of branch pulmonary artery abnormalities in children following surgery for TOF. (orig.) With 2 figs., 3 tabs., 11 refs.

Cathelicidin host defence peptide augments clearance of pulmonary Pseudomonas aeruginosa infection by its influence on neutrophil function in vivo.

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Paula E Beaumont

Full Text Available Cathelicidins are multifunctional cationic host-defence peptides (CHDP; also known as antimicrobial peptides and an important component of innate host defence against infection. In addition to microbicidal potential, these peptides have properties with the capacity to modulate inflammation and immunity. However, the extent to which such properties play a significant role during infection in vivo has remained unclear. A murine model of acute P. aeruginosa lung infection was utilised, demonstrating cathelicidin-mediated enhancement of bacterial clearance in vivo. The delivery of exogenous synthetic human cathelicidin LL-37 was found to enhance a protective pro-inflammatory response to infection, effectively promoting bacterial clearance from the lung in the absence of direct microbicidal activity, with an enhanced early neutrophil response that required both infection and peptide exposure and was independent of native cathelicidin production. Furthermore, although cathelicidin-deficient mice had an intact early cellular inflammatory response, later phase neutrophil response to infection was absent in these animals, with significantly impaired clearance of P. aeruginosa. These findings demonstrate the importance of the modulatory properties of cathelicidins in pulmonary infection in vivo and highlight a key role for cathelicidins in the induction of protective pulmonary neutrophil responses, specific to the infectious milieu. In additional to their physiological roles, CHDP have been proposed as future antimicrobial therapeutics. Elucidating and utilising the modulatory properties of cathelicidins has the potential to inform the development of synthetic peptide analogues and novel therapeutic approaches based on enhancing innate host defence against infection with or without direct microbicidal targeting of pathogens.

Neutrophils at work

DEFF Research Database (Denmark)

Nauseef, William M; Borregaard, Niels

2014-01-01

In this Review we discuss data demonstrating recently recognized aspects of neutrophil homeostasis in the steady state, granulopoiesis in 'emergency' conditions and interactions of neutrophils with the adaptive immune system. We explore in vivo observations of the recruitment of neutrophils from ...

Chronic obstructive pulmonary disease (COPD): neutrophils, macrophages and lymphocytes in patients with anterior tuberculosis compared to tobacco related COPD.

Science.gov (United States)

Guiedem, Elise; Ikomey, George Mondinde; Nkenfou, Céline; Walter, Pefura-Yone Eric; Mesembe, Martha; Chegou, Novel Njweipi; Jacobs, Graeme Brendon; Okomo Assoumou, Marie Claire

2018-03-27

The inflammatory profile of chronic obstructive pulmonary disease (COPD) related to tobacco is known in certain studies while that of the post tuberculosis form is not yet known. This study aimed to evaluate the levels of neutrophils, macrophages and lymphocytes cells in sputum of COPD patients with history of smoking or anterior tuberculosis. Enumeration of cells in samples was analyzed using standard microscopy. We enrolled 92 participants, 46 (50%) were COPD subjects comprising 22 (47.83%) smokers and 24 (52.17%) with anterior tuberculosis while 46 (50%) healthy persons constituted the control group. The levels of neutrophils, lymphocytes and monocytes were statistically higher in COPD patients compared to the control group with p-values of 0.0001 respectively. Neutrophils levels were higher in COPD patients with history of tobacco than in COPD patients with anterior tuberculosis with a mean rate of 4.72 × 10 6 /ml and 2.48 × 10 6 /ml respectively (p = 0.04). The monocytes and lymphocytes levels were not statistically different between the two sub-groups of COPD patients with p-value of 0.052 and 0.91 respectively. Neutrophils are the only inflammatory cells that were significantly higher in COPD patients with history of smoking as compared to COPD patients with anterior tuberculosis.

Pleuro-pulmonary abnormalities in patients with systemic lupus erythematosus assessment with high resolution computed tomography, chest radiography and pulmonary function tests

Energy Technology Data Exchange (ETDEWEB)

Sant, S.M.; Doran, M.; Fenelon, H.M.; Breatnach, E.S. [University of Michigan (United States)

1998-04-01

The objective has to assess the nature of pleuro-pulmonary abnormalities, with particular reference to interstitial lung disease (ILD), in patients with systemic lupus erythematosus (SLE) In conclusion, HRCT is more sensitive than PFTs or CXR in the evaluation of pleuro-pulmonary disease in SLE. We report an unusually high prevalence of HRCT appearances suggestive of ILD in patients with SLE. subclinical lung disease is common in patients with SLE. (author)

Pleuro-pulmonary abnormalities in patients with systemic lupus erythematosus assessment with high resolution computed tomography, chest radiography and pulmonary function tests

International Nuclear Information System (INIS)

Sant, S.M.; Doran, M.; Fenelon, H.M.; Breatnach, E.S.

1998-01-01

The objective has to assess the nature of pleuro-pulmonary abnormalities, with particular reference to interstitial lung disease (ILD), in patients with systemic lupus erythematosus (SLE) In conclusion, HRCT is more sensitive than PFTs or CXR in the evaluation of pleuro-pulmonary disease in SLE. We report an unusually high prevalence of HRCT appearances suggestive of ILD in patients with SLE. subclinical lung disease is common in patients with SLE. (author)

Clinical features of usual interstitial pneumonia with anti-neutrophil cytoplasmic antibody in comparison with idiopathic pulmonary fibrosis.

Science.gov (United States)

Hosoda, Chiaki; Baba, Tomohisa; Hagiwara, Eri; Ito, Hiroyuki; Matsuo, Norikazu; Kitamura, Hideya; Iwasawa, Tae; Okudela, Koji; Takemura, Tamiko; Ogura, Takashi

2016-07-01

Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) is occasionally positive in patients with usual interstitial pneumonia (UIP). However, the differences from idiopathic pulmonary fibrosis (IPF/UIP) have not been well documented. We aimed to clarify the clinical, radiological and pathological features of UIP associated with MPO-ANCA (ANCA/UIP). We retrospectively reviewed the medical records of 12 consecutive ANCA/UIP patients not manifesting microscopic polyangiitis and 108 IPF/UIP patients with no autoantibodies, both diagnosed by surgical lung biopsy. There was no significant difference in clinical background, laboratory results and pulmonary function tests between ANCA/UIP patients and IPF/UIP patients except for the percentage of bronchoalveolar lavage neutrophils. HRCT showed subpleural reticulation in both groups. Increased attenuation around honeycombing and cysts was significantly observed in ANCA/UIP. Pathologically, ANCA/UIP had more prominent inflammatory cell infiltration, lymphoid follicles with germinal centres and cellular bronchiolitis. During the disease course, three of 12 patients (25%) developed microscopic polyangiitis. Immunosuppressive treatment tended to be more effective in ANCA/UIP patients, and the survival time in ANCA/UIP patients tended to be longer than those with IPF/UIP. ANCA/UIP may be distinguishable from IPF/UIP with a combination of HRCT findings of increased attenuation around honeycombing and cysts and some of the characteristic pathological findings. In contrast to IPF/UIP, immunosuppressive treatment could be a therapeutic option for ANCA/UIP. © 2016 Asian Pacific Society of Respirology.

Sphingosine kinase inhibition alleviates endothelial permeability induced by thrombin and activated neutrophils.

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Itagaki, Kiyoshi; Zhang, Qin; Hauser, Carl J

2010-04-01

Inflammation and microvascular thrombosis are interrelated causes of acute lung injury in the systemic inflammatory response syndrome. Neutrophils (polymorphonuclear neutrophil [PMN]) and endothelial cells (EC) activated by systemic inflammatory response syndrome interact to increase pulmonary vascular permeability, but the interactions between PMN and EC are difficult to study. Recently, we reported that sphingosine 1-phosphate is a second messenger eliciting store-operated calcium entry (SOCE) in response to inflammatory agonists in both PMN and EC. Store-operated calcium entry is therefore a target mechanism for the therapeutic modulation of inflammatory PMN-EC interactions. Here, we isolated, modeled, and studied the effects of pharmacologic SOCE inhibition using real-time systems to monitor EC permeability after exposure to activated PMN. We created systems to continuously assess permeability of human pulmonary artery endothelial cells and human microvascular endothelial cells from lung. Endothelial cells show increased permeability after challenge by activated PMN. Such permeability increases can be attenuated by exposure of the cocultures to sphingosine kinase (SK) inhibitors (SKI-2, N,N-dimethylsphingosine [DMS]) or Ca2+ entry inhibitors (Gd3+, MRS-1845). Human microvascular endothelial cells from lung pretreated with SKI-2 or DMS showed decreased permeability when later exposed to activated PMN. Likewise, when PMNs were activated with thapsigargin (TG) in the presence of SKI-2, DMS, Gd, or MRS-1845, their ability to cause EC permeability subsequently was reduced. SKI-2 also inhibited the activation of human pulmonary artery ECs by thrombin. These studies will provide a firm mechanistic foundation for understanding how systemic SOCE inhibition may be used to prevent acute lung injury in vivo.

With Friends Like These: The Complex Role of Neutrophils in the Progression of Severe Pneumonia

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Roger D. Pechous

2017-05-01

Full Text Available Pneumonia is a leading cause of death from infection in the United States and across the globe. During pulmonary infection, clear resolution of host inflammatory responses occurs in the absence of appreciable lung damage. Neutrophils are the first wave of leukocytes to arrive in the lung upon infection. After activation, neutrophils traffic from the vasculature via transendothelial migration through the lung interstitium and into the alveolar space. Successful pulmonary immunity requires neutrophil-mediated killing of invading pathogens by phagocytosis and release of a myriad of antimicrobial molecules, followed by resolution of inflammation, neutrophil apoptosis, and clearing of dead or dying neutrophils by macrophages. In addition to their antimicrobial role, it is becoming clear that neutrophils are also important modulators of innate and adaptive immune responses, primarily through the release of cytokines and recruitment of additional waves of neutrophils into the airways. Though typically essential to combating severe pneumonia, neutrophil influx into the airways is a double-edged sword: Overzealous neutrophil activation can cause severe tissue damage as a result of the release of toxic agents including proteases, cationic polypeptides, cytokines, and reactive oxygen species (ROS aimed at killing invading microbes. In extreme cases, the damage caused by neutrophils and other innate immune mediators become the primary source of morbidity and mortality. Here, we review the complex role of neutrophils during severe pneumonia by highlighting specific molecules and processes that contribute to pulmonary immunity, but can also drive progression of severe disease. Depending on the identity of the infectious agent, enhancing or suppressing neutrophil-mediated responses may be key to effectively treating severe and typically lethal pneumonia.

Abnormal lung gallium-67 uptake preceding pulmonary physiologic impairment in an asymptomatic patient with Pneumocystis carinii pneumonia

International Nuclear Information System (INIS)

Reiss, T.F.; Golden, J.

1990-01-01

Pneumocystis carinii pneumonia was suggested by a diffuse, bilateral pulmonary uptake of gallium-67 in an asymptomatic, homosexual male with the antibody to the immunodeficiency virus (HIV) who was undergoing staging evaluation for lymphoma clinically localized to a left inguinal lymph node. Chest radiograph and pulmonary function evaluation, including lung volumes, diffusing capacity and arterial blood gases, were within normal limits. Bronchoalveolar lavage revealed Pneumocystis carinii organisms. In this asymptomatic, HIV-positive patient, active alveolar infection, evidenced by abnormal gallium-67 scanning, predated pulmonary physiologic abnormalities. This observation raises questions concerning the natural history of this disease process and the specificity of physiologic tests for excluding disease. It also has implications for the treatment of neoplasia in the HIV-positive patient population

Neutrophil elastase and elastin-derived peptides in BAL fluid and emphysematous changes on CT scans

International Nuclear Information System (INIS)

Betsuyaku, Tomoko; Nishimura, Masaharu; Yoshioka, Aya; Takeyabu, Kimihiro; Miyamoto, Kenji; Kawakami, Yoshikazu

1996-01-01

We examined the relationship between neutrophil elastase, elastin-derived peptides in bronchoalveolar lavage (BAL) fluid, and the development of pulmonary emphysema. The level of neutrophil elastase was higher in asymptomatic current smokers with emphysematous changes on computed tomographic scans than in current smokers without emphysematous changes, and was found to be correlated with the level of elastin-derived peptides in BAL fluid. Subjects with high levels of neutrophil elastase in BAL fluid had faster annual declines in FEV 1 . We conclude that the level of neutrophil elastase in BAL fluid can be used to differentiate asymptomatic cigarette smokers who are at risk for pulmonary emphysema from those who are not. (author)

Abnormal pulmonary function and associated risk factors in children and adolescents with sickle cell anemia

Science.gov (United States)

Arteta, Manuel; Campbell, Andrew; Nouraie, Mehdi; Rana, Sohail; Onyekwere, Onyinye; Ensing, Gregory; Sable, Craig; Dham, Niti; Darbari, Deepika; Luchtman-Jones, Lori; Kato, Gregory J.; Gladwin, Mark T.; Castro, Oswaldo L.; Minniti, Caterina P.; Gordeuk, Victor R.

2015-01-01

Obstructive and restrictive pulmonary changes develop in children with sickle cell disease, but reports conflict as to the type of change that predominates. We prospectively performed spirometry, plethysmography and lung diffusing capacity in 146 children aged 7–20 years with hemoglobin SS or Sβ0-thalassemia. Nineteen percent of the patients had obstructive physiology as defined according to guidelines of the American Thoracic Society. In addition, 9% had restrictive physiology and 11% had abnormal but not categorized physiology. Increasing age, patient- or family-reported history of asthma or wheezing, and higher lactate dehydrogenase concentration were independent predictors of obstruction as reflected in lower FEV1/FVC. In conclusion, abnormal pulmonary function, most often obstructive, is common in children with hemoglobin SS and Sβ0-thalassemia. Full pulmonary function testing should be performed in children with hemoglobin SS or Sβ0 thalassemia, especially with history of asthma or wheezing and accentuated elevations in hemolytic markers. PMID:24309610

Focal Bronchiectasis Causing Abnormal Pulmonary Radioiodine Uptake in a Patient with Well-Differentiated Papillary Thyroid Carcinoma

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Ash Gargya

2012-01-01

Full Text Available Background. False-positive pulmonary radioactive iodine uptake in the followup of differentiated thyroid carcinoma has been reported in patients with certain respiratory conditions. Patient Findings. We describe a case of well-differentiated papillary thyroid carcinoma treated by total thyroidectomy and radioiodine ablation therapy. Postablation radioiodine whole body scan and subsequent diagnostic radioiodine whole body scans have shown persistent uptake in the left hemithorax despite an undetectable stimulated serum thyroglobulin in the absence of interfering thyroglobulin antibodies. Contrast-enhanced chest computed tomography has confirmed that the abnormal pulmonary radioiodine uptake correlates with focal bronchiectasis. Summary. Bronchiectasis can cause abnormal chest radioactive iodine uptake in the followup of differentiated thyroid carcinoma. Conclusions. Recognition of potential false-positive chest radioactive iodine uptake, simulating pulmonary metastases, is needed to avoid unnecessary exposure to further radiation from repeated therapeutic doses of radioactive iodine.

Hypomelanosis of Ito with an unusual pulmonary abnormality in an infant

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Ramesh Y Bhat

2014-01-01

Full Text Available Hypomelanosis of Ito (HI is a neurocutaneous syndrome characterized by hypopigmented cutaneous lesions and extracutaneous manifestations frequently affecting the nervous system and the musculoskeletal system. Dysmorphic features, dental, ophthalmic, gastrointestinal, cardiac, and renal abnormalities are described in a minority of patients. The authors describe a 4-month-old infant having HI with unusual pulmonary hypoplasia that has not been reported so far.

Impaired neutrophil function in intestinal lymphangiectasia.

OpenAIRE

Bolton, R P; Cotter, K L; Losowsky, M S

1986-01-01

Impaired neutrophil chemotaxis and phagocytosis were shown in three patients with intestinal lymphangiectasia. Abnormalities in cell associated and serum derived activity occurred, and possible mechanisms are suggested.

GMP-140 binds to a glycoprotein receptor on human neutrophils: Evidence for a lectin-like interaction

International Nuclear Information System (INIS)

Moore, K.L.; Varki, A.; McEver, R.P.

1991-01-01

GMP-140 is a rapidly inducible receptor for neutrophils and monocytes expressed on activated platelets and endothelial cells. It is a member of the selectin family of lectin-like cell surface molecules that mediate leukocyte adhesion. We used a radioligand binding assay to characterize the interaction of purified GMP-140 with human neutrophils. Unstimulated neutrophils rapidly bound [125I]GMP-140 at 4 degrees C, reaching equilibrium in 10-15 min. Binding was Ca2+ dependent, reversible, and saturable at 3-6 nM free GMP-140 with half-maximal binding at approximately 1.5 nM. Receptor density and apparent affinity were not altered when neutrophils were stimulated with 4 beta-phorbol 12-myristate 13-acetate. Treatment of neutrophils with proteases abolished specific binding of [125I]GMP-140. Binding was also diminished when neutrophils were treated with neuraminidase from Vibrio cholerae, which cleaves alpha 2-3-, alpha 2-6-, and alpha 2-8-linked sialic acids, or from Newcastle disease virus, which cleaves only alpha 2-3- and alpha 2-8-linked sialic acids. Binding was not inhibited by an mAb to the abundant myeloid oligosaccharide, Lex (CD15), or by the neoglycoproteins Lex-BSA and sialyl-Lex-BSA. We conclude that neutrophils constitutively express a glycoprotein receptor for GMP-140, which contains sialic acid residues that are essential for function. These findings support the concept that GMP-140 interacts with leukocytes by a lectin-like mechanism

Changes in neutrophil morphology and morphometry following exposure to cigarette smoke.

Science.gov (United States)

Lannan, S.; McLean, A.; Drost, E.; Gillooly, M.; Donaldson, K.; Lamb, D.; MacNee, W.

1992-01-01

Acute cigarette smoking delays neutrophils within the pulmonary circulation in some smokers. Evidence from an in-vitro Micropore filter model of the pulmonary capillaries indicates that this may be due to a smoke induced decrease in cell deformability. In order to determine whether changes in cell shape are associated with the observed decrease in neutrophil deformability following smoke exposure, cell morphology, using scanning electron microscopy, and morphometric measurements, made using transmission electron microscopy, were performed on aliquots of neutrophils harvested from whole blood in non-smoking subjects before and after exposure in vitro to cigarette smoke. Smoke exposure increased the maximum diameter and circumference of neutrophils, without changing their area. There was also a change in the maximum to minimum cell diameter ratio, which indicated that the cells had become less spherical. Scanning electron microscopy showed that smoke exposed cells had developed blebbing of their surface membranes, suggestive of an oxidative injury to the cell membrane rather than the shape changes associated with cell activation. These changes in the morphology and morphometry of smoke exposed neutrophils may contribute to the reduction in cell deformability induced by cigarette smoke. Images Fig. 3 Fig. 4 Fig. 5 PMID:1571278

Pseudomonas aeruginosa ExoU augments neutrophil transepithelial migration.

Science.gov (United States)

Pazos, Michael A; Lanter, Bernard B; Yonker, Lael M; Eaton, Alex D; Pirzai, Waheed; Gronert, Karsten; Bonventre, Joseph V; Hurley, Bryan P

2017-08-01

Excessive neutrophil infiltration of the lungs is a common contributor to immune-related pathology in many pulmonary disease states. In response to pathogenic infection, airway epithelial cells produce hepoxilin A3 (HXA3), initiating neutrophil transepithelial migration. Migrated neutrophils amplify this recruitment by producing a secondary gradient of leukotriene B4 (LTB4). We sought to determine whether this two-step eicosanoid chemoattractant mechanism could be exploited by the pathogen Pseudomonas aeruginosa. ExoU, a P. aeruginosa cytotoxin, exhibits phospholipase A2 (PLA2) activity in eukaryotic hosts, an enzyme critical for generation of certain eicosanoids. Using in vitro and in vivo models of neutrophil transepithelial migration, we evaluated the impact of ExoU expression on eicosanoid generation and function. We conclude that ExoU, by virtue of its PLA2 activity, augments and compensates for endogenous host neutrophil cPLA2α function, leading to enhanced transepithelial migration. This suggests that ExoU expression in P. aeruginosa can circumvent immune regulation at key signaling checkpoints in the neutrophil, resulting in exacerbated neutrophil recruitment.

Pseudomonas aeruginosa ExoU augments neutrophil transepithelial migration.

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Michael A Pazos

2017-08-01

Full Text Available Excessive neutrophil infiltration of the lungs is a common contributor to immune-related pathology in many pulmonary disease states. In response to pathogenic infection, airway epithelial cells produce hepoxilin A3 (HXA3, initiating neutrophil transepithelial migration. Migrated neutrophils amplify this recruitment by producing a secondary gradient of leukotriene B4 (LTB4. We sought to determine whether this two-step eicosanoid chemoattractant mechanism could be exploited by the pathogen Pseudomonas aeruginosa. ExoU, a P. aeruginosa cytotoxin, exhibits phospholipase A2 (PLA2 activity in eukaryotic hosts, an enzyme critical for generation of certain eicosanoids. Using in vitro and in vivo models of neutrophil transepithelial migration, we evaluated the impact of ExoU expression on eicosanoid generation and function. We conclude that ExoU, by virtue of its PLA2 activity, augments and compensates for endogenous host neutrophil cPLA2α function, leading to enhanced transepithelial migration. This suggests that ExoU expression in P. aeruginosa can circumvent immune regulation at key signaling checkpoints in the neutrophil, resulting in exacerbated neutrophil recruitment.

Abnormal gallium scan patterns of the salivary gland in pulmonary sarcoidosis

International Nuclear Information System (INIS)

Mishkin, F.S.; Tanaka, T.T.; Niden, A.H.

1978-01-01

The findings of gallium imaging suggest that parotid abnormalities in sarcoidosis are common. Correlation with lung and mediastinal uptake suggests that this represents an early disease state and that it responds to steroid administration. That the findings after therapy do not simply represent suppression of the uptake mechanism for gallium is supported by objective improvement in pulmonary function as well as symptomatic relief. Salivary gland accumulation of gallium citrate occurred in one third of our control group patients--in those who had collagen disease and presumably either were alcoholic or had infectious parotitis. This may also be seen in lymphoma and after radiation therapy. Although the combination of salivary gland, pulmonary, and hilar concentration of gallium is not specific, in the appropriate clinical setting the pattern may be helpful in suggesting the correct diagnosis

Abnormal gallium scan patterns of the salivary gland in pulmonary sarcoidosis

Energy Technology Data Exchange (ETDEWEB)

Mishkin, F.S.; Tanaka, T.T.; Niden, A.H.

1978-12-01

The findings of gallium imaging suggest that parotid abnormalities in sarcoidosis are common. Correlation with lung and mediastinal uptake suggests that this represents an early disease state and that it responds to steroid administration. That the findings after therapy do not simply represent suppression of the uptake mechanism for gallium is supported by objective improvement in pulmonary function as well as symptomatic relief. Salivary gland accumulation of gallium citrate occurred in one third of our control group patients--in those who had collagen disease and presumably either were alcoholic or had infectious parotitis. This may also be seen in lymphoma and after radiation therapy. Although the combination of salivary gland, pulmonary, and hilar concentration of gallium is not specific, in the appropriate clinical setting the pattern may be helpful in suggesting the correct diagnosis.

Pulmonary dysfunction in advanced liver disease: frequent occurrence of an abnormal diffusing capacity

International Nuclear Information System (INIS)

Hourani, J.M.; Bellamy, P.E.; Tashkin, D.P.; Batra, P.; Simmons, M.S.

1991-01-01

Abnormalities in pulmonary function have been reported in association with chronic liver disease of varied etiology. The aim of this study was to better define the frequency and nature of these abnormalities in patients who were being evaluated for liver transplantation. We performed a battery of pulmonary function tests and chest radiographs in 116 consecutive patients (50 men, 66 women; aged 19 to 70 years, mean 44.6 years) with severe advanced liver disease who were hospitalized specifically for evaluation for possible orthotopic liver transplantation and were able to perform technically satisfactory tests. In 17 patients, quantitative whole-body technetium-99m macroaggregated albumin perfusion scanning was also performed for assessment of possible right-to-left shunting through intrapulmonary vascular dilatations. The most commonly affected test of lung function was the single-breath diffusing capacity for carbon monoxide (DLCO), which was abnormal in 48%, 45%, and 71% of patients who never smoked, former smokers, and current smokers, respectively. Ventilatory restriction was noted in 25% of all patients, airflow obstruction (reduced ratio of forced expiratory volume in 1 second to forced vital expiratory volume in 1 second to forced vital capacity) in only 3%, and a widened alveolar-arterial oxygen gradient in 45%. Diffusion impairment was accompanied by a restrictive defect in only 35% of the patients and by an abnormally widened alveolar-arterial oxygen gradient in 60%. When diffusion impairment was accompanied by an oxygenation defect, it was also associated with a significantly increased right-to-left shunt fraction (mean 24.9%) assessed from quantitative whole-body perfusion imaging

Chest Abnormalities in Juvenile-Onset Mixed Connective Tissue Disease: Assessment with High-Resolution Computed Tomography and Pulmonary Function Tests

International Nuclear Information System (INIS)

Aaloekken, T.M.; Mynarek, G.; Kolbenstvedt, A.; Lilleby, V.; Foerre, Oe.; Soeyseth, V.; Pripp, A.H.; Johansen, B.

2009-01-01

Background: Mixed connective tissue disease (MCTD) is associated with several chest manifestations. Only a few studies have focused on chest manifestations in juvenile-onset MCTD (jMCTD), and the true prevalence of pulmonary abnormalities on high-resolution computed tomography (HRCT) in these patients is unknown. Purpose: To investigate the occurrence of pulmonary abnormalities in jMCTD with particular reference to interstitial lung disease (ILD), and to evaluate a possible association between pulmonary findings and disease-related variables. Material and Methods: Twenty-four childhood-onset MCTD patients with median disease duration of 10.5 years (range 1-21 years) were investigated in a cross-sectional study by means of HRCT, pulmonary function tests (PFT), and clinical assessment. Results: Discrete ILD was identified in six patients (25%). Median extent of ILD was 2.0%, and all except one of the patients had very mild disease in which 5% or less of the parenchyma was affected. The CT features of fibrosis were mainly microcystic and fine intralobular. The most frequently abnormal PFT was carbon monoxide uptake from the lung, which was abnormal in 33% of the patients. PFT and disease duration were not significantly associated with HRCT findings of ILD. Conclusion: The prevalence of ILD in childhood-onset MCTD patients was lower than previously believed. In most of the patients with ILD, the findings were subtle and without clinical correlation. The results suggest a low extent of ILD in childhood-onset MCTD, even after long-term disease duration

α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8.

LENUS (Irish Health Repository)

Bergin, David A

2010-12-01

Hereditary deficiency of the protein α-1 antitrypsin (AAT) causes a chronic lung disease in humans that is characterized by excessive mobilization of neutrophils into the lung. However, the reason for the increased neutrophil burden has not been fully elucidated. In this study we have demonstrated using human neutrophils that serum AAT coordinates both CXCR1- and soluble immune complex (sIC) receptor-mediated chemotaxis by divergent pathways. We demonstrated that glycosylated AAT can bind to IL-8 (a ligand for CXCR1) and that AAT-IL-8 complex formation prevented IL-8 interaction with CXCR1. Second, AAT modulated neutrophil chemotaxis in response to sIC by controlling membrane expression of the glycosylphosphatidylinositol-anchored (GPI-anchored) Fc receptor FcγRIIIb. This process was mediated through inhibition of ADAM-17 enzymatic activity. Neutrophils isolated from clinically stable AAT-deficient patients were characterized by low membrane expression of FcγRIIIb and increased chemotaxis in response to IL-8 and sIC. Treatment of AAT-deficient individuals with AAT augmentation therapy resulted in increased AAT binding to IL-8, increased AAT binding to the neutrophil membrane, decreased FcγRIIIb release from the neutrophil membrane, and normalization of chemotaxis. These results provide new insight into the mechanism underlying the effect of AAT augmentation therapy in the pulmonary disease associated with AAT deficiency.

Use of CFSE staining of borreliae in studies on the interaction between borreliae and human neutrophils

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Hytönen Jukka

2006-10-01

Full Text Available Abstract Background Species of the tick-transmitted spirochete group Borrelia burgdorferi sensu lato (B. burgdorferi cause Lyme borreliosis. Acute borrelial infection of the skin has unusual characteristics with only a mild local inflammatory response suggesting that the interaction between borreliae and the cells of the first-line defence might differ from that of other bacteria. It has been reported that human neutrophils phagocytose motile borreliae through an unconventional mechanism (tube phagocytosis which is not observed with non-motile borreliae. Therefore, it would be of great interest to visualise the bacteria by a method not affecting motility and viability of borreliae to be able to study their interaction with the cells of the innate immunity. Carboxyfluorescein diacetate, succinimidyl ester (CFSE labelling has been previously used for studying the adhesion of labelled bacteria to host cells and the uptake of labelled substrates by various cells using flow cytometry. Results In this study, CFSE was shown to efficiently stain different genospecies of B. burgdorferi without affecting bacterial viability or motility. Use of CFSE staining allowed subsequent quantification of borreliae associated with human neutrophils with flow cytometry and confocal microscopy. As a result, no difference in association between different borrelial genospecies (Borrelia burgdorferi sensu stricto, Borrelia afzelii, Borrelia garinii, or between borreliae and the pyogenic bacterium Streptococcus pyogenes, with neutrophils could be detected. Borrelial virulence, on the other hand, affected association with neutrophils, with significantly higher association of a non-virulent mutant B. burgdorferi sensu stricto strain compared to the parental virulent wild type strain. Conclusion These results suggest that the flow cytometric assay using CFSE labelled borreliae is a valuable tool in the analysis of the interaction between borreliae and human neutrophils. The

Utility of electrocardiogram in the assessment and monitoring of pulmonary hypertension (idiopathic or secondary to pulmonary developmental abnormalities) in patients≤18 years of age.

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Lau, Kelvin C; Frank, David B; Hanna, Brian D; Patel, Akash R

2014-07-15

Electrocardiograms have utility in disease stratification and monitoring in adult pulmonary arterial hypertension (PAH). We examined the electrocardiographic findings that are common in pediatric PAH and assessed for correlation with disease severity and progression. We retrospectively identified patients aged≤18 years followed at a single institution from January 2001 to June 2012 with catheterization-confirmed diagnosis of idiopathic PAH and PAH secondary to pulmonary developmental abnormalities. Patients with an electrocardiography performed within 60 days of catheterization were included. Primary and secondary outcomes are the prevalence of abnormal electrocardiographic findings at the time of catheterization and the association between electrocardiographic and hemodynamic findings and electrocardiographic changes with disease progression on follow-up catheterization, respectively. Of the 100 electrocardiography-catheterization pairs derived from the 46 patients identified, 93% had an electrocardiographic abnormality: 78% had right ventricular hypertrophy (RVH) and 52% had right axis deviation (RAD) for age. In patients with idiopathic PAH, the presence of RVH and RAD correlated with pulmonary vascular resistance and transpulmonary gradient. RAD and RVH on baseline electrocardiogram was associated with an increased risk of disease progression on subsequent catheterization (odds ratio 11.0, 95% confidence interval 1.3 to 96.2, p=0.03) after adjusting for PAH subgroup. The sensitivity, specificity, and positive and negative predictive values of RAD and RVH on baseline electrocardiogram for disease progression were 92%, 48%, 33%, and 95%, respectively. In conclusion, electrocardiographic abnormalities are common in pediatric PAH. RAD and RVH on electrocardiogram were associated with worse hemodynamics, whereas their absence is suggestive of a lack of disease progression. Copyright © 2014 Elsevier Inc. All rights reserved.

The role of phagocytosis, oxidative burst and neutrophil extracellular traps in the interaction between neutrophils and the periodontal pathogen Porphyromonas gingivalis.

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Jayaprakash, K; Demirel, I; Khalaf, H; Bengtsson, T

2015-10-01

Neutrophils are regarded as the sentinel cells of innate immunity and are found in abundance within the gingival crevice. Discovery of neutrophil extracellular traps (NETs) within the gingival pockets prompted us to probe the nature of the interactions of neutrophils with the prominent periopathogen Porphyromonas gingivalis. Some of the noted virulence factors of this Gram-negative anaerobe are gingipains: arginine gingipains (RgpA/B) and lysine gingipain (Kgp). The aim of this study was to evaluate the role of gingipains in phagocytosis, formation of reactive oxygen species, NETs and CXCL8 modulation by using wild-type strains and isogenic gingipain mutants. Confocal imaging showed that gingipain mutants K1A (Kgp) and E8 (RgpA/B) induced extracellular traps in neutrophils, whereas ATCC33277 and W50 were phagocytosed. The viability of both ATCC33277 and W50 dwindled as the result of phagocytosis and could be salvaged by cytochalasin D, and the bacteria released high levels of lipopolysaccharide in the culture supernatant. Porphyromonas gingivalis induced reactive oxygen species and CXCL8 with the most prominent effect being that of the wild-type strain ATCC33277, whereas the other wild-type strain W50 was less effective. Quantitative real-time polymerase chain reaction revealed a significant CXCL8 expression by E8. All the tested P. gingivalis strains increased cytosolic free calcium. In conclusion, phagocytosis is the primary neutrophil response to P. gingivalis, although NETs could play an accessory role in infection control. Although gingipains do not seem to directly regulate phagocytosis, NETs or oxidative burst in neutrophils, their proteolytic properties could modulate the subsequent outcomes such as nutrition acquisition and survival by the bacteria. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Abnormal intraluminal signal within the pulmonary arteries on MR imaging: Differentiation between slow blood flow and thrombus using an ECG-gated; multiphasic: Spin-echo technique

International Nuclear Information System (INIS)

White, R.D.; Higgins, C.B.

1986-01-01

The authors evaluated abnormal MR imaging signal patterns in the pulmonary arteries of 22 patients with pulmonary hypertension (n = 13), pulmonary embolus (n = 4), or both (n = 5). Using multiphasic (five or six phases; 19 patients) or standard (three patients with pulmonary embolus) ECG-gated, double spin-echo techniques, they were able to differentiate between causes of such abnormal signal patterns. The pattern of slow blood flow (abnormal signal in systole with fluctuating distribution during cardiac cycle, and intensity increasing visually from first to second echo) was noted in 89% of patients with pulmonary hypertension alone or in combination with pulmonary embolism, and was characteristic of high systolic pulmonary pressures (12 of 12 patients with pressure > 80 mm Hg, vs. 3 of 5 patients with pressure 55 mm Hg vs. 5 of 7 patients with pressures <55 mm Hg). This pattern was differentiated from that of thrombus (persistent signal with fixed distribution during cardiac cycle, and little to no visible intensity change from first to second echo), which was noted in six of seven proved embolus cases. Thus, gated multiphase MR imaging shows potential for the noninvasive visualization of pulmonary embolus and the differentiation of this entity from the slow blood flow of pulmonary hypertension

Bronchovesicular bundle abnormalities and pathologic basis in diffuse pulmonary diseases on high resolution CT

International Nuclear Information System (INIS)

Nie Yongkang; Ma Daqing; Li Tieyi

2000-01-01

Objective: To investigate CT appearances of the normal and abnormal bronchovesicular bundles (BVB) and their corresponding pathologic basis, and to evaluate the role of these findings in diagnosing diffuse lung diseases. Methods: 6 fresh lungs obtained at autopsy and 8 surgical lung lobe specimens were studied. All lung specimens were inflated and fixed by Heitzman's method. HRCT with 10 mm thickness slice soft X-ray radiography was performed and HRCT-pathologic correlation was done. HRCT images of 100 cases with diffuse pulmonary disease were analyzed. Results: Thickened BVB with coarse margin and distorted structure correlated pathologically with peri-bronchovesicular pulmonary parenchyma inflammation and fibrosis, as well as peri-bronchovesicular interstitial disorder. Abnormalities of centrilobular BVB were recognizable by an increase in prominence of centrilobular structure on HRCT. In pathology, there were centrilobular peri-bronchovesicular dust induced granuloma in coal-miner's pneumoconiosis and centrilobular lymphangitis dilatation and filling with tumor cell in lymphangitis carcinomatosis. Increased centrilobular branching structure correlated pathologically with the presence of dilate intra-lobular bronchioles, inflammatory bronchiolar wall thickening, intraluminal secretions, and peri-bronchiolar inflammation. In 80 patients with predominant pulmonary interstitial diseases, thickened BVB with coarse margin or distortion were common in patients with pulmonary fibrosis. Nodular bronchovesicular bundle thickening were seen in sarcoidosis, lymphangitis carcinomatosis, and lymphoma. These were demonstrated in 8 of 20 sarcoidosis, 6 of 8 lymphangitis carcinomatosis , 3 of 5 lymphoma, and 2 of 15 coal-miner's pneumoconiosis. Increased centrilobular branching structures were seen in 14 of 20 patients with predominant bronchial diseases. Conclusion: Authors can limit the differential diagnostic range of diffuse lung diseases according to the appearances of BVB

Neutrophil extracellular traps in patients with pulmonary tuberculosis

NARCIS (Netherlands)

van der Meer, Anne Jan; Zeerleder, Sacha; Blok, Dana C.; Kager, Liesbeth M.; Lede, Ivar O.; Rahman, Wahid; Afroz, Rumana; Ghose, Aniruddha; Visser, Caroline E.; Zahed, Abu Shahed Md; Husain, Md Anwar; Alam, Khan Mashrequl; Barua, Pravat Chandra; Hassan, Mahtabuddin; Tayab, Md Abu; Dondorp, Arjen M.; van der Poll, Tom

2017-01-01

Tuberculosis is a devastating infectious disease causing many deaths worldwide. Recent investigations have implicated neutrophil extracellular traps (NETs) in the host response to tuberculosis. The aim of the current study was to obtain evidence for NETs release in the circulation during human

111Indium-labeled neutrophil migration into the lungs of bleomycin-treated rabbits assessed noninvasively by external scintigraphy

International Nuclear Information System (INIS)

Haslett, C.; Shen, A.S.; Feldsien, D.C.; Allen, D.; Henson, P.M.; Cherniack, R.M.

1989-01-01

Factors controlling neutrophil migration into the lung are poorly understood, but their identification is important for our understanding of the pathogenesis of inflammatory lung diseases. Pulmonary inflammation is difficult to quantify, and neutrophils in tissues and BAL may not accurately represent cell migration. In this study, intravenously delivered pulses of rabbit neutrophils labeled with Indium-111 (111In-neutrophils) were used to monitor neutrophil migration into the lungs. Radioactivity quantified in the lung region of interest (ROI) of external gamma camera scintigrams recorded 24 h after intravenous 111In-neutrophil injection accurately reflected the actual neutrophil-associated lung tissue radioactivity. ROI radioactivity at 24 h also correlated closely with the percent of 111In-neutrophils that had migrated into lavageable air spaces, and this parameter therefore provided an index of total lung 111In-neutrophil migration. Using 24-h ROI radioactivity and percent of injected 111In-neutrophils recovered in BAL at 24 h as indices of neutrophil migration into the lung, it was found that intratracheal saline caused only a transient neutrophil migration, whereas 10 U/kg intratracheal bleomycin induced migration that persisted for as long as 3 wk. 111In-neutrophil migration into the lung, assessed by external scintigraphy, correlated with total neutrophils quantified in histologic sections (r = 0.71, p = 0.006). The data suggest that this approach will be valuable in investigating mechanisms controlling neutrophil migration in lung inflammation, and that 111In-neutrophil scintigraphy may provide a noninvasive index of total lung neutrophil load that might be useful in staging inflammation in patchy diseases such as idiopathic pulmonary fibrosis

A novel scoring system to measure radiographic abnormalities and related spirometric values in cured pulmonary tuberculosis.

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Renata Báez-Saldaña

Full Text Available BACKGROUND: Despite chemotherapy, patients with cured pulmonary tuberculosis may result in lung functional impairment. OBJECTIVE: To evaluate a novel scoring system based on the degree of radiographic abnormalities and related spirometric values in patients with cured pulmonary tuberculosis. METHODS: One hundred and twenty seven patients with cured pulmonary tuberculosis were prospectively enrolled in a referral hospital specializing in respiratory diseases. Spirometry was performed and the extent of radiographic abnormalities was evaluated twice by each of two readers to generate a novel quantitative score. Scoring reproducibility was analyzed by the intra-class correlation coefficient (ICC and the Bland-Altman method. Multiple linear regression models were performed to assess the association of the extent of radiographic abnormalities with spirometric values. RESULTS: The intra-observer agreement for scoring of radiographic abnormalities (SRA showed an ICC of 0.81 (CI:95%, 0.67-0.95 and 0.78 (CI:95%, 0.65-0.92, for reader 1 and 2, respectively. Inter-observer reproducibility for the first measurement was 0.83 (CI:95%, 0.71-0.95, and for the second measurement was 0.74 (CI:95%, 0.58-0.90. The Bland-Altman analysis of the intra-observer agreement showed a mean bias of 0.87% and -0.55% and an inter-observer agreement of -0.35% and -1.78%, indicating a minor average systematic variability. After adjustment for age, gender, height, smoking status, pack-years of smoking, and degree of dyspnea, the scoring degree of radiographic abnormalities was significantly and negatively associated with absolute and percent predicted values of FVC: -0.07 (CI:95%, -0.01 to -0.04; -2.48 (CI:95%, -3.45 to -1.50; and FEV1 -0.07 (CI:95%, -0.10 to -0.05; -2.92 (CI:95%, -3.87 to -1.97 respectively, in the patients studied. CONCLUSION: The extent of radiographic abnormalities, as evaluated through our novel scoring system, was inversely associated with spirometric values

A Novel Scoring System to Measure Radiographic Abnormalities and Related Spirometric Values in Cured Pulmonary Tuberculosis

Science.gov (United States)

Báez-Saldaña, Renata; López-Arteaga, Yesenia; Bizarrón-Muro, Alma; Ferreira-Guerrero, Elizabeth; Ferreyra-Reyes, Leticia; Delgado-Sánchez, Guadalupe; Cruz-Hervert, Luis Pablo; Mongua-Rodríguez, Norma; García-García, Lourdes

2013-01-01

Background Despite chemotherapy, patients with cured pulmonary tuberculosis may result in lung functional impairment. Objective To evaluate a novel scoring system based on the degree of radiographic abnormalities and related spirometric values in patients with cured pulmonary tuberculosis. Methods One hundred and twenty seven patients with cured pulmonary tuberculosis were prospectively enrolled in a referral hospital specializing in respiratory diseases. Spirometry was performed and the extent of radiographic abnormalities was evaluated twice by each of two readers to generate a novel quantitative score. Scoring reproducibility was analyzed by the intra-class correlation coefficient (ICC) and the Bland-Altman method. Multiple linear regression models were performed to assess the association of the extent of radiographic abnormalities with spirometric values. Results The intra-observer agreement for scoring of radiographic abnormalities (SRA) showed an ICC of 0.81 (CI:95%, 0.67–0.95) and 0.78 (CI:95%, 0.65–0.92), for reader 1 and 2, respectively. Inter-observer reproducibility for the first measurement was 0.83 (CI:95%, 0.71–0.95), and for the second measurement was 0.74 (CI:95%, 0.58–0.90). The Bland-Altman analysis of the intra-observer agreement showed a mean bias of 0.87% and -0.55% and an inter-observer agreement of -0.35% and -1.78%, indicating a minor average systematic variability. After adjustment for age, gender, height, smoking status, pack-years of smoking, and degree of dyspnea, the scoring degree of radiographic abnormalities was significantly and negatively associated with absolute and percent predicted values of FVC: -0.07 (CI:95%, -0.01 to -0.04); -2.48 (CI:95%, -3.45 to -1.50); and FEV1 -0.07 (CI:95%, -0.10 to -0.05); -2.92 (CI:95%, -3.87 to -1.97) respectively, in the patients studied. Conclusion The extent of radiographic abnormalities, as evaluated through our novel scoring system, was inversely associated with spirometric values, and

Nasobronchial allergy and pulmonary function abnormalities among coir workers of Alappuzha.

Science.gov (United States)

Panicker, Venugopal; Karunakaran, Raseela; Ravindran, C

2010-07-01

Coir is a commercially important natural fiber obtained from the coconut husk. Coir can be woven into strong twine or rope, and is used for padding mattresses, upholstery, etc. Coir industry provides a major share of occupation to the natives of Alappuzha district of Kerala State. It has been noticed earlier that there is increased incidence of nasobronchial allergy among the population involved in this industry. This study was aimed at recognizing the symptomatology and pulmonary functional impairment among symptomatic coir workers. All coir workers who attended our institute over a period of three years were included in the study. Detailed occupational history was taken; symptom profile was studied in detail, clinical examination and pulmonary function tests conducted. Among the 624 symptomatic coir workers selected for this purpose, 64 patients had purely nasal symptoms, while 560 had symptoms of nasobronchial allergy. 357 patients had reversible obstruction on PFT, while 121 had only small airway obstruction. We conclude that coir work induced nasobronchial allergy and pulmonary function abnormalities. In absence of CT scan and bronchial challenge testing it may be inappropriate to label coir work as occupational hazard. However the present study may be used as thought provoking study to initiate further understanding.

CXCR1 regulates pulmonary anti-Pseudomonas host defense

Science.gov (United States)

Carevic, M.; Öz, H.; Fuchs, K.; Laval, J.; Schroth, C.; Frey, N.; Hector, A.; Bilich, T.; Haug, M.; Schmidt, A.; Autenrieth, S. E.; Bucher, K.; Beer-Hammer, S.; Gaggar, A.; Kneilling, M.; Benarafa, C.; Gao, J.; Murphy, P.; Schwarz, S.; Moepps, B.; Hartl, D.

2016-01-01

Pseudomonas aeruginosa is a key opportunistic pathogen causing disease in cystic fibrosis (CF) and other lung diseases such as chronic obstructive pulmonary disease (COPD). However, the pulmonary host defense mechanisms regulating anti-Pseudomonas aeruginosa immunity remain incompletely understood. Here we demonstrate, by studying an airway Pseudomonas aeruginosa infection model, in vivo bioluminescence imaging, neutrophil effector responses and human airway samples, that the chemokine receptor CXCR1 regulates pulmonary host defense against Pseudomonas aeruginosa. Mechanistically, CXCR1 regulated anti-Pseudomonas neutrophil responses through modulation of reactive oxygen species and interference with toll-like receptor 5 expression. These studies define CXCR1 as a novel non-canonical chemokine receptor that regulates pulmonary anti-Pseudomonas host defense with broad implications for CF, COPD and other infectious lung diseases. PMID:26950764

Bone marrow transplantation for an infant with neutrophil dysfunction

Energy Technology Data Exchange (ETDEWEB)

Camitta, B M; Quesenberry, P J; Parkman, R; Boxer, L A; Stossel, T P; Cassady, J R; Rappeport, J M; Nathan, D G [Harvard Medical School, Boston, Mass. (USA); Tufts Univ., Boston, Mass. (USA). School of Medicine)

1977-01-01

A child with severe neutrophil dysfunction and intractable infections received bone marrow transplants from histocompatible siblings. After a first transplant preceded by cyclophosphamide (CY), antithymocyte serum (ATS) and procarbazine (PCB) preconditioning, there was no evidence for engraftment and autologous marrow function rapidly returned. Cell mediated lysis showed no evidence of patient sensitization against the marrow donor suggesting that graft rejection did not cause the transplant failure. A second transplant was performed utilizing another matched sibling donor. Total body irradiation was added to CY, ATS, and PCB for preconditioning after in vitro studies of the colony forming capacity (CFUsub(c)) of the patient's marrow cells showed normal sensitivity to radiation. Full engraftment ensued with correction of granulocyte function abnormalities. The patient eventually died of intractable pulmonary disease. Experience with this child suggests that cyclophosphamide alone may be insufficient preparation for marrow transplantation in some patients with non-neoplastic hematologic disorders. Experimental and clinical data supporting this contention are reviewed.

The effect of cigarette smoking on neutrophil kinetics in human lungs [see comments

International Nuclear Information System (INIS)

MacNee, W.; Wiggs, B.; Belzberg, A.S.; Hogg, J.C.

1989-01-01

Neutrophils may play a part in the pathogenesis of the centrilobular emphysema associated with cigarette smoking. The capillary bed of the lungs concentrates neutrophils approximately 100-fold with respect to erythrocytes, producing a large pool of marginated cells. We examined the effect of cigarette smoking on the kinetics of this pool of cells, using 99mTc-labeled erythrocytes to measure regional blood velocity and 111In-labeled neutrophils to measure the removal of neutrophils during the first passage through the pulmonary circulation, their subsequent washout from the lungs, and the effect of local blood velocity on the number of neutrophils retained in each lung region. We observed no difference in these measurements between subjects who had never smoked (n = 6) and smokers who did not smoke during the study (n = 12). However, subjects who did smoke during the study (n = 12) had a significantly slower rate of washout of radiolabeled neutrophils from the lung (0.08 +/- 0.04 of the total per minute, as compared with 0.13 +/- 0.06 in smokers who did not smoke during the experiment and 0.14 +/- 0.08 in non-smokers) (P = 0.02). We also observed an increase in the regional retention of labeled neutrophils with respect to blood velocity in 5 of the 12 subjects who smoked during the study, but in none of the other subjects. We conclude that the presence of cigarette smoke in the lungs of some subjects increases the local concentration of neutrophils, and suggest that the lesions that characterize emphysema may be a result of the destruction of lung tissue by neutrophils that remain within pulmonary microvessels

Innate Defense against Influenza A Virus: Activity of Human Neutrophil Defensins and Interactions of Defensins with Surfactant Protein D

DEFF Research Database (Denmark)

Hartshorn, Kevan L.; White, Mitchell R.; Tecle, Tesfaldet

2006-01-01

Surfactant protein D (SP-D) plays important roles in innate host defense against influenza A virus (IAV) infection, in part by modifying interactions with neutrophils. Human neutrophil defensins (HNPs) inhibit infectivity of enveloped viruses, including IAV. Our goal in this study was to characte......Surfactant protein D (SP-D) plays important roles in innate host defense against influenza A virus (IAV) infection, in part by modifying interactions with neutrophils. Human neutrophil defensins (HNPs) inhibit infectivity of enveloped viruses, including IAV. Our goal in this study...... was to characterize antiviral interactions between SP-D and HNPs. Recombinant and/or natural forms of SP-D and related collectins and HNPs were tested for antiviral activity against two different strains of IAV. HNPs 1 and 2 did not inhibit viral hemagglutination activity, but they interfered...... with the hemagglutination-inhibiting activity of SP-D. HNPs had significant viral neutralizing activity against divergent IAV strains. However, the HNPs generally had competitive effects when combined with SP-D in assays using an SP-D-sensitive IAV strain. In contrast, cooperative antiviral effects were noted in some...

Innate Defense against Influenza A Virus: Activity of Human Neutrophil Defensins and Interactions of Defensins with Surfactant Protein D

DEFF Research Database (Denmark)

Hartshorn, Kevan L.; White, Mitchell R.; Tecle, Tesfaldet

2006-01-01

Surfactant protein D (SP-D) plays important roles in innate host defense against influenza A virus (IAV) infection, in part by modifying interactions with neutrophils. Human neutrophil defensins (HNPs) inhibit infectivity of enveloped viruses, including IAV. Our goal in this study...

Right pulmonary aplasia, aberrant left pulmonary artery, and bronchopulmonary sequestration with an esophageal bronchus

International Nuclear Information System (INIS)

Lee, Peter; McCauley, Roy; Westra, Sjirk; Baba, Timothy

2006-01-01

Pulmonary aplasia and bronchopulmonary foregut malformations in which a patent communication between the foregut and the pulmonary system is present are rare congenital abnormalities. Pulmonary aplasia associated with a pulmonary sling is an even rarer abnormality. We report a unique case of right pulmonary aplasia, aberrant left pulmonary artery, and bronchopulmonary sequestration with an esophageal bronchus diagnosed by multidetector helical CT. (orig.)

Abnormal pulmonary vein drainage in upper right lobe associated with double aortic arch : magnetic resonance angiography

International Nuclear Information System (INIS)

Busto, M.; Dolz, J.L.; Capdevilla, A.; Castanon, M.; Mulet, J.

1997-01-01

We present the magnetic resonance (MR) and magnetic resonance angiography (MRA) findings in a case of abnormal pulmonary vein drainage from upper right lobe to superior vena cava, associated with double aortic arch, in a six-month-old boy. (Author) 9 refs

Metabolomic changes in patients with chronic obstructive pulmonary disease with abnormal Savda syndrome.

Science.gov (United States)

Xu, Wei-Fang; Upur, Halmurat; Wu, Yu-Hua; Mamtimin, Batur; Yang, Jian; Ga, Yong-Juan; You, Li

2015-02-01

The aim of this study was to determine the metabolic biomarkers for abnormal Savda syndrome in patients with chronic obstructive pulmonary disease (COPD). Based on Traditional Uyghur Medicine (TUM) theory, a total of 103 patients with COPD were classified into abnormal Savda and non-abnormal Savda syndrome groups and 52 healthy volunteers acted as the control group. Blood samples from the three groups were analyzed using nuclear magnetic resonance (NMR) spectroscopy combined with orthogonal projection to latent structure-discriminant analysis. NMR tests showed that the regional distributions of the patients with COPD with abnormal Savda syndrome, those with non-abnormal Savda syndrome and the control group were completely separate (P>0.05). The patients with COPD with abnormal Savda syndrome exhibited relatively low levels of amino acids, glycoproteins and unsaturated lipids (PAbnormal Savda syndrome was one of the main types of syndrome among the patients with COPD; increased age, a longer duration of illness and a higher disease severity were characteristic of this type of syndrome. In addition, the present study provided biochemical evidence for the TUM theory-based classification of patients with COPD; these biomarkers can be used in the clinic for the diagnosis of COPD with abnormal Savda syndrome. The study also demonstrated that the plasma metabolic disorder in patients with COPD with abnormal Savda syndrome was more serious than that in the control and COPD with non-abnormal Savda syndrome groups. The plasma metabolic disorder was also associated with a low immune function of the body and endocrine and energy metabolism disorders.

Effects of acrolein on leukotriene biosynthesis in human neutrophils.

Science.gov (United States)

Berry, Karin A Zemski; Henson, Peter M; Murphy, Robert C

2008-12-01

Acrolein is a toxic, highly reactive alpha,beta-unsaturated aldehyde that is present in high concentrations in cigarette smoke. In the current study, the effect of acrolein on eicosanoid synthesis in stimulated human neutrophils was examined. Eicosanoid synthesis in neutrophils was initiated by priming with granulocyte-macrophage colony-stimulating factor (GM-CSF) and subsequent stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP) and 5-lipoxygenase (5-LO) products in addition to small amounts of cyclooxygenase (COX) products were detected using LC/MS/MS. A dose-dependent decrease in the formation of 5-LO products was observed in GM-CSF/fMLP-stimulated neutrophils when acrolein (0-50 microM) was present with almost complete inhibition at > or = 25 microM acrolein. The production of COX products was not affected by acrolein in these cells. The effect of acrolein was examined on key parts of the eicosanoid pathway, such as arachidonic acid release, intracellular calcium ion concentration, and adenosine production. In addition, the direct effect of acrolein on 5-LO enzymatic activity was probed using a recombinant enzyme. Some of these factors were affected by acrolein but did not completely explain the almost complete inhibition of 5-LO product formation in GM-CSF/fMLP-treated cells with acrolein. In addition, the effect of acrolein on different stimuli that initiate the 5-LO pathway [platelet-activating factor (PAF)/fMLP, GM-CSF/PAF, opsonized zymosan, and A23187] was examined. Acrolein had no significant effect on the leukotriene production in neutrophils stimulated with PAF/fMLP, GM-CSF/ PAF, or OPZ. Additionally, 50% inhibition of the 5-LO pathway was observed in A23187-stimulated neutrophils. Our results suggest that acrolein has a profound effect on the 5-LO pathway in neutrophils, which may have implications in disease states, such as chronic obstructive pulmonary disease and other pulmonary disease, where both activated neutrophils and acrolein are

[Progressive cutaneous and pulmonary lesions without infectious etiology: two cases reports of sweet syndrome with pulmonary involvement].

Science.gov (United States)

Lang, Noémie; Vernez, Maxime; Vollenweider, Peter; Pasche, Antoine

2014-09-17

Sweet syndrome is a non infectious febrile disease with a neutrophilic infiltrate of dermis. Extracutaneous involvement can occur. We report two cases of Sweet syndrome with cutaneous and pulmonary involvement and give a short review of the literature of pulmonary involvement in Sweet syndrome.

Targeting Neutrophil Protease-Mediated Degradation of Tsp-1 to Induce Metastatic Dormancy

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-16-1-0615 TITLE: Targeting Neutrophil Protease-Mediated Degradation of Tsp-1 to Induce Metastatic Dormancy PRINCIPAL...29 Sep 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeting Neutrophil Protease-Mediated Degradation of Tsp-1 to Induce Metastatic Dormancy...infection or cigarette smoke enhanced pulmonary metastasis from breast cancer in humans and mice. Similarly, autoimmune arthritis, characterized by

Efficacy and safety of inhaled carbon monoxide during pulmonary inflammation in mice.

Directory of Open Access Journals (Sweden)

Michael R Wilson

2010-07-01

Full Text Available Pulmonary inflammation is a major contributor to morbidity in a variety of respiratory disorders, but treatment options are limited. Here we investigate the efficacy, safety and mechanism of action of low dose inhaled carbon monoxide (CO using a mouse model of lipopolysaccharide (LPS-induced pulmonary inflammation.Mice were exposed to 0-500 ppm inhaled CO for periods of up to 24 hours prior to and following intratracheal instillation of 10 ng LPS. Animals were sacrificed and assessed for intraalveolar neutrophil influx and cytokine levels, flow cytometric determination of neutrophil number and activation in blood, lung and lavage fluid samples, or neutrophil mobilisation from bone marrow.When administered for 24 hours both before and after LPS, inhaled CO of 100 ppm or more reduced intraalveolar neutrophil infiltration by 40-50%, although doses above 100 ppm were associated with either high carboxyhemoglobin, weight loss or reduced physical activity. This anti-inflammatory effect of CO did not require pre-exposure before induction of injury. 100 ppm CO exposure attenuated neutrophil sequestration within the pulmonary vasculature as well as LPS-induced neutrophilia at 6 hours after LPS, likely due to abrogation of neutrophil mobilisation from bone marrow. In contrast to such apparently beneficial effects, 100 ppm inhaled CO induced an increase in pulmonary barrier permeability as determined by lavage fluid protein content and translocation of labelled albumin from blood to the alveolar space.Overall, these data confirm some protective role for inhaled CO during pulmonary inflammation, although this required a dose that produced carboxyhemoglobin values close to potentially toxic levels for humans, and increased lung permeability.

[Tracheobronchial and pulmonary parenchymatous congenital abnormalities requiring surgical treatment in adults].

Science.gov (United States)

Mordant, P; De Dominicis, F; Berna, P; Riquet, M

2012-04-01

Most tracheobronchial and parenchymatous congenital abnormalities of the respiratory system are diagnosed in early life. However, some lesions may be initially silent and diagnosed only in adulthood. These cases included congenital abnormalies of the tracheobronchial tract (tracheal and/or bronchial stenosis, bronchogenic cysts, bronchial atresia, oesotracheal fistula, oesobronchial fistula, and tracheal diverticulum), and lung parenchyma itself (pulmonary sequestration, congenital cystic adenomatoïd malformation, lobar emphysema, lobar or lung hypoplasia). To avoid dreadful complications, these rare cases deserve surgical management, and must be known by chest physicians and surgeons. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Quantitation of abnormal Ga-67 uptake in idiopathic pulmonary fibrosis

International Nuclear Information System (INIS)

O'Donnell, J.K.; Golish, J.A.; Cordasco, E.M.; Go, R.T.; Feiglin, D.H.; MacIntyre, W.J.

1987-01-01

Gallium-67 is useful in differentiating active pneumonitis from the underlying changes of diffuse idiopathic pulmonary fibrosis (IPF), especially when advanced disease precludes detection of subtle radiographic changes. Diffuse Ga-67 uptake, however, is often difficult to estimate. For 22 patients with IPF, they employed both emission tomography (SPECT) of the thorax and a modified Ga-67 index technique for digital planar images basing lung regions on Tc-99m MAA outlines and background on thigh soft-tissue activity. The degree of abnormal Ga-67 uptake measured by these techniques correlated closely with disease activity by all clinical criteria. Repeat studies for six patients after steroid therapy paralleled clinical response (4+/2-)

Endothelial cell SHP-2 negatively regulates neutrophil adhesion and promotes transmigration by enhancing ICAM-1-VE-cadherin interaction.

Science.gov (United States)

Yan, Meiping; Zhang, Xinhua; Chen, Ao; Gu, Wei; Liu, Jie; Ren, Xiaojiao; Zhang, Jianping; Wu, Xiaoxiong; Place, Aaron T; Minshall, Richard D; Liu, Guoquan

2017-11-01

Intercellular adhesion molecule-1 (ICAM-1) mediates the firm adhesion of leukocytes to endothelial cells and initiates subsequent signaling that promotes their transendothelial migration (TEM). Vascular endothelial (VE)-cadherin plays a critical role in endothelial cell-cell adhesion, thereby controlling endothelial permeability and leukocyte transmigration. This study aimed to determine the molecular signaling events that originate from the ICAM-1-mediated firm adhesion of neutrophils that regulate VE-cadherin's role as a negative regulator of leukocyte transmigration. We observed that ICAM-1 interacts with Src homology domain 2-containing phosphatase-2 (SHP-2), and SHP-2 down-regulation via silencing of small interfering RNA in endothelial cells enhanced neutrophil adhesion to endothelial cells but inhibited neutrophil transmigration. We also found that VE-cadherin associated with the ICAM-1-SHP-2 complex. Moreover, whereas the activation of ICAM-1 leads to VE-cadherin dissociation from ICAM-1 and VE-cadherin association with actin, SHP-2 down-regulation prevented ICAM-1-VE-cadherin association and promoted VE-cadherin-actin association. Furthermore, SHP-2 down-regulation in vivo promoted LPS-induced neutrophil recruitment in mouse lung but delayed neutrophil extravasation. These results suggest that SHP-2- via association with ICAM-1-mediates ICAM-1-induced Src activation and modulates VE-cadherin switching association with ICAM-1 or actin, thereby negatively regulating neutrophil adhesion to endothelial cells and enhancing their TEM.-Yan, M., Zhang, X., Chen, A., Gu, W., Liu, J., Ren, X., Zhang, J., Wu, X., Place, A. T., Minshall, R. D., Liu, G. Endothelial cell SHP-2 negatively regulates neutrophil adhesion and promotes transmigration by enhancing ICAM-1-VE-cadherin interaction. © FASEB.

The fibrinogen cleavage product Aα-Val360, a specific marker of neutrophil elastase activity in vivo

DEFF Research Database (Denmark)

Carter, Richard I; Mumford, Richard A; Treonze, Kelly M

2011-01-01

Alpha-1-antitrypsin (A1AT) deficiency is the only recognised genetic risk factor for chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality worldwide. Since A1AT is the major inhibitor of neutrophil elastase (NE), this enzyme has become widely implicated in the p......Alpha-1-antitrypsin (A1AT) deficiency is the only recognised genetic risk factor for chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality worldwide. Since A1AT is the major inhibitor of neutrophil elastase (NE), this enzyme has become widely implicated...

18F-fluoro-2-deoxyglucose PET informs neutrophil accumulation and activation in lipopolysaccharide-induced acute lung injury.

Science.gov (United States)

Rodrigues, Rosana S; Bozza, Fernando A; Hanrahan, Christopher J; Wang, Li-Ming; Wu, Qi; Hoffman, John M; Zimmerman, Guy A; Morton, Kathryn A

2017-05-01

Molecular imaging of the earliest events related to the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) could facilitate therapeutic development and patient management. We previously reported that 18 F-fluoro-2-deoxyglucose ( 18 F-FDG) PET identifies ALI/ARDS prior to radiographic abnormalities. The purpose of this study was to establish the time courses of 18 F-FDG uptake, edema and neutrophil recruitment in an endotoxin-induced acute lung injury model and to examine molecular events required for 14 C-2DG uptake in activated neutrophils. Lung uptake of 18 F-FDG was measured by PET in control male Sprague Dawley rats and at 2, 6 and 24h following the intraperitoneal injection of 10mg/kg LPS. Lung edema (attenuation) was measured by microCT. Neutrophil influx into the lungs was measured by myeloperoxidase assay. Control and activated human donor neutrophils were compared for uptake of 14 C-2DG, transcription and content of hexokinase and GLUT isoforms and for hexokinase (HK) activity. Significant uptake of 18 F-FDG occurred by 2h following LPS, and progressively increased to 24h. Lung uptake of 18 F-FDG preceded increased CT attenuation (lung edema). Myeloperoxidase activity in the lungs, supporting neutrophil influx, paralleled 18 F-FDG uptake. Activation of isolated human neutrophils resulted in increased uptake of 14 C-2DG, expression of GLUT 3 and GLUT 4 and expression and increased HK1 activity. Systemic endotoxin-induced ALI results in very early and progressive uptake of 18 F-FDG, parallels neutrophil accumulation and occurs earlier than lung injury edema. Activated neutrophils show increased uptake of 14 C-2DG, expression of specific GLUT3, GLUT4 and HK1 protein and HK activity. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: 18 F-FDG pulmonary uptake is an early biomarker of neutrophil recruitment in ALI and is associated with specific molecular events that mediate 14 C-2DG uptake in activated neutrophils. 18 F

Distinct Trypanosoma cruzi isolates induce activation and apoptosis of human neutrophils.

Directory of Open Access Journals (Sweden)

Luísa M D Magalhães

Full Text Available Neutrophils are critical players in the first line of defense against pathogens and in the activation of subsequent cellular responses. We aimed to determine the effects of the interaction of Trypanosoma cruzi with human neutrophils, using isolates of the two major discrete type units (DTUs associated with Chagas' disease in Latin America (clone Col1.7G2 and Y strain, DTU I and II, respectively. Thus, we used CFSE-stained trypomastigotes to measure neutrophil-T. cruzi interaction, neutrophil activation, cytokine expression and death, after infection with Col1.7G2 and Y strain. Our results show that the frequency of CFSE+ neutrophils, indicative of interaction, and CFSE intensity on a cell-per-cell basis were similar when comparing Col1.7G2 and Y strains. Interaction with T. cruzi increased neutrophil activation, as measured by CD282, CD284, TNF and IL-12 expression, although at different levels between the two strains. No change in IL-10 expression was observed after interaction of neutrophils with either strain. We observed that exposure to Y and Col1.7G2 caused marked neutrophil death. This was specific to neutrophils, since interaction of either strain with monocytes did not cause death. Our further analysis showed that neutrophil death was a result of apoptosis, which was associated with an upregulation of TNF-receptor, TNF and FasLigand, but not of Fas. Induction of TNF-associated neutrophil apoptosis by the different T. cruzi isolates may act as an effective common mechanism to decrease the host's immune response and favor parasite survival.

Pulmonary venous abnormalities encountered on pre ...

African Journals Online (AJOL)

Multidetector computed tomography (MDCT) elegantly renders pulmonary venous anatomy. With increasing numbers of radiofrequency ablation procedures being performed, there is now a greater emphasis on pre-procedure imaging to delineate this anatomy. Pulmonary venous mapping studies can be performed with or ...

Phrenic Nerve Conduction Abnormalities Correlate with Diaphragmatic Descent in Chronic Obstructive Pulmonary Disease.

Science.gov (United States)

El-Tantawi, Gihan A Younis; Imam, Mohamed H; Morsi, Tamer S

2015-01-01

Diaphragmatic weakness in chronic obstructive pulmonary disease (COPD) is ascribed to hyperinflation-induced diaphragm shortening as well as impairment in cellular and subcellular structures. Although phrenic neuropathy is known to cause diaphragmatic weakness, phrenic neuropathy is rarely considered in COPD. This work aimed at assessing phrenic nerve conduction in COPD and its relation to radiographic hyperinflation and pulmonary function. Forty COPD patients were evaluated. Radiographic parameters of lung hyperinflation were measured on postero-anterior and lateral chest x-ray films. Flow volume loop parameters were obtained from all patients. Motor conduction study of the phrenic nerves was performed and potentials were recorded over the xiphoid process and the ipsilateral 7th intercostal space. Twenty-seven healthy subjects were enrolled as controls. Parameters of phrenic nerve conduction differed significantly in patients compared to controls. Phrenic nerve abnormalities were detected in 17 patients (42.5%). Electrophysiological measures correlated with diaphragmatic angle of depression on lateral view films and with lung height on postero-anterior films. They did not correlate with the flow volume loop data or disease severity score. Phrenic nerve conduction abnormality is an appreciated finding in COPD. Nerve stretching associated with diaphragmatic descent can be a suggested mechanism for nerve lesion. The presence of phrenic neuropathy may be an additional contributing factor to diaphragmatic dysfunction in COPD patients.

Intracellular Secretory Leukoprotease Inhibitor Modulates Inositol 1,4,5-Triphosphate Generation and Exerts an Anti-Inflammatory Effect on Neutrophils of Individuals with Cystic Fibrosis and Chronic Obstructive Pulmonary Disease

Directory of Open Access Journals (Sweden)

Emer P. Reeves

2013-01-01

Full Text Available Secretory leukoprotease inhibitor (SLPI is an anti-inflammatory protein present in respiratory secretions. Whilst epithelial cell SLPI is extensively studied, neutrophil associated SLPI is poorly characterised. Neutrophil function including chemotaxis and degranulation of proteolytic enzymes involves changes in cytosolic calcium (Ca2+ levels which is mediated by production of inositol 1,4,5-triphosphate (IP3 in response to G-protein-coupled receptor (GPCR stimuli. The aim of this study was to investigate the intracellular function of SLPI and the mechanism-based modulation of neutrophil function by this antiprotease. Neutrophils were isolated from healthy controls (n=10, individuals with cystic fibrosis (CF (n=5 or chronic obstructive pulmonary disease (COPD (n=5. Recombinant human SLPI significantly inhibited fMet-Leu-Phe (fMLP and interleukin(IL-8 induced neutrophil chemotaxis (P<0.05 and decreased degranulation of matrix metalloprotease-9 (MMP-9, hCAP-18, and myeloperoxidase (MPO (P<0.05. The mechanism of inhibition involved modulation of cytosolic IP3 production and downstream Ca2+ flux. The described attenuation of Ca2+ flux was overcome by inclusion of exogenous IP3 in electropermeabilized cells. Inhibition of IP3 generation and Ca2+ flux by SLPI may represent a novel anti-inflammatory mechanism, thus strengthening the attractiveness of SLPI as a potential therapeutic molecule in inflammatory airway disease associated with excessive neutrophil influx including CF, non-CF bronchiectasis, and COPD.

Omega-3 Fatty acids and inflammation: novel interactions reveal a new step in neutrophil recruitment.

Directory of Open Access Journals (Sweden)

Samantha P Tull

2009-08-01

Full Text Available Inflammation is a physiological response to tissue trauma or infection, but leukocytes, which are the effector cells of the inflammatory process, have powerful tissue remodelling capabilities. Thus, to ensure their precise localisation, passage of leukocytes from the blood into inflamed tissue is tightly regulated. Recruitment of blood borne neutrophils to the tissue stroma occurs during early inflammation. In this process, peptide agonists of the chemokine family are assumed to provide a chemotactic stimulus capable of supporting the migration of neutrophils across vascular endothelial cells, through the basement membrane of the vessel wall, and out into the tissue stroma. Here, we show that, although an initial chemokine stimulus is essential for the recruitment of flowing neutrophils by endothelial cells stimulated with the inflammatory cytokine tumour necrosis factor-alpha, transit of the endothelial monolayer is regulated by an additional and downstream stimulus. This signal is supplied by the metabolism of the omega-6-polyunsaturated fatty acid (n-6-PUFA, arachidonic acid, into the eicosanoid prostaglandin-D(2 (PGD(2 by cyclooxygenase (COX enzymes. This new step in the neutrophil recruitment process was revealed when the dietary n-3-PUFA, eicosapentaenoic acid (EPA, was utilised as an alternative substrate for COX enzymes, leading to the generation of PGD(3. This alternative series eicosanoid inhibited the migration of neutrophils across endothelial cells by antagonising the PGD(2 receptor. Here, we describe a new step in the neutrophil recruitment process that relies upon a lipid-mediated signal to regulate the migration of neutrophils across endothelial cells. PGD(2 signalling is subordinate to the chemokine-mediated activation of neutrophils, but without the sequential delivery of this signal, neutrophils fail to penetrate the endothelial cell monolayer. Importantly, the ability of the dietary n-3-PUFA, EPA, to inhibit this process not

In vivo characterization of neutrophil extracellular traps in various organs of a murine sepsis model.

Directory of Open Access Journals (Sweden)

Koji Tanaka

Full Text Available Neutrophil extracellular traps (NETs represent extracellular microbial trapping and killing. Recently, it has been implicated in thrombogenesis, autoimmune disease, and cancer progression. The aim of this study was to characterize NETs in various organs of a murine sepsis model in vivo and to investigate their associations with platelets, leukocytes, or vascular endothelium. NETs were classified as two distinct forms; cell-free NETs that were released away from neutrophils and anchored NETs that were anchored to neutrophils. Circulating cell-free NETs were characterized as fragmented or cotton-like structures, while anchored NETs were characterized as linear, reticular, membranous, or spot-like structures. In septic mice, both anchored and cell-free NETs were significantly increased in postcapillary venules of the cecum and hepatic sinusoids with increased leukocyte-endothelial interactions. NETs were also observed in both alveolar space and pulmonary capillaries of the lung. The interactions of NETs with platelet aggregates, leukocyte-platelet aggregates or vascular endothelium of arterioles and venules were observed in the microcirculation of septic mice. Microvessel occlusions which may be caused by platelet aggregates or leukocyte-platelet aggregates and heterogeneously decreased blood flow were also observed in septic mice. NETs appeared to be associated with the formation of platelet aggregates or leukocyte-platelet aggregates. These observational findings may suggest the adverse effect of intravascular NETs on the host during a sepsis.

Inhibition of chlorine-induced pulmonary inflammation and edema by mometasone and budesonide

Energy Technology Data Exchange (ETDEWEB)

Chen, Jing; Mo, Yiqun; Schlueter, Connie F.; Hoyle, Gary W., E-mail: Gary.Hoyle@louisville.edu

2013-10-15

Chlorine gas is a widely used industrial compound that is highly toxic by inhalation and is considered a chemical threat agent. Inhalation of high levels of chlorine results in acute lung injury characterized by pneumonitis, pulmonary edema, and decrements in lung function. Because inflammatory processes can promote damage in the injured lung, anti-inflammatory therapy may be of potential benefit for treating chemical-induced acute lung injury. We previously developed a chlorine inhalation model in which mice develop epithelial injury, neutrophilic inflammation, pulmonary edema, and impaired pulmonary function. This model was used to evaluate nine corticosteroids for the ability to inhibit chlorine-induced neutrophilic inflammation. Two of the most potent corticosteroids in this assay, mometasone and budesonide, were investigated further. Mometasone or budesonide administered intraperitoneally 1 h after chlorine inhalation caused a dose-dependent inhibition of neutrophil influx in lung tissue sections and in the number of neutrophils in lung lavage fluid. Budesonide, but not mometasone, reduced the levels of the neutrophil attractant CXCL1 in lavage fluid 6 h after exposure. Mometasone or budesonide also significantly inhibited pulmonary edema assessed 1 day after chlorine exposure. Chlorine inhalation resulted in airway hyperreactivity to inhaled methacholine, but neither mometasone nor budesonide significantly affected this parameter. The results suggest that mometasone and budesonide may represent potential treatments for chemical-induced lung injury. - Highlights: • Chlorine causes lung injury when inhaled and is considered a chemical threat agent. • Corticosteroids may inhibit lung injury through their anti-inflammatory actions. • Corticosteroids inhibited chlorine-induced pneumonitis and pulmonary edema. • Mometasone and budesonide are potential rescue treatments for chlorine lung injury.

The role of the endothelium in asthma and chronic obstructive pulmonary disease (COPD).

Science.gov (United States)

Green, Clara E; Turner, Alice M

2017-01-18

COPD and asthma are important chronic inflammatory disorders with a high associated morbidity. Much research has concentrated on the role of inflammatory cells, such as the neutrophil, in these diseases, but relatively little focus has been given to the endothelial tissue, through which inflammatory cells must transmigrate to reach the lung parenchyma and cause damage. There is evidence that there is an abnormal amount of endothelial tissue in COPD and asthma and that this tissue and its' progenitor cells behave in a dysfunctional manner. This article reviews the evidence of the involvement of pulmonary endothelium in COPD and asthma and potential treatment options for this.

Clinical impact of abnormal FDG uptake in pulmonary nodules detected by CT in patients with only history of non-lung cancers

International Nuclear Information System (INIS)

Wong, C.O.; Nunez, R.; Welsh, R.J.; Chmielewski, G.W.; Hill, E.A.; Hill, J.C.; Ravikrishnan, K.P.; Darlene Fink-Bennett; Dworkin, H.J.

2001-01-01

Objective: The aim is to assess the clinical impact of positive FDG uptake in single (SPN) or multiple (MPN) pulmonary nodules detected by CT in patients with known past history of non-lung cancers (but no known lung cancers). Materials and Methods: Twenty-eight sequential patients with non-lung cancers (15 breast, 8 colon, 5 prostate) referred for evaluation of SPN or MPN by PET over a period of two years were included. F-18 FDG PET images, covering chest and upper abdomen, were interpreted blindly and then correlated with CT findings for the precise location of abnormal FDG uptake in the chest. Results: There was a significant number of abnormal FDG uptake in both SPN or MPN. Positive abnormal uptake suggestive of malignancy was found in 25% of patients in the form of SPN and 39% of patients in the form of MPN (p<0.03). Positive cases in the pattern of multiple foci of pulmonary uptake were attributed to metastatic disease. Otherwise positive cases were followed by tissue diagnosis and/or surgical attention. The negative cases were followed clinically. Of the 11 positive cases of MPN, 2 patients (18%) showed only abnormal FDG uptake in just one of the nodules, which was later confirmed at surgery to be a primary cancer of lung in both patients. Conclusion: These results suggest that PET scan would be just as useful in patients with SPN and known non-lung cancers as other patients with no history of any cancers. Not all patients with non-lung cancer and MPN have pulmonary metastasis by PET criteria. PET may single out a primary lung malignancy in patients with non-lung cancer and MPN. PET has thus great clinical impact in these patients with pulmonary nodules and known non-lung cancers as the management would otherwise be completely different in situations revealed by the study

18F-fluoro-2-deoxyglucose PET informs neutrophil accumulation and activation in lipopolysaccharide-induced acute lung injury genetic algorithm

International Nuclear Information System (INIS)

Rodrigues, Rosana S.; Bozza, Fernando A.; Hanrahan, Christopher J.; Wang, Li-Ming; Wu, Qi; Hoffman, John M.; Zimmerman, Guy A.; Morton, Kathryn A.

2017-01-01

Introduction: Molecular imaging of the earliest events related to the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) could facilitate therapeutic development and patient management. We previously reported that 18 F-fluoro-2-deoxyglucose ( 18 F-FDG) PET identifies ALI/ARDS prior to radiographic abnormalities. The purpose of this study was to establish the time courses of 18 F-FDG uptake, edema and neutrophil recruitment in an endotoxin-induced acute lung injury model and to examine molecular events required for 14 C-2DG uptake in activated neutrophils. Methods: Lung uptake of 18 F-FDG was measured by PET in control male Sprague Dawley rats and at 2, 6 and 24 h following the intraperitoneal injection of 10 mg/kg LPS. Lung edema (attenuation) was measured by microCT. Neutrophil influx into the lungs was measured by myeloperoxidase assay. Control and activated human donor neutrophils were compared for uptake of 14 C-2DG, transcription and content of hexokinase and GLUT isoforms and for hexokinase (HK) activity. Results: Significant uptake of 18 F-FDG occurred by 2 h following LPS, and progressively increased to 24 h. Lung uptake of 18 F-FDG preceded increased CT attenuation (lung edema). Myeloperoxidase activity in the lungs, supporting neutrophil influx, paralleled 18 F-FDG uptake. Activation of isolated human neutrophils resulted in increased uptake of 14 C-2DG, expression of GLUT 3 and GLUT 4 and expression and increased HK1 activity. Conclusion: Systemic endotoxin-induced ALI results in very early and progressive uptake of 18 F-FDG, parallels neutrophil accumulation and occurs earlier than lung injury edema. Activated neutrophils show increased uptake of 14 C-2DG, expression of specific GLUT3, GLUT4 and HK1 protein and HK activity. Advances in knowledge and implications for patient care: 18 F-FDG pulmonary uptake is an early biomarker of neutrophil recruitment in ALI and is associated with specific molecular events that mediate 14

Assessment of the efficiency of Brentuximab Vedotin in patients with pulmonary Hodgkin Lymphoma by the mean of neutrophil to lymphocyte ratio

Directory of Open Access Journals (Sweden)

Gokhan Erdem

2018-04-01

Full Text Available Background: Lung involvement, an uncommon initial presentation of Hodgkin Lymphoma (HL, may appear as primary or secondary pulmonary HL. Although the combination of Brentuximab vedotin (BV with AVD is suggested as an alternative treatment to combinations including bleomycin for patients with pulmonary involvement. The efficacy and adverse effects of BV have not been specialized on pulmonary HL. There is insufficient data about neutrophil to lymphocyte ratio (NLR of cases treated with BV. We performed this retrospective study to evaluate the efficacy and toxicity of BV in patients with pulmonary HL and to demonstrate the prognostic role of NLR in patients treated with BV. Methods: Data of 10 CD 30 (+ HL patients who treated with BV between years 2011–2016 were analyzed retrospectively. Relapsed cases after autologous bone marrow transplantation (ABMT and/or resistant cases to at least two lines of chemotherapy, and treated with BV were included in the study. Results: Patients underwent a median of 8.5 cycles BV. Eight patients (80% achieved an objective response including 2 of them (20% with complete response and six of them (60% with a partial response at the end of the 3rd cycle. At a median follow-up of 16.8 months, median progression-free survival for all patients was 6 months and 3 patients died because of progression. BV, as a single agent, revealed well response in HL cases with pulmonary involvement and other clinical types. No pulmonary toxicity has been occurred due to BV. NLR was found to be o good indicator of prognosis and mortality in pulmonary HL patients and other HL patients. While NLR was not influenced by BV, it can be suggested as an easy prognostic marker in patients treated with BV. Conclusion: BV may be used as a bridge therapy to the next curative treatment in order to obtain minimal tumor burden in pulmonary HL patients, and NLR can be used as a prognostic marker in these patients. We believe that this study contributes

Candida albicans escapes from mouse neutrophils

DEFF Research Database (Denmark)

Ermert, David; Niemiec, Maria J; Röhm, Marc

2013-01-01

is the most widely used model organism. Neutrophils are essential immune cells to prevent opportunistic mycoses. To explore potential differences between the rodent infection model and the human host, we compared the interactions of C. albicans with neutrophil granulocytes from mice and humans. We revealed...

Activated prostaglandin D2 receptors on macrophages enhance neutrophil recruitment into the lung

Science.gov (United States)

Jandl, Katharina; Stacher, Elvira; Bálint, Zoltán; Sturm, Eva Maria; Maric, Jovana; Peinhaupt, Miriam; Luschnig, Petra; Aringer, Ida; Fauland, Alexander; Konya, Viktoria; Dahlen, Sven-Erik; Wheelock, Craig E.; Kratky, Dagmar; Olschewski, Andrea; Marsche, Gunther; Schuligoi, Rufina; Heinemann, Akos

2016-01-01

Background Prostaglandin (PG) D2 is an early-phase mediator in inflammation, but its action and the roles of the 2 D-type prostanoid receptors (DPs) DP1 and DP2 (also called chemoattractant receptor–homologous molecule expressed on TH2 cells) in regulating macrophages have not been elucidated to date. Objective We investigated the role of PGD2 receptors on primary human macrophages, as well as primary murine lung macrophages, and their ability to influence neutrophil action in vitro and in vivo. Methods In vitro studies, including migration, Ca2+ flux, and cytokine secretion, were conducted with primary human monocyte-derived macrophages and neutrophils and freshly isolated murine alveolar and pulmonary interstitial macrophages. In vivo pulmonary inflammation was assessed in male BALB/c mice. Results Activation of DP1, DP2, or both receptors on human macrophages induced strong intracellular Ca2+ flux, cytokine release, and migration of macrophages. In a murine model of LPS-induced pulmonary inflammation, activation of each PGD2 receptor resulted in aggravated airway neutrophilia, tissue myeloperoxidase activity, cytokine contents, and decreased lung compliance. Selective depletion of alveolar macrophages abolished the PGD2-enhanced inflammatory response. Activation of PGD2 receptors on human macrophages enhanced the migratory capacity and prolonged the survival of neutrophils in vitro. In human lung tissue specimens both DP1 and DP2 receptors were located on alveolar macrophages along with hematopoietic PGD synthase, the rate-limiting enzyme of PGD2 synthesis. Conclusion For the first time, our results show that PGD2 markedly augments disease activity through its ability to enhance the proinflammatory actions of macrophages and subsequent neutrophil activation. PMID:26792210

Ring down artefacts on abdominal sonography to predict pulmonary abnormalities in the emergency department.

Science.gov (United States)

Tsai, C-L; Wang, H-P; Lien, W-C; Chen, C-C; Lai, T-I; Chen, W-J

2005-10-01

Ring down artefacts are sometimes found when emergency physicians perform abdominal ultrasound to differentiate between various abdominal problems. We describe a patient who presented with right upper quadrant abdominal pain and whose ultrasound examination showed ring down artefacts posterior to the right hemidiaphragm, which led to the eventual diagnosis of pneumonia. Ring down artefacts on ultrasound may be used to predict pulmonary abnormalities. Awareness of this sonographic finding may assist in accurate diagnosis and administration of appropriate treatment without delay.

CT pulmonary angiography of adult pulmonary vascular diseases: Technical considerations and interpretive pitfalls

International Nuclear Information System (INIS)

Taslakian, Bedros; Latson, Larry A.; Truong, Mylene T.; Aaltonen, Eric; Shiau, Maria C.; Girvin, Francis; Alpert, Jeffrey B.; Wickstrom, Maj; Ko, Jane P.

2016-01-01

Highlights: • CTPA plays a key role in the evaluation of pulmonary vascular diseases. • Improvements in CT technology have improved visualization of pulmonary arteries. • Knowledge of the technical pitfalls is essential for accurate diagnosis. • Dual energy CT imaging enables parenchymal iodine evaluation. • An awareness of the entities affecting the pulmonary arteries is important. - Abstract: Computed tomography pulmonary angiography (CTPA) has become the primary imaging modality for evaluating the pulmonary arteries. Although pulmonary embolism is the primary indication for CTPA, various pulmonary vascular abnormalities can be detected in adults. Knowledge of these disease entities and understanding technical pitfalls that can occur when performing CTPA are essential to enable accurate diagnosis and allow timely management. This review will cover a spectrum of acquired abnormalities including pulmonary embolism due to thrombus and foreign bodies, primary and metastatic tumor involving the pulmonary arteries, pulmonary hypertension, as well as pulmonary artery aneurysms and stenoses. Additionally, methods to overcome technical pitfalls and interventional treatment options will be addressed.

CT pulmonary angiography of adult pulmonary vascular diseases: Technical considerations and interpretive pitfalls

Energy Technology Data Exchange (ETDEWEB)

Taslakian, Bedros, E-mail: bedros.taslakian@nyumc.org [Department of Radiology, NYU Langone Medical Center, NY (United States); Latson, Larry A., E-mail: larry.latson@nyumc.org [Department of Radiology, NYU Langone Medical Center, NY (United States); Truong, Mylene T., E-mail: mtruong@mdanderson.org [Department of Radiology, University of Texas, MD Anderson Cancer Center, TX (United States); Aaltonen, Eric, E-mail: Eric.Aaltonen@nyumc.org [Department of Radiology, NYU Langone Medical Center, NY (United States); Shiau, Maria C., E-mail: Maria.Shiau@nyumc.org [Department of Radiology, NYU Langone Medical Center, NY (United States); Girvin, Francis, E-mail: Francis.Girvin@nyumc.org [Department of Radiology, NYU Langone Medical Center, NY (United States); Alpert, Jeffrey B., E-mail: Jeffrey.Alpert@nyumc.org [Department of Radiology, NYU Langone Medical Center, NY (United States); Wickstrom, Maj, E-mail: Maj.Wickstrom@nyumc.org [Department of Radiology, NYU Langone Medical Center, NY (United States); Ko, Jane P., E-mail: Jane.Ko@nyumc.org [Department of Radiology, NYU Langone Medical Center, NY (United States)

2016-11-15

Highlights: • CTPA plays a key role in the evaluation of pulmonary vascular diseases. • Improvements in CT technology have improved visualization of pulmonary arteries. • Knowledge of the technical pitfalls is essential for accurate diagnosis. • Dual energy CT imaging enables parenchymal iodine evaluation. • An awareness of the entities affecting the pulmonary arteries is important. - Abstract: Computed tomography pulmonary angiography (CTPA) has become the primary imaging modality for evaluating the pulmonary arteries. Although pulmonary embolism is the primary indication for CTPA, various pulmonary vascular abnormalities can be detected in adults. Knowledge of these disease entities and understanding technical pitfalls that can occur when performing CTPA are essential to enable accurate diagnosis and allow timely management. This review will cover a spectrum of acquired abnormalities including pulmonary embolism due to thrombus and foreign bodies, primary and metastatic tumor involving the pulmonary arteries, pulmonary hypertension, as well as pulmonary artery aneurysms and stenoses. Additionally, methods to overcome technical pitfalls and interventional treatment options will be addressed.

Accuracy of pulmonary auscultation to detect abnormal respiratory mechanics: a cross-sectional diagnostic study.

Science.gov (United States)

Xavier, Glaciele Nascimento; Duarte, Antonio Carlos Magalhães; Melo-Silva, César Augusto; dos Santos, Carlos Eduardo Ventura Gaio; Amado, Veronica Moreira

2014-12-01

Pulmonary auscultation is a method used in clinical practice for the evaluation and detection of abnormalities relating to the respiratory system. This method has limitations, as it depends on the experience and hearing acuity of the examiner to determine adventitious sounds. In this context, it's important to analyze whether there is a correlation between auscultation of lung sounds and the behavior of the respiratory mechanical properties of the respiratory system in patients with immediate postoperative cardiac surgery. Copyright © 2014 Elsevier Ltd. All rights reserved.

Physiologic assessment before video thoracoscopic resection for lung cancer in patients with abnormal pulmonary function.

Science.gov (United States)

Benattia, Amira; Debeaumont, David; Guyader, Vincent; Tardif, Catherine; Peillon, Christophe; Cuvelier, Antoine; Baste, Jean-Marc

2016-06-01

Impaired respiratory function may prevent curative surgery for patients with non-small cell lung cancer (NSCLC). Video-assisted thoracoscopic surgery (VATS) reduces postoperative morbility-mortality and could change preoperative assessment practices and therapeutic decisions. We evaluated the relation between preoperative pulmonary function tests and the occurrence of postoperative complications after VATS pulmonary resection in patients with abnormal pulmonary function. We included 106 consecutive patients with ≤80% predicted value of presurgical expiratory volume in one second (FEV1) and/or diffusing capacity of carbon monoxide (DLCO) and who underwent VATS pulmonary resection for NSCLC from a prospective surgical database. Patients (64±9.5 years) had lobectomy (n=91), segmentectomy (n=7), bilobectomy (n=4), or pneumonectomy (n=4). FEV1 and DLCO preoperative averages were 68%±21% and 60%±18%. Operative mortality was 1.89%. Only FEV1 was predictive of postoperative complications [odds ratio (OR), 0.96; 95% confidence interval (CI), 0.926-0.991, P=0.016], but there was no determinable threshold. Twenty-five patients underwent incremental exercise testing. Desaturations during exercise (OR, 0.462; 95% CI, 0.191-0.878, P=0.039) and heart rate (HR) response (OR, 0.953; 95% CI, 0.895-0.993, P=0.05) were associated with postoperative complications. FEV1 but not DLCO was a significant predictor of pulmonary complications after VATS pulmonary resection despite a low rate of severe morbidity. Incremental exercise testing seems more discriminating. Further investigation is required in a larger patient population to change current pre-operative threshold in a new era of minimally invasive surgery.

Measurement of regional pulmonary blood volume in patients with increased pulmonary blood flow or pulmonary arterial hypertension

International Nuclear Information System (INIS)

Wollmer, P.; Rozcovek, A.; Rhodes, C.G.; Allan, R.M.; Maseri, A.

1984-01-01

The effects of chronic increase in pulmonary blood flow and chronic pulmonary hypertension on regional pulmonary blood volume was measured in two groups of patients. One group of patients had intracardiac, left-to-right shunts without appreciable pulmonary hypertension, and the other consisted of patients with Eisenmenger's syndrome or primary pulmonary hypertension, i.e. patients with normal or reduced blood flow and severe pulmonary hypertension. A technique based on positron tomography was used to measure lung density (by transmission scanning) and regional pulmonary blood volume (after inhalation of /sup 11/CO). The distribution of pulmonary blood volume was more uniform in patients with chronic increase in pulmonary blood flow than in normal subjects. There were also indications of an absolute increase in intrapulmonary blood volume by about 15%. In patients with chronic pulmonary arterial hypertension, the distribution of pulmonary blood volume was also abnormally uniform. There was, however, no indication that overall intrapulmonary blood volume was substantially different from normal subjects. The abnormally uniform distribution of pulmonary blood volume can be explained by recruitment and/or dilatation of vascular beds. Intrapulmonary blood volume appears to be increased in patients with intracardiac, left-to-right shunts. With the development of pulmonary hypertension, intrapulmonary blood volume falls, which may be explained by reactive changes in the vasculature and/or obliteration of capillaries

Correlative magnetic resonance imaging in the evaluation of aortic and pulmonary artery abnormalities

Energy Technology Data Exchange (ETDEWEB)

Risius, B.; O' Donnell, J.K.; Geisinger, M.A.; Zelch, M.G.; George, C.R.; Graor, R.A.; Moodie, D.S.

1985-05-01

Magnetic resonance imaging (MRI) yields excellent quality images of the cardiovascular system utilizing the inherent natural contrast between flowing blood and the surrounding anatomic structures. To evaluate the clinical usefulness of MRI in the noninvasive diagnosis of large vessel disorders, the authors have performed MRI on 40 pts with either aortic or pulmonary artery abnormalities (18 thoracic or abdominal aortic aneurysms, 8 aorto-occlusive disease, 6 dissecting aneurysms, 4 Marfan's syndrome, 2 pulmonary artery aneurysms 1 pulmonary artery occlusion, 1 aortic coarctation). Images were obtained in the transverse, coronal and sagital body planes utilizing a 0.6T superconductive magnet. Cardiac and/or respiratory gating was employed in most cases. Correlation was made for all studies with conventional or digital subtraction angiography, computed tomography, and/or ultrasound. The diagnostic information obtained by MRI equaled or exceeded that obtained by other imaging techniques except for the few cases where cardiac arrhythmias precluded adequate gated acquisition. All aneurysms and their relationships to adjacent structures were readily demonstrated as were the presence or absence of mural thrombi and dissecting intimal flaps. Angiographically demonstrated atherosclerotic plaques and luminal stenoses were seen by MRI in all patients without arrhythmias. The authors concluded that MRI is a powerful noninvasive diagnostic aid in the delineation of large vessel disorders, especially where knowledge of anatomic interrelationships can guide surgical or other interventional planning.

Early detection of interstitial pneumonia by WXGa-citrate scintigraphy. Cases of abnormal pulmonary WXGa uptake with normal chest radiographs

Energy Technology Data Exchange (ETDEWEB)

Ito, Shinsaku; Mikami, Riichiro; Ryujin, Yoshitada

1985-04-01

In this paper we report our recent experience indicating usefulness of WXGa-citrate scintigraphy in 4 cases with inflammatory pulmonary diseases. These cases showed abnormal pulmonary WXGa uptake with normal chest radiographs. The first case with malignant lymphoma and the second one with lung cancer suffered from pulmonary infection following secondary immuno-insufficiency due to radiotherapy and chemotherapy. Pneumocystis carinii was suspected as causative agent in the first case, and gram negative bacilli in the second case. The third case with lung cancer developed radiation pneumonia after radiotherapy. The fourth case with acute bronchitis developed drug induced interstitial pneumonia presumably due to minocycline administration. It is concluded that WXGa-citrate scintigraphy is more sensitive for early detection of interstitial pneumonia than routine chest radiography.

Neutrophil migration under normal and sepsis conditions.

Science.gov (United States)

Lerman, Yelena V; Kim, Minsoo

2015-01-01

Neutrophil migration is critical for pathogen clearance and host survival during severe sepsis. Interaction of neutrophil adhesion receptors with ligands on endothelial cells results in firm adhesion of the circulating neutrophils, followed by neutrophil activation and directed migration to sites of infection through the basement membrane and interstitial extracellular matrix. Proteolytic enzymes and reactive oxygen species are produced and released by neutrophils in response to a variety of inflammatory stimuli. Although these mediators are important for host defense, they also promote tissue damage. Excessive neutrophil migration during the early stages of sepsis may lead to an exaggerated inflammatory response with associated tissue damage and subsequent organ dysfunction. On the other hand, dysregulation of migration and insufficient migratory response that occurs during the latter stages of severe sepsis contributes to neutrophils' inability to contain and control infection and impaired wound healing. This review discusses the major steps and associated molecules involved in the balance of neutrophil trafficking, the precise regulation of which during sepsis spells life or death for the host.

Pulmonary interstitial glycogenosis in the setting of lung growth abnormality: radiographic and pathologic correlation

Energy Technology Data Exchange (ETDEWEB)

Castillo, Monette; Vade, Aruna; Lim-Dunham, Jennifer Eden [Loyola University Health System, Department of Radiology, Maywood, IL (United States); Masuda, Emi [Henry Ford Hospital, Department of Radiology, Detroit, MI (United States); Massarani-Wafai, Rasan [Loyola University Health System, Department of Pathology, Maywood, IL (United States)

2010-09-15

Pulmonary interstitial glycogenosis (PIG) is a rare pediatric interstitial lung disease. We report a case of a term boy presenting with tachypnea at birth requiring supplemental oxygen. Chest radiographs followed by high-resolution CT (HRCT) demonstrated hyperinflation and diffuse interstitial markings interspersed with multiple cystic spaces. An open lung biopsy demonstrated a minor component of PIG superimposed upon poor alveolarization. PIG in the setting of lung growth abnormality might be more common than previously described. Additionally, radiographic findings associated with most pediatric interstitial lung diseases are nonspecific, and histopathologic correlation is essential for diagnosis. (orig.)

Tumor-Associated Macrophages and Neutrophils in Tumor Microenvironment

Directory of Open Access Journals (Sweden)

Jaehong Kim

2016-01-01

Full Text Available Distinct tumor microenvironment forms in each progression step of cancer and has diverse capacities to induce both adverse and beneficial consequences for tumorigenesis. It is now known that immune cells can be activated to favor tumor growth and progression, most probably influenced by the tumor microenvironment. Tumor-associated macrophages and tumor-associated neutrophils can exert protumoral functions, enhancing tumor cell invasion and metastasis, angiogenesis, and extracellular matrix remodeling, while inhibiting the antitumoral immune surveillance. Considering that neutrophils in inflammatory environments recruit macrophages and that recruited macrophages affect neutrophil functions, there may be various degrees of interaction between tumor-associated macrophages and tumor-associated neutrophils. Platelets also play an important role in the recruitment and regulation of monocytic and granulocytic cells in the tumor tissues, suggesting that platelet function may be essential for generation of tumor-associated macrophages and tumor-associated neutrophils. In this review, we will explore the biology of tumor-associated macrophages and tumor-associated neutrophils and their possible interactions in the tumor microenvironment. Special attention will be given to the recruitment and activation of these tumor-associated cells and to the roles they play in maintenance of the tumor microenvironment and progression of tumors.

Targeting prolyl endopeptidase with valproic acid as a potential modulator of neutrophilic inflammation

NARCIS (Netherlands)

Abdul Roda, Mojtaba; Sadik, Mariam; Gaggar, Amit; Hardison, Matthew T; Jablonsky, Michael J; Braber, Saskia; Blalock, James Edwin; Redegeld, Frank A; Folkerts, Gert; Jackson, Patricia L

2014-01-01

A novel neutrophil chemoattractant derived from collagen, proline-glycine-proline (PGP), has been recently characterized in chronic obstructive pulmonary disease (COPD). This peptide is derived via the proteolytic activity of matrix metalloproteases (MMP's)-8/9 and PE, enzymes produced by

Imaging neutrophil migration dynamics using micro-optical coherence tomography (Conference Presentation)

Science.gov (United States)

Chu, Kengyeh K.; Yonker, Lael; Som, Avira; Pazos, Michael; Kusek, Mark E.; Hurley, Bryan P.; Tearney, Guillermo J.

2016-03-01

Neutrophils are immune cells that undergo chemotaxis, detecting and migrating towards a chemical signal gradient. Neutrophils actively migrate across epithelial boundaries, interacting with the epithelium to selectively permit passage without compromising the epithelial barrier. In many inflammatory disorders, excessive neutrophil migration can cause damage to the epithelium itself. The signaling pathways and mechanisms that facilitate trans-epithelial migration are not fully characterized. Our laboratory has developed micro-optical coherence tomography (μOCT), which has 2 μm lateral resolution and 1 μm axial resolution. As a high-resolution native contrast modality, μOCT can directly visualize individual neutrophils as they interact with a cell layer cultured on a transwell filter. A chemoattractant can be applied to the apical side of inverted monolayer, and human neutrophils placed in the basolateral compartment, while μOCT captures 3D images of the chemotaxis. μOCT images can also generate quantitative metrics of migration volume to study the dependence of chemotaxis on monolayer cell type, chemoattractant type, and disease state of the neutrophils. For example, a disease known as leukocyte adhesion deficiency (LAD) can be simulated by treating neutrophils with antibodies that interfere with the CD18 receptor, a facilitator of trans-epithelial migration. We conducted a migration study of anti-CD18 treated and control neutrophils using T84 intestinal epithelium as a barrier. After one hour, μOCT time-lapse imaging indicated a strong difference in the fraction of neutrophils that remain attached to the epithelium after migration (0.67 +/- 0.12 attached anti-CD18 neutrophils, 0.23 +/- 0.08 attached control neutrophils, n = 6, p < 0.05), as well as a modest but non-significant decrease in total migration volume for treated neutrophils. We can now integrate μOCT-derived migration metrics with simultaneously acquired measurements of transepithelial electrical

Interactive lung segmentation in abnormal human and animal chest CT scans

International Nuclear Information System (INIS)

Kockelkorn, Thessa T. J. P.; Viergever, Max A.; Schaefer-Prokop, Cornelia M.; Bozovic, Gracijela; Muñoz-Barrutia, Arrate; Rikxoort, Eva M. van; Brown, Matthew S.; Jong, Pim A. de; Ginneken, Bram van

2014-01-01

Purpose: Many medical image analysis systems require segmentation of the structures of interest as a first step. For scans with gross pathology, automatic segmentation methods may fail. The authors’ aim is to develop a versatile, fast, and reliable interactive system to segment anatomical structures. In this study, this system was used for segmenting lungs in challenging thoracic computed tomography (CT) scans. Methods: In volumetric thoracic CT scans, the chest is segmented and divided into 3D volumes of interest (VOIs), containing voxels with similar densities. These VOIs are automatically labeled as either lung tissue or nonlung tissue. The automatic labeling results can be corrected using an interactive or a supervised interactive approach. When using the supervised interactive system, the user is shown the classification results per slice, whereupon he/she can adjust incorrect labels. The system is retrained continuously, taking the corrections and approvals of the user into account. In this way, the system learns to make a better distinction between lung tissue and nonlung tissue. When using the interactive framework without supervised learning, the user corrects all incorrectly labeled VOIs manually. Both interactive segmentation tools were tested on 32 volumetric CT scans of pigs, mice and humans, containing pulmonary abnormalities. Results: On average, supervised interactive lung segmentation took under 9 min of user interaction. Algorithm computing time was 2 min on average, but can easily be reduced. On average, 2.0% of all VOIs in a scan had to be relabeled. Lung segmentation using the interactive segmentation method took on average 13 min and involved relabeling 3.0% of all VOIs on average. The resulting segmentations correspond well to manual delineations of eight axial slices per scan, with an average Dice similarity coefficient of 0.933. Conclusions: The authors have developed two fast and reliable methods for interactive lung segmentation in

G-CSF maintains controlled neutrophil mobilization during acute inflammation by negatively regulating CXCR2 signaling

Science.gov (United States)

Bajrami, Besnik; Zhu, Haiyan; Zhang, Yu C.

2016-01-01

Cytokine-induced neutrophil mobilization from the bone marrow to circulation is a critical event in acute inflammation, but how it is accurately controlled remains poorly understood. In this study, we report that CXCR2 ligands are responsible for rapid neutrophil mobilization during early-stage acute inflammation. Nevertheless, although serum CXCR2 ligand concentrations increased during inflammation, neutrophil mobilization slowed after an initial acute fast phase, suggesting a suppression of neutrophil response to CXCR2 ligands after the acute phase. We demonstrate that granulocyte colony-stimulating factor (G-CSF), usually considered a prototypical neutrophil-mobilizing cytokine, was expressed later in the acute inflammatory response and unexpectedly impeded CXCR2-induced neutrophil mobilization by negatively regulating CXCR2-mediated intracellular signaling. Blocking G-CSF in vivo paradoxically elevated peripheral blood neutrophil counts in mice injected intraperitoneally with Escherichia coli and sequestered large numbers of neutrophils in the lungs, leading to sterile pulmonary inflammation. In a lipopolysaccharide-induced acute lung injury model, the homeostatic imbalance caused by G-CSF blockade enhanced neutrophil accumulation, edema, and inflammation in the lungs and ultimately led to significant lung damage. Thus, physiologically produced G-CSF not only acts as a neutrophil mobilizer at the relatively late stage of acute inflammation, but also prevents exaggerated neutrophil mobilization and the associated inflammation-induced tissue damage during early-phase infection and inflammation. PMID:27551153

Pathogenic Bacterium Acinetobacter baumannii Inhibits the Formation of Neutrophil Extracellular Traps by Suppressing Neutrophil Adhesion

Science.gov (United States)

Kamoshida, Go; Kikuchi-Ueda, Takane; Nishida, Satoshi; Tansho-Nagakawa, Shigeru; Ubagai, Tsuneyuki; Ono, Yasuo

2018-01-01

Hospital-acquired infections caused by Acinetobacter baumannii have become problematic because of high rates of drug resistance. A. baumannii is usually harmless, but it may cause infectious diseases in an immunocompromised host. Although neutrophils are the key players of the initial immune response against bacterial infection, their interactions with A. baumannii remain largely unknown. A new biological defense mechanism, termed neutrophil extracellular traps (NETs), has been attracting attention. NETs play a critical role in bacterial killing by bacterial trapping and inactivation. Many pathogenic bacteria have been reported to induce NET formation, while an inhibitory effect on NET formation is rarely reported. In the present study, to assess the inhibition of NET formation by A. baumannii, bacteria and human neutrophils were cocultured in the presence of phorbol 12-myristate 13-acetate (PMA), and NET formation was evaluated. NETs were rarely observed during the coculture despite neutrophil PMA stimulation. Furthermore, A. baumannii prolonged the lifespan of neutrophils by inhibiting NET formation. The inhibition of NET formation by other bacteria was also investigated. The inhibitory effect was only apparent with live A. baumannii cells. Finally, to elucidate the mechanism of this inhibition, neutrophil adhesion was examined. A. baumannii suppressed the adhesion ability of neutrophils, thereby inhibiting PMA-induced NET formation. This suppression of cell adhesion was partly due to suppression of the surface expression of CD11a in neutrophils. The current study constitutes the first report on the inhibition of NET formation by a pathogenic bacterium, A. baumannii, and prolonging the neutrophil lifespan. This novel pathogenicity to inhibit NET formation, thereby escaping host immune responses might contribute to a development of new treatment strategies for A. baumannii infections. PMID:29467765

Pathogenic Bacterium Acinetobacter baumannii Inhibits the Formation of Neutrophil Extracellular Traps by Suppressing Neutrophil Adhesion

Directory of Open Access Journals (Sweden)

Go Kamoshida

2018-02-01

Full Text Available Hospital-acquired infections caused by Acinetobacter baumannii have become problematic because of high rates of drug resistance. A. baumannii is usually harmless, but it may cause infectious diseases in an immunocompromised host. Although neutrophils are the key players of the initial immune response against bacterial infection, their interactions with A. baumannii remain largely unknown. A new biological defense mechanism, termed neutrophil extracellular traps (NETs, has been attracting attention. NETs play a critical role in bacterial killing by bacterial trapping and inactivation. Many pathogenic bacteria have been reported to induce NET formation, while an inhibitory effect on NET formation is rarely reported. In the present study, to assess the inhibition of NET formation by A. baumannii, bacteria and human neutrophils were cocultured in the presence of phorbol 12-myristate 13-acetate (PMA, and NET formation was evaluated. NETs were rarely observed during the coculture despite neutrophil PMA stimulation. Furthermore, A. baumannii prolonged the lifespan of neutrophils by inhibiting NET formation. The inhibition of NET formation by other bacteria was also investigated. The inhibitory effect was only apparent with live A. baumannii cells. Finally, to elucidate the mechanism of this inhibition, neutrophil adhesion was examined. A. baumannii suppressed the adhesion ability of neutrophils, thereby inhibiting PMA-induced NET formation. This suppression of cell adhesion was partly due to suppression of the surface expression of CD11a in neutrophils. The current study constitutes the first report on the inhibition of NET formation by a pathogenic bacterium, A. baumannii, and prolonging the neutrophil lifespan. This novel pathogenicity to inhibit NET formation, thereby escaping host immune responses might contribute to a development of new treatment strategies for A. baumannii infections.

Pulmonary Artery Agenesis: A Case Series

Directory of Open Access Journals (Sweden)

Meltem Ağca

2015-04-01

Full Text Available Pulmonary artery agenesis is a rare congenital abnormality in which atresia was encountered in the short segment of the right or left pulmonary arteries. It can be isolated or associated with cardiac abnormalities such as tetralogy of Fallot, septal defects or pulmonary stenosis.The majority of cases are diagnosed in childhood whereas some cases yield no symptoms until adulthood. We evaluated retrospectively 5 pulmonary artery agenesis cases diagnosed in our clinics between 1998-2010 with respect to the literature.

The pulmonary vasculature in a neonatal porcine model with increased pulmonary blood flow and pressure

DEFF Research Database (Denmark)

Stenbøg, Elisabeth Vidstid; Steinbruchel, Daniel Andreas; Thomsen, Anne Bloch

2001-01-01

Introduction: Hypertension and hyperperfusion of the pulmonary vascular bed in the setting of congenital cardiac malformations may lead to progressive pulmonary vascular disease. To improve the understanding of the basic mechanisms of this disease, there is a need for clinically relevant animal....... By three months of age, nearly all shunts had closed spontaneously, and haemodynamics were normal. Ligation of the left pulmonary artery resulted in a normal total pulmonary blood flow, despite only the right lung being perfused, and a 33% increase in systolic pulmonary arterial pressure...... in humans. Elevated circulating levels of endothelin were associated with abnormal haemodynamics rather than abnormal pathology. These findings could be valuable for future studies on the pathogenesis of hypertensive pulmonary vascular disease associated with congenital cardiac malformations....

Pulmonary Venous Obstruction in Cancer Patients

Directory of Open Access Journals (Sweden)

Chuang-Chi Liaw

2015-01-01

Full Text Available Background. We study the clinical significance and management of pulmonary venous obstruction in cancer patients. Methods. We conducted a prospective cohort study to characterize the syndrome that we term “pulmonary vein obstruction syndrome” (PVOS between January 2005 and March 2014. The criteria for inclusion were (1 episodes of shortness of breath; (2 chest X-ray showing abnormal pulmonary hilum shadow with or without presence of pulmonary edema and/or pleural effusion; (3 CT scan demonstrating pulmonary vein thrombosis/tumor with or without tumor around the vein. Results. Two hundred and twenty-two patients developed PVOS. Shortness of breath was the main symptom, which was aggravated by chemotherapy in 28 (13%, and medical/surgical procedures in 21 (9% and showed diurnal change in intensity in 32 (14%. Chest X-rays all revealed abnormal pulmonary hilum shadows and presence of pulmonary edema in 194 (87% and pleural effusion in 192 (86%. CT scans all showed pulmonary vein thrombosis/tumor (100% and surrounding the pulmonary veins by tumor lesions in 140 patients (63%. PVOS was treated with low molecular weight heparin in combination with dexamethasone, and 66% of patients got clinical/image improvement. Conclusion. Physicians should be alert to PVOS when shortness of breath occurs and chest X-ray reveals abnormal pulmonary hilum shadows.

A Potential Role for Acrolein in Neutrophil-Mediated Chronic Inflammation.

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Noerager, Brett D; Xu, Xin; Davis, Virginia A; Jones, Caleb W; Okafor, Svetlana; Whitehead, Alicia; Blalock, J Edwin; Jackson, Patricia L

2015-12-01

Neutrophils (PMNs) are key mediators of inflammatory processes throughout the body. In this study, we investigated the role of acrolein, a highly reactive aldehyde that is ubiquitously present in the environment and produced endogenously at sites of inflammation, in mediating PMN-mediated degradation of collagen facilitating proline-glycine-proline (PGP) production. We treated peripheral blood neutrophils with acrolein and analyzed cell supernatants and lysates for matrix metalloproteinase-9 (MMP-9) and prolyl endopeptidase (PE), assessed their ability to break down collagen and release PGP, and assayed for the presence of leukotriene A4 hydrolase (LTA4H) and its ability to degrade PGP. Acrolein treatment induced elevated production and functionality of collagen-degrading enzymes and generation of PGP fragments. Meanwhile, LTA4H levels and triaminopeptidase activity declined with increasing concentrations of acrolein thereby sparing PGP from enzymatic destruction. These findings suggest that acrolein exacerbates the acute inflammatory response mediated by neutrophils and sets the stage for chronic pulmonary and systemic inflammation.

[Lymphocyte transformation test following stimulation with a protein factor from neutrophilic granulocytes (PMNL) in psoriasis patients].

Science.gov (United States)

Ruszczak, Z; Ciborska, L; Kaszuba, A

1988-12-01

The lymphocyte transformation test (LTT) was given to 20 healthy subjects and 43 patients with generalized psoriasis vulgaris: it was given right after stimulation with PHA (spontaneous) and after stimulation with allogenic and autogenic protein factor (NPF). NPF was isolated from secondary lysosome granules of peripheral blood neutrophils. The results were analyzed using computer statistic tests. No distinct differences were noticed between the spontaneous transformation test in psoriatic patients compared to the controls. After stimulation with PHA, the percentage of blast cells was significantly lower in patients with psoriasis. When allogenic and autogenic NPF was used for stimulation, the LTT values were significantly higher in the psoriasis group than in the control subjects. This fact points out the increase in sensitivity of lymphocytes to NPF in active psoriasis and the possibility of abnormal neutrophil-lymphocyte interactions in vivo. This phenomenon may be intensified when under the influence of bacterial or viral agents, or medicaments; the degranulation of secondary lysosome granules of neutrophils occurs, causing the release of NPF. These investigations support our opinion that psoriasis is a systemic disease and that NPF plays a considerable role in the psoriatic reaction.

Multi-slice CT pulmonary function evaluation in emphysema

International Nuclear Information System (INIS)

Ge Xiaojun; Zhang Guozhen; Zhu Yanping; Shan Lin; Mao Dingbiao; Ding Qiyong; Hua Yanqing

2007-01-01

Objective: To explore the feasibility of evaluating the lung function by MSCT in emphysema. Methods: The MSCT scan and pulmonary function tests (PFT) were respectively performed in 147 receptors within one week. They were randomly divided into 2 groups: group A (120 receptors), including normal, mild, moderate and severe abnormal pulmonary function based on the PFT, for comparing the correlation between pulmonary quantitative indexes of MSCT pulmonary function and PFT and settingup the primary, grade criteria of abnormal pulmonary, function in emphysema, group B (27 receptors) for evaluating the diagnostic accuracy in group A. The total lung was respectively scanned at the full inspiration and full expiration with MSCT. The pulmonary quantitative indexes of MSCT were measured with Siemens Pulmo pulmonary quantitative software. Results: There was correlation between pulmonary quantitative indexes of MSCT and PFT. The Piex/in -910 showed best correlation with FEV 1 % (r= -0. 905, P -910 (χ 2 0.267, P=0.966, accuracy 81.5%), and the primary criteria for abnormal pulmonary, function of emphysema was normal (0-9.9), mild (10.0-34.9), moderate (35.0-74.9) and severe (≥75.0). Conclusion: It is feasible to evaluate the abnormal lung function of emphysema with pulmonary quantitative indexes of CT. The Piex/in 910 was the most effective one in various indexes. (authors)

Autophagy Primes Neutrophils for Neutrophil Extracellular Trap Formation during Sepsis.

Science.gov (United States)

Park, So Young; Shrestha, Sanjeeb; Youn, Young-Jin; Kim, Jun-Kyu; Kim, Shin-Yeong; Kim, Hyun Jung; Park, So-Hee; Ahn, Won-Gyun; Kim, Shin; Lee, Myung Goo; Jung, Ki-Suck; Park, Yong Bum; Mo, Eun-Kyung; Ko, Yousang; Lee, Suh-Young; Koh, Younsuck; Park, Myung Jae; Song, Dong-Keun; Hong, Chang-Won

2017-09-01

Neutrophils are key effectors in the host's immune response to sepsis. Excessive stimulation or dysregulated neutrophil functions are believed to be responsible for sepsis pathogenesis. However, the mechanisms regulating functional plasticity of neutrophils during sepsis have not been fully determined. We investigated the role of autophagy in neutrophil functions during sepsis in patients with community-acquired pneumonia. Neutrophils were isolated from patients with sepsis and stimulated with phorbol 12-myristate 13-acetate (PMA). The levels of reactive oxygen species generation, neutrophil extracellular trap (NET) formation, and granule release, and the autophagic status were evaluated. The effect of neutrophil autophagy augmentation was further evaluated in a mouse model of sepsis. Neutrophils isolated from patients who survived sepsis showed an increase in autophagy induction, and were primed for NET formation in response to subsequent PMA stimulation. In contrast, neutrophils isolated from patients who did not survive sepsis showed dysregulated autophagy and a decreased response to PMA stimulation. The induction of autophagy primed healthy neutrophils for NET formation and vice versa. In a mouse model of sepsis, the augmentation of autophagy improved survival via a NET-dependent mechanism. These results indicate that neutrophil autophagy primes neutrophils for increased NET formation, which is important for proper neutrophil effector functions during sepsis. Our study provides important insights into the role of autophagy in neutrophils during sepsis.

Prevalence of respiratory symptoms and their correlation to pulmonary function abnormalities in individuals exposed to environmental pollution

International Nuclear Information System (INIS)

Khalid, G.H.; Ali, M.; Ahmed, J.; Abbas, M.N.

1999-01-01

To find out the prevalence of respiratory symptoms and their correlation to pulmonary function abnormalities in individuals exposed to polluted air, 438 workers, and their family members were studied at Thermal Power Station (TPS), Sheikhmanda (Quetta). Individuals with a stay of less than three years at TPS and patients with known chronic respiratory infections (tuberculosis and its squelae, bronchiectasis) were excluded from the study. Remaining 175 males (mean age 43.4 years) and 71 females (mean age 34.2 years) were divided into three groups A, B, C on the basis of their exposure time to polluted air per day during the three years. Each groups was further subdivided into smoker and non-smoker members. Prevalence of respiratory symptoms was significantly higher in the individuals exposed to polluted air as compared to non-exposed individuals (P<0.05). A strong positive correlation (r=0.91) exists between respiratory symptoms and respiratory function abnormalities in smoker groups; however, no definite correlation (r=0.06) was found between respiratory symptoms and respiratory function abnormalities in non-smoker groups. Function abnormalities was noted only in smoker groups and non-smokers of even maximally exposed group (group C) had almost no respiratory function abnormalities. (author)

The effect of midazolam on neutrophil mitogen-activated protein kinase.

LENUS (Irish Health Repository)

Ghori, Kamran

2010-06-01

Neutrophil p38 mitogen-activated protein kinase (MAPK) is a key enzyme in the intracellular signalling pathway that is responsible for many neutrophil functions, which are important in neutrophil-endothelial interaction. The imidazole compounds are inhibitors of this enzyme system. The objectives of this in-vitro investigation were to examine the effect of midazolam on neutrophil p38 MAPK activation (phosphorylation) following in-vitro ischaemia-reperfusion injury, and the expression of adhesion molecule CD11b\\/CD18.

Circumventing Y. pestis Virulence by Early Recruitment of Neutrophils to the Lungs during Pneumonic Plague.

Directory of Open Access Journals (Sweden)

Yaron Vagima

2015-05-01

Full Text Available Pneumonic plague is a fatal disease caused by Yersinia pestis that is associated with a delayed immune response in the lungs. Because neutrophils are the first immune cells recruited to sites of infection, we investigated the mechanisms responsible for their delayed homing to the lung. During the first 24 hr after pulmonary infection with a fully virulent Y. pestis strain, no significant changes were observed in the lungs in the levels of neutrophils infiltrate, expression of adhesion molecules, or the expression of the major neutrophil chemoattractants keratinocyte cell-derived chemokine (KC, macrophage inflammatory protein 2 (MIP-2 and granulocyte colony stimulating factor (G-CSF. In contrast, early induction of chemokines, rapid neutrophil infiltration and a reduced bacterial burden were observed in the lungs of mice infected with an avirulent Y. pestis strain. In vitro infection of lung-derived cell-lines with a YopJ mutant revealed the involvement of YopJ in the inhibition of chemoattractants expression. However, the recruitment of neutrophils to the lungs of mice infected with the mutant was still delayed and associated with rapid bacterial propagation and mortality. Interestingly, whereas KC, MIP-2 and G-CSF mRNA levels in the lungs were up-regulated early after infection with the mutant, their protein levels remained constant, suggesting that Y. pestis may employ additional mechanisms to suppress early chemoattractants induction in the lung. It therefore seems that prevention of the early influx of neutrophils to the lungs is of major importance for Y. pestis virulence. Indeed, pulmonary instillation of KC and MIP-2 to G-CSF-treated mice infected with Y. pestis led to rapid homing of neutrophils to the lung followed by a reduction in bacterial counts at 24 hr post-infection and improved survival rates. These observations shed new light on the virulence mechanisms of Y. pestis during pneumonic plague, and have implications for the

Partial abnormal pulmonary venous return in Turner syndrome

NARCIS (Netherlands)

van Wassenaer, A. G.; Lubbers, L. J.; Losekoot, G.

1988-01-01

Three cases of partial anomalous pulmonary venous return, in one case combined with coarctation of the aorta and in another with discrete subaortic stenosis, are described in patients with Turner syndrome. In two of them the right and left superior pulmonary veins drained into the right superior

Attenuation of pancreatitis-induced pulmonary injury by aerosolized hypertonic saline.

LENUS (Irish Health Repository)

Shields, C J

2012-02-03

BACKGROUND: The immunomodulatory effects of hypertonic saline (HTS) provide potential strategies to attenuate inappropriate inflammatory reactions. This study tested the hypothesis that administration of intratracheal aerosolized HTS modulates the development of lung injury in pancreatitis. METHODS: Pancreatitis was induced in 24 male Sprague-Dawley rats by intraperitoneal injection of 20% L-arginine (500 mg\\/100 g body weight). At 24 and 48 h, intratracheal aerosolized HTS (7.5% NaCl, 0.5 mL) was administered to 8 rats, while a further 8 received 0.5 mL of aerosolized normal saline (NS). At 72 hours, pulmonary neutrophil infiltration (myeloperoxidase activity) and endothelial permeability (bronchoalveolar lavage and wet:dry weight ratios) were assessed. In addition, histological assessment of representative lung tissue was performed by a blinded assessor. In a separate experiment, polymorphonucleocytes (PMN) were isolated from human donors, and exposed to increments of HTS. Neutrophil transmigration across an endothelial cell layer, VEGF release, and apoptosis at 1, 6, 12, 18, and 24 h were assessed. RESULTS: Histopathological lung injury scores were significantly reduced in the HTS group (4.78 +\\/- 1.43 vs. 8.64 +\\/- 0.86); p < 0.001). Pulmonary neutrophil sequestration (1.40 +\\/- 0.2) and increased endothelial permeability (6.77 +\\/- 1.14) were evident in the animals resuscitated with normal saline when compared with HTS (0.70 +\\/- 0.1 and 3.57 +\\/- 1.32), respectively; p < 0.04). HTS significantly reduced PMN transmigration (by 97.1, p = 0.002, and induced PMN apoptosis (p < 0.03). HTS did not impact significantly upon neutrophil VEGF release (p > 0.05). CONCLUSIONS: Intratracheal aerosolized HTS attenuates the neutrophil-mediated pulmonary insult subsequent to pancreatitis. This may represent a novel therapeutic strategy.

Dose-dependent pulmonary response of well-dispersed titanium dioxide nanoparticles following intratracheal instillation

International Nuclear Information System (INIS)

Oyabu, Takako; Morimoto, Yasuo; Hirohashi, Masami; Horie, Masanori; Kambara, Tatsunori; Lee, Byeong Woo; Hashiba, Masayoshi; Mizuguchi, Yohei; Myojo, Toshihiko; Kuroda, Etsushi

2013-01-01

In order to investigate the relationship between pulmonary inflammation and particle clearance of nanoparticles, and also their dose dependency, we performed an instillation study of well-dispersed TiO 2 nanoparticles and examined the pulmonary inflammations, the particle clearance rate and histopathological changes. Wistar rats were intratracheally administered 0.1 mg (0.33 mg/kg), 0.2 mg (0.66 mg/kg), 1 mg (3.3 mg/kg), and 3 mg (10 mg/kg) of well-dispersed TiO 2 nanoparticles (diameter of agglomerates: 25 nm), and the pulmonary inflammation response and the amount of TiO 2 in the lung were determined from 3 days up to 12 months sequentially after the instillation. There were no increases of total cell or neutrophil counts in bronchoalveolar lavage fluid (BALF) in the 0.1 and the 0.2 mg-administered groups. On the other hand, mild infiltration of neutrophils was observed in the 1 and 3 mg-administered groups. Histopathological findings showed infiltration of neutrophils in the 1 and 3 mg-administered groups. Of special note, a granulomatous lesion including a local accumulation of TiO 2 was observed in the bronchioli-alveolar space in the 3 mg-administered group. The biological half times of the TiO 2 in the lung were 4.2, 4.4, 6.7, and 10.8 months in the 0.1, 0.2, 1, and 3 mg-administered groups, respectively. Neutrophil infiltration was observed as the particle clearance was delayed, suggesting that an excessive dose of TiO 2 nanoparticles may induce pulmonary inflammation and clearance delay.

Familial idiopathic pulmonary fibrosis. Evidence of lung inflammation in unaffected family members

International Nuclear Information System (INIS)

Bitterman, P.B.; Rennard, S.I.; Keogh, B.A.; Wewers, M.D.; Adelberg, S.; Crystal, R.G.

1986-01-01

We evaluated 17 clinically unaffected members of three families with an autosomal dominant form of idiopathic pulmonary fibrosis for evidence of alveolar inflammation. Each person in the study was examined by gallium-67 scanning for a general estimate of pulmonary inflammation, and by bronchoalveolar lavage for characterization of the types of recovered cells and their state of activation. Eight of the 17 subjects had evidence of alveolar inflammation on the lavage studies. Supporting data included increased numbers of neutrophils and activated macrophages that released one or more neutrophil chemoattractants, and growth factors for lung fibroblasts--findings similar to those observed in patients with overt idiopathic pulmonary fibrosis. Four of these eight also had a positive gallium scan; in all the other clinically unaffected subjects the scan was normal. During a follow-up of two to four years in seven of the eight subjects who had evidence of inflammation, no clinical evidence of pulmonary fibrosis has appeared. These results indicate that alveolar inflammation occurs in approximately half the clinically unaffected family members at risk of inheriting autosomal dominant idiopathic pulmonary fibrosis. Whether these persons with evidence of pulmonary inflammation but no fibrosis will proceed to have clinically evident pulmonary fibrosis is not yet known

Intravascular pulmonary metastases

International Nuclear Information System (INIS)

Shepard, J.A.O.; Moore, E.H.; Templeton, P.A.; McLoud, T.C.

1988-01-01

The diagnosis of intravascular metastatic tumor emboli to the lungs is rarely made. The authors present a characteristic radiographic finding of intravascular lung metastases that they observed in four patients with diagnoses or right atrial myoxoma, invasive renal cell carcinoma, invasive pelvic osteosarcoma, and recurrent pelvic chondrosarcoma. Substantiation of intravascular pulmonary metastases was achieved by means of autopsy, pulmonary artery biopsy, and surgical documentation of tumor invasion of the inferior vena cava or pelvic veins. In all four cases, chest computed tomography (CT) demonstrated branching, beaded opacities extending from the hila into the periphery of the lung in the distribution of pulmonary arteries. In one case, similar findings were observed in magnetic resonance (MR) images of the chest. Follow-up studies in three cases showed progressive enlargement and varicosity of the abnormal pulmonary artery consistent with proliferation of intravascular tumor. In the case of metastatic osteosarcoma, intraluminal ossification was also observed at CT. In three of four cases, pulmonary infarction was demonstrated in the distribution of the abnormal pulmonary arteries seen at CT as small, peripheral, wedge-shaped opacities. The demonstration of progressively dilated and beaded pulmonary arteries in patients with extrathoracic malignancies is suggestive of intravascular lung metastases, particularly when accompanied by peripheral infarction

Genetics Home Reference: pulmonary arterial hypertension

Science.gov (United States)

... Home Health Conditions Pulmonary arterial hypertension Pulmonary arterial hypertension Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Pulmonary arterial hypertension is a progressive disorder characterized by abnormally high ...

Yersinia pestis targets neutrophils via complement receptor 3

Science.gov (United States)

Merritt, Peter M.; Nero, Thomas; Bohman, Lesley; Felek, Suleyman; Krukonis, Eric S.; Marketon, Melanie M.

2015-01-01

Yersinia species display a tropism for lymphoid tissues during infection, and the bacteria select innate immune cells for delivery of cytotoxic effectors by the type III secretion system. Yet the mechanism for target cell selection remains a mystery. Here we investigate the interaction of Yersinia pestis with murine splenocytes to identify factors that participate in the targeting process. We find that interactions with primary immune cells rely on multiple factors. First, the bacterial adhesin Ail is required for efficient targeting of neutrophils in vivo. However, Ail does not appear to directly mediate binding to a specific cell type. Instead, we find that host serum factors direct Y. pestis to specific innate immune cells, particularly neutrophils. Importantly, specificity towards neutrophils was increased in the absence of bacterial adhesins due to reduced targeting of other cell types, but this phenotype was only visible in the presence of mouse serum. Addition of antibodies against complement receptor 3 and CD14 blocked target cell selection, suggesting that a combination of host factors participate in steering bacteria toward neutrophils during plague infection. PMID:25359083

Pulmonary ventilation and perfusion scintigraphy in patients with bronchial asthma

International Nuclear Information System (INIS)

Ono, Seiji; Hoshi, Hiroaki; Watanabe, Katsushi.

1988-01-01

Pulmonary ventilation and perfusion scan using Xe-133 gas and Tc-99m MAA were performed in 18 patients with bronchial asthma to evaluate the regional pulmonary function. The scintigraphic findings were compared with the results of the auscultation and the conventional pulmonary functioning examination (%FVC, %FEV 1.0 ). Ventilation image showed abnormality in 12 (70.6%) out of the asymptomatic 17 patients and perfusion image showed abnormality in 7 (41.2%) out of 17 patients. These 7 patients with abnormality on perfusion image all showed abnormality on ventilation image. The grade of abnormality in scintigraphic findings was compatible with the values of %FVC and %FEV 1.0 . In conclusion Xe-133 ventilation and Tc-99m MAA perfusion scan were useful procedures to estimate the pulmonary function of patients with bronchial asthma. (author)

Fibroblasts are in a position to provide directional information to migrating neutrophils during pneumonia in rabbit lungs.

Science.gov (United States)

Behzad, A R; Chu, F; Walker, D C

1996-05-01

Previous findings have shown that pulmonary fibroblasts are associated with preexisting holes in the endothelial and epithelial basal laminae through which neutrophils appear to enter and leave the interstitium as they migrate from capillaries to alveoli. To determine their role in neutrophil migration, fibroblast organization within the interstitium was assessed by transmission electron microscope observations of serial-sectioned rabbit lung tissue. Interstitial fibroblasts were found to physically interconnect the endothelial basal lamina holes to epithelial basal lamina holes. Morphometric assessment of rabbit lung tissue instilled with Streptococcus pneumoniae revealed that approximately 70% of the surface area density of migrating neutrophils is in close contact (15 nm or less) with interstitial fibroblasts and extracellular matrix elements (30 and 40%, respectively). Although migrating neutrophils were close enough to adhere to both fibroblasts and extracellular elements, the interstitial fibroblasts are organized in a manner that would allow them to provide directional information to the neutrophils. A model illustrating this process is proposed.

A case of intralobar pulmonary sequestration

International Nuclear Information System (INIS)

Misawa, Takuo; Hongo, Minoru; Okubo, Shinichi; Yamada, Hiroyoshi; Matsuoka, Ken; Soga, Naoko; Kono, Jun; Kusama, Shozo

1985-01-01

A 57-year-old female was admitted to our hospital, complaining of hemoptysis. On auscultation, moist rales were audible at the lower portion of left posterior chest. Plain chest roentgenogram showed a round shadow in the left lower lung field. Computed tomography with contrast enhancement revealed an abnormal structure which was contiguous to a strand structure. Dynamic scanning demonstrated opacification of the strand structure and that of the greater part of the abnormal structure during peak opacification of the descending aorta. A part of the abnormal structure was opacified during the same phase as the opacification of the right ventricle and pulmonary artery. A diagnosis of intralobar pulmonary sequestration associated with pulmonary arterio-venous malformation was confirmed by thoracic aortography and left pulmonary arteriography. The hemoptysis was found to be caused by chronic bronchitis. It was emphasized that dynamic computed tomography is very useful to diagnose intralobar pulmonary sequestration and to assess the presence of pulmonary arterio-venous malformation. In addition, it is of particular interest that this case cannot be assigned to any category of Pryce's classification although it resembles both type I and IV. (author)

Pulmonary mucormycosis. Serial morphologic changes on computed tomography correlate with clinical and pathologic findings

International Nuclear Information System (INIS)

Nam, Bo Da; Kim, Tae Jung; Lee, Kyung Soo; Kim, Tae Sung; Chung, Myung Jin; Han, Joungho

2018-01-01

To evaluate serial computed tomography (CT) findings of pulmonary mucormycosis correlated with peripheral blood absolute neutrophil count (ANC). Between February 1997 and June 2016, 20 immunocompromised patients (10 males, 10 females; mean age, 48.9 years) were histopathologically diagnosed as pulmonary mucormycosis. On initial (n=20) and follow-up (n=15) CT scans, the patterns of lung abnormalities and their changing features on follow-up scans were evaluated, and the pattern changes were correlated with ANC changes. All patients were immunocompromised. On initial CT scans, nodule (≤3cm)/mass (>3cm) or consolidation with surrounding ground-glass opacity halo (18/20, 90%) was the most common pattern. On follow-up CT, morphologic changes (13/15, 87%) could be seen and they included reversed halo (RH) sign, central necrosis, and air-crescent sign. Although all cases did not demonstrate the regular morphologic changes at the same timeline, various combinations of pattern change could be seen in all patients. Sequential morphologic changes were related with recovering of ANC in 13 of 15 patients. Pulmonary mucormycosis most frequently presents as consolidation or nodule/mass with halo sign at CT. Morphologic changes into RH sign, central necrotic cavity or air-crescent sign occur with treatment and recovery of ANC. (orig.)

Pulmonary mucormycosis. Serial morphologic changes on computed tomography correlate with clinical and pathologic findings

Energy Technology Data Exchange (ETDEWEB)

Nam, Bo Da; Kim, Tae Jung; Lee, Kyung Soo; Kim, Tae Sung; Chung, Myung Jin [Samsung Medical Centre, Sungkyunkwan University School of Medicine, Department of Radiology and Centre for Imaging Science, Seoul (Korea, Republic of); Han, Joungho [Samsung Medical Centre, Sungkyunkwan University School of Medicine, Department of Pathology, Seoul (Korea, Republic of)

2018-02-15

To evaluate serial computed tomography (CT) findings of pulmonary mucormycosis correlated with peripheral blood absolute neutrophil count (ANC). Between February 1997 and June 2016, 20 immunocompromised patients (10 males, 10 females; mean age, 48.9 years) were histopathologically diagnosed as pulmonary mucormycosis. On initial (n=20) and follow-up (n=15) CT scans, the patterns of lung abnormalities and their changing features on follow-up scans were evaluated, and the pattern changes were correlated with ANC changes. All patients were immunocompromised. On initial CT scans, nodule (≤3cm)/mass (>3cm) or consolidation with surrounding ground-glass opacity halo (18/20, 90%) was the most common pattern. On follow-up CT, morphologic changes (13/15, 87%) could be seen and they included reversed halo (RH) sign, central necrosis, and air-crescent sign. Although all cases did not demonstrate the regular morphologic changes at the same timeline, various combinations of pattern change could be seen in all patients. Sequential morphologic changes were related with recovering of ANC in 13 of 15 patients. Pulmonary mucormycosis most frequently presents as consolidation or nodule/mass with halo sign at CT. Morphologic changes into RH sign, central necrotic cavity or air-crescent sign occur with treatment and recovery of ANC. (orig.)

Dose-dependent pulmonary response of well-dispersed titanium dioxide nanoparticles following intratracheal instillation

Energy Technology Data Exchange (ETDEWEB)

Oyabu, Takako [Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Department of Environmental Health Engineering (Japan); Morimoto, Yasuo, E-mail: yasuom@med.uoeh-u.ac.jp; Hirohashi, Masami; Horie, Masanori; Kambara, Tatsunori [Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Department of Occupational Pneumology (Japan); Lee, Byeong Woo [Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Department of Environmental Health Engineering (Japan); Hashiba, Masayoshi [Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Department of Occupational Pneumology (Japan); Mizuguchi, Yohei; Myojo, Toshihiko [Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Department of Environmental Health Engineering (Japan); Kuroda, Etsushi [Osaka University, Laboratory of Vaccine Science, WPI Immunology Frontier Research Center (Japan)

2013-04-15

In order to investigate the relationship between pulmonary inflammation and particle clearance of nanoparticles, and also their dose dependency, we performed an instillation study of well-dispersed TiO{sub 2} nanoparticles and examined the pulmonary inflammations, the particle clearance rate and histopathological changes. Wistar rats were intratracheally administered 0.1 mg (0.33 mg/kg), 0.2 mg (0.66 mg/kg), 1 mg (3.3 mg/kg), and 3 mg (10 mg/kg) of well-dispersed TiO{sub 2} nanoparticles (diameter of agglomerates: 25 nm), and the pulmonary inflammation response and the amount of TiO{sub 2} in the lung were determined from 3 days up to 12 months sequentially after the instillation. There were no increases of total cell or neutrophil counts in bronchoalveolar lavage fluid (BALF) in the 0.1 and the 0.2 mg-administered groups. On the other hand, mild infiltration of neutrophils was observed in the 1 and 3 mg-administered groups. Histopathological findings showed infiltration of neutrophils in the 1 and 3 mg-administered groups. Of special note, a granulomatous lesion including a local accumulation of TiO{sub 2} was observed in the bronchioli-alveolar space in the 3 mg-administered group. The biological half times of the TiO{sub 2} in the lung were 4.2, 4.4, 6.7, and 10.8 months in the 0.1, 0.2, 1, and 3 mg-administered groups, respectively. Neutrophil infiltration was observed as the particle clearance was delayed, suggesting that an excessive dose of TiO{sub 2} nanoparticles may induce pulmonary inflammation and clearance delay.

Pulmonary, neurological and hepatic compromise in paragonimiasis: case report

International Nuclear Information System (INIS)

Uriza Carrasco, Alfonso Jose; Cuervo Valencia, Catalina; Valencia M, Andres Mauricio; Echeverri Toro, Lina Maria

2011-01-01

Paragonimiasis is a parasitic infectious disease, frequently with pulmonary abnormalities, although erratic parasite migration can compromise other organs. this disease is endemic in areas of southeast Asia, but it has been described in other tropical and subtropical regions. In this article, we report a case of indigenous patient with pulmonary abnormalities by Paragonimiasis, neurologic and hepatic abnormalities too.

Pulmonary abnormalities in mitral valve disease. Comparison between pulmonary wedge pressure, regional pulmonary blood flow and chest films

Energy Technology Data Exchange (ETDEWEB)

Andersen, L H; Andersen, Jr, P E [Odense Univ. (Denmark)

1978-01-01

Chest films, right sided heart catheterization, and measurement of the regional lung perfusion, using /sup 133/Xe, were carried out 31 times on patients with mitral valve disease. A relationship was found between the radiologic evaluation in 3 grades, and the values of pulmonary wedge pressure and the apical and basal perfusion. Changes in flow distribution as reflected in altered appearance of the vessels and the presence of interstitial edema were found to be the most sensitive factors in the evaluation of pulmonary wedge pressure. Chest radiography was thus found suitable for the evaluation of pulmonary wedge pressure in mitral valve disease.

Preliminary studies of pulmonary perfusion scanning in patients with pulmonary hypertension

International Nuclear Information System (INIS)

Shi Rongfang; Liu Xiujie; Wang Yanqun

1986-01-01

A comparative analysis of pulmonary perfusion scanning through cardiac catheterization of 57 patients including 32 patients with congenital heart disease, 8 patients with chronic pulmonary thromboembolism and 7 patients with primary pulmonary hypertension is reported. The lung scintigram obtained with In-113m or Tc-99m-MAA represents the distribution of pulmonary blood. It has been found that the lung scintigram was abnormal in patients of congenital heart disease with pulmonary hypertension (i. e. pulmonary artery pressure between 41-80 mmHg) and the extent of radoiactive regional defects is proportional to the level of pulmonary hypertension. The results of the analysis indicated that pulmonary perfusion scanning being a noninvasive technique would be a useful method in evaluating the level of pulmonary hypertension in patients with left to right shunt before and after surgical operation

Prostaglandin D2 Attenuates Bleomycin-Induced Lung Inflammation and Pulmonary Fibrosis.

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Kida, Taiki; Ayabe, Shinya; Omori, Keisuke; Nakamura, Tatsuro; Maehara, Toko; Aritake, Kosuke; Urade, Yoshihiro; Murata, Takahisa

2016-01-01

Pulmonary fibrosis is a progressive and fatal lung disease with limited therapeutic options. Although it is well known that lipid mediator prostaglandins are involved in the development of pulmonary fibrosis, the role of prostaglandin D2 (PGD2) remains unknown. Here, we investigated whether genetic disruption of hematopoietic PGD synthase (H-PGDS) affects the bleomycin-induced lung inflammation and pulmonary fibrosis in mouse. Compared with H-PGDS naïve (WT) mice, H-PGDS-deficient mice (H-PGDS-/-) represented increased collagen deposition in lungs 14 days after the bleomycin injection. The enhanced fibrotic response was accompanied by an increased mRNA expression of inflammatory mediators, including tumor necrosis factor-α, monocyte chemoattractant protein-1, and cyclooxygenase-2 on day 3. H-PGDS deficiency also increased vascular permeability on day 3 and infiltration of neutrophils and macrophages in lungs on day 3 and 7. Immunostaining showed that the neutrophils and macrophages expressed H-PGDS, and its mRNA expression was increased on day 3and 7 in WT lungs. These observations suggest that H-PGDS-derived PGD2 plays a protective role in bleomycin-induced lung inflammation and pulmonary fibrosis.

Abnormal pulmonary artery stiffness in pulmonary arterial hypertension: in vivo study with intravascular ultrasound.

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Edmund M T Lau

Full Text Available BACKGROUND: There is increasing recognition that pulmonary artery stiffness is an important determinant of right ventricular (RV afterload in pulmonary arterial hypertension (PAH. We used intravascular ultrasound (IVUS to evaluate the mechanical properties of the elastic pulmonary arteries (PA in subjects with PAH, and assessed the effects of PAH-specific therapy on indices of arterial stiffness. METHOD: Using IVUS and simultaneous right heart catheterisation, 20 pulmonary segments in 8 PAH subjects and 12 pulmonary segments in 8 controls were studied to determine their compliance, distensibility, elastic modulus and stiffness index β. PAH subjects underwent repeat IVUS examinations after 6-months of bosentan therapy. RESULTS: AT BASELINE, PAH SUBJECTS DEMONSTRATED GREATER STIFFNESS IN ALL MEASURED INDICES COMPARED TO CONTROLS: compliance (1.50±0.11×10(-2 mm(2/mmHg vs 4.49±0.43×10(-2 mm(2/mmHg, p<0.0001, distensibility (0.32±0.03%/mmHg vs 1.18±0.13%/mmHg, p<0.0001, elastic modulus (720±64 mmHg vs 198±19 mmHg, p<0.0001, and stiffness index β (15.0±1.4 vs 11.0±0.7, p = 0.046. Strong inverse exponential associations existed between mean pulmonary artery pressure and compliance (r(2 = 0.82, p<0.0001, and also between mean PAP and distensibility (r(2 = 0.79, p = 0.002. Bosentan therapy, for 6-months, was not associated with any significant changes in all indices of PA stiffness. CONCLUSION: Increased stiffness occurs in the proximal elastic PA in patients with PAH and contributes to the pathogenesis RV failure. Bosentan therapy may not be effective at improving PA stiffness.

Neutrophil-mediated protection of cultured human vascular endothelial cells from damage by growing Candida albicans hyphae

International Nuclear Information System (INIS)

Edwards, J.E. Jr.; Rotrosen, D.; Fontaine, J.W.; Haudenschild, C.C.; Diamond, R.D.

1987-01-01

Interactions were studied between human neutrophils and cultured human umbilical vein endothelial cells invaded by Candida albicans. In the absence of neutrophils, progressive Candida germination and hyphal growth extensively damaged endothelial cell monolayers over a period of 4 to 6 hours, as determined both by morphological changes and release of 51 Cr from radiolabeled endothelial cells. Monolayers were completely destroyed and replaced by hyphae after 18 hours of incubation. In contrast, when added 2 hours after the monolayers had been infected with Candida, neutrophils selectively migrated toward and attached to hyphae at points of hyphal penetration into individual endothelial cells (observed by time-lapse video-microscopy). Attached neutrophils spread over hyphal surfaces both within and beneath the endothelial cells; neutrophil recruitment to initial sites of leukocyte-Candida-endothelial cell interactions continued throughout the first 60 minutes of observation. Neutrophil spreading and stasis were observed only along Candida hyphae and at sites of Candida-endothelial cell interactions. These events resulted in 58.0% killing of Candida at 2 hours and subsequent clearance of Candida from endothelial cell monolayers, as determined by microcolony counts and morphological observation. On introduction of additional neutrophils to yield higher ratios of neutrophils to endothelial cells (10 neutrophils:1 endothelial cell), neutrophil migration toward hyphal elements continued. Despite retraction or displacement of occasional endothelial cells by invading Candida and neutrophils, most endothelial cells remained intact, viable, and motile as verified both by morphological observations and measurement of 51 Cr release from radiolabeled monolayers

A novel bacterial transport mechanism of Acinetobacter baumannii via activated human neutrophils through interleukin-8.

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Kamoshida, Go; Tansho-Nagakawa, Shigeru; Kikuchi-Ueda, Takane; Nakano, Ryuichi; Hikosaka, Kenji; Nishida, Satoshi; Ubagai, Tsuneyuki; Higashi, Shouichi; Ono, Yasuo

2016-12-01

Hospital-acquired infections as a result of Acinetobacter baumannii have become problematic because of high rates of drug resistance. Although neutrophils play a critical role in early protection against bacterial infection, their interactions with A. baumannii remain largely unknown. To elucidate the interactions between A. baumannii and human neutrophils, we cocultured these cells and analyzed them by microscopy and flow cytometry. We found that A. baumannii adhered to neutrophils. We next examined neutrophil and A. baumannii infiltration into Matrigel basement membranes by an in vitro transmigration assay. Neutrophils were activated by A. baumannii, and invasion was enhanced. More interestingly, A. baumannii was transported together by infiltrating neutrophils. Furthermore, we observed by live cell imaging that A. baumannii and neutrophils moved together. In addition, A. baumannii-activated neutrophils showed increased IL-8 production. The transport of A. baumannii was suppressed by inhibiting neutrophil infiltration by blocking the effect of IL-8. A. baumannii appears to use neutrophils for transport by activating these cells via IL-8. In this study, we revealed a novel bacterial transport mechanism that A. baumannii exploits human neutrophils by adhering to and inducing IL-8 release for bacterial portage. This mechanism might be a new treatment target. © Society for Leukocyte Biology.

Pulmonary toxicity of well-dispersed cerium oxide nanoparticles following intratracheal instillation and inhalation

Energy Technology Data Exchange (ETDEWEB)

Morimoto, Yasuo, E-mail: yasuom@med.uoeh-u.ac.jp; Izumi, Hiroto; Yoshiura, Yukiko; Tomonaga, Taisuke; Oyabu, Takako; Myojo, Toshihiko; Kawai, Kazuaki; Yatera, Kazuhiro [University of Occupational and Environmental Health (Japan); Shimada, Manabu; Kubo, Masaru [Hiroshima University (Japan); Yamamoto, Kazuhiro [National Institute of Advanced Industrial Science and Technology (AIST) (Japan); Kitajima, Shinichi [National Sanatorium Hoshizuka Keiaien (Japan); Kuroda, Etsushi [Osaka University, Laboratory of Vaccine Science, WPI Immunology Frontier Research Center (Japan); Kawaguchi, Kenji; Sasaki, Takeshi [National Institute of Advanced Industrial Science and Technology (AIST) (Japan)

2015-11-15

We performed inhalation and intratracheal instillation studies of cerium dioxide (CeO{sub 2}) nanoparticles in order to investigate their pulmonary toxicity, and observed pulmonary inflammation not only in the acute and but also in the chronic phases. In the intratracheal instillation study, F344 rats were exposed to 0.2 mg or 1 mg of CeO{sub 2} nanoparticles. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed from 3 days to 6 months following the instillation. In the inhalation study, rats were exposed to the maximum concentration of inhaled CeO{sub 2} nanoparticles (2, 10 mg/m{sup 3}, respectively) for 4 weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were examined from 3 days to 3 months after the end of the exposure. The intratracheal instillation of CeO{sub 2} nanoparticles caused a persistent increase in the total and neutrophil number in BALF and in the concentration of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in BALF during the observation time. The inhalation of CeO{sub 2} nanoparticles also induced a persistent influx of neutrophils and expression of CINC-1, CINC-2, and HO-1 in BALF. Pathological features revealed that inflammatory cells, including macrophages and neutrophils, invaded the alveolar space in both studies. Taken together, the CeO{sub 2} nanoparticles induced not only acute but also chronic inflammation in the lung, suggesting that CeO{sub 2} nanoparticles have a pulmonary toxicity that can lead to irreversible lesions.

Pulmonary exposure to carbonaceous nanomaterials and sperm quality.

Science.gov (United States)

Skovmand, Astrid; Jacobsen Lauvås, Anna; Christensen, Preben; Vogel, Ulla; Sørig Hougaard, Karin; Goericke-Pesch, Sandra

2018-01-31

Semen quality parameters are potentially affected by nanomaterials in several ways: Inhaled nanosized particles are potent inducers of pulmonary inflammation, leading to the release of inflammatory mediators. Small amounts of particles may translocate from the lungs into the lung capillaries, enter the systemic circulation and ultimately reach the testes. Both the inflammatory response and the particles may induce oxidative stress which can directly affect spermatogenesis. Furthermore, spermatogenesis may be indirectly affected by changes in the hormonal milieu as systemic inflammation is a potential modulator of endocrine function. The aim of this study was to investigate the effects of pulmonary exposure to carbonaceous nanomaterials on sperm quality parameters in an experimental mouse model. Effects on sperm quality after pulmonary inflammation induced by carbonaceous nanomaterials were investigated by intratracheally instilling sexually mature male NMRI mice with four different carbonaceous nanomaterials dispersed in nanopure water: graphene oxide (18 μg/mouse/i.t.), Flammruss 101, Printex 90 and SRM1650b (0.1 mg/mouse/i.t. each) weekly for seven consecutive weeks. Pulmonary inflammation was determined by differential cell count in bronchoalveolar lavage fluid. Epididymal sperm concentration and motility were measured by computer-assisted sperm analysis. Epididymal sperm viability and morphological abnormalities were assessed manually using Hoechst 33,342/PI flourescent and Spermac staining, respectively. Epididymal sperm were assessed with regard to sperm DNA integrity (damage). Daily sperm production was measured in the testis, and testosterone levels were measured in blood plasma by ELISA. Neutrophil numbers in the bronchoalveolar fluid showed sustained inflammatory response in the nanoparticle-exposed groups one week after the last instillation. No significant changes in epididymal sperm parameters, daily sperm production or plasma testosterone levels

Pulmonary and cardiac pathology in sudden unexpected death in epilepsy (SUDEP).

Science.gov (United States)

Nascimento, Fábio A; Tseng, Zian H; Palmiere, Cristian; Maleszewski, Joseph J; Shiomi, Takayuki; McCrillis, Aileen; Devinsky, Orrin

2017-08-01

To review studies on structural pulmonary and cardiac changes in SUDEP cases as well as studies showing pulmonary or cardiac structural changes in living epilepsy patients. We conducted electronic literature searches using the PubMed database for articles published in English, regardless of publication year, that included data on cardiac and/or pulmonary structural abnormalities in SUDEP cases or in living epilepsy patients during the postictal period. Fourteen postmortem studies reported pulmonary findings in SUDEP cases. Two focused mainly on assessing lung weights in SUDEP cases versus controls; no group difference was found. The other 12 reported descriptive autopsy findings. Among all SUDEP cases with available descriptive postmortem pulmonary examination, 72% had pulmonary changes, most often pulmonary edema/congestion, and, less frequently, intraalveolar hemorrhage. Eleven studies reported on cardiac pathology in SUDEP. Cardiac abnormalities were found in approximately one-fourth of cases. The most common findings were myocyte hypertrophy and myocardial fibrosis of various degrees. Among living epilepsy patients, postictal pulmonary pathology was the most commonly reported pulmonary abnormality and the most common postictal cardiac abnormality was transient left ventricular dysfunction - Takotsubo or neurogenic stunned myocardium. Cardiac and pulmonary pathological abnormalities are frequent among SUDEP cases, most commonly pulmonary edema/congestion and focal interstitial myocardial fibrosis. Most findings are not quantified, with subjective elements and undefined interobserver reliability, and lack of controls such as matched epilepsy patients who died from other causes. Further, studies have not systematically evaluated potential confounding factors, including postmortem interval to autopsy, paramedic resuscitation and IV fluids administration, underlying heart/lung disease, and risk factors for cardiac or pulmonary disease. Prospective studies with

Distinct cellular sources of hepoxilin A3 and leukotriene B4 are used to coordinate bacterial-induced neutrophil transepithelial migration.

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Pazos, Michael A; Pirzai, Waheed; Yonker, Lael M; Morisseau, Christophe; Gronert, Karsten; Hurley, Bryan P

2015-02-01

Neutrophilic infiltration is a leading contributor to pathology in a number of pulmonary disease states, including cystic fibrosis. Hepoxilin A3 (HXA3) is a chemotactic eicosanoid shown to mediate the transepithelial passage of neutrophils in response to infection in several model systems and at multiple mucosal surfaces. Another well-known eicosanoid mediating general neutrophil chemotaxis is leukotriene B4 (LTB4). We sought to distinguish the roles of each eicosanoid in the context of infection of lung epithelial monolayers by Pseudomonas aeruginosa. Using human and mouse in vitro transwell model systems, we used a combination of biosynthetic inhibitors, receptor antagonists, as well as mutant sources of neutrophils to assess the contribution of each chemoattractant in driving neutrophil transepithelial migration. We found that following chemotaxis to epithelial-derived HXA3 signals, neutrophil-derived LTB4 is required to amplify the magnitude of neutrophil migration. LTB4 signaling is not required for migration to HXA3 signals, but LTB4 generation by migrated neutrophils plays a significant role in augmenting the initial HXA3-mediated migration. We conclude that HXA3 and LTB4 serve independent roles to collectively coordinate an effective neutrophilic transepithelial migratory response. Copyright © 2015 by The American Association of Immunologists, Inc.

Variable pulmonary manifestations in hemodialysis patients

International Nuclear Information System (INIS)

Kim, Yoo Kyung; Shim, Sung Shine; Shin, Jung Hee; Choi, Gyu Bock; Lee, Kyung Soo; Yi, Chin A; Oh, Yu Whan

2003-01-01

A wide variety of pulmonary disorders related to hemodialysis or pre-existing renal disease occurs in hemodialysis patients. The disorders may be classified as 1) pulmonary abnormalities associated with chronic renal failures; 2) pulmonary complications arising during hemodialysis; 3) pulmonary infection; or 4) pulmonary-renal syndrome. An awareness of the various possible pulmonary disorders arising in hemodialysis patients may be helpful for the proper and timely management of such patients. We describe and illustrate various radiographic and CT findings of variable pulmonary disorders in hemodialysis patients

Anti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles.

LENUS (Irish Health Repository)

Hong, Ying

2012-01-01

The mechanisms by which anti-neutrophil cytoplasmic antibodies (ANCAs) may contribute to the pathogenesis of ANCA-associated vasculitis are not well understood. In this study, both polyclonal ANCAs isolated from patients and chimeric proteinase 3-ANCA induced the release of neutrophil microparticles from primed neutrophils. These microparticles expressed a variety of markers, including the ANCA autoantigens proteinase 3 and myeloperoxidase. They bound endothelial cells via a CD18-mediated mechanism and induced an increase in endothelial intercellular adhesion molecule-1 expression, production of endothelial reactive oxygen species, and release of endothelial IL-6 and IL-8. Removal of the neutrophil microparticles by filtration or inhibition of reactive oxygen species production with antioxidants abolished microparticle-mediated endothelial activation. In addition, these microparticles promoted the generation of thrombin. In vivo, we detected more neutrophil microparticles in the plasma of children with ANCA-associated vasculitis compared with that in healthy controls or those with inactive vasculitis. Taken together, these results support a role for neutrophil microparticles in the pathogenesis of ANCA-associated vasculitis, potentially providing a target for future therapeutics.

Chronic neutrophilic leukemia.

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Bredeweg, Arthur; Burch, Micah; Krause, John R

2018-01-01

Chronic neutrophilic leukemia is a rare myeloproliferative disorder characterized by a sustained peripheral blood neutrophilia, absence of the BCR/ABL oncoprotein, bone marrow hypercellularity with less than 5% myeloblasts and normal neutrophil maturation, and no dysplasia. This leukemia has been associated with mutations in the colony-stimulating factor 3 receptor (CSF3R) that may activate this receptor, leading to the proliferation of neutrophils that are the hallmark of chronic neutrophilic leukemia. We present a case of chronic neutrophilic leukemia and discuss the criteria for diagnosis and the significance of mutations found in this leukemia.

Interleukin-17A and Neutrophils in a Murine Model of Bird-Related Hypersensitivity Pneumonitis.

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Masahiro Ishizuka

Full Text Available Hypersensitivity pneumonitis (HP is an immune mediated lung disease induced by the repeated inhalation of a wide variety of antigens. Bird-related hypersensitivity pneumonitis (BRHP is one of the most common forms of HP in human and results from the inhalation of avian antigens. The findings of a recent clinical analysis suggest that in addition to Th1 factors, the levels of interleukin(IL-17 and IL-17-associated transcripts are increased in the setting of HP, and that both IL-17A and neutrophils are crucial for the development of pulmonary inflammation in murine models of HP. Our objectives were to investigate the roles of IL-17A and neutrophils in granuloma-forming inflammation in an acute HP model. We developed a mouse model of acute BRHP using pigeon dropping extract. We evaluated the process of granuloma formation and the roles of both IL-17A and neutrophils in a model. We found that the neutralization of IL-17A by the antibody attenuated granuloma formation and the recruitment of neutrophils, and also decreased the expression level of chemokine(C-X-C motif ligand 5 (CXCL5 in the acute HP model. We confirmed that most of the neutrophils in the acute HP model exhibited immunoreactivity to the anti-IL-17 antibody. We have identified the central roles of both IL-17A and neutrophils in the pathogenesis of granuloma formation in acute HP. We have also assumed that neutrophils are an important source of IL-17A in an acute HP model, and that the IL-17A-CXCL5 pathway may be responsible for the recruitment of neutrophils.

Unusual ventilation perfusion scintigram in a case of immunologic pulmonary edema clinically simulating pulmonary embolism

International Nuclear Information System (INIS)

Campeau, R.J.; Faust, J.M.; Ahmad, S.

1987-01-01

A case of immunologic pulmonary edema secondary to hydrochlorothiazide allergy developed in a 55-year-old woman that clinically simulated pulmonary embolism. The patient had abnormal washin images with normal washout images on an Xe-133 ventilation study. On the perfusion study, large bilateral central and posterior perfusion defects were present that showed an unusual mirror image pattern on the lateral and posterior oblique views. Resolution of radiographic and scintigraphic abnormalities occurred over a 3-day period in conjunction with corticosteroid therapy

Aspirin reduces lipopolysaccharide-induced pulmonary inflammation in human models of ARDS.

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Hamid, U; Krasnodembskaya, A; Fitzgerald, M; Shyamsundar, M; Kissenpfennig, A; Scott, C; Lefrancais, E; Looney, M R; Verghis, R; Scott, J; Simpson, A J; McNamee, J; McAuley, D F; O'Kane, C M

2017-11-01

Platelets play an active role in the pathogenesis of acute respiratory distress syndrome (ARDS). Animal and observational studies have shown aspirin's antiplatelet and immunomodulatory effects may be beneficial in ARDS. To test the hypothesis that aspirin reduces inflammation in clinically relevant human models that recapitulate pathophysiological mechanisms implicated in the development of ARDS. Healthy volunteers were randomised to receive placebo or aspirin 75  or 1200 mg (1:1:1) for seven days prior to lipopolysaccharide (LPS) inhalation, in a double-blind, placebo-controlled, allocation-concealed study. Bronchoalveolar lavage (BAL) was performed 6 hours after inhaling 50 µg of LPS. The primary outcome measure was BAL IL-8. Secondary outcome measures included markers of alveolar inflammation (BAL neutrophils, cytokines, neutrophil proteases), alveolar epithelial cell injury, systemic inflammation (neutrophils and plasma C-reactive protein (CRP)) and platelet activation (thromboxane B2, TXB2). Human lungs, perfused and ventilated ex vivo (EVLP) were randomised to placebo or 24 mg aspirin and injured with LPS. BAL was carried out 4 hours later. Inflammation was assessed by BAL differential cell counts and histological changes. In the healthy volunteer (n=33) model, data for the aspirin groups were combined. Aspirin did not reduce BAL IL-8. However, aspirin reduced pulmonary neutrophilia and tissue damaging neutrophil proteases (Matrix Metalloproteinase (MMP)-8/-9), reduced BAL concentrations of tumour necrosis factor α and reduced systemic and pulmonary TXB2. There was no difference between high-dose and low-dose aspirin. In the EVLP model, aspirin reduced BAL neutrophilia and alveolar injury as measured by histological damage. These are the first prospective human data indicating that aspirin inhibits pulmonary neutrophilic inflammation, at both low and high doses. Further clinical studies are indicated to assess the role of aspirin in the

Association between cystatin C and the interaction of pulmonary ...

African Journals Online (AJOL)

Purpose: To determine the association between Cystatin C (Cys C) levels and the interaction of pulmonary tuberculosis (PTB) with chronic diseases (CD). Methods: Participants (n = 356) were selected randomly from The First Affiliated Hospital of Wannan Medical College, China, and divided into 4 groups: normal control ...

Usefulness of decrease in oxygen uptake efficiency to identify gas exchange abnormality in patients with idiopathic pulmonary arterial hypertension.

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Xiaoyue Tan

Full Text Available BACKGROUND: Decline in oxygen uptake efficiency (OUE, especially during exercise, is found in patients with chronic heart failure. In this study we aimed to test the validity and usefulness of OUE in evaluating gas exchange abnormality of patients with idiopathic pulmonary arterial hypertension (IPAH. METHODS: We retrospectively investigated the cardiopulmonary exercise test (CPET with gas exchange measurements in 32 patients with confirmed IPAH. All patients also had resting hemodynamic measurements and pulmonary function test (PFT. Sixteen healthy subjects, matched by age, sex, and body size were used as controls, also had CPET and PFT measurements. RESULTS: In IPAH patients, the magnitude of absolute and percentage of predicted (%pred oxygen uptake efficiency slope (OUES and oxygen uptake efficiency plateau (OUEP, as well as several other CPET parameters, were strikingly worse than healthy subjects (P<0.0001. Pattern of changes in OUE in patients is similar to that in controls, In IPAH patients, OUE values at rest, warming up, anaerobic threshold and peak exercise were all significantly lower than in normal (P<0.0001. OUEP%pred, better than OUES%pred, correlated significantly with New York Heart Association (NYHA functional Class (r = -0.724, P<0.005, Total Pulmonary Vascular Resistance (TPVR (r = -0.694, P<0.005, diffusing capacity for carbon monoxide (DLCO (r = 0.577, P<0.05, and the lowest ventilation versus CO2 output ratio during exercise (LowestV˙E/V˙CO2 (r = -0.902, P<0.0001. In addition, the coefficient of variation (COV of OUEP was lower (20.9% markedly than OUES (34.3% (P<0.0001. CONCLUSIONS: In patients with IPAH, OUES and OUEP are both significantly lower than the healthy subjects. OUEP is a better physiological parameter than OUES in evaluating the gas exchange abnormality of patients with IPAH.

Enhanced magnetic resonance pulmonary perfusion imaging in diagnosing pulmonary embolism: preliminary investigation

International Nuclear Information System (INIS)

Huang Xiaoyong; Du Jing; Zhang Zhaoqi; Guo Xi; Yan Zixu; Jiang Hong; Wang Wei

2005-01-01

Objective: This study was designed to investigate the sensitivity and specificity of magnetic resonance pulmonary perfusion imaging (MRPP) in diagnosing pulmonary embolism (PE) compared with enhanced magnetic resonance pulmonary angiography (MRPA) and pulmonary radionuclide perfusion imaging. Methods: Fourteen patients were definitely diagnosed as PE, whose ages were from 19 to 71 years old and mean 45.5 ± 19.8 years old. All patients under went MRPA and MRPP and 3 patients were examined again after thrombolytic treatment. Five patients underwent pulmonary radionuclide perfusion imaging. Setting ROI in top, middle, bottom of lung area and abnormal area respectively, we detected signal intensity and time-signal curve to obtain the transformation rate of signal (TROS) during perfusion peak value. Results: In 14 pulmonary embolism patients, MRPA found 62 branches of pulmonary artery obstruction. Fifty-five abnormal pulmonary perfusion zones were found by MRPP, and the above results were very alike. The coincidence was 88.71%. In 14 cases, MRPP could show 25 subsegments lesion below segments. In 5 patients who had both results Of MRPP and ECT at the same time. MRPP shows 33 perfusion defect zones and 37 segments were found by ECT, the sensitivity was 89.19%. After thrombolytic treatment, both the status of the affected pulmonary artery improved markedly and perfusion defect zones reduced obviously in 3 cases by MRPP and MRPA. TROS in normal perfusion zones perfusion defect zones and low perfusion zones had significant difference (t=22.882, P<0.01). Conclusion: Contrast enhanced MR pulmonary perfusion can show both perfusion defect zones and low perfusion zones in pulmonary embolism. Time-signal curve can show the period of maximum no perfusion zones in pulmonary artery embolism zones. And the amplitude of fluctuation is small with miminum TROS. MRPP has significant values especially in showing pulmonary artery embolism in segments and subsegments. Using both MRPP and

Decreased numbers of chemotactic factor receptors in chronic neutropenia with defective chemotaxis: spontaneous recovery from the neutrophil abnormalities during early childhood

International Nuclear Information System (INIS)

Yasui, K.; Yamazaki, M.; Miyagawa, Y.; Komiyama, A.; Akabane, T.

1987-01-01

Childhood chronic neutropenia with decreased numbers of chemotactic factor receptors as well as defective chemotaxis was first demonstrated in an 8-month-old girl. Chemotactic factor receptors on neutrophils were assayed using tritiated N-formyl-methionyl-leucyl-phenylalanine ( 3 H-FMLP). The patient's neutrophils had decreased numbers of the receptors: numbers of the receptors were 20,000 (less than 3 SD) as compared with those of control cells of 52,000 +/- 6000 (mean +/- SD) (n = 10). The neutropenia disappeared spontaneously by 28 months of age parallel with the improvement of chemotaxis and increase in numbers of chemotactic factor receptors. These results demonstrate a transient decrease of neutrophil chemotactic factor receptors as one of the pathophysiological bases of a transient defect of neutrophil chemotaxis in this disorder

Genetics and Early Detection in Idiopathic Pulmonary Fibrosis

Science.gov (United States)

Putman, Rachel K.; Rosas, Ivan O.

2014-01-01

Genetic studies hold promise in helping to identify patients with early idiopathic pulmonary fibrosis (IPF). Recent studies using chest computed tomograms (CTs) in smokers and in the general population have demonstrated that imaging abnormalities suggestive of an early stage of pulmonary fibrosis are not uncommon and are associated with respiratory symptoms, physical examination abnormalities, and physiologic decrements expected, but less severe than those noted in patients with IPF. Similarly, recent genetic studies have demonstrated strong and replicable associations between a common promoter polymorphism in the mucin 5B gene (MUC5B) and both IPF and the presence of abnormal imaging findings in the general population. Despite these findings, it is important to note that the definition of early-stage IPF remains unclear, limited data exist to definitively connect abnormal imaging findings to IPF, and genetic studies assessing early-stage pulmonary fibrosis remain in their infancy. In this perspective we provide updated information on interstitial lung abnormalities and their connection to IPF. We summarize information on the genetics of pulmonary fibrosis by focusing on the recent genetic findings of MUC5B. Finally, we discuss the implications of these findings and suggest a roadmap for the use of genetics in the detection of early IPF. PMID:24547893

Neutrophils, dendritic cells and Toxoplasma.

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Denkers, Eric Y; Butcher, Barbara A; Del Rio, Laura; Bennouna, Soumaya

2004-03-09

Toxoplasma gondii rapidly elicits strong Type 1 cytokine-based immunity. The necessity for this response is well illustrated by the example of IFN-gamma and IL-12 gene knockout mice that rapidly succumb to the effects of acute infection. The parasite itself is skilled at sparking complex interactions in the innate immune system that lead to protective immunity. Neutrophils are one of the first cell types to arrive at the site of infection, and the cells release several proinflammatory cytokines and chemokines in response to Toxoplasma. Dendritic cells are an important source of IL-12 during infection with T. gondii and other microbial pathogens, and they are also specialized for high-level antigen presentation to T lymphocytes. Tachyzoites express at least two types of molecules that trigger innate immune cell cytokine production. One of these involves Toll-like receptor/MyD88 pathways common to many microbial pathogens. The second pathway is less conventional and involves molecular mimicry between a parasite cyclophilin and host CC chemokine receptor 5-binding ligands. Neutrophils, dendritic cells and Toxoplasma work together to elicit the immune response required for host survival. Cytokine and chemokine cross-talk between parasite-triggered neutrophils and dendritic cells results in recruitment, maturation and activation of the latter. Neutrophil-empowered dendritic cells possess properties expected of highly potent antigen presenting cells that drive T helper 1 generation.

The Resolution of Inflammation: A Mathematical Model of Neutrophil and Macrophage Interactions

KAUST Repository

Dunster, J. L.

2014-07-23

© 2014, Society for Mathematical Biology. There is growing interest in inflammation due to its involvement in many diverse medical conditions, including Alzheimer’s disease, cancer, arthritis and asthma. The traditional view that resolution of inflammation is a passive process is now being superceded by an alternative hypothesis whereby its resolution is an active, anti-inflammatory process that can be manipulated therapeutically. This shift in mindset has stimulated a resurgence of interest in the biological mechanisms by which inflammation resolves. The anti-inflammatory processes central to the resolution of inflammation revolve around macrophages and are closely related to pro-inflammatory processes mediated by neutrophils and their ability to damage healthy tissue. We develop a spatially averaged model of inflammation centring on its resolution, accounting for populations of neutrophils and macrophages and incorporating both pro- and anti-inflammatory processes. Our ordinary differential equation model exhibits two outcomes that we relate to healthy and unhealthy states. We use bifurcation analysis to investigate how variation in the system parameters affects its outcome. We find that therapeutic manipulation of the rate of macrophage phagocytosis can aid in resolving inflammation but success is critically dependent on the rate of neutrophil apoptosis. Indeed our model predicts that an effective treatment protocol would take a dual approach, targeting macrophage phagocytosis alongside neutrophil apoptosis.

Pulmonary function abnormalities and airway irritation symptoms of metal fumes exposure on automobile spot welders.

Science.gov (United States)

Luo, Jiin-Chyuan John; Hsu, Kuang-Hung; Shen, Wu-Shiun

2006-06-01

Spot or resistance welding has been considered less hazardous than other types of welding. Automobile manufacturing is a major industry in Taiwan. Spot and arc welding are common processes in this industry. The respiratory effects on automobile spot welders exposed to metal fumes are investigated. The cohort consisted of 41 male auto-body spot welders, 76 male arc welders, 71 male office workers, and 59 assemblers without welding exposure. Inductivity Coupled Plasma Mass Spectrophotometer (ICP-MS) was applied to detect metals' (zinc, copper, nickel) levels in the post-shift urine samples. Demographic data, work history, smoking status, and respiratory tract irritation symptoms were gathered by a standard self-administered questionnaire. Pulmonary function tests were also performed. There were significantly higher values for average urine metals' (zinc, copper, nickel) levels in spot welders and arc welders than in the non-welding controls. There were 4 out of 23 (17.4%) abnormal forced vital capacity (FVC) among the high-exposed spot welders, 2 out of 18 (11.1%) among the low-exposed spot welders, and 6 out of 130 (4.6%) non-welding-exposed workers. There was a significant linear trend between spot welding exposure and the prevalence of restrictive airway abnormalities (P = 0.036) after adjusting for other factors. There were 9 out of 23 (39.1%) abnormal peak expiratory flow rate (PEFR) among high-exposed spot welders, 5 out of 18 (27.8%) among the low-exposed spot welders, and 28 out of 130 (21.5%) non-welding-exposed workers. There was a borderline significant linear trend between spot welding exposure and the prevalence of obstructive lung function abnormalities (P = 0.084) after adjusting for other factors. There was also a significant dose-response relationship of airway irritation symptoms (cough, phlegm, chronic bronchitis) among the spot welders. Arc welders with high exposure status also had a significant risk of obstructive lung abnormalities (PEFR

Neutrophil adhesion and chemotaxis depend on substrate mechanics

International Nuclear Information System (INIS)

Jannat, Risat A; Hammer, Daniel A; Robbins, Gregory P; Ricart, Brendon G; Dembo, Micah

2010-01-01

Neutrophil adhesion to the vasculature and chemotaxis within tissues play critical roles in the inflammatory response to injury and pathogens. Unregulated neutrophil activity has been implicated in the progression of numerous chronic and acute diseases such as rheumatoid arthritis, asthma and sepsis. Cell migration of anchorage-dependent cells is known to depend on both chemical and mechanical interactions. Although neutrophil responses to chemical cues have been well characterized, little is known about the effect of underlying tissue mechanics on neutrophil adhesion and migration. To address this question, we quantified neutrophil migration and traction stresses on compliant hydrogel substrates with varying elasticity in a micromachined gradient chamber in which we could apply either a uniform concentration or a precise gradient of the bacterial chemoattractant fMLP. Neutrophils spread more extensively on substrates of greater stiffness. In addition, increasing the stiffness of the substrate leads to a significant increase in the chemotactic index for each fMLP gradient tested. As the substrate becomes stiffer, neutrophils generate higher traction forces without significant changes in cell speed. These forces are often displayed in pairs and focused in the uropod. Increases in the mean fMLP concentration beyond the K D of the receptor lead to a decrease in chemotactic index on all surfaces. Blocking with an antibody against β 2 -integrins leads to a significant reduction, but not an elimination, of directed motility on stiff materials, but no change in motility on soft materials, suggesting neutrophils can display both integrin-dependent and integrin-independent motility. These findings are critical for understanding how neutrophil migration may change in different mechanical environments in vivo and can be used to guide the design of migration inhibitors that more efficiently target inflammation.

Neutrophil adhesion and chemotaxis depend on substrate mechanics

Energy Technology Data Exchange (ETDEWEB)

Jannat, Risat A; Hammer, Daniel A [Department of Bioengineering, University of Pennsylvania, 240 Skirkanich Hall, 210 South 33rd Street, Philadelphia, PA 19104 (United States); Robbins, Gregory P; Ricart, Brendon G [Department of Chemical and Biomolecular Engineering, University of Pennsylvania, 311A Towne Building, 220 South 33rd Street, Philadelphia, PA 19104 (United States); Dembo, Micah, E-mail: hammer@seas.upenn.ed [Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, MA 02215 (United States)

2010-05-19

Neutrophil adhesion to the vasculature and chemotaxis within tissues play critical roles in the inflammatory response to injury and pathogens. Unregulated neutrophil activity has been implicated in the progression of numerous chronic and acute diseases such as rheumatoid arthritis, asthma and sepsis. Cell migration of anchorage-dependent cells is known to depend on both chemical and mechanical interactions. Although neutrophil responses to chemical cues have been well characterized, little is known about the effect of underlying tissue mechanics on neutrophil adhesion and migration. To address this question, we quantified neutrophil migration and traction stresses on compliant hydrogel substrates with varying elasticity in a micromachined gradient chamber in which we could apply either a uniform concentration or a precise gradient of the bacterial chemoattractant fMLP. Neutrophils spread more extensively on substrates of greater stiffness. In addition, increasing the stiffness of the substrate leads to a significant increase in the chemotactic index for each fMLP gradient tested. As the substrate becomes stiffer, neutrophils generate higher traction forces without significant changes in cell speed. These forces are often displayed in pairs and focused in the uropod. Increases in the mean fMLP concentration beyond the K{sub D} of the receptor lead to a decrease in chemotactic index on all surfaces. Blocking with an antibody against {beta}{sub 2}-integrins leads to a significant reduction, but not an elimination, of directed motility on stiff materials, but no change in motility on soft materials, suggesting neutrophils can display both integrin-dependent and integrin-independent motility. These findings are critical for understanding how neutrophil migration may change in different mechanical environments in vivo and can be used to guide the design of migration inhibitors that more efficiently target inflammation.

Idiopathic pulmonary fibrosis. A rare cause of scintigraphic ventilation-perfusion mismatch

International Nuclear Information System (INIS)

Pochis, W.T.; Krasnow, A.Z.; Collier, B.D.; Mewissen, M.W.; Almagro, U.A.; Hellman, R.S.; Isitman, A.T.

1990-01-01

A case of idiopathic pulmonary fibrosis with multiple areas of mismatch on ventilation-perfusion lung imaging in the absence of pulmonary embolism is presented. Idiopathic pulmonary fibrosis is one of the few nonembolic diseases producing a pulmonary ventilation-perfusion mismatch. In this condition, chest radiographs may not detect the full extent of disease, and xenon-133 ventilation imaging may be relatively insensitive to morbid changes in small airways. Thus, when examining patients with idiopathic pulmonary fibrosis, one should be aware that abnormal perfusion imaging patterns without matching ventilation abnormalities are not always due to embolism. In this setting, contrast pulmonary angiography is often needed for accurate differential diagnosis

Idiopathic pulmonary fibrosis. A rare cause of scintigraphic ventilation-perfusion mismatch

Energy Technology Data Exchange (ETDEWEB)

Pochis, W.T.; Krasnow, A.Z.; Collier, B.D.; Mewissen, M.W.; Almagro, U.A.; Hellman, R.S.; Isitman, A.T. (Medical College of Wisconsin, Milwaukee (USA))

1990-05-01

A case of idiopathic pulmonary fibrosis with multiple areas of mismatch on ventilation-perfusion lung imaging in the absence of pulmonary embolism is presented. Idiopathic pulmonary fibrosis is one of the few nonembolic diseases producing a pulmonary ventilation-perfusion mismatch. In this condition, chest radiographs may not detect the full extent of disease, and xenon-133 ventilation imaging may be relatively insensitive to morbid changes in small airways. Thus, when examining patients with idiopathic pulmonary fibrosis, one should be aware that abnormal perfusion imaging patterns without matching ventilation abnormalities are not always due to embolism. In this setting, contrast pulmonary angiography is often needed for accurate differential diagnosis.

CT appearance of pulmonary ligament

Energy Technology Data Exchange (ETDEWEB)

Im, Jung Gi; Han, Man Chung; Chin, Soo Yil [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1984-03-15

Pulmonary ligament consists of 2 serosal of pleura that connect the lower to the mediastinum. Author analyse and present CT appearance of pulmonary ligament of the 40 normal and abnormal patients on the basis of anatomic knowledge from the cross section of cadaver. Left pulmonary ligament is more frequency visualized than the right. The most important CT landmark in localizing pulmonary ligament is the esophagus where the ligament attaches on its lateral wall. Pitfalls in CT identification of pulmonary ligament are right phrenic nerve and right pericardiacophrenic vessels which emerge from lateral wall of the IVC and wall of the emphysematous bulla in the region of the pulmonary ligament.

CT appearance of pulmonary ligament

International Nuclear Information System (INIS)

Im, Jung Gi; Han, Man Chung; Chin, Soo Yil

1984-01-01

Pulmonary ligament consists of 2 serosal of pleura that connect the lower to the mediastinum. Author analyse and present CT appearance of pulmonary ligament of the 40 normal and abnormal patients on the basis of anatomic knowledge from the cross section of cadaver. Left pulmonary ligament is more frequency visualized than the right. The most important CT landmark in localizing pulmonary ligament is the esophagus where the ligament attaches on its lateral wall. Pitfalls in CT identification of pulmonary ligament are right phrenic nerve and right pericardiacophrenic vessels which emerge from lateral wall of the IVC and wall of the emphysematous bulla in the region of the pulmonary ligament

Pulmonary manifestation of leptospirosis: Clinical and experimental correlation

International Nuclear Information System (INIS)

Im, J.G.; Yeon, K.M.; Han, M.C.; Kim, C.W.; Chang, W.H.; Lee, J.S.

1987-01-01

Pulmonary radiographic findings were noted in 24 (56%) of 43 patients with leptospirosis, proved by positive serology. Three radiographic patterns were evident: (1) small nodular densities (n = 11), (2) patchy or confluent consolidation (n = 4), and (3) diffuse ill-defined groundglass density (n = 9). Abnormalities were bilateral, nonlobar, and peripheral. Pulmonary abnormalities all resolved within 10 days, except in three patients who died. Artificial infection was induced through intraperitoneal injection of Leptospira interohemorrhagiae into 20 guinea pigs. The lungs from the guinea pigs initially showed petechial hemorrhage which progressed to large confluent ares of hemorrhage. The typical pulmonary radiographic findings of leptopirosis are compatible with the multifocal pulmonary hemorrhage seen in the guinea pigs

Neutrophil extracellular traps - the dark side of neutrophils

DEFF Research Database (Denmark)

Sørensen, Ole E.; Borregaard, Niels

2016-01-01

Neutrophil extracellular traps (NETs) were discovered as extracellular strands of decondensed DNA in complex with histones and granule proteins, which were expelled from dying neutrophils to ensnare and kill microbes. NETs are formed during infection in vivo by mechanisms different from those ori...

Pulmonary ventilation and perfusion abnormalities and ventilation perfusion imbalance in children with pulmonary atresia or extreme tetralogy of Fallot

Energy Technology Data Exchange (ETDEWEB)

Dowdle, S.C.; Human, D.G.; Mann, M.D. (Univ. of Cape Town (South Africa))

1990-08-01

Xenon-133 lung ventilation and perfusion scans were done preoperatively after cardiac catheterization and cineangiocardiography in 19 children; 6 had pulmonary atresia with an intact ventricular septum and hypoplastic right ventricle, 4 pulmonary atresia with associated complex univentricular heart, and 9 extreme Tetralogy of Fallot. The four patients with discrepancies in the sizes of the left and right pulmonary arteries on angiography had marked asymmetry of pulmonary perfusion and ventilation-perfusion imbalance on scintigraphy. Similar degrees of asymmetry and imbalance were present in 6 of the 15 children with equal-size pulmonary vessels. Asymmetry of pulmonary perfusion and ventilation-perfusion imbalance were associated with a poor prognosis.

Pulmonary ventilation and perfusion abnormalities and ventilation perfusion imbalance in children with pulmonary atresia or extreme tetralogy of Fallot

International Nuclear Information System (INIS)

Dowdle, S.C.; Human, D.G.; Mann, M.D.

1990-01-01

Xenon-133 lung ventilation and perfusion scans were done preoperatively after cardiac catheterization and cineangiocardiography in 19 children; 6 had pulmonary atresia with an intact ventricular septum and hypoplastic right ventricle, 4 pulmonary atresia with associated complex univentricular heart, and 9 extreme Tetralogy of Fallot. The four patients with discrepancies in the sizes of the left and right pulmonary arteries on angiography had marked asymmetry of pulmonary perfusion and ventilation-perfusion imbalance on scintigraphy. Similar degrees of asymmetry and imbalance were present in 6 of the 15 children with equal-size pulmonary vessels. Asymmetry of pulmonary perfusion and ventilation-perfusion imbalance were associated with a poor prognosis

Congenital Pulmonary Malformation in Children

OpenAIRE

Nadeem, Montasser; Elnazir, Basil; Greally, Peter

2012-01-01

Congenital Pulmonary Malformations (CPMs) are a group of rare lung abnormalities affecting the airways, parenchyma, and vasculature. They represent a spectrum of abnormal development rather than discrete pathological entities. They are caused by aberrant embryological lung development which occurs at different stages of intrauterine life.

Ozone-induced airway hyperresponsiveness in patients with asthma: role of neutrophil-derived serine proteinases.

Science.gov (United States)

Hiltermann, T J; Peters, E A; Alberts, B; Kwikkers, K; Borggreven, P A; Hiemstra, P S; Dijkman, J H; van Bree, L A; Stolk, J

1998-04-01

Proteinase inhibitors may be of potential therapeutic value in the treatment of respiratory diseases such as chronic obstructive pulmonary disease (COPD) or asthma. Our aim was to study the role of neutrophils, and neutrophil-derived serine proteinases in an acute model in patients with asthma. Exposure to ozone induces an acute neutrophilic inflammatory reaction accompanied by an increase in airway hyperresponsiveness. It is thought that these two effects of ozone are linked, and that neutrophil-derived serine proteinases (i.e. elastase) may play a role in the ozone-induced airway hyperresponsiveness. Therefore, we examined the effect of recombinant antileukoprotease (rALP), one of the major serine proteinase inhibitors in the lung, on ozone-induced changes in airway hyperresponsiveness in this model. We observed that 16 h after exposure to ozone, airway hyperresponsiveness to methacholine was increased both following placebo and rALP treatment. There was no significant difference between placebo and rALP treatment (change in area under the dose-response curve to methacholine: 117.3+/-59.0 vs 193.6+/-59.6 % fall x DD; p=.12). Moreover, the immediate decrease in FEV1 after ozone exposure was not significantly different between the two groups (placebo: -29.6+/-6.7%; rALP: -20.9+/-3.8%; p=.11). In addition, no significant differences were observed in plasma levels of fibrinogen degradation products generated by neutrophil serine proteinases before and after exposure to ozone. We conclude that neutrophil-derived serine proteinases are not important mediators for ozone-induced hyperresponsiveness.

Hereditary Hemorrhagic Telangiectasia (HHT) and Pulmonary Hypertension

Science.gov (United States)

... has said these might be symptoms of pulmonary hypertension. How does this relate to my HHT? About ... differences are significant. In HHT-associated pulmonary arterial hypertension, abnormal blood flow through the blood vessels in ...

A correlative study of CT findings and pulmonary function in patients with pulmonary involvement during the active phase of rheumatoid arthritis

International Nuclear Information System (INIS)

Zhu Xiaolei; Xu Defu

2006-01-01

Objective: It is a correlative study of CT findings and pulmonary function in patients with pulmonary involvement during the active phase of rheumatoid arthritis. Methods: The CT images of 28 cases of pulmonary involvement during the active phase of rheumatoid arthritis were retrospectively analyzed. The pulmonary abnormalities revealed on CT images including distribution and extend of the lesions were quantitatively analyzed and scored. The correlation of CT scores with the results of pulmonary function tests was compared statistically. Results: Interlobular septa thickening was shown in 16 cases; ground-glass opacification was revealed in 14 cases; irregular lines were found in 11 cases; bronchiolectasis was noted in 7 cases; micro nodules were demonstrated in 4 cases; and honey combing alteration was visualized in 3 cases. The abnormality most frequent seen on CT images was reticular shadow and ground-glass opacification. CT visual score had a negative correlation with pulmonary function. Conclusion: CT visual score provides quantitative evaluation of the pulmonary involvement during the active phase of rheumatoid arthritis, and also indicates the pulmonary function and prognosis as well. (authors)

A case of intralobar pulmonary sequestration

International Nuclear Information System (INIS)

Hongo, Minoru; Kambayashi, TakayukiF; Okubo, Shinichi

1983-01-01

A 41 year-old male was admitted to our hospital, complaining of slight fever, dry cough and general fatigue. On auscultation, bubbling rales were audible at the mid to lower portion of left posterior chest. Plain chest roentgenogram showed multiple cystic shadows with an air-fluid level in the left lower lobe. An abnormal finger-like shadow, which extended from the left hemidiaphragm to the multiple cysts, was found on lateral chest tomogram. Bronchogram revealed cystic dilatation of left B6 and B10. Computed tomogram with contrast enhancement demonstrated multiple cysts and an abnormal round-shaped structure, consisted of high density material, in the left lower lung. At the level of 12 mm below the round-shaped structure, an abnormal finger-like structure contiguous to the thoracic descending aorta was demonstrated. The density of these abnormal structures was 80 Hounsfield units, which was the same as that of the descending aorta. Thoracic aortogram disclosed an abnormal artery arising from the thoracic descending aorta, just above the left hemidiaphragm, which proceeded to the left lower lung horizontally, and extended to superior direction and divided into multiple branches. These vessels drained into the left atrium via left lower pulmonary vein. Diagnosis of intralobar pulmonary sequestration was confirmed by operation and consequently, the sequestered lung and the abnormal artery were successfully removed. It is emphasized that computed tomography with contrast enhancement is useful to detect the abnormal artery of pulmonary sequestration and that this method should be used to evaluate the vascular relationship of lung lesions. (author)

Abnormal Gas Diffusing Capacity and Portosystemic Shunt in Patients With Chronic Liver Disease

Science.gov (United States)

Park, Moon-Seung; Lee, Min-Ho; Park, Yoo-Sin; Kim, Shin-Hee; Kwak, Min-Jung; Kang, Ju-Seop

2012-01-01

Background Pulmonary dysfunctions including the hepatopulmonary syndrome and portosystemic shunt are important complications of hepatic cirrhosis. To investigate the severity and nature of abnormal gas diffusing capacity and its correlation to portosystemic shunt in patients with chronic liver disease. Methods Forty-four patients with chronic liver disease (15 chronic active hepatitis (CAH), 16 Child-Pugh class A, and 13 Child-Pugh class B) without other diseases history were enrolled in the study. Evaluation of liver function tests, arterial blood gases analysis, ultrasonography, pulmonary function test including lung diffusing capacity of carbon monoxide (DLco), forced vital capacity(FVC), forced expiratory volume 1 seconds(FEV1), total lung capacity(TLC), DLco/AV(alveolar volume) and thallium-201 per rectum scintigraphy were performed. We were analyzed correlations between pulmonary function abnormalities and heart/liver (H/L) ratio in patients with chronic liver diseases. Results In CAH, percentage of patients with DLco and DLco/VA (Child-Pugh class A and B patients. The means of DLco and DLco/VA were significantly (P Child-Pugh class. The mean H/L ratio in Child-Pugh class B increased markedly (P Child-Pugh class A. The frequency of specific pulmonary function abnormality in patients with Child-Pugh class B was significantly (P Child-Pugh class A and CAH. There was a inverse linear correlation between H/L ratio and DLco (r = -0.339, P < 0.05) and DLco/VA (r = -0.480, P < 0.01). Conclusion A total of 62% of patients with advanced liver disease have abnormal pulmonary diffusion capacity with a reduced DLco or DLco/VA and abnormal portosystemic shunt (increased H/L ratio) is common hemodynamic abnormality. Therefore, inverse linear correlation between DLco or DLco/VA and H/L ratio may be an important factor in predicting pulmonary complication and meaningful diagnostic and prognostic parameters in patients with advanced chronic liver disease. PMID:27785203

Targeting neutrophilic inflammation in severe neutrophilic asthma : can we target the disease-relevant neutrophil phenotype?

NARCIS (Netherlands)

Bruijnzeel, Piet L B; Uddin, Mohib; Koenderman, Leo

2015-01-01

In severe, neutrophilic asthma, neutrophils are thought to have an important role in both the maintenance of the disease and during exacerbations. These patients often display excessive, mucosal airway inflammation with unresolving neutrophilia. Because this variant of asthma is poorly controlled by

Cytokine–Ion Channel Interactions in Pulmonary Inflammation

Science.gov (United States)

Hamacher, Jürg; Hadizamani, Yalda; Borgmann, Michèle; Mohaupt, Markus; Männel, Daniela Narcissa; Moehrlen, Ueli; Lucas, Rudolf; Stammberger, Uz

2018-01-01

The lungs conceptually represent a sponge that is interposed in series in the bodies’ systemic circulation to take up oxygen and eliminate carbon dioxide. As such, it matches the huge surface areas of the alveolar epithelium to the pulmonary blood capillaries. The lung’s constant exposure to the exterior necessitates a competent immune system, as evidenced by the association of clinical immunodeficiencies with pulmonary infections. From the in utero to the postnatal and adult situation, there is an inherent vital need to manage alveolar fluid reabsorption, be it postnatally, or in case of hydrostatic or permeability edema. Whereas a wealth of literature exists on the physiological basis of fluid and solute reabsorption by ion channels and water pores, only sparse knowledge is available so far on pathological situations, such as in microbial infection, acute lung injury or acute respiratory distress syndrome, and in the pulmonary reimplantation response in transplanted lungs. The aim of this review is to discuss alveolar liquid clearance in a selection of lung injury models, thereby especially focusing on cytokines and mediators that modulate ion channels. Inflammation is characterized by complex and probably time-dependent co-signaling, interactions between the involved cell types, as well as by cell demise and barrier dysfunction, which may not uniquely determine a clinical picture. This review, therefore, aims to give integrative thoughts and wants to foster the unraveling of unmet needs in future research. PMID:29354115

A patient with common glycogen storage disease type Ib mutations without neutropenia or neutrophil dysfunction

NARCIS (Netherlands)

Martens, DHJ; Kuijpers, TW; Maianski, NA; Rake, JP; Smit, GPA; Visser, G

We describe a 16-year old boy with glycogen storage disease type Ib, homozygous for the common 1211-1212delCT mutation, who never experienced neutropenia, and did not suffer from frequent infections or inflammatory bowel disease. In addition, neutrophil function tests showed no abnormalities.

CT of pleural abnormalities

International Nuclear Information System (INIS)

Webb, W.R.

1995-01-01

Briefly discussed were CT diagnosis of pleural thickening, CT technique for examining the pleura or pleuro-pulmonary disease, diagnosis of pleural collections, diagnosis of pleural fluid abnormalities in patients with pneumonia, pleural neoplasms, malignant (diffuse) mesothelioma, metastases, local fibrous tumor of the pleura (benign mesothelioma) (21 refs.)

CT of pleural abnormalities

Energy Technology Data Exchange (ETDEWEB)

Webb, W R [California Univ., San Francisco, CA (United States). Dept. of Radiology

1996-12-31

Briefly discussed were CT diagnosis of pleural thickening, CT technique for examining the pleura or pleuro-pulmonary disease, diagnosis of pleural collections, diagnosis of pleural fluid abnormalities in patients with pneumonia, pleural neoplasms, malignant (diffuse) mesothelioma, metastases, local fibrous tumor of the pleura (benign mesothelioma) (21 refs.).

Congenital Pulmonary Malformation in Children

Directory of Open Access Journals (Sweden)

Montasser Nadeem

2012-01-01

Full Text Available Congenital Pulmonary Malformations (CPMs are a group of rare lung abnormalities affecting the airways, parenchyma, and vasculature. They represent a spectrum of abnormal development rather than discrete pathological entities. They are caused by aberrant embryological lung development which occurs at different stages of intrauterine life.

Clinical application of gadolinium-enhanced three-dimensional pulmonary MR angiography

International Nuclear Information System (INIS)

Takano, Katsuyuki

1999-01-01

Twenty-nine patients with suspected pulmonary lesions, and three normal volunteers, underwent gadolinium-enhanced three-dimensional (3D) pulmonary MR angiography (MRA). The MRA were obtained during intravenous administration of gadolinium-based contrast material, in a single breath-hold. Conspicuity of the normal pulmonary segmental arteries was estimated on the MRA. Abnormal findings such as ''vascular involvement'', ''abnormal connection'', stenosis'', or ''dilatation'' on the MRA were compared with those on conventional angiography or CT. Normal pulmonary segmental arteries, except for A 4,5,6,8and9 of the left pulmonary artery, could be clearly visualized. Blind reading of four different findings lead to characteristic findings for each pulmonary disease that can be aid in their differential diagnoses. This technique shows promise as a noninvasive diagnosis of lung diseases. (author)

Neutrophil evasion strategies by Streptococcus pneumoniae and Staphylococcus aureus.

Science.gov (United States)

Lewis, Megan L; Surewaard, Bas G J

2018-03-01

Humans are well equipped to defend themselves against bacteria. The innate immune system employs diverse mechanisms to recognize, control and initiate a response that can destroy millions of different microbes. Microbes that evade the sophisticated innate immune system are able to escape detection and could become pathogens. The pathogens Streptococcus pneumoniae and Staphylococcus aureus are particularly successful due to the development of a wide variety of virulence strategies for bacterial pathogenesis and they invest significant efforts towards mechanisms that allow for neutrophil evasion. Neutrophils are a primary cellular defense and can rapidly kill invading microbes, which is an indispensable function for maintaining host health. This review compares the key features of Streptococcus pneumoniae and Staphylococcus aureus in epidemiology, with a specific focus on virulence mechanisms utilized to evade neutrophils in bacterial pathogenesis. It is important to understand the complex interactions between pathogenic bacteria and neutrophils so that we can disrupt the ability of pathogens to cause disease.

Pulmonary vascular anomalies: a review of clinical and radiological findings of cases presenting with different complaints in childhood.

Science.gov (United States)

Nacaroğlu, Hikmet Tekin; Ünsal-Karkıner, Canan Şule; Bahçeci-Erdem, Semiha; Özdemir, Rahmi; Karkıner, Aytaç; Alper, Hüdaver; Can, Demet

2016-01-01

Congenital pulmonary vascular abnormalities arise from several etiologies. These anomalies are difficult to categorize and sorted into distinct classifications. Major pulmonary vascular abnormalities can be ranked as interruption of the main pulmonary artery or its absence, emergence of the left pulmonary artery in the right pulmonary artery, pulmonary venous drainage abnormalities, and pulmonary arteriovenous malformations (PAVMs). Some of the cases are asymptomatic and diagnosed by coincidence, whereas a few of them are diagnosed by typical findings in the newborn and infancy period, symptoms, and radiological appearances. Early diagnosis is important, since death may occur as a result of pulmonary and cardiac pathologies developed in patients with pulmonary vascular anomalies. In this case presentation, the clinical and radiological findings of patients that presented with different complaints and were diagnosed with pulmonary vascular anomalies were introduced.

Genomic profiling of neutrophil transcripts in Asian Qigong practitioners: a pilot study in gene regulation by mind-body interaction.

Science.gov (United States)

Li, Quan-Zhen; Li, Ping; Garcia, Gabriela E; Johnson, Richard J; Feng, Lili

2005-02-01

The great similarity of the genomes of humans and other species stimulated us to search for genes regulated by elements associated with human uniqueness, such as the mind-body interaction. DNA microarray technology offers the advantage of analyzing thousands of genes simultaneously, with the potential to determine healthy phenotypic changes in gene expression. The aim of this study was to determine the genomic profile and function of neutrophils in Falun Gong (FLG, an ancient Chinese Qigong) practitioners, with healthy subjects as controls. Six (6) Asian FLG practitioners and 6 Asian normal healthy controls were recruited for our study. The practitioners have practiced FLG for at least 1 year (range, 1-5 years). The practice includes daily reading of FLG books and daily practice of exercises lasting 1-2 hours. Selected normal healthy controls did not perform Qigong, yoga, t'ai chi, or any other type of mind-body practice, and had not followed any conventional physical exercise program for at least 1 year. Neutrophils were isolated from fresh blood and assayed for gene expression, using microarrays and RNase protection assay (RPA), as well as for function (phagocytosis) and survival (apoptosis). The changes in gene expression of FLG practitioners in contrast to normal healthy controls were characterized by enhanced immunity, downregulation of cellular metabolism, and alteration of apoptotic genes in favor of a rapid resolution of inflammation. The lifespan of normal neutrophils was prolonged, while the inflammatory neutrophils displayed accelerated cell death in FLG practitioners as determined by enzyme-linked immunosorbent assay. Correlating with enhanced immunity reflected by microarray data, neutrophil phagocytosis was significantly increased in Qigong practitioners. Some of the altered genes observed by microarray were confirmed by RPA. Qigong practice may regulate immunity, metabolic rate, and cell death, possibly at the transcriptional level. Our pilot study

Protective effect of Galectin-9 in murine model of lung emphysema: Involvement of neutrophil migration and MMP-9 production

Science.gov (United States)

Horio, Yuko; Ichiyasu, Hidenori; Kojima, Keisuke; Saita, Naoki; Migiyama, Yohei; Iriki, Toyohisa; Fujii, Kazuhiko; Niki, Toshiro; Hirashima, Mitsuomi; Kohrogi, Hirotsugu

2017-01-01

Purpose Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and pulmonary emphysema. Persistent inflammation and remodeling of the lungs and airways result in reduced lung function and a lower quality of life. Galectin (Gal)-9 plays a crucial role as an immune modulator in various diseases. However, its role in the pathogenesis of pulmonary emphysema is unknown. This study investigates whether Gal-9 is involved in pulmonary inflammation and changes in emphysema in a porcine pancreatic elastase (PPE)-induced emphysema model. Materials and methods Gal-9 was administered to mice subcutaneously once daily from 1 day before PPE instillation to day 5. During the development of emphysema, lung tissue and bronchoalveolar lavage fluid (BALF) were collected. Histological and cytological findings, concentrations of chemokines and matrix metalloproteinases (MMPs) in the BALF, and the influence of Gal-9 treatment on neutrophils were analyzed. Results Gal-9 suppressed the pathological changes of PPE-induced emphysema. The mean linear intercept (Lm) of Gal-9-treated emphysema mice was significantly lower than that of PBS-treated emphysema mice (66.1 ± 3.3 μm vs. 118.8 ± 14.8 μm, respectively; p emphysema progressed significantly compared with that in wild–type (WT) mice (108.7 ± 6.58 μm vs. 77.19 ± 6.97 μm, respectively; p emphysema by inhibiting the infiltration of neutrophils and decreasing MMPs levels. Exogenous Gal-9 could be a potential therapeutic agent for COPD. PMID:28704475

Fibrosis pulmonar asociada a vasculitis con anticuerpos anticitoplasmáticos positivos Pulmonary fibrosis associated with anti-neutrophil cytoplasmic antibody-positive vasculitis

Directory of Open Access Journals (Sweden)

Marcelo Fernández Casares

2012-08-01

Full Text Available Las complicaciones pulmonares más conocidas de las vasculitis con anticuerpos anticitoplasmáticos de los neutrófilos (ANCA positivos (VAA, son la hemorragia alveolar, los granulomas y la estenosis de la vía aérea. En los últimos años han aparecido algunos informes aislados que muestran la asociación con fibrosis pulmonar (FP, sugiriendo que ésta sería otra complicación de las VAA. En este trabajo informamos dos casos con dicha asociación describiendo sus características clínicas, tomográficas e inmunológicas. Dado que en la asociación de FP y VAA notificada en los últimos años, la FP puede ser su primera manifestación, podría ser necesaria la búsqueda de ANCA en pacientes con FP, como causa de la misma y por el posible desarrollo posterior de vasculitis.The most frequently observed pulmonary complications of vasculitis (AAV with anti-neutrophil cytoplasmic positive antibodies (ANCA are alveolar hemorrhage, granulomas and airway stenosis. In recent years, some reports have been published that show the association of vasculitis with pulmonary fibrosis (PF, suggesting that it may be another complication of AAV. We report and describe here two cases with such association, and their clinical, tomographic and immunological characteristics. Given that in the association between PF and AAV, as reported in the last years, PF could be the first manifestation of AAV, the search for ANCA in patients with PF may be necessary, as a cause of it and for the possible subsequent development of vasculitis.

Prognostic value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in acute pulmonary embolism: a systematic review and meta-analysis.

Science.gov (United States)

Wang, Qian; Ma, Junfen; Jiang, Zhiyun; Ming, Liang

2018-02-01

Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been reported to predict prognosis of acute pulmonary embolism (PE). However, the prognostic value of NLR and PLR remained inconsistent between studies. The aim of this meta-analysis was to assess the prognostic role of NLR and PLR in acute PE. We systematically searched Pubmed, Embase, Web of Science and CNKI for relative literature up to March 2017. The pooled statistics for all outcomes were expressed as odds ratio (OR) and 95% confidence intervals (95% CI). The statistical analyses were performed using Review Manager 5.3.5 analysis software and Stata software. Totally 7 eligible studies consisting of 2323 patients were enrolled in our meta-analysis. Elevated NLR was significantly associated with overall (short-term and long-term) mortality (OR 10.13, 95% CI 6.57-15.64, Panalysis revealed that NLR and PLR are promising biomarkers in predicting prognosis in acute PE patients. We suggest NLR and PLR be used routinely in the PE prognostic assessment.

Pulmonary epithelial clearance of 99mTc-DTPA after thrombin-induced pulmonary microembolism

International Nuclear Information System (INIS)

Cooper, J.A.; Feustel, P.J.; Line, B.R.; Malik, A.B.

1986-01-01

We investigated the effect of thrombin-induced pulmonary microembolism on the pulmonary clearance rate of aerosolized 99mTc diethylenetriamine pentaacetic acid (99mTc-DTPA) in awake, chronically prepared sheep. Chest activity was recorded after administration of a 0.44 micron aerosol of 99mTc-DTPA. Decay-corrected data were fit to an exponential and expressed as percent decrease per min (%/min). Sheep were given alpha-thrombin intravenously (80 U/kg for 10 min) 60 min after the aerosol administration. The clearance rate prior to alpha-thrombin was 0.35 +/- 0.05 %/min (mean +/- SEM). During alpha-thrombin administration, the clearance rate increased to 5.84 +/- 0.70 %/min (p less than 0.001 from baseline), but returned to 0.41 +/- 0.06 %/min within 30 min after the end of the thrombin infusion. The increased clearance rate during alpha-thrombin administration was not due to increased lung volume since alpha-thrombin did not change functional residual capacity. Moreover, the clearance rate was unchanged during gamma-thrombin administration, which does not induce coagulation, or during alpha-thrombin challenge in defibrinogenated animals. alpha-thrombin administration in neutrophil-depleted sheep caused a transient increase in DTPA clearance similar to that in control sheep, suggesting that the increase occurred independently of neutrophils. The results indicate that alpha-thrombin causes a large, transient increase in 99mTc-DTPA clearance, which may be the result of increased epithelial permeability. This response is dependent on the activation of intravascular coagulation

Pleural and pulmonary alterations caused by rheumatoid arthritis

International Nuclear Information System (INIS)

Bankier, A.A.; Fleischmann, D.; Kiener, H.P.; Wiesmayr, M.N.; Herold, C.J.

1996-01-01

Pulmonary complications caused by rheumatoid arthritis are a clinically relevant aspect of this chronic arthropathy. This article reviews pulmonary abnormalities induced by rheumatoid arthritis and their clinical and radiological findings. In addition, the role of different imaging modalities in the diagnostic work-up of pulmonary complications caused by rheumatoid arthritis is discussed. (orig./MG) [de

Pulmonary function in infants with swallowing dysfunction.

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James D Tutor

Full Text Available Swallowing dysfunction can lead to recurring aspiration and is frequently associated with chronic symptoms such as cough and wheezing in infants. Our objective was to describe the characteristics of infants with swallowing dysfunction, determine if pulmonary function abnormalities are detectable, and if they improve after therapy.We studied 38 infants with a history of coughing and wheezing who had pulmonary function tests performed within two weeks of their diagnosis of swallowing dysfunction. The raised lung volume rapid thoracoabdominal compression technique was used. After 6 months of therapy, 17 of the infants repeated the tests.Initially, 25 had abnormal spirometry, 18 had abnormal plethysmography, and 15 demonstrated bronchodilator responsiveness. Six months later test were repeated for seventeen patients. Ten patients had continued abnormal spirometry, two patients remained normal, three patients' abnormal spirometry had normalized, and two patients' previously normal studies became abnormal. Eight of the 17 patients had continued abnormal plethysmography, six had continued normal plethysmography, and three patients' normal plethysmography became abnormal. After 6 months of treatment, eight patients demonstrated bronchodilator responsiveness, of which five continued to demonstrate bronchodilator responsiveness and three developed responsiveness. The remainder either continued to be non- bronchodilator responsive (two or lost responsiveness (three. The findings of the abnormal tests in most infants tested is complicated by frequent occurrence of other co-morbidities in this population, including gastroesophageal reflux in 23 and passive smoke exposure in 13 of the infants.The interpretation of lung function changes is complicated by the frequent association of swallowing dysfunction with gastroesophageal reflux and passive smoke exposure in this population. Six months of medical therapy for swallowing dysfunction/gastroesophageal reflux

Histopathology of the great vessels in patients with pulmonary arterial hypertension in association with congenital heart disease: large pulmonary arteries matter too.

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Prapa, Matina; McCarthy, Karen P; Dimopoulos, Konstantinos; Sheppard, Mary N; Krexi, Dimitra; Swan, Lorna; Wort, S John; Gatzoulis, Michael A; Ho, Siew Yen

2013-10-03

Pulmonary arterial hypertension (PAH) is considered primarily a disease of the distal pulmonary arteries whereas little is known on the effect of long-standing pulmonary hypertension on the larger proximal pulmonary arteries. This study aims to investigate the structural changes in the great arteries of adults who developed PAH in association with congenital heart disease (CHD), with severe cases termed Eisenmenger syndrome. We performed macroscopic and light microscopy analyses on the great arteries of 10 formalin-fixed human hearts from patients with PAH/CHD and compared them to age-matched healthy controls. A detailed histology grading score was used to assess the severity of medial wall abnormalities. Severe atherosclerotic lesions were found macroscopically in the elastic pulmonary arteries of 4 PAH/CHD specimens and organised thrombi in 3; none were present in the controls. Significant medial wall abnormalities were present in the pulmonary trunk (PT), including fibrosis (80%), and atypical elastic pattern (80%). Cyst-like formations were present in less than one third of patients and were severe in a single case leading to wall rupture. The cumulative PT histology grading score was significantly higher in PAH/CHD cases compared to controls (parteries. These abnormalities are likely to affect haemodynamics and contribute to morbidity and mortality in this cohort. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Concomitant elevations of MMP-9, NGAL, proMMP-9/NGAL and neutrophil elastase in serum of smokers with chronic obstructive pulmonary disease.

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Bchir, Sarra; Nasr, Hela Ben; Bouchet, Sandrine; Benzarti, Mohamed; Garrouch, Abdelhamid; Tabka, Zouhair; Susin, Santos; Chahed, Karim; Bauvois, Brigitte

2017-07-01

A growing body of evidence points towards smoking-related phenotypic differences in chronic obstructive pulmonary disease (COPD). As COPD is associated with systemic inflammation, we determined whether smoking status is related to serum levels of matrix metalloproteinase-9 (pro- and active MMP-9), neutrophil gelatinase-associated lipocalin (NGAL) and the proMMP-9/NGAL complex in patients with COPD. Serum samples were collected in 100 stable-phase COPD patients (82 smokers, 18 never-smokers) and 28 healthy adults (21 smokers, 7 never-smokers). Serum levels of studied factors were measured in ELISA. Our data provide the first evidence of simultaneously elevated serum levels of MMP-9, NGAL and proMMP-9/NGAL in COPD smokers. While the triad discriminated between smokers and non-smokers in the COPD group, MMP-9 and proMMP-9/NGAL (but not NGAL) discriminated between smokers with and without COPD. Adjustment for age and smoking pack-years did not alter the findings. Serum MMP-9, NGAL and proMMP-9/NGAL levels were not correlated with the GOLD stage or FEV1 decline. Furthermore, serum levels of neutrophil elastase (NE) and MMP-3 (but not of IL-6 and MMP-12) were also higher in COPD smokers than in healthy smokers before and after adjustment for age and pack-years. Among COPD smokers, levels of MMP-9, NGAL and proMMP-9/NGAL were positively correlated with NE (P < 0.0001) but not with the remaining factors. Gelatin zymography detected proMMP-9 in serum samples of healthy and COPD smoking groups. Our results suggest that associated serum levels of proMMP-9, NGAL, proMMP-9/NGAL and NE may reflect the state of systemic inflammation in COPD related to cigarette smoking. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

The role of heparanase in pulmonary cell recruitment in response to an allergic but not non-allergic stimulus.

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Abigail Morris

Full Text Available Heparanase is an endo-β-glucuronidase that specifically cleaves heparan sulfate proteoglycans in the extracellular matrix. Expression of this enzyme is increased in several pathological conditions including inflammation. We have investigated the role of heparanase in pulmonary inflammation in the context of allergic and non-allergic pulmonary cell recruitment using heparanase knockout (Hpa-/- mice as a model. Following local delivery of LPS or zymosan, no significant difference was found in the recruitment of neutrophils to the lung between Hpa-/- and wild type (WT control. Similarly neutrophil recruitment was not inhibited in WT mice treated with a heparanase inhibitor. However, in allergic inflammatory models, Hpa-/- mice displayed a significantly reduced eosinophil (but not neutrophil recruitment to the airways and this was also associated with a reduction in allergen-induced bronchial hyperresponsiveness, indicating that heparanase expression is associated with allergic reactions. This was further demonstrated by pharmacological treatment with a heparanase inhibitor in the WT allergic mice. Examination of lung specimens from patients with different severity of chronic obstructive pulmonary disease (COPD found increased heparanase expression. Thus, it is established that heparanase contributes to allergen-induced eosinophil recruitment to the lung and could provide a novel therapeutic target for the development of anti-inflammatory drugs for the treatment of asthma and other allergic diseases.

γδ T cells are required for pulmonary IL-17A expression after ozone exposure in mice: role of TNFα.

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Joel A Mathews

Full Text Available Ozone is an air pollutant that causes pulmonary symptoms. In mice, ozone exposure causes pulmonary injury and increases bronchoalveolar lavage macrophages and neutrophils. We have shown that IL-17A is important in the recruitment of neutrophils after subacute ozone exposure (0.3 ppm for 24-72 h. We hypothesized that γδ T cells are the main producers of IL-17A after subacute ozone. To explore this hypothesis we exposed wildtype mice and mice deficient in γδ T cells (TCRδ-/- to ozone or room air. Ozone-induced increases in BAL macrophages and neutrophils were attenuated in TCRδ-/- mice. Ozone increased the number of γδ T cells in the lungs and increased pulmonary Il17a mRNA expression and the number of IL-17A+ CD45+ cells in the lungs and these effects were abolished in TCRδ-/- mice. Ozone-induced increases in factors downstream of IL-17A signaling, including G-CSF, IL-6, IP-10 and KC were also decreased in TCRδ-/- versus wildtype mice. Neutralization of IL-17A during ozone exposure in wildtype mice mimicked the effects of γδ T cell deficiency. TNFR2 deficiency and etanercept, a TNFα antagonist, also reduced ozone-induced increases in Il17a mRNA, IL-17A+ CD45+ cells and BAL G-CSF as well as BAL neutrophils. TNFR2 deficient mice also had decreased ozone-induced increases in Ccl20, a chemoattractant for IL-17A+ γδ T cells. Il17a mRNA and IL-17A+ γδ T cells were also lower in obese Cpefat versus lean WT mice exposed to subacute ozone, consistent with the reduced neutrophil recruitment observed in the obese mice. Taken together, our data indicate that pulmonary inflammation induced by subacute ozone requires γδ T cells and TNFα-dependent recruitment of IL-17A+ γδ T cells to the lung.

Quantitative proteomics reveals differential biological processes in healthy neonatal cord neutrophils and adult neutrophils

KAUST Repository

Zhu, Jiang; Zhang, Huoming; Guo, Tiannan; Li, Wenying; Li, Huiyu; Zhu, Yi; Huang, Shiang

2014-01-01

Neonatal neutrophils are characterized by the immaturity of bactericidal mechanisms that contributes largely to neonatal mortality. However, underlying molecular mechanism associated with the immaturity remains incompletely understood. In this study, we performed comparative proteomic analysis on neonatal neutrophils derived from human cord blood and adult peripheral neutrophils. A total of 1332 proteins were identified and quantified, and 127 proteins were characterized as differentially expressed between adult and cord neutrophils. The differentially expressed proteins are mapped in KEGG pathways into five clusters and indicated impaired functions of neonatal neutrophils in proteasome, lysosome, phagosome, and leukocyte transendothelial migration. In particular, many proteins associated with NETosis, a critical mechanism for antimicrobial process and auto-clearance, were also found to be downregulated in cord neutrophils. This study represents a first comparative proteome profiling of neonatal and adult neutrophils, and provides a global view of differentially expressed proteome for enhancing our understanding of their various functional difference. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantitative proteomics reveals differential biological processes in healthy neonatal cord neutrophils and adult neutrophils

KAUST Repository

Zhu, Jiang

2014-06-11

Neonatal neutrophils are characterized by the immaturity of bactericidal mechanisms that contributes largely to neonatal mortality. However, underlying molecular mechanism associated with the immaturity remains incompletely understood. In this study, we performed comparative proteomic analysis on neonatal neutrophils derived from human cord blood and adult peripheral neutrophils. A total of 1332 proteins were identified and quantified, and 127 proteins were characterized as differentially expressed between adult and cord neutrophils. The differentially expressed proteins are mapped in KEGG pathways into five clusters and indicated impaired functions of neonatal neutrophils in proteasome, lysosome, phagosome, and leukocyte transendothelial migration. In particular, many proteins associated with NETosis, a critical mechanism for antimicrobial process and auto-clearance, were also found to be downregulated in cord neutrophils. This study represents a first comparative proteome profiling of neonatal and adult neutrophils, and provides a global view of differentially expressed proteome for enhancing our understanding of their various functional difference. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Late cardiac, thyroid, and pulmonary sequelae of mantle radiotherapy for Hodgkin's disease

International Nuclear Information System (INIS)

Morgan, G.W.; Freeman, A.P.; McLean, R.G.; Jarvie, B.H.; Giles, R.W.

1985-01-01

Cardiac, thyroid and pulmonary function were evaluated in 25 patients aged 35 years or under, treated for Hodgkin's disease by mantle radiotherapy 5-16 years previously. No patient had symptoms of heart disease. Although thallium myocardial perfusion scintigraphy was normal in all patients, abnormalities of myocardial function were detected in 6 (24%) patients using gated equilibrium rest and exercise radionuclide ventriculography. Resting left ventricular ejection fraction (LVEF) was abnormal in 1 patient, and in 3 patients there was an abnormal LVEF response to exercise. All 6 patients had right ventricular dilatation. Apical hypokinesia was present in 4 of these patients. A small asymptomatic pericardial effusion was detected by M-Mode echocardiography in only 2 (8%) patients. Twenty-three (92%) patients had evidence of abnormal thyroid function. Two (8%) patients had become clinically hypothyroid. Serum TSH was elevated in 13 (52%) patients and TRH stimulation test was abnormal in a further 10 (40%) patients in whom TSH was normal. Pulmonary function studies showed a moderate decrease in diffusing capacity (72% of predicted) and a minor reduction in lung volume. Although a high incidence of cardiac, thyroid and pulmonary abnormalities was detected, only the 2 patients who had become hypothyroid were symptomatic. Modification of the irradiation technique may reduce the incidence of cardiac abnormalities, but is unlikely to alter significantly the thyroid or pulmonary sequelae

Imaging findings of disseminated pulmonary tuberculosis in patients with acquired immunodeficiency syndrome

International Nuclear Information System (INIS)

Song Wenyan; Zhao Zuqi; Zhao Dawei; Jia Cuiyu; Zhang Ruichi; Liu JinXin; Guan Wanhua; Liang Yi

2013-01-01

Objective: To study the imaging findings of disseminated pulmonary tuberculosis in patients with acquired immunodeficiency syndrome (AIDS). Methods: X-ray and multi-slice CT (MSCT) data from 33 AIDS patients with disseminated pulmonary tuberculosis confirmed by clinical manifestations and laboratory tests were analyzed retrospectively. Results: Thirty patients underwent initial chest radiography examination, 29 patients showed abnormal appearances, including bilateral disseminations in 21 patients and unilateral multiple disseminations in 8 patients. All patients underwent MSCT examination, 26 patients showed bilateral disseminations and 7 patients showed unilateral multiple disseminations. The abnormal pulmonary appearances included nodule (n = 25), miliary nodule (n = 22), air-space consolidation (n = 22), cavity (n = 11), fibrosis (n = 7), ground-glass opacity (n = 7), pneumatocele (n = 4), calcification (n = 2). There were 20 patients with more than 3 abnormal appearances and 13 patients with one or two abnormal appearances. The extra-pulmonary tuberculosis included pleural effusion (n = 33), lymphadenopathy (n = 30), intestinal tuberculosis (n = 3), splenic tuberculosis (n = 1) and cerebral tuberculosis (n = 1). Conclusion: Disseminated pulmonary tuberculosis should be highly suspected in AIDS patients with diffused nodules, miliary nodules, air-space consolidations or multiple cavities, accompanied with pleural effusion and lymphadenopathy. (authors)

Pulmonary perfusion scintigraphy in children with chronic pulmonary damage: Preliminary results from application of the SPECT technique

International Nuclear Information System (INIS)

Lobo S, Gabriel; Ladron de Guevara H, David; Munoz G, Maria Angelica; Araya A, Fernando; Coll C, Claudia; Donoso R, Gilda; Jimenez J, Cesar; Perez R; Andres

2003-01-01

The aim was to describe lung perfusion SPECT (LPS) findings in children with chronic pulmonary damage. Material and Method: We revised 106 LPS of children (age:3.9 ± 3.3 yr) with chronic pulmonary damage, performed with a two headed gamma camera. The most common clinical diagnosis were adenovirus bronchopneumonia sequelae (ADV)(29%), unknown origin chronic pulmonary damage (UOPD) (21%), bronchopulmonary dysplasia (BPD)(15%), and chronic obstructed bronchitis (COB)(14%). Severity of pulmonary alterations were evaluated using a Score, which considered extent and type of lung involvement and differential pulmonary perfusion. Pattern of involvement and Score were correlated with diagnosis and gender. Results: Ninety one percent (96/106) of LPS were abnormal (62% boys). Fifty two (54%) showed bilateral alterations, being this finding (p:0.019) more frequent in boys. ADV group showed mainly a mixed bilateral pattern (35%), UOPD a focal unilateral pattern (32%), COB a diffuse unilateral pattern (33%), and BPD a normal pattern (25%). Miscellaneous and UOPD showed the highest score values, and BPD and COB the lowest ones. Conclusion: In this population, LPS is abnormal in high proportion, with some differential characteristics according gender and original diagnosis (au)

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

Science.gov (United States)

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.

Oral neutrophil responses to acute prolonged exercise may not be representative of blood neutrophil responses.

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Davison, Glen; Jones, Arwel Wyn

2015-03-01

Neutrophil numbers and function (oxidative burst) were assessed in peripheral blood and oral samples before and after prolonged exercise. Blood neutrophil count increased (∼3.5-fold, P < 0.001) and function decreased (30% ± 19% decrease, P = 0.005) postexercise. Oral neutrophil count (P = 0.392) and function (P = 0.334) were unchanged. Agreement between oral and blood neutrophil function responses to exercise was poor. These findings highlight the importance of studying neutrophils within various compartments/sample types.

Synergistic interaction between a PDE5 inhibitor (sildenafil) and a new adenosine A2A receptor agonist (LASSBio-1359) improves pulmonary hypertension in rats.

Science.gov (United States)

Alencar, Allan K; Carvalho, Fábio I; Silva, Ananssa M; Martinez, Sabrina T; Calasans-Maia, Jorge A; Fraga, Carlos M; Barreiro, Eliezer J; Zapata-Sudo, Gisele; Sudo, Roberto T

2018-01-01

Pulmonary hypertension (PH) is characterized by enhanced pulmonary vascular resistance, which causes right ventricle (RV) pressure overload and results in right sided heart failure and death. This work investigated the effectiveness of a combined therapy with PDE5 inhibitor (PDE5i) and a new adenosine A2A receptor (A2AR) agonist in mitigating monocrotaline (MCT) induced PH in rats. An in vitro isobolographic analysis was performed to identify possible synergistic relaxation effect between sildenafil and LASSBio 1359 in rat pulmonary arteries (PAs). In the in vivo experiments, PH was induced in male Wistar rats by a single intraperitoneal injection of 60 mg/kg MCT. Rats were divided into the following groups: control (saline injection only), MCT + vehicle, MCT + sildenafil, MCT + LASSBio 1359 and MCT + combination of sildenafil and LASSBio 1359. Fourteen days after the MCT injection, rats were treated daily with oral administration of the regimen therapies or vehicle for 14 days. Cardiopulmonary system function and structure were evaluated by echocardiography. RV systolic pressure and PA endothelial function were measured. Isobolographic analysis showed a synergistic interaction between sildenafil and LASSBio 1359 in rat PAs. Combined therapy with sildenafil and LASSBio 1359 but not monotreatment with low dosages of either sildenafil or LASSBio 1359 ameliorated all of PH related abnormalities in cardiopulmonary function and structure in MCT challenged rats. The combination of sildenafil and LASSBio 1359 has a synergistic interaction, suggesting that combined use of these pharmacological targets may be an alternative to improve quality of life and outcomes for PH patients.

Assessment of anatomic relation between pulmonary perfusion and morphology in pulmonary emphysema with breath-hold SPECT-CT fusion images

International Nuclear Information System (INIS)

Suga, Kazuyoshi; Kawakami, Yasuhiko; Iwanaga, Hideyuki; Hayashi, Noriko; Seto, Akiko; Matsunaga, Naofumi

2008-01-01

Anatomic relation between pulmonary perfusion and morphology in pulmonary emphysema was assessed on deep-inspiratory breath-hold (DIBrH) perfusion single-photon emission computed tomography (SPECT)-CT fusion images. Subjects were 38 patients with pulmonary emphysema and 11 non-smoker controls, who successfully underwent DIBrH and non-BrH perfusion SPECT using a dual-headed SPECT system during the period between January 2004 and June 2006. DIBrH SPECT was three-dimensionally co-registered with DIBrH CT to comprehend the relationship between lung perfusion defects and CT low attenuation areas (LAA). By comparing the appearance of lung perfusion on DIBrH with non-BrH SPECT, the correlation with the rate constant for the alveolar-capillary transfer of carbon monoxide (DLCO/VA) was compared between perfusion abnormalities on these SPECTs and LAA on CT. DIBrH SPECT provided fairly uniform perfusion in controls, but significantly enhanced perfusion heterogeneity when compared with non-BrH SPECT in pulmonary emphysema patients (P<0.001). The reliable DIBrH SPECT-CT fusion images confirmed more extended perfusion defects than LAA on CT in majority (73%) of patients. Perfusion abnormalities on DIBrH SPECT were more closely correlated with DLCO/VA than LAA on CT (P<0.05). DIBrH SPECT identifies affected lungs with perfusion abnormality better than does non-BrH SPECT in pulmonary emphysema. DIBrH SPECT-CT fusion images are useful for more accurately localizing affected lungs than morphologic CT alone in this disease. (author)

Pulmonary functional MR imaging for COPD

International Nuclear Information System (INIS)

Ohno, Yoshiharu

2008-01-01

Chronic obstructive pulmonary disease (COPD) is a slowly progressive disease characterized by airflow limitation, cough, sputum production, and, at later stages, dyspnea. COPD is currently the fourth-leading cause of mortality and the twelfth-leading cause of disability, and by the year 2020 it is expected to be the third-leading cause of death and the fifth-leading cause of disability worldwide. The diagnosis of COPD largely relies on a history of exposure to noxious stimuli and abnormal lung function test results. Since the pathology of COPD varies and the molecular mechanisms are only slightly understood, the diagnosis and stage assessment of COPD have relied on the results of pulmonary function test. In addition, CT and nuclear medicine study are utilized for assessment of regional morphological and functional abnormalities. Recently, pulmonary functional MR imaging is suggested as a new technique for assessment of regional physiopathologic information in various pulmonary diseases including COPD, pulmonary thromboembolism, lung cancer and interstitial lung diseases. This review article covers the brief description of theory and clinical application of contrast-enhanced perfusion MR imaging; hyperpolarized noble gas MR imaging and oxygen-enhanced MR imaging in COPD subjects. We believe that further basic studies as well as clinical applications of this new technique will define the real significance of pulmonary functional MR imaging for the future of pulmonary functional imaging and its usefulness for diagnosis and patients' management in COPD. (author)

Study of pathophysiology of pulmonary circulation in polycythemia using scintigraphy

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Fujii, Tadashige; Tanaka, Masao; Takeda, Tadashi; Kawashima, Akira; Kubo, Keiji; Kobayashi, Toshio; Handa, Kenjiro; Yoshimura, Kazuhiko (Shinshu Univ., Matsumoto, Nagano (Japan). Faculty of Medicine)

1993-09-01

In order to evaluate the pathophysiology of pulmonary circulation in polycythemia, Tl-201 myocardial scintigraphy and perfusion lung scintigraphy with 99m-Tc-MAA were performed in 19 cases of polycythemia including polycythemia rubra vera and in 11 cases of secondary polycythemia due to pulmonary diseases. Tl-201 lung uptake, right ventricular visualization and pulmonary perfusion impairment were studied. In the 19 cases, Tl-201 lung uptake was observed in all cases and 54.5% of them showed moderate lung uptake. The grade of right ventricular visualization was moderate in one case and slight in 16 cases; right ventricular hypertrophy was shown in 89.5% of all cases by Tl-201 scintigraphy, only one of which showed right ventricular hypertrophy on electrocardiography. Abnormalities of lung perfusion consisted of scattered small areas of hypoperfusion in 36.8%, peripheral hypoperfusion in 78.9% and uneven distribution of pulmonary perfusion in 94.7%. The degree of hypoperfusion was slightly related to decrease in FEV 1.0%, V25 and PaO[sub 2] and increase in circulating blood volume and peripheral red blood cell counts. Abnormalities of pulmonary function consisted of increased RV/TLC in 50.0%, increased CV/VC in 35.7% and decreased V25 in 36.8%. Arterial blood gases showed hypoxemia in 57.1%, the degree of which was slightly related to increase in RV/TLC and CV/VC and decrease in V25. Cases of secondary polycythemia due to pulmonary diseases showed more marked right ventricular visualization, pulmonary perfusion impairment and abnormalities of various kinds of pulmonary function than polycythemia rubra vera cases. It seems to be important to evaluate the pathophysiology of pulmonary circulation in polycythemia rubra vera as well as secondary polycythemia due to cardio-pulmonary diseases, because pulmonary perfusion impairment and moderate right ventricular visualization are observed frequently in polycythemia rubra vera. (author).

Study of pathophysiology of pulmonary circulation in polycythemia using scintigraphy

International Nuclear Information System (INIS)

Fujii, Tadashige; Tanaka, Masao; Takeda, Tadashi; Kawashima, Akira; Kubo, Keiji; Kobayashi, Toshio; Handa, Kenjiro; Yoshimura, Kazuhiko

1993-01-01

In order to evaluate the pathophysiology of pulmonary circulation in polycythemia, Tl-201 myocardial scintigraphy and perfusion lung scintigraphy with 99m-Tc-MAA were performed in 19 cases of polycythemia including polycythemia rubra vera and in 11 cases of secondary polycythemia due to pulmonary diseases. Tl-201 lung uptake, right ventricular visualization and pulmonary perfusion impairment were studied. In the 19 cases, Tl-201 lung uptake was observed in all cases and 54.5% of them showed moderate lung uptake. The grade of right ventricular visualization was moderate in one case and slight in 16 cases; right ventricular hypertrophy was shown in 89.5% of all cases by Tl-201 scintigraphy, only one of which showed right ventricular hypertrophy on electrocardiography. Abnormalities of lung perfusion consisted of scattered small areas of hypoperfusion in 36.8%, peripheral hypoperfusion in 78.9% and uneven distribution of pulmonary perfusion in 94.7%. The degree of hypoperfusion was slightly related to decrease in FEV 1.0%, V25 and PaO 2 and increase in circulating blood volume and peripheral red blood cell counts. Abnormalities of pulmonary function consisted of increased RV/TLC in 50.0%, increased CV/VC in 35.7% and decreased V25 in 36.8%. Arterial blood gases showed hypoxemia in 57.1%, the degree of which was slightly related to increase in RV/TLC and CV/VC and decrease in V25. Cases of secondary polycythemia due to pulmonary diseases showed more marked right ventricular visualization, pulmonary perfusion impairment and abnormalities of various kinds of pulmonary function than polycythemia rubra vera cases. It seems to be important to evaluate the pathophysiology of pulmonary circulation in polycythemia rubra vera as well as secondary polycythemia due to cardio-pulmonary diseases, because pulmonary perfusion impairment and moderate right ventricular visualization are observed frequently in polycythemia rubra vera. (author)

A comparative analysis of pulmonary ventilation-perfusion imaging with pulmonary angiography in the diagnosis of pulmonary embolism

International Nuclear Information System (INIS)

Wang Jincheng; Mi Hongzhi; Wang Qian; Zhang Weijun; Lu Biao; Yang Hao; Ding Jian; Lu Yao

2001-01-01

Objective: To assess the value of ventilation-perfusion imaging in the diagnosis of pulmonary embolism (PE). Methods: Thirty consecutive patients with clinically suspected pulmonary embolism were studied, male: female 15:15, mean age was (36.2 +- 13.9) years. The chest radiograms were obtained in all 30 patients. All patients underwent radionuclide ventilation-perfusion imaging and pulmonary angiography. Results: Of the 30 patients, 22 with lobe, multiple segment or multi-subsegment perfusion defects and normal or nearly normal ventilation images were reported as PE. 20 of them were confirmed to be with PE by pulmonary angiography, 2 patients were not confirmed. Eight of 30 patients with multiple perfusion defects, ventilative abnormalities were reported as non-PE and the diagnoses were confirmed by pulmonary angiography. The sensitivity, specificity and accuracy of diagnosis of PE by ventilation-perfusion imaging was 100%, 80.0% and 93.3% respectively. Conclusions: (1) Ventilation-perfusion imaging is one of the most valuable methods in the diagnosis of PE. (2) The results suggest that pulmonary embolism can be diagnosed non-invasively in most patients on the basis of clinical manifestation, chest radiograms and ventilation-perfusion imaging findings. (3) Pulmonary angiography is required while clinical manifestation and ventilation-perfusion imaging findings are discordant with each other

Coccidioides Endospores and Spherules Draw Strong Chemotactic, Adhesive, and Phagocytic Responses by Individual Human Neutrophils.

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Cheng-Yuk Lee

Full Text Available Coccidioides spp. are dimorphic pathogenic fungi whose parasitic forms cause coccidioidomycosis (Valley fever in mammalian hosts. We use an innovative interdisciplinary approach to analyze one-on-one encounters between human neutrophils and two forms of Coccidioides posadasii. To examine the mechanisms by which the innate immune system coordinates different stages of the host response to fungal pathogens, we dissect the immune-cell response into chemotaxis, adhesion, and phagocytosis. Our single-cell technique reveals a surprisingly strong response by initially quiescent neutrophils to close encounters with C. posadasii, both from a distance (by complement-mediated chemotaxis as well as upon contact (by serum-dependent adhesion and phagocytosis. This response closely resembles neutrophil interactions with Candida albicans and zymosan particles, and is significantly stronger than the neutrophil responses to Cryptococcus neoformans, Aspergillus fumigatus, and Rhizopus oryzae under identical conditions. The vigorous in vitro neutrophil response suggests that C. posadasii evades in vivo recognition by neutrophils through suppression of long-range mobilization and recruitment of the immune cells. This observation elucidates an important paradigm of the recognition of microbes, i.e., that intact immunotaxis comprises an intricate spatiotemporal hierarchy of distinct chemotactic processes. Moreover, in contrast to earlier reports, human neutrophils exhibit vigorous chemotaxis toward, and frustrated phagocytosis of, the large spherules of C. posadasii under physiological-like conditions. Finally, neutrophils from healthy donors and patients with chronic coccidioidomycosis display subtle differences in their responses to antibody-coated beads, even though the patient cells appear to interact normally with C. posadasii endospores.

Molecular imaging of the human pulmonary vascular endothelium in pulmonary hypertension: a phase II safety and proof of principle trial

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Harel, Francois [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Universite de Montreal, Department of Nuclear Medicine, Montreal, Quebec (Canada); Langleben, David; Abikhzer, Gad [McGill University, Lady Davis Institute and Jewish General Hospital, Montreal, Quebec (Canada); Provencher, Steve; Guimond, Jean [Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Quebec (Canada); Fournier, Alain; Letourneau, Myriam [INRS-Institut Armand-Frappier, Laval, Quebec (Canada); Finnerty, Vincent; Nguyen, Quang T.; Levac, Xavier [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Mansour, Asmaa; Guertin, Marie-Claude [Montreal Health Innovation Coordination Center, Montreal, QC (Canada); Dupuis, Jocelyn [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Universite de Montreal, Department of Medicine, Montreal, Quebec (Canada)

2017-07-15

The adrenomedullin receptor is densely expressed in the pulmonary vascular endothelium. PulmoBind, an adrenomedullin receptor ligand, was developed for molecular diagnosis of pulmonary vascular disease. We evaluated the safety of PulmoBind SPECT imaging and its capacity to detect pulmonary vascular disease associated with pulmonary hypertension (PH) in a human phase II study. Thirty patients with pulmonary arterial hypertension (PAH, n = 23) or chronic thromboembolic PH (CTEPH, n = 7) in WHO functional class II (n = 26) or III (n = 4) were compared to 15 healthy controls. Lung SPECT was performed after injection of 15 mCi {sup 99m}Tc-PulmoBind in supine position. Qualitative and semi-quantitative analyses of lung uptake were performed. Reproducibility of repeated testing was evaluated in controls after 1 month. PulmoBind injection was well tolerated without any serious adverse event. Imaging was markedly abnormal in PH with ∝50% of subjects showing moderate to severe heterogeneity of moderate to severe extent. The abnormalities were unevenly distributed between the right and left lungs as well as within each lung. Segmental defects compatible with pulmonary embolism were present in 7/7 subjects with CTEPH and in 2/23 subjects with PAH. There were no segmental defects in controls. The PulmoBind activity distribution index, a parameter indicative of heterogeneity, was elevated in PH (65% ± 28%) vs. controls (41% ± 13%, p = 0.0003). In the only subject with vasodilator-responsive idiopathic PAH, PulmoBind lung SPECT was completely normal. Repeated testing 1 month later in healthy controls was well tolerated and showed no significant variability of PulmoBind distribution. In this phase II study, molecular SPECT imaging of the pulmonary vascular endothelium using {sup 99m}Tc-PulmoBind was safe. PulmoBind showed potential to detect both pulmonary embolism and abnormalities indicative of pulmonary vascular disease in PAH. Phase III studies with this novel tracer and

Alteration of pulmonary blood flow in tetralogy of Fallot

International Nuclear Information System (INIS)

Hashimoto, Kazuhiro; Matsui, Michihiko; Kurosawa, Hiromi; Arai, Tatsuta; Nakamura, Yuzuru.

1992-01-01

The pulmonary blood distribution was examined in 17 patients with tetralogy of Fallot (TOF) pre and postoperatively with macroaggregates of 99m TC-labeled human serum albumin. Most of the patients with TOF demonstrated an abnormal preoperative distribution pattern. The abnormalities included not only an unbalanced distribution between the right and left lungs but also a maldistribution of peripheral vessels in each lung. The right/left lung counts ratio and pulmonary peripheral index (calculated in order to express the severity of peripheral maldistribution) correlated neither to the diameter nor the cross-sectional area of either right or left pulmonary arteries which were measured angiographically. Postoperatively, the pulmonary blood was shunted toward the developed side of the lung which further contributed to maldistribution of blood flow and unbalanced pulmonary growth. Since the patients with an unbalanced pulmonary blood distribution demonstrated a higher right ventricular pressure one year after the operation, a palliative operation facilitating the growth of the underdeveloped side of the lung might be considered as an effective procedure to precede intracardiac repair. (author)

Complement Activation Induces Neutrophil Adhesion and Neutrophil-Platelet Aggregate Formation on Vascular Endothelial Cells

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Magdalena Riedl

2017-01-01

Discussion: Therefore, our findings of (i neutrophils adhering to complement-activated endothelial cells, (ii the formation of neutrophil-platelet aggregates on endothelial cells, and (iii the ability of aHUS serum to induce similar effects identify a possible role for neutrophils in aHUS manifestation.

Evaluation of the relationship between radiological abnormalities and both pulmonary function and pulmonary hypertension in coal workers' pneumoconiosis

Energy Technology Data Exchange (ETDEWEB)

Yildiz, O.A.; Gulbay, B.E.; Saryal, S.; Karabiylkoglu, G. [Ankara University, Ankara (Turkey). School of Medicine

2007-05-15

The aim of this study was to investigate the effect of the radiological evidence of emphysema, and the extent of interstitial involvement, on lung function and pulmonary arterial pressure (PAP) in patients with coal workers' pneumoconiosis (CWP). All patients showed a mild decrease in FEV1/FVC and a mild increase in FRC. Forty-four per cent of patients developed mild to moderate pulmonary hypertension. Emphysema scores correlated significantly with airflow rates, including FEV1%, FEV1/FVC and FEF25-75%, and with carbon monoxide diffusing capacity (DLCO)% predicted as well as FRC% predicted and the ratio RV/TLC, which are indices of air trapping. Additionally, profusion and global profusion scores showed significant correlation with FEV1/FVC, DLCO% predicted, specific airway conductance and smoking. Mean PAP showed a significant negative correlation with FEF50% predicted, DLCO% predicted and profusion score. The impairment of pulmonary function (mainly disturbance in airflow rates and air trapping) and pulmonary hypertension may be present, even in a simple form of CWP. The pulmonary function impairment in patients with CWP is likely to be attributable to the occurrence of emphysema. However, pulmonary hypertension was directly related to the profusion of pneumoconiotic nodules, which may result in obliteration of the vascular bed.

Analysis of the degree of pulmonary thallium washout after exercise in patients with coronary artery disease

International Nuclear Information System (INIS)

Levy, R.; Rozanski, A.; Berman, D.S.; Garcia, E.; Van Train, K.; Maddahi, J.; Swan, H.J.

1983-01-01

An abnormal increase in pulmonary thallium activity may be visualized on post-stress thallium images in patients with coronary artery disease. Because this increased pulmonary thallium activity usually disappears by the time of redistribution imaging, this study was designed to assess whether measurement of the degree of pulmonary thallium washout between stress and redistribution might improve the detection of increased pulmonary thallium activity in patients with coronary artery disease. Quantitative analysis revealed abnormal (that is, greater than 2 standard deviations of normal values) pulmonary thallium washouts in 59 (64%) of 92 patients with coronary artery disease, but in only 2 (25%) of 8 subjects with angiographically normal arteries (p less than 0.06). By comparison, the visual analysis of pulmonary thallium washout and use of initial pulmonary to myocardial thallium ratio were significantly (p less than 0.05) less sensitive in detecting abnormality in patients with coronary artery disease. Abnormal pulmonary thallium washout was related to both the anatomic extent and functional severity of disease: it occurred with greatest frequency in patients with multivessel disease and in those with exercise-induced left ventricular dysfunction (p less than 0.005). When added to the quantitative analysis of myocardial scintigraphy, the analysis of pulmonary thallium washout increased the detection of coronary artery disease from 84 to 93% (p less than 0.05), but the sample size was too small to assess specificity

Transcriptional blood signatures distinguish pulmonary tuberculosis, pulmonary sarcoidosis, pneumonias and lung cancers.

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Bloom, Chloe I; Graham, Christine M; Berry, Matthew P R; Rozakeas, Fotini; Redford, Paul S; Wang, Yuanyuan; Xu, Zhaohui; Wilkinson, Katalin A; Wilkinson, Robert J; Kendrick, Yvonne; Devouassoux, Gilles; Ferry, Tristan; Miyara, Makoto; Bouvry, Diane; Valeyre, Dominique; Dominique, Valeyre; Gorochov, Guy; Blankenship, Derek; Saadatian, Mitra; Vanhems, Phillip; Beynon, Huw; Vancheeswaran, Rama; Wickremasinghe, Melissa; Chaussabel, Damien; Banchereau, Jacques; Pascual, Virginia; Ho, Ling-Pei; Lipman, Marc; O'Garra, Anne

2013-01-01

New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the heterogeneity of their profiles and their transcriptional response to treatment.

A diagnostic strategy for pulmonary embolism based on standardised pretest probability and perfusion lung scanning: a management study

International Nuclear Information System (INIS)

Miniati, Massimo; Monti, Simonetta; Bauleo, Carolina; Scoscia, Elvio; Tonelli, Lucia; Dainelli, Alba; Catapano, Giosue; Formichi, Bruno; Di Ricco, Giorgio; Prediletto, Renato; Carrozzi, Laura; Marini, Carlo

2003-01-01

Pulmonary embolism remains a challenging diagnostic problem. We developed a simple diagnostic strategy based on combination of assessment of the pretest probability with perfusion lung scan results to reduce the need for pulmonary angiography. We studied 390 consecutive patients (78% in-patients) with suspected pulmonary embolism. The pretest probability was rated low ( 10%, ≤50%), moderately high (>50%, ≤90%) or high (>90%) according to a structured clinical model. Perfusion lung scans were independently assigned to one of four categories: normal; near-normal; abnormal, suggestive of pulmonary embolism (wedge-shaped perfusion defects); abnormal, not suggestive of pulmonary embolism (perfusion defects other than wedge shaped). Pulmonary embolism was diagnosed in patients with abnormal scans suggestive of pulmonary embolism and moderately high or high pretest probability. Patients with normal or near-normal scans and those with abnormal scans not suggestive of pulmonary embolism and low pretest probability were deemed not to have pulmonary embolism. All other patients were allocated to pulmonary angiography. Patients in whom pulmonary embolism was excluded were left untreated. All patients were followed up for 1 year. Pulmonary embolism was diagnosed non-invasively in 132 patients (34%), and excluded in 191 (49%). Pulmonary angiography was required in 67 patients (17%). The prevalence of pulmonary embolism was 41% (n=160). Patients in whom pulmonary embolism was excluded had a thrombo-embolic risk of 0.4% (95% confidence interval: 0.0%-2.8%). Our strategy permitted a non-invasive diagnosis or exclusion of pulmonary embolism in 83% of the cases (95% confidence interval: 79%-86%), and appeared to be safe. (orig.)

Time course of pulmonary burden in mice exposed to residual oil fly ash

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Giovanna Marcella Cavalcante Carvalho

2014-09-01

Full Text Available Residual oil fly ash (ROFA is a common pollutant in areas where oil is burned. This particulate matter with a broad distribution of particle diameters can be inhaled by human beings and putatively damage their respiratory system. Although some studies deal with cultured cells, animals, and even epidemiological issues, so far a comprehensive analysis of respiratory outcomes as a function of the time elapsed after exposure to a low dose of ROFA is wanted. Thus, we aimed to investigate the time course of mechanical, histological, and inflammatory lung changes, as well as neutrophils in the blood, in mice exposed to ROFA until 5 days after exposure. BALB/c mice (25±5 g were randomly divided into 7 groups and intranasally instilled with either 10 µL of sterile saline solution (0.9% NaCl, CTRL or ROFA (0.2 µg in 10 L of saline solution. Pulmonary mechanics, histology (normal and collapsed alveoli, mononuclear and polymorphonuclear cells, and ultrastructure, neutrophils (in blood and bronchoalveolar lavage fluid were determined at 6 h in CTRL and at 6, 24, 48, 72, 96 and 120 h after ROFA exposure. ROFA contained metal elements, especially iron, polycyclic aromatic hydrocarbons, and organochlorines. Lung resistive pressure augmented early (6 h in the course of lung injury and other mechanical, histological and inflammatory parameters increased at 24 h, returning to control values at 120 h. Blood neutrophilia was present only at 24 and 48 h after exposure. Swelling of endothelial cells with adherent neutrophils was detected after ROFA instillation. No neutrophils were present in the lavage fluid. In conclusion, the exposure to ROFA, even in low doses, induced early changes in pulmonary mechanics, lung histology and accumulation of neutrophils in blood of mice that lasted for four days and disappeared spontaneously.

Time course of pulmonary burden in mice exposed to residual oil fly ash.

Science.gov (United States)

Carvalho, Giovanna Marcella Cavalcante; Nagato, Lilian Katiê da Silva; Fagundes, Sheila da Silva; Dos Santos, Flávia Brandão; Calheiros, Andrea Surrage; Malm, Olaf; Bozza, Patricia Torres; Saldiva, Paulo Hilário N; Faffe, Débora Souza; Rocco, Patricia Rieken Macedo; Zin, Walter Araujo

2014-01-01

Residual oil fly ash (ROFA) is a common pollutant in areas where oil is burned. This particulate matter (PM) with a broad distribution of particle diameters can be inhaled by human beings and putatively damage their respiratory system. Although some studies deal with cultured cells, animals, and even epidemiological issues, so far a comprehensive analysis of respiratory outcomes as a function of the time elapsed after exposure to a low dose of ROFA is wanted. Thus, we aimed to investigate the time course of mechanical, histological, and inflammatory lung changes, as well as neutrophils in the blood, in mice exposed to ROFA until 5 days after exposure. BALB/c mice (25 ± 5 g) were randomly divided into 7 groups and intranasally instilled with either 10 μL of sterile saline solution (0.9% NaCl, CTRL) or ROFA (0.2 μg in 10 μL of saline solution). Pulmonary mechanics, histology (normal and collapsed alveoli, mononuclear and polymorphonuclear cells, and ultrastructure), neutrophils (in blood and bronchoalveolar lavage fluid) were determined at 6 h in CTRL and at 6, 24, 48, 72, 96, and 120 h after ROFA exposure. ROFA contained metal elements, especially iron, polycyclic aromatic hydrocarbons (PAHs), and organochlorines. Lung resistive pressure augmented early (6 h) in the course of lung injury and other mechanical, histological and inflammatory parameters increased at 24 h, returning to control values at 120 h. Blood neutrophilia was present only at 24 and 48 h after exposure. Swelling of endothelial cells with adherent neutrophils was detected after ROFA instillation. No neutrophils were present in the lavage fluid. In conclusion, the exposure to ROFA, even in low doses, induced early changes in pulmonary mechanics, lung histology and accumulation of neutrophils in blood of mice that lasted for 4 days and disappeared spontaneously.

Does exercise pulmonary hypertension exist?

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Lau, Edmund M; Chemla, Denis; Whyte, Kenneth; Kovacs, Gabor; Olschewski, Horst; Herve, Philippe

2016-09-01

The exercise definition of pulmonary hypertension using a mean pulmonary artery pressure threshold of greater than 30 mmHg was abandoned following the 4th World Pulmonary Hypertension Symposium in 2008, as this definition was not supported by evidence and healthy individuals frequently exceed this threshold. Meanwhile, the clinical value of exercise pulmonary hemodynamic testing has also been questioned. Recent data support the notion that an abnormal pulmonary hemodynamic response during exercise (or exercise pulmonary hypertension) is associated with symptoms and exercise limitation. Pathophysiologic mechanisms accounting for the development of exercise pulmonary hypertension include increased vascular resistance, excessive elevation in left atrial pressure and/or increased volume of trapped air during exercise, resulting in a steep rise in pulmonary artery pressure relative to cardiac output. Recent evidence suggests that exercise pulmonary hypertension may be defined by a mean pulmonary artery pressure surpassing 30 mmHg together with a simultaneous total pulmonary resistance exceeding 3 WU. Exercise pulmonary hypertension is a clinically relevant entity and an improved definition has been suggested based on new evidence. Exercise pulmonary hemodynamics may help unmask early or latent disease, particularly in populations that are at high risk for the development of pulmonary hypertension.

The pathophysiology of chronic thromboembolic pulmonary hypertension

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Gérald Simonneau

2017-03-01

Full Text Available Chronic thromboembolic pulmonary hypertension (CTEPH is a rare, progressive pulmonary vascular disease that is usually a consequence of prior acute pulmonary embolism. CTEPH usually begins with persistent obstruction of large and/or middle-sized pulmonary arteries by organised thrombi. Failure of thrombi to resolve may be related to abnormal fibrinolysis or underlying haematological or autoimmune disorders. It is now known that small-vessel abnormalities also contribute to haemodynamic compromise, functional impairment and disease progression in CTEPH. Small-vessel disease can occur in obstructed areas, possibly triggered by unresolved thrombotic material, and downstream from occlusions, possibly because of excessive collateral blood supply from high-pressure bronchial and systemic arteries. The molecular processes underlying small-vessel disease are not completely understood and further research is needed in this area. The degree of small-vessel disease has a substantial impact on the severity of CTEPH and postsurgical outcomes. Interventional and medical treatment of CTEPH should aim to restore normal flow distribution within the pulmonary vasculature, unload the right ventricle and prevent or treat small-vessel disease. It requires early, reliable identification of patients with CTEPH and use of optimal treatment modalities in expert centres.

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

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John W Semple

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

Significance of Intratracheal Instillation Tests for the Screening of Pulmonary Toxicity of Nanomaterials.

Science.gov (United States)

Morimoto, Yasuo; Izumi, Hiroto; Yoshiura, Yukiko; Fujisawa, Yuri; Fujita, Katsuhide

Inhalation tests are the gold standard test for the estimation of the pulmonary toxicity of respirable materials. Intratracheal instillation tests have been used widely, but they yield limited evidence of the harmful effects of respirable materials. We reviewed the effectiveness of intratracheal instillation tests for estimating the hazards of nanomaterials, mainly using research papers featuring intratracheal instillation and inhalation tests centered on a Japanese national project. Compared to inhalation tests, intratracheal instillation tests induced more acute inflammatory responses in the animal lung due to a bolus effect regardless of the toxicity of the nanomaterials. However, nanomaterials with high toxicity induced persistent inflammation in the chronic phase, and nanomaterials with low toxicity induced only transient inflammation. Therefore, in order to estimate the harmful effects of a nanomaterial, an observation period of 3 months or 6 months following intratracheal instillation is necessary. Among the endpoints of pulmonary toxicity, cell count and percentage of neutrophil, chemokines for neutrophils and macrophages, and oxidative stress markers are considered most important. These markers show persistent and transient responses in the lung from nanomaterials with high and low toxicity, respectively. If the evaluation of the pulmonary toxicity of nanomaterials is performed in not only the acute but also the chronic phase in order to avoid the bolus effect of intratracheal instillation and inflammatory-related factors that are used as endpoints of pulmonary toxicity, we speculate that intratracheal instillation tests can be useful for screening for the identification of the hazard of nanomaterials through pulmonary inflammation.

The Resolution of Inflammation: A Mathematical Model of Neutrophil and Macrophage Interactions

KAUST Repository

Dunster, J. L.; Byrne, H. M.; King, J. R.

2014-01-01

to damage healthy tissue. We develop a spatially averaged model of inflammation centring on its resolution, accounting for populations of neutrophils and macrophages and incorporating both pro- and anti-inflammatory processes. Our ordinary differential

Osthol attenuates neutrophilic oxidative stress and hemorrhagic shock-induced lung injury via inhibition of phosphodiesterase 4.

Science.gov (United States)

Tsai, Yung-Fong; Yu, Huang-Ping; Chung, Pei-Jen; Leu, Yann-Lii; Kuo, Liang-Mou; Chen, Chun-Yu; Hwang, Tsong-Long

2015-12-01

Oxidative stress caused by neutrophils is an important pathogenic factor in trauma/hemorrhagic (T/H)-induced acute lung injury (ALI). Osthol, a natural coumarin found in traditional medicinal plants, has therapeutic potential in various diseases. However, the pharmacological effects of osthol in human neutrophils and its molecular mechanism of action remain elusive. In this study, our data showed that osthol potently inhibited the production of superoxide anion (O2(•-)) and reactive oxidants derived therefrom as well as expression of CD11b in N-formylmethionylleucylphenylalanine (FMLP)-activated human neutrophils. However, osthol inhibited neutrophil degranulation only slightly and it failed to inhibit the activity of subcellular NADPH oxidase. FMLP-induced phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) was inhibited by osthol. Notably, osthol increased the cAMP concentration and protein kinase A (PKA) activity in activated neutrophils. PKA inhibitors reversed the inhibitory effects of osthol, suggesting that these are mediated through cAMP/PKA-dependent inhibition of ERK and Akt activation. Furthermore, the activity of cAMP-specific phosphodiesterase (PDE) 4, but not PDE3 or PDE7, was significantly reduced by osthol. In addition, osthol reduced myeloperoxidase activity and pulmonary edema in rats subjected to T/H shock. In conclusion, our data suggest that osthol has effective anti-inflammatory activity in human neutrophils through the suppression of PDE4 and protects significantly against T/H shock-induced ALI in rats. Osthol may have potential for future clinical application as a novel adjunct therapy to treat lung inflammation caused by adverse circulatory conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

Human neutrophils in auto-immunity.

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Thieblemont, Nathalie; Wright, Helen L; Edwards, Steven W; Witko-Sarsat, Véronique

2016-04-01

Human neutrophils have great capacity to cause tissue damage in inflammatory diseases via their inappropriate activation to release reactive oxygen species (ROS), proteases and other tissue-damaging molecules. Furthermore, activated neutrophils can release a wide variety of cytokines and chemokines that can regulate almost every element of the immune system. In addition to these important immuno-regulatory processes, activated neutrophils can also release, expose or generate neoepitopes that have the potential to break immune tolerance and result in the generation of autoantibodies, that characterise a number of human auto-immune diseases. For example, in vasculitis, anti-neutrophil cytoplasmic antibodies (ANCA) that are directed against proteinase 3 or myeloperoxidase are neutrophil-derived autoantigens and activated neutrophils are the main effector cells of vascular damage. In other auto-immune diseases, these neutrophil-derived neoepitopes may arise from a number of processes that include release of granule enzymes and ROS, changes in the properties of components of their plasma membrane as a result of activation or apoptosis, and via the release of Neutrophil Extracellular Traps (NETs). NETs are extracellular structures that contain chromatin that is decorated with granule enzymes (including citrullinated proteins) that can act as neo-epitopes to generate auto-immunity. This review therefore describes the processes that can result in neutrophil-mediated auto-immunity, and the role of neutrophils in the molecular pathologies of auto-immune diseases such as vasculitis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We discuss the potential role of NETs in these processes and some of the debate in the literature regarding the role of this phenomenon in microbial killing, cell death and auto-immunity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Phase-contrast MR assessment of pulmonary venous blood flow in children with surgically repaired pulmonary veins

International Nuclear Information System (INIS)

Valsangiacomo, Emanuela R.; Yoo, Shi-Joon; Barrea, Catherine; Smallhorn, Jeffrey F.; Macgowan, Christopher K.; Coles, John G.

2003-01-01

Pulmonary venous (PV) obstruction may complicate surgical repair of PV abnormalities. By combining phase-contrast cine (PC) imaging and contrast-enhanced angiography, magnetic resonance (MR) imaging can provide physiological information complementing anatomical diagnosis. To compare the PV flow pattern observed after surgical repair of PV abnormalities with normal PV flow pattern and to investigate the changes occurring in the presence of PV stenosis by using PC MR in children. By using PC MR, PV flow was evaluated in 14 patients (3 months-14 years) who underwent surgical repair for PV abnormalities. Eleven children (8-18 years) were studied as normal controls. Peak flow velocities and patterns were compared among three groups: normal veins (n=23), surgically repaired veins without (n=44) and with stenosis (n=10). Normal and unobstructed pulmonary veins after surgery showed a biphasic or triphasic flow pattern with one or two systolic peaks and a diastolic peak. Unobstructed surgically repaired veins showed decreased peak systolic velocity (P =0.001) and an increased peak diastolic velocity (P=0.005) when compared to normal values. Obstructed veins showed decreased systolic and diastolic velocities when measured upstream from the stenosis. PC MR shows different flow patterns among normal, surgically repaired pulmonary veins with and without stenosis. (orig.)

Correlation of pulmonary function and usual interstitial pneumonia computed tomography patterns in idiopathic pulmonary fibrosis.

Science.gov (United States)

Arcadu, Antonella; Byrne, Suzanne C; Pirina, Pietro; Hartman, Thomas E; Bartholmai, Brian J; Moua, Teng

2017-08-01

Little is known about presenting 'inconsistent' or 'possible' usual interstitial pneumonia (UIP) computed tomography (CT) patterns advancing to 'consistent' UIP as disease progresses in idiopathic pulmonary fibrosis (IPF). We hypothesized that if 'consistent' UIP represented more advanced disease, such a pattern on presentation should also correlate with more severe pulmonary function test (PFT) abnormalities. Consecutive IPF patients (2005-2013) diagnosed by international criteria with baseline PFT and CT were included. Presenting CTs were assessed by three expert radiologists for consensus UIP pattern ('consistent', 'possible', and 'inconsistent'). Approximation of individual and combined interstitial abnormalities was also performed with correlation of interstitial abnormalities and UIP CT pattern made with PFT findings and survival. Three-hundred and fifty patients (70% male) were included with a mean age of 68.3 years. Mean percent predicted forced vital capacity (FVC%) and diffusion capacity (DLCO%) was 64% and 45.5% respectively. Older age and male gender correlated more with 'consistent' UIP CT pattern. FVC% was not associated with any UIP pattern but did correlate with total volume of radiologist assessed interstitial abnormalities. DLCO% was lower in those with 'consistent' UIP pattern. A 'consistent' UIP CT pattern was also not independently predictive of survival after correction for age, gender, FVC%, and DLCO%. PFT findings appear to correlate with extent of radiologic disease but not specific morphologic patterns. Whether such UIP patterns represent different stages of disease severity or radiologic progression is not supported by coinciding pulmonary function decline. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pulmonary dysfunction in obese early adolescents

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Bambang Supriyatno

2010-08-01

Full Text Available Aim Obesity leads to various complications, including pulmonary dysfunction. Studies on pulmonary function of obese children are limited and the results are controversial. This study was aimed to determine proportion of pulmonary dysfunction on early adolescents with obesity and to evaluate correlation between obesity degree with pulmonary dysfunction degree.Methods A cross-sectional study was conducted at the Department of Child Health, Medical School, University of Indonesia, from November 2007 to December 2008. Subjects were 10 to 12 year-old adolescents with obesity. Subjects underwent pulmonary function test (PFT to assess FEV1/FVC, FEV1, FVC, V50, and V25.Results 110 subjects fulfilled study criteria, 83 (75.5% were male and 27 (24.5% were female with median BMI 26.7 (22.6-54.7 kg/m2; 92 subjects (83.6% were superobese. History of asthma and allergic rhinitis were found in 32 (29.1% and 46 (41.8% subjects, respectively. 64 (58.2% subjects had abnormal PFT results consisting of restrictive type in 28 (25.5% subjects, obstructive in 3 (2.7%, and combined type in 33 (30%. Mean FEV1, FVC, V50, and V25 values were below normal, while mean FEV1/FVC ratio was normal. There was no statistically significant correlation between BMI and PFT parameters. No significant correlation was found between degree of obesity and the severity of pulmonary dysfunction.Conclusions Pulmonary dysfunction occurs in 58.2% obese early adolescents. The most common abnormality was combined type (30%, followed by restrictive (25.5%, and obstructive type (2.7%. There was no correlation between BMI and pulmonary function test parameters. (Med J Indones 2010;19:179-84Key words: early adolescents, obesity, pulmonary function test

Pathogenesis of pulmonary emphysema – cellular and molecular events

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Antonio Di Petta

2010-06-01

Full Text Available Pulmonary emphysema is a chronic obstructive disease, resulting fromimportant alterations in the whole distal structure of terminal bronchioles, either by enlargement of air spaces or by destruction of the alveolar wall, leading to loss of respiratory surface, decreased elastic recoil and lung hyperinflation. For many years, the hypothesis of protease-antiprotease unbalance prevailed as the central theme in the pathogenesis of pulmonary emphysema. According to this hypothesis, the release of active proteolytic enzymes, produced mainly by neutrophils and macrophages, degrades the extracellular matrix, affecting the integrity of its components, especially collagen and elastic fibers. However, new concepts involving cellular and molecular events were proposed, including oxidative stress, cell apoptosis, cellular senescence and failed lung tissue repair. The aim of this review paper was to evaluate the cellular and molecular mechanisms seen in the pathogenesis of pulmonary emphysema.

Combined Pulmonary Fibrosis and Emphysema Syndrome

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Rounds, Sharon I. S.

2012-01-01

There is increasing clinical, radiologic, and pathologic recognition of the coexistence of emphysema and pulmonary fibrosis in the same patient, resulting in a clinical syndrome known as combined pulmonary fibrosis and emphysema (CPFE) that is characterized by dyspnea, upper-lobe emphysema, lower-lobe fibrosis, and abnormalities of gas exchange. This syndrome frequently is complicated by pulmonary hypertension, acute lung injury, and lung cancer. The CPFE syndrome typically occurs in male smokers, and the mortality associated with this condition, especially if pulmonary hypertension is present, is significant. In this review, we explore the current state of the literature and discuss etiologic factors and clinical characteristics of the CPFE syndrome. PMID:22215830

Obstructive lung disease as a complication in post pulmonary TB

Science.gov (United States)

Tarigan, A. P.; Pandia, P.; Eyanoer, P.; Tina, D.; Pratama, R.; Fresia, A.; Tamara; Silvanna

2018-03-01

The case of post TB is a problem that arises in the community. Pulmonary tuberculosis (TB) can affect lung function. Therefore, we evaluated impaired pulmonary function in subjects with diagnosed prior pulmonary TB. A Case Series study, pulmonary function test was performed in subjects with a history of pulmonary tuberculosis; aged ≥18 years were included. Exclusion criteria was a subject who had asthma, obesity, abnormal thorax and smoking history. We measured FEV1 and FVC to evaluate pulmonary function. Airflow obstruction was FEV1/FVC%pulmonary TB, 5 subjects (23%) had airflow obstruction with FEV1/FVC% value pulmonary TB.

The dynamics of neutrophils in zebrafish (Danio rerio) during infection with the parasite Ichthyophthirius multifiliis

DEFF Research Database (Denmark)

Jørgensen, Louise von Gersdorff

2016-01-01

Ichthyophthirius multifiliis is a ciliated protozoan parasite infecting the skin and gills of freshwater fish. Neutrophils are attracted to the infection sites, as a part of the innate immune response. In this study a transgenic line of zebrafish (Tg(MPO:GFP)i114) with GFP-tagged neutrophils was ...... the infection. Neutrophils interacted directly with the parasites with pseudopod formation projecting towards the pathogen. These results indicate a strong innate immune response immediately following infection and/or a subsequent immune evasion by the parasite....

A gender difference in circulating neutrophils in malnourished patients with COPD

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Sven Larsson

2011-01-01

Full Text Available Sven Larsson1, Anita Nordenson1, Pernilla Glader1, Shigemi Yoshihara2, Anders Lindén1, Frode Slinde31Department of Internal Medicine/Respiratory Medicine and Allergology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden; 2Department of Pediatrics, Dokkyo Medical University, Tochigi, Japan; 3Department of Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SwedenBackground: Circulating markers of inflammation in chronic obstructive pulmonary disease (COPD may correlate to disease progression and extrapulmonary complications such as malnourishment. However, surprisingly little is known about gender-related differences for circulating inflammatory markers in COPD.Purpose: To characterize differences in circulating markers of inflammation in malnourished female and male patients with COPD.Subjects: Thirty female and 11 male patients with a clinical diagnosis of COPD and malnourishment were examined. A group of control subjects without evidence of COPD was recruited for comparison of some variables.Methods: Blood samples were drawn, and the following parameters were studied: leukocytes and differential counts, C-reactive protein (CRP, tumor necrosis factor-α, interleukin (IL-6 and IL-8, myeloperoxidase (MPO, neutrophil elastase (NE, intracellular adhesion molecule-1, vascular endothelial adhesion molecule-1, and E-selectin.Results: The mean neutrophil concentration was significantly (P = 0.019 higher in female (4.5 × 109/L than in male patients with COPD (3.5 × 109/L and significantly higher than in female control subjects (3.1 × 109/L (P , 0.01, n = 85. The mean CRP values were considerably higher in female (4.9 mg/mL than in male patients with COPD (1.5 mg/mL, but the difference was not statistically significant (P = 0.20. The mean concentrations of IL-6 and IL-8 tended to be higher in female than in male patients with COPD, but these differences did not reach statistical

Congenital pulmonary arteriovenous malformation: a rare cause of ...

African Journals Online (AJOL)

Pulmonary arteriovenous malformation (PAVM) is a rare condition in which there is abnormal connection between pulmonary arteries and veins. The disorder usually appears in late childhood or early adult life, with dyspnea on exertion, clubbing or cyanosis. We present two patients with severe cyanosis and their work-up ...

Localized pulmonary crystal-storing histiocytosis complicating pulmonary mucosa-associated lymphoid tissue lymphoma presenting with multiple mass lesions.

Science.gov (United States)

Kokuho, Nariaki; Terasaki, Yasuhiro; Kunugi, Shinobu; Onda, Naomi; Urushiyama, Hirokazu; Terasaki, Mika; Hino, Mitsunori; Gemma, Akihiko; Hatori, Tsutomu; Shimizu, Akira

2017-07-01

Crystal-storing histiocytosis (CSH) is an uncommon finding in lymphoplasmacytic disorders that presents histiocytes with abnormal intralysosomal accumulations of immunoglobulin light chains as crystals of unknown etiology. A 38-year-old woman with antiphospholipid syndrome had a surgical lung biopsy because of multiple lung mass lesions. In a right middle lobe lesion, lymphoplasmacytic cells had a monocytoid appearance, destructive lymphoepithelial lesions, and positive immunoglobulin heavy chain (IGH) gene rearrangements. A right upper lobe lesion manifested proliferating rounded histiocytes with abundant, deeply eosinophilic cytoplasm and negative IGH gene rearrangements. Electron microscopy and mass spectrometry revealed a case of pulmonary CSH: abnormal proliferation of the immunoglobulin κ chain of a variable region that may be crystallized within plasma cells and histiocytes. We report a rare case of localized pulmonary CSH complicating pulmonary mucosa-associated lymphoid tissue lymphoma with multiple mass lesions. We demonstrate advances in the understanding of the pathogenesis of CSH by various analyses of these lesions. Copyright © 2017 Elsevier Inc. All rights reserved.

Unusual radiological findings of adult-onset pulmonary tuberculosis

International Nuclear Information System (INIS)

Lee, Yong Chul; Lee, Jong Beum; Kim, Sue Hyun

1987-01-01

Usual chest radiographic findings in pulmonary tuberculosis are well described in radiologic literatures for both primary and postprimary phases of disease. During the last decade, many authors have enumerated the unusual manifestations of pulmonary tuberculosis in adult population. These unusual findings usually have been involved in the frequent failure of both radiologist and clinician to recognize that tuberculosis could be the cause of a abnormal chest radiograph in patients who are finally and surprisingly proven to have tuberculosis. Authors have evaluated 249 patients who were admitted and newly proven to have adult-onset pulmonary tuberculosis at Chung-Ang University Hospital from January, 1985 to December, 1986. Unusual findings were noted in 76 (30.5%) of the 249 patients with adult-onset pulmonary tuberculosis. These unusual findings most frequently could be seen in 3rd decades and showed no sex difference in incidence. A broad spectrum of abnormal findings including usual and unusual abnormalities were procedure by adult-onset pulmonary tuberculosis. The unusual radiographic findings were arbitrarily classified. Pleural effusion without parenchymal disease (10.0%), unusual location of infiltrate (5.6%) and atelectasis (3.2%) were relatively common. Hilar and / or mediastinal lymphnode enlargement (1.6%), cavity without parenchymal infiltrates (1.6%), septic lung-like infiltrates (1.6%), completely clear lungs (1.2%), miliary infiltrates (1.2%), fibrocalcific scar-like infiltrates (1.2%), masslike density (1.2%) and rheumatoid lung-like infiltrates (1.2%) were occasionally noted. Pneumothorax without parenchymal disease (0.4%) and bron chocutaneous fistula (0.4%) are. The recognition of these unusual findings could further improve the detection and diagnosis of adult-onset pulmonary tuberculosis

Lack of effect of deferoxamine, dimethyl sulfoxide, and catalase on monocrotaline pyrrole pulmonary injury

International Nuclear Information System (INIS)

Bruner, L.H.; Johnson, K.; Carpenter, L.J.; Roth, R.A.

1987-01-01

Monocrotaline pyrrole (MCTP) is a reactive metabolite of the pyrrolizidine alkaloid monocrotaline. MCTP given intravenously to rats causes pulmonary hypertension and right ventricular hypertrophy. Lesions in lungs after MCTP treatment contain macrophages and neutrophils, which may contribute to the damage by generation of reactive oxygen metabolites. Rats were treated with MCTP and agents known to protect against oxygen radical-mediated damage in acute models of neutrophil-dependent lung injury. Rats received MCTP and deferoxamine mesylate (DF), dimethyl sulfoxide (DMSO), or polyethylene glycol-coupled catalase (PEG-CAT). MCTP/vehicle-treated controls developed lung injury manifested as increased lung weight, release of lactate dehydrogenase into the airway, and sequestration of 125 I-labeled bovine serum albumin in the lungs. Cotreatment of rats with DF, DMSO, or PEG-CAT did not protect against the injury due to MCTP. These results suggest that toxic oxygen metabolites do not play an important role in the pathogenesis of MCTP-induced pulmonary injury

Lack of effect of deferoxamine, dimethyl sulfoxide, and catalase on monocrotaline pyrrole pulmonary injury

Energy Technology Data Exchange (ETDEWEB)

Bruner, L.H.; Johnson, K.; Carpenter, L.J.; Roth, R.A.

1987-01-01

Monocrotaline pyrrole (MCTP) is a reactive metabolite of the pyrrolizidine alkaloid monocrotaline. MCTP given intravenously to rats causes pulmonary hypertension and right ventricular hypertrophy. Lesions in lungs after MCTP treatment contain macrophages and neutrophils, which may contribute to the damage by generation of reactive oxygen metabolites. Rats were treated with MCTP and agents known to protect against oxygen radical-mediated damage in acute models of neutrophil-dependent lung injury. Rats received MCTP and deferoxamine mesylate (DF), dimethyl sulfoxide (DMSO), or polyethylene glycol-coupled catalase (PEG-CAT). MCTP/vehicle-treated controls developed lung injury manifested as increased lung weight, release of lactate dehydrogenase into the airway, and sequestration of SVI-labeled bovine serum albumin in the lungs. Cotreatment of rats with DF, DMSO, or PEG-CAT did not protect against the injury due to MCTP. These results suggest that toxic oxygen metabolites do not play an important role in the pathogenesis of MCTP-induced pulmonary injury.

Pulmonary agenesis: two cases reported

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Denis Yaraví Solano-Vázquez

2014-11-01

Full Text Available Background: Pulmonary agenesis is a rare anomaly (1 in 15 000 live births which consists in a total absence or severe hypoplasia of one or both lungs. The clinical spectrum of the unilateral agenesis could vary from early and severe respiratory distress, recurrent pneumonia to being an incidental finding. The prognosis is based on the presence of associated congenital abnormalities. Material and methods: We present two cases of unilateral pulmonary agenesis in patients at Tlaxcala’s Children Hospital during 2012. Results: Report details the case of a one-month old boy with left pulmonary agenesis and interatrial communication and mild pulmonary arterial hypertension. He had two resolved pneumonia incidents. The other case was a one-month old girl with right pulmonary agenesis, associated to multiple heart malformations who evolved to respiratory failure, heart failure and death.Conclusions: Pulmonary agenesis is a rare anomaly. Its outcome and prognosis varies with the hemodynamics related to its location and associated malformations.

Interaction between Ester-Type Tea Catechins and Neutrophil Gelatinase-Associated Lipocalin: Inhibitory Mechanism.

Science.gov (United States)

Zhang, Wei; Li, Xiao; Hua, Fang; Chen, Wei; Wang, Wei; Chu, Gang-Xiu; Bao, Guan-Hu

2018-02-07

Tea is thought to alleviate neurotoxicity due to the antioxidative effect of ester-type tea catechins (ETC). Neutrophil gelatinase-associated lipocalin (NGAL) can sensitize β-amyloid (Aβ) induced neurotoxicity, and inhibitors of NGAL may relieve associated symptoms. As such, the interactions of ETC with NGAL were investigated by fluorescence spectrometry and molecular simulation. NGAL fluorescence is quenched regularly when being added with six processing types of tea infusion (SPTT) and ETC. Thermodynamic analyses suggest that ETC with more catechol moieties has a stronger binding capacity with NGAL especially in the presence of Fe 3+ . (-)-Epicatechin 3-O-caffeoate (ECC), a natural product isolated from Zijuan green tea, shows the strongest binding ability with NGAL (K d = 15.21 ± 8.68 nM in the presence of Fe 3+ ). All ETC are effective in protecting nerve cells against H 2 O 2 or Aβ 1-42 induced injury. The inhibitory mechanism of ETC against NGAL supports its potential use in attenuation of neurotoxicity.

Evaluation of In-111 neutrophils in a model of the adult respiratory distress syndrome

International Nuclear Information System (INIS)

Cooper, J.A.; Solano, S.J.; Bizios, R.; Line, B.R.; Malik, A.B.

1984-01-01

Neutrophils (PMNs) have been implicated in the pathogenesis of the adult respiratory distress syndrome. To further define their role, the authors studied the kinetics of In-111 labeled PMNs in a sheep model of acute pulmonary vascular injury. PMNs isolated by Percoll-plasma gradient centrifugation, and labeled with 500 uCi of In-111-oxine. Following i.v. reinfusion of the labeled PMNs, lung activity was monitored with the labeled PMNs, lung activity was monitored with a gamma camera. After a two hour baseline, pulmonary vascular injury secondary to intravascular coagulation was induced by the i.v. infusion of 100 units/kg of thrombin (n=5). Pulmonary time activity curves demonstrated increases in pulmonary PMN activity averaging 14% over baseline following thrombin infusion. A portion of the uptake was transient, lasting about 20 to 30 min., but PMN activity remained above baseline for the remainder of the study. Following the infusion of gamma thrombin, a form of thrombin unable to cleave fibrinogen, increased PMN uptake was not observed. Inhibition of fibrinolysis with tranaxemic acid, reduced the PMN response to thrombin to less than a 3% increase over baseline (n=2). The findings demonstrate that PMNs are involved in acute pulmonary vascular injury, and suggest a potential role for labeled PMNs in the clinical investigation of the adult respiratory distress syndrome

Evasion of Neutrophil Extracellular Traps by Respiratory Pathogens.

Science.gov (United States)

Storisteanu, Daniel M L; Pocock, Joanna M; Cowburn, Andrew S; Juss, Jatinder K; Nadesalingam, Angalee; Nizet, Victor; Chilvers, Edwin R

2017-04-01

The release of neutrophil extracellular traps (NETs) is a major immune mechanism intended to capture pathogens. These histone- and protease-coated DNA structures are released by neutrophils in response to a variety of stimuli, including respiratory pathogens, and have been identified in the airways of patients with respiratory infection, cystic fibrosis, acute lung injury, primary graft dysfunction, and chronic obstructive pulmonary disease. NET production has been demonstrated in the lungs of mice infected with Staphylococcus aureus, Klebsiella pneumoniae, and Aspergillus fumigatus. Since the discovery of NETs over a decade ago, evidence that "NET evasion" might act as an immune protection strategy among respiratory pathogens, including group A Streptococcus, Bordetella pertussis, and Haemophilus influenzae, has been growing, with the majority of these studies being published in the past 2 years. Evasion strategies fall into three main categories: inhibition of NET release by down-regulating host inflammatory responses; degradation of NETs using pathogen-derived DNases; and resistance to the microbicidal components of NETs, which involves a variety of mechanisms, including encapsulation. Hence, the evasion of NETs appears to be a widespread strategy to allow pathogen proliferation and dissemination, and is currently a topic of intense research interest. This article outlines the evidence supporting the three main strategies of NET evasion-inhibition, degradation, and resistance-with particular reference to common respiratory pathogens.

Radiologic findings of diffuse Pulmonary hemorrhage

Energy Technology Data Exchange (ETDEWEB)

Seo, Mi Ra; Song, Koun Sik; Lee, Jin Seong; Lim, Tae Hwan [Ulsan Univ. College of Medicine, Seoul (Korea, Republic of)

1998-12-01

To describe the chest radiographic and CT findings of diffuse pulmonary hemorrhage. Two radiologists retrospectively analysed the chest radiographic and CT findings of six patients with diffuse pulmonary hemorrhage. Using open lung biopsy(n=3D2) and transbronchial lung biopsy or bronchoalveolar lavage(n=3D4), diagnosis was based on the presence of hemosiderin-laden macrophage or intra-alveolar hemorrhage. Underlying diseases were Wegener's granulomatosis(n=3D2), antiphospholipid antibody syndrome(n=3D2), Henoch-Schonlein purpura(n=3D1), and idopathic pulmonary hemosiderosis(n=3D1). In all patients, sequential chest radiographs, obtained during a one to six-month period, were available. HRCT scans were obtained in five patinets, and conventional CT scans in one. Follow-up HRCT scans were obtained in two. We also analyzed the patterns of involvement, distribution and sequential changes in the pulmonary abnormalities seen on chest radiographs and CT scans. Chest radiographs showed multifocal patchy consolidation(n=3D6), ground-glass opacity(n=3D3), and multiple granular or nodular opacity(n=3D3). These lesions were intermingled in five patients, while in one there was consolidation only. Sequential chest radiographs demonstrated the improvement of initial pulmonary abnormalities and appearance of new lesions elsewhere within 5-6 days, though within 7-25 (average, 13) days, these had almost normalized. HRCT scans showed patchy consolidation(n=3D5), multiple patchy ground-glass opacity(n=3D5), or ill-defined air space nodules(n=3D4). These lesions were intermingled in five patients, and in one, ground-glass opacity only was noted. In two patients there were interlobular septal thickening and intalobular reticular opacity. The distribution of these abnormalities was almost always bilateral, diffuse with no zonal predominancy, and spared the apex of the lung and subpleural region were less affected. Although chest radiographic and CT findings of diffuse pulmonary

Radiologic findings of diffuse Pulmonary hemorrhage

International Nuclear Information System (INIS)

Seo, Mi Ra; Song, Koun Sik; Lee, Jin Seong; Lim, Tae Hwan

1998-01-01

To describe the chest radiographic and CT findings of diffuse pulmonary hemorrhage. Two radiologists retrospectively analysed the chest radiographic and CT findings of six patients with diffuse pulmonary hemorrhage. Using open lung biopsy(n=3D2) and transbronchial lung biopsy or bronchoalveolar lavage(n=3D4), diagnosis was based on the presence of hemosiderin-laden macrophage or intra-alveolar hemorrhage. Underlying diseases were Wegener's granulomatosis(n=3D2), antiphospholipid antibody syndrome(n=3D2), Henoch-Schonlein purpura(n=3D1), and idopathic pulmonary hemosiderosis(n=3D1). In all patients, sequential chest radiographs, obtained during a one to six-month period, were available. HRCT scans were obtained in five patinets, and conventional CT scans in one. Follow-up HRCT scans were obtained in two. We also analyzed the patterns of involvement, distribution and sequential changes in the pulmonary abnormalities seen on chest radiographs and CT scans. Chest radiographs showed multifocal patchy consolidation(n=3D6), ground-glass opacity(n=3D3), and multiple granular or nodular opacity(n=3D3). These lesions were intermingled in five patients, while in one there was consolidation only. Sequential chest radiographs demonstrated the improvement of initial pulmonary abnormalities and appearance of new lesions elsewhere within 5-6 days, though within 7-25 (average, 13) days, these had almost normalized. HRCT scans showed patchy consolidation(n=3D5), multiple patchy ground-glass opacity(n=3D5), or ill-defined air space nodules(n=3D4). These lesions were intermingled in five patients, and in one, ground-glass opacity only was noted. In two patients there were interlobular septal thickening and intalobular reticular opacity. The distribution of these abnormalities was almost always bilateral, diffuse with no zonal predominancy, and spared the apex of the lung and subpleural region were less affected. Although chest radiographic and CT findings of diffuse pulmonary

Neutrophil Extracellular Traps in Ulcerative Colitis

DEFF Research Database (Denmark)

Bjerg Bennike, Tue; Carlsen, Thomas Gelsing; Ellingsen, Torkell

2015-01-01

microscopy and confocal microscopy. RESULTS: We identified and quantified 5711 different proteins with proteomics. The abundance of the proteins calprotectin and lactotransferrin in the tissue correlated with the degree of tissue inflammation as determined by histology. However, fecal calprotectin did...... not correlate. Forty-six proteins were measured with a statistically significant differences in abundances between the UC colon tissue and controls. Eleven of the proteins with increased abundances in the UC biopsies were associated with neutrophils and neutrophil extracellular traps. The findings were...... validated by microscopy, where an increased abundance of neutrophils and the presence of neutrophil extracellular traps by extracellular DNA present in the UC colon tissue were confirmed. CONCLUSIONS: Neutrophils, induced neutrophil extracellular traps, and several proteins that play a part in innate...

Taurine modulates neutrophil function but potentiates uropathogenic E. coli infection in the murine bladder.

LENUS (Irish Health Repository)

Condron, Claire

2010-08-01

Eradication of a urinary tract infection (UTI) appears to be related to a number of innate host defence mechanisms and their interactions with invading bacteria. Recurrent UTIs (rUTIs) pose a difficult problem in that these bacteria use both host and bacterial factors to evade elimination. Neutrophil bactericidal function is depressed, both systemically and in urine, in patients with a history of recurrent UTI. Taurine is a semi-essential amino acid and is successful in preserving neutrophil bactericidal function in urine. Taurine may preserve neutrophil function at the urothelium and thus aid UTI resolution. Adult female (6 weeks old) C57Bl\\/6 mice were randomised into three groups: a saline gavage only control group, a saline gavage + E. coli group, and a taurine gavage + E. coli group [21 g\\/70 kg taurine in 0.9% normal saline (N\\/S) for 5 days]. Whilst taurine gavage pre-treatment resulted in increased serum neutrophils respiratory burst activity, at the urothelial-endothelial interface it caused higher colony forming units in the urine and a higher incidence of E. coli invasion in the bladder wall with no evidence of increased bladder wall neutrophils infiltration on MPO assay of histological assessment. Histologically there was also evidence of reduced bladder inflammation and urothelial cell apoptosis. In conclusion, taurine effectively increases neutrophils activity but given its anti-inflammatory properties, at the expense of decreased urothelial-endothelial activation thus preventing clearance of active E. coli infection in the bladder. Despite the negative results, this study demonstrates the importance of modulating interactions at the urothelial interface.

Pulmonary langerhans cell histiocytosis

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Suri Harpreet S

2012-03-01

Full Text Available Abstract Pulmonary Langerhans Cell Histiocytosis (PLCH is a relatively uncommon lung disease that generally, but not invariably, occurs in cigarette smokers. The pathologic hallmark of PLCH is the accumulation of Langerhans and other inflammatory cells in small airways, resulting in the formation of nodular inflammatory lesions. While the overwhelming majority of patients are smokers, mechanisms by which smoking induces this disease are not known, but likely involve a combination of events resulting in enhanced recruitment and activation of Langerhans cells in small airways. Bronchiolar inflammation may be accompanied by variable lung interstitial and vascular involvement. While cellular inflammation is prominent in early disease, more advanced stages are characterized by cystic lung destruction, cicatricial scarring of airways, and pulmonary vascular remodeling. Pulmonary function is frequently abnormal at presentation. Imaging of the chest with high resolution chest CT scanning may show characteristic nodular and cystic abnormalities. Lung biopsy is necessary for a definitive diagnosis, although may not be required in instances were imaging findings are highly characteristic. There is no general consensus regarding the role of immunosuppressive therapy in smokers with PLCH. All smokers must be counseled on the importance of smoking cessation, which may result in regression of disease and obviate the need for systemic immunosuppressive therapy. The prognosis for most patients is relatively good, particularly if longitudinal lung function testing shows stability. Complications like pneumothoraces and secondary pulmonary hypertension may shorten life expectancy. Patients with progressive disease may require lung transplantation.

Chronic obstructive pulmonary disease: nature-nurture interactions.

Science.gov (United States)

Clancy, John; Nobes, Maggie

A person's health status is rarely constant, it is usually subject to continual change as a person moves from health to illness and usually back to health again; the health-illness continuum illustrates this dynamism. This highlights the person's various states of health and illness (ranging from extremely good health to clinically defined mild, moderate and severe illness) and their fluctuations throughout the life span, until ultimately leading to the pathology associated with the person's death. Maintenance of a stable homeostatic environment within the body to support the stability of this continuum depends on a complex series of ultimately intracellular chemical reactions. These reactions are activated by environmental factors that cause the expression of genes associated with healthy phenotypes as well as illness susceptibility genes associated with homeostatic imbalances. Obviously, the body aims to support intracellular and extracellular environments allied with health; however, the complexity of these nature-nurture interactions results in illness throughout an individual's life span. This paper will discuss the nature-nurture interactions of chronic obstructive pulmonary disease.

The clinical presentation of pulmonary embolism

International Nuclear Information System (INIS)

Otto, A.C.; Dunn, M.; Van der Merwe, B.; Katz, M.

2004-01-01

Full text: Introduction: Pulmonary embolism is often misdiagnosed by many clinicians because of confusion with pulmonary infarction. According to present literature, the latter seldomly occurs, thus pleuritic pain and hemoptysis are usually absent. The purpose of our study was to re-evaluate the clinical presentation of pulmonary embolism with specific reference to the presence of pulmonary hypertension and pulmonary infarction. Materials and methods: Ethical committee approval was obtained to study fifteen patients with abnormal lung perfusion and high probability for pulmonary embolism retrospectively. Clinical data will be presented in table format. Appropriate symptoms and signs not mentioned was considered absent. Specific investigations not available was considered not done. Results: Will be displayed in table format. The main findings can be summarized as follows: 1. Dyspnea was present in all the patients; 2. Pleuritic pain and hemoptysis was absent in all the patients; 3. None of the patients had clinical signs of pulmonary hypertension or infarction; 4. The available special investigations confirmed the above mentioned findings. Conclusion: The absence of pulmonary infarction and pulmonary hypertension with submassive pulmonary embolism (<60% of pulmonary vascular bed occluded) was reconfirmed and should be emphasized more in clinical practice. (author)

Neutrophils reduce the parasite burden in Leishmania (Leishmania amazonensis-infected macrophages.

Directory of Open Access Journals (Sweden)

Erico Vinícius de Souza Carmo

2010-11-01

Full Text Available Studies on the role of neutrophils in Leishmania infection were mainly performed with L. (L major, whereas less information is available for L. (L amazonensis. Previous results from our laboratory showed a large infiltrate of neutrophils in the site of infection in a mouse strain resistant to L. (L. amazonensis (C3H/HePas. In contrast, the susceptible strain (BALB/c displayed a predominance of macrophages harboring a high number of amastigotes and very few neutrophils. These findings led us to investigate the interaction of inflammatory neutrophils with L. (L. amazonensis-infected macrophages in vitro.Mouse peritoneal macrophages infected with L. (L. amazonensis were co-cultured with inflammatory neutrophils, and after four days, the infection was quantified microscopically. Data are representative of three experiments with similar results. The main findings were 1 intracellular parasites were efficiently destroyed in the co-cultures; 2 the leishmanicidal effect was similar when cells were obtained from mouse strains resistant (C3H/HePas or susceptible (BALB/c to L. (L. amazonensis; 3 parasite destruction did not require contact between infected macrophages and neutrophils; 4 tumor necrosis factor alpha (TNF-α, neutrophil elastase and platelet activating factor (PAF were involved with the leishmanicidal activity, and 5 destruction of the parasites did not depend on generation of oxygen or nitrogen radicals, indicating that parasite clearance did not involve the classical pathway of macrophage activation by TNF-α, as reported for other Leishmania species.The present results provide evidence that neutrophils in concert with macrophages play a previously unrecognized leishmanicidal effect on L. (L. amazonensis. We believe these findings may help to understand the mechanisms involved in innate immunity in cutaneous infection by this Leishmania species.

Neutrophils: potential therapeutic targets in tularemia?

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Lee-Ann H Allen

2013-12-01

Full Text Available The central role of neutrophils in innate immunity and host defense has long been recognized, and the ability of these cells to efficiently engulf and kill invading bacteria has been extensively studied, as has the role of neutrophil apoptosis in resolution of the inflammatory response. In the past few years additional immunoregulatory properties of neutrophils were discovered, and it is now clear that these cells play a much greater role in control of the immune response than was previously appreciated. In this regard, it is noteworthy that Francisella tularensis is one of relatively few pathogens that can successfully parasitize neutrophils as well as macrophages, DC and epithelial cells. Herein we will review the mechanisms used by F. tularensis to evade elimination by neutrophils. We will also reprise effects of this pathogen on neutrophil migration and lifespan as compared with other infectious and inflammatory disease states. In addition, we will discuss the evidence which suggests that neutrophils contribute to disease progression rather than effective defense during tularemia, and consider whether manipulation of neutrophil migration or turnover may be suitable adjunctive therapeutic strategies.

iNKT Cell Emigration out of the Lung Vasculature Requires Neutrophils and Monocyte-Derived Dendritic Cells in Inflammation

Directory of Open Access Journals (Sweden)

Ajitha Thanabalasuriar

2016-09-01

Full Text Available iNKT cells are a subset of innate T cells that recognize glycolipids presented on CD1d molecules and protect against bacterial infections, including S. pneumoniae. Using lung intravital imaging, we examined the behavior and mechanism of pulmonary iNKT cell activation in response to the specific iNKT cell ligand α-galactosylceramide or S. pneumoniae infection. In untreated mice, the major fraction of iNKT cells resided in the vasculature, but a small critical population resided in the extravascular space in proximity to monocyte-derived DCs. Administration of either α-GalCer or S. pneumoniae induced CD1d-dependent rapid recruitment of neutrophils out of the vasculature. The neutrophils guided iNKT cells from the lung vasculature via CCL17. Depletion of monocyte-derived DCs abrogated both the neutrophil and subsequent iNKT cell extravasation. Moreover, impairing iNKT cell recruitment by blocking CCL17 increased susceptibility to S. pneumoniae infection, suggesting a critical role for the influx of iNKT cells in host defense.

Pulmonary Cryptococcosis: Imaging Findings in 23 Non-AIDS Patients

Energy Technology Data Exchange (ETDEWEB)

Song, Kyoung Doo; Lee, Kyung Soo; Kim, Tae Sung; Yi, Chin A; Chung, Myung Jin [Samsung Medical Center, Seoul (Korea, Republic of); Man Pyo Chung; O Jung Kwon [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2010-08-15

We aimed to review the patterns of lung abnormalities of pulmonary cryptococcosis on CT images, position emission tomography (PET) findings of the disease, and the response of lung abnormalities to the therapies in non-AIDS patients. We evaluated the initial CT (n = 23) and 18F-fluorodeoxyglucose (FDG) PET (n = 10), and follow-up (n = 23) imaging findings of pulmonary cryptococcosis in 23 non-AIDS patients. Lung lesions were classified into five patterns at CT: single nodular, multiple clustered nodular, multiple scattered nodular, mass-like, and bronchopneumonic patterns. The CT pattern analyses, PET findings, and therapeutic responses were recorded. A clustered nodular pattern was the most prevalent and was observed in 10 (43%) patients. This pattern was followed by solitary pulmonary nodular (n = 4, 17%), scattered nodular (n = 3, 13%), bronchopneumonic (n = 2, 9%), and single mass (n = 1, 4%) patterns. On PET scans, six (60%) of 10 patients showed higher FDG uptake and four (40%) demonstrated lower FDG uptake than the mediastinal blood pool. With specific treatment of the disease, a complete clearance of lung abnormalities was noted in 15 patients, whereas a partial response was noted in seven patients. In one patient where treatment was not performed, the disease showed progression. Pulmonary cryptococcosis most commonly appears as clustered nodules and is a slowly progressive and slowly resolving pulmonary infection. In two-thirds of patients, lung lesions show high FDG uptake, thus simulating a possible malignant condition

Effect of sevoflurane on human neutrophil apoptosis.

LENUS (Irish Health Repository)

Tyther, R

2012-02-03

BACKGROUND AND OBJECTIVE: Both chronic occupational exposure to volatile anaesthetic agents and acute in vitro exposure of neutrophils to isoflurane have been shown to inhibit the rate of apoptosis of human neutrophils. It is possible that inhibition of neutrophil apoptosis arises through delaying mitochondrial membrane potential collapse. We assessed mitochondrial depolarization and apoptosis in unexposed neutrophils and neutrophils exposed to sevoflurane in vivo. METHODS: A total of 20 mL venous blood was withdrawn pre- and postinduction of anaesthesia, the neutrophils isolated and maintained in culture. At 1, 12 and 24 h in culture, the percentage of neutrophil apoptosis was assessed by dual staining with annexin V-FITC and propidium iodide. Mitochondrial depolarization was measured using the dual emission styryl dye JC-1. RESULTS: Apoptosis was significantly inhibited in neutrophils exposed to sevoflurane in vivo at 24 (exposed: 38 (12)% versus control: 28 (11)%, P = 0.001), but not at 1 or 12 h, in culture. Mitochondrial depolarization was not delayed in neutrophils exposed to sevoflurane. CONCLUSIONS: The most important findings are that sevoflurane inhibits neutrophil apoptosis in vivo and that inhibition is not mediated primarily by an effect on mitochondrial depolarization.

Neutrophil programming dynamics and its disease relevance.

Science.gov (United States)

Ran, Taojing; Geng, Shuo; Li, Liwu

2017-11-01

Neutrophils are traditionally considered as first responders to infection and provide antimicrobial host defense. However, recent advances indicate that neutrophils are also critically involved in the modulation of host immune environments by dynamically adopting distinct functional states. Functionally diverse neutrophil subsets are increasingly recognized as critical components mediating host pathophysiology. Despite its emerging significance, molecular mechanisms as well as functional relevance of dynamically programmed neutrophils remain to be better defined. The increasing complexity of neutrophil functions may require integrative studies that address programming dynamics of neutrophils and their pathophysiological relevance. This review aims to provide an update on the emerging topics of neutrophil programming dynamics as well as their functional relevance in diseases.

Value of the ventilation/perfusion scan in acute pulmonary embolism: Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED)

International Nuclear Information System (INIS)

Anon.

1990-01-01

To determine the sensitivities and specificities of ventilation/perfusion lung scans for acute pulmonary embolism, a random sample of 933 of 1,493 patients was studied prospectively. Nine hundred thirty-one underwent scintigraphy and 755 underwent pulmonary angiography; 251 (33%) of 755 demonstrated pulmonary embolism. Almost all patients with pulmonary embolism had abnormal scans of high, intermediate, or low probability, but so did most without pulmonary embolism. Of 116 patients with high-probability scans and definitive angiograms, 102 (88%) had pulmonary embolism, but only a minority with pulmonary embolism had high-probability scans. Of 322 with intermediate-probability scans and definitive angiograms, 105 (33%) had pulmonary embolism. Follow-up and angiography together suggest pulmonary embolism occurred among 12% of patients with low-probability scans. Clinical assessment combined with the ventilation/perfusion scan established the diagnosis or exclusion of pulmonary embolism only for a minority of patients--those with clear and concordant clinical and ventilation/perfusion scan findings

Torsed pulmonary sequestration presenting as a painful chest mass

International Nuclear Information System (INIS)

Shah, Ricki; Carver, Terrence W.; Rivard, Douglas C.

2010-01-01

Pulmonary sequestration is a congenital abnormality that can be divided into intralobar or extralobar types. Both types are characterized by pulmonary tissue that does not communicate with the bronchial tree or pulmonary arteries and typically has its arterial supply arising from the descending aorta. We report a case of an 11-year-old girl with extralobar sequestration who presented with torsion causing abdominal pain and pleuritic chest pain. (orig.)

RIPK3/Fas-Associated Death Domain Axis Regulates Pulmonary Immunopathology to Cryptococcal Infection Independent of Necroptosis

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Zhenzong Fa

2017-09-01

Full Text Available Fas-associated death domain (FADD and receptor interacting protein kinase 3 (RIPK3 are multifunctional regulators of cell death and immune response. Using a mouse model of cryptococcal infection, the roles of FADD and RIPK3 in anti-cryptococcal defense were investigated. Deletion of RIPK3 alone led to increased inflammatory cytokine production in the Cryptococcus neoformans-infected lungs, but in combination with FADD deletion, it led to a robust Th1-biased response with M1-biased macrophage activation. Rather than being protective, these responses led to paradoxical C. neoformans expansion and rapid clinical deterioration in Ripk3−/− and Ripk3−/−Fadd−/− mice. The increased mortality of Ripk3−/− and even more accelerated mortality in Ripk3−/−Fadd−/− mice was attributed to profound pulmonary damage due to neutrophil-dominant infiltration with prominent upregulation of pro-inflammatory cytokines. This phenomenon was partially associated with selective alterations in the apoptotic frequency of some leukocyte subsets, such as eosinophils and neutrophils, in infected Ripk3−/−Fadd−/− mice. In conclusion, our study shows that RIPK3 in concert with FADD serve as physiological “brakes,” preventing the development of excessive inflammation and Th1 bias, which in turn contributes to pulmonary damage and defective fungal clearance. This novel link between the protective effect of FADD and RIPK3 in antifungal defense and sustenance of immune homeostasis may be important for the development of novel immunomodulatory therapies against invasive fungal infections.

Neonatal Pulmonary Hemosiderosis

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Boris Limme

2014-01-01

Full Text Available Idiopathic pulmonary hemosiderosis (IPH is a rare complex entity characterized clinically by acute or recurrent episodes of hemoptysis secondary to diffuse alveolar hemorrhage. The radiographic features are variable, including diffuse alveolar-type infiltrates, and interstitial reticular and micronodular patterns. We describe a 3-week-old infant presenting with hemoptysis and moderate respiratory distress. Idiopathic pulmonary hemosiderosis was the first working diagnosis at the Emergency Department and was confirmed, 2 weeks later, by histological studies (bronchoalveolar lavage. The immunosuppressive therapy by 1 mg/kg/d prednisone was immediately started, the baby returned home on steroid therapy at a dose of 0,5 mg/kg/d. The diagnosis of idiopathic pulmonary hemosiderosis should be evocated at any age, even in the neonate, when the clinical presentation (hemoptysis and abnormal radiological chest images is strongly suggestive.

[Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease].

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Barberán, José; Mensa, José

2014-01-01

Invasive pulmonary aspergillosis (IPA) is a common infection in immunocompromised patients with hematological malignancies or allogenic stem cell transplantation, and is less frequent in the context of chronic obstructive pulmonary disease (COPD). Mucociliary activity impairment, immunosuppression due to the inhibition of alveolar macrophages and neutrophils by steroids, and receiving broad-spectrum antibiotics, play a role in the development of IPA in COPD patients. Colonized patients or those with IPA are older, with severe CODP stage (GOLD≥III), and have a higher number of comorbidities. The mortality rate is high due to the fact that having a definitive diagnosis of IPA in COPD patients is often difficult. The main clinical and radiological signs of IPA in these types of patients are non-specific, and tissue samples for definitive diagnosis are often difficult to obtain. The poor prognosis of IPA in COPD patients could perhaps be improved by faster diagnosis and prompt initiation of antifungal treatment. Some tools, such as scales and algorithms based on risk factors of IPA, may be useful for its early diagnosis in these patients. Copyright © 2014 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

Pulmonary Function in Ulcerative Colitis

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A.H. Faghihi-Kashani; A. Kabir; S.A. Javad-Moosavi

2008-01-01

Background:Pulmonary involvement in ulcerative colitis (UC) is thought to be rare. There is not a definite document about the question that "Is the lung a target organ in inflammatory bowel disease?"The aim of the present study is to compare lung function between cases with UC and healthy controls. This study will also be of interest about searching the outbreak of pulmonary function abnormalities in a sample of Iranian patients with UC and factors associated with severity of UC. Me...

Role of nuclear medicine in pulmonary neoplastic processes

International Nuclear Information System (INIS)

Waxman, A.D.

1986-01-01

It has been demonstrated that the single most important factor in determining survival in patients with bronchogenic carcinoma is the extent of spread of metastasis from the primary lesion. This explains the extensive efforts in developing accurate staging tests for pulmonary tumors, both primary and metastatic, with special emphasis on the determination of pulmonary hilar and mediastinal spread of disease. Continued improvements in nuclear medicine instrumentation along with the development of tumor specific radiopharmaceuticals, as well as agents that have the capability of tracking tumor viability, have changed the orientation of scintigraphic techniques in the evaluation of pulmonary neoplastic processes. Gallium scintigraphy is no longer considered as a primary imaging modality in the staging of pulmonary tumors, and in most institutions has been replaced by computed tomography (CT) for this purpose. It has been demonstrated that gallium, relative to other imaging modalities, is a sensitive indicator of hilar spread of tumor. However, because of the normally high background activity within the sternum and spine, mediastinal abnormalities are poorly detected. Since most pulmonary tumors metastasize via regional nodes to the pulmonary hilum and then to the mediastinum, the high sensitivity for the detection of pulmonary hilar abnormalities and the high specificity for mediastinal lesion detection suggest that gallium scintigraphy is a valuable adjunctive test when used appropriately. Thallium 201 as a tumor agent is being studied by several institutions. Preliminary results indicate a high degree of sensitivity for the detection of pulmonary hilar and mediastinal lesions and there are early indications that thallium is a promising agent to evaluate tumor viability. 52 references

Serum progranulin as an indicator of neutrophilic airway inflammation and asthma severity.

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Park, So Young; Hong, Gyong Hwa; Park, Sunjoo; Shin, Bomi; Yoon, Sun-Young; Kwon, Hyouk-Soo; Kim, Tae-Bum; Moon, Hee-Bom; Cho, You Sook

2016-12-01

Progranulin, a protein secreted from the airway epithelium, is known to attenuate the downstream cascade of neutrophilic inflammation in particular. We hypothesized that progranulin may have a role in inflammatory regulation in asthma. To investigate the association between serum progranulin levels and various clinical features in patients with asthma. Serum samples and clinical data of 475 patients with asthma and 35 healthy controls at a tertiary referral hospital and its affiliated health promotion center were collected. Serum progranulin levels were compared between patients with asthma and healthy controls and then were compared within the patients with asthma in terms of pulmonary function and measures of inflammatory status. Univariate and multivariate analyses were performed to identify factors associated with severity of asthma. Serum progranulin levels were significantly lower in the asthma group than in healthy group and were positively correlated with prebronchodilator forced expiratory volume in 1 second predicted within patients with asthma. We found a negative correlation between serum progranulin levels and blood neutrophil counts. Multivariate analysis revealed that higher serum progranulin levels were associated with a lower risk of severe asthma (odds ratio, 0.888; 95% confidence interval, 0.846-0.932; P progranulin remains unknown, we suggest that serum progranulin may be an indicator of severe asthma with airflow limitation. Future studies with comprehensive airway sampling strategies are warranted to clarify its role, particularly in neutrophilic asthma. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

A synthetic eicosanoid LX-mimetic unravels host-donor interactions in allogeneic BMT-induced GvHD to reveal an early protective role for host neutrophils.

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Devchand, Pallavi R; Schmidt, Birgitta A; Primo, Valeria C; Zhang, Qing-yin; Arnaout, M Amin; Serhan, Charles N; Nikolic, Boris

2005-02-01

Lipoxin A(4) (LXA(4)) and aspirin-triggered 15-epi-LXA(4) are potent endogenous lipid mediators thought to define the inflammatory set-point. We used single prophylactic administrations of a synthetic aspirin-triggered lipoxin A(4) signal mimetic, ATLa, to probe dynamics of early host-donor interactions in a mouse model for the inflammation-associated multifactorial disease of allogeneic bone marrow transplant (BMT) -induced graft-vs.-host disease (GvHD). We first demonstrated that both host and donor are responsive to the ATLa signals. The simple and restricted regimen of a single prophylactic administration of ATLa [100 ng/mL to donor cells or 1 microg (approximately 50 microg/kg) i.v. to host] was sufficient to delay death. Clinical indicators of weight, skin lesions, diarrhea and eye inflammation were monitored. Histological analyses on day 45 post-BMT showed that the degree of cellular trafficking, particularly neutrophil infiltrate, and protection of end-organ target pathology are different, depending on whether the host or donor was treated with ATLa. Taken together, these results chart some ATLa protective effects on GvHD cellular dynamics over time and identify a previously unrecognized effect of host neutrophils in the early phase post-BMT as important determinants in the dynamics of GvHD onset and progression.-Devchand, P. R., Schmidt, B. A., Primo, V. C., Zhang, Q.-y., Arnaout, M. A., Serhan, C. N., Nikolic, B. A synthetic eicosanoid LX-mimetic unravels host-donor interactions in allogeneic BMT-induced GvHD to reveal an early protective role for host neutrophils.

Biomaterial associated impairment of local neutrophil function.

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Kaplan, S S; Basford, R E; Kormos, R L; Hardesty, R L; Simmons, R L; Mora, E M; Cardona, M; Griffith, B L

1990-01-01

The effect of biomaterials on neutrophil function was studied in vitro to determine if these materials activated neutrophils and to determine the subsequent response of these neutrophils to further stimulation. Two biomaterials--polyurethane, a commonly used substance, and Velcro pile (used in the Jarvik 7 heart)--were evaluated. Two control substances, polyethylene and serum-coated polystyrene, were used for comparison. Neutrophil superoxide release was measured following incubation with these materials for 10, 30, and 120 min in the absence of additional stimulation and after stimulation with formylmethionylleucylphenylalanine (fMLP) or phorbol myristate acetate (PMA). The authors observed that the incubation of neutrophils on both polyurethane and Velcro resulted in substantially increased superoxide release that was greater after the 10 min than after the 30 or 120 min association. These activated neutrophils exhibited a poor additional response to fMLP but responded well to PMA. The effect of implantation of the Novacor left ventricular assist device on peripheral blood neutrophil function was also evaluated. The peripheral blood neutrophils exhibited normal superoxide release and chemotaxis. These studies suggest that biomaterials may have a profound local effect on neutrophils, which may predispose the patient to periprosthetic infection, but that the reactivity of circulating neutrophils is unimpaired.

Neutrophils Compromise Retinal Pigment Epithelial Barrier Integrity

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Jiehao Zhou

2010-01-01

Full Text Available We hypothesized that neutrophils and their secreted factors mediate breakdown of the integrity of the outer blood-retina-barrier by degrading the apical tight junctions of the retinal pigment epithelium (RPE. The effect of activated neutrophils or neutrophil cell lysate on apparent permeability of bovine RPE-Choroid explants was evaluated by measuring [H] mannitol flux in a modified Ussing chamber. The expression of matrix metalloproteinase- (MMP- 9 in murine peritoneal neutrophils, and the effects of neutrophils on RPE tight-junction protein expression were assessed by confocal microscopy and western blot. Our results revealed that basolateral incubation of explants with neutrophils decreased occludin and ZO-1 expression at 1 and 3 hours and increased the permeability of bovine RPE-Choroid explants by >3-fold (P<.05. Similarly, basolateral incubation of explants with neutrophil lysate decreased ZO-1 expression at 1 and 3 hours (P<.05 and increased permeability of explants by 75%. Further, we found that neutrophils prominently express MMP-9 and that incubation of explants with neutrophils in the presence of anti-MMP-9 antibody inhibited the increase in permeability. These data suggest that neutrophil-derived MMP-9 may play an important role in disrupting the integrity of the outer blood-retina barrier.

Paraseptal emphysema: Prevalence and distribution on CT and association with interstitial lung abnormalities

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Araki, Tetsuro; Nishino, Mizuki; Zazueta, Oscar E.; Gao, Wei; Dupuis, Josée; Okajima, Yuka; Latourelle, Jeanne C.; Rosas, Ivan O.; Murakami, Takamichi; O’Connor, George T.; Washko, George R.; Hunninghake, Gary M.

2015-01-01

Highlights: • The prevalence of pure paraseptal emphysema was 3% (85/2633) in the Framingham Heart Study population, predominantly affects the upper lung zone, and contributes to slightly decreased pulmonary function. • There was significant association between paraseptal emphysema and interstitial lung abnormalities, which is a novel finding. • Prevalence of paraseptal emphysema and its impact on pulmonary function could have been underestimated in the previous reports. - Abstract: Objective: To investigate the prevalence and distribution of paraseptal emphysema on chest CT images in the Framingham Heart Study (FHS) population, and assess its impact on pulmonary function. Also pursued was the association with interstitial lung abnormalities. Materials and methods: We assessed 2633 participants in the FHS for paraseptal emphysema on chest CT. Characteristics of the participants, including age, sex, smoking status, clinical symptoms, and results of pulmonary function tests, were compared between those with and without paraseptal emphysema. The association between paraseptal emphysema and interstitial lung abnormalities was investigated. Results: Of the 2633 participants, 86 (3%) had pure paraseptal emphysema (defined as paraseptal emphysema with no other subtypes of emphysema other than paraseptal emphysema or a very few centrilobular emphysema involved) in at least one lung zone. The upper zone of the lungs was almost always involved. Compared to the participants without paraseptal emphysema, those with pure paraseptal emphysema were significantly older, and were more frequently male and smokers (mean 64 years, 71% male, mean 36 pack-years, P < 0.001) and had significantly decreased FEV 1 /FVC% (P = 0.002), and diffusion capacity of carbon monoxide (DLCO) (P = 0.002). There was a significant association between pure paraseptal emphysema and interstitial lung abnormalities (P < 0.001). Conclusions: The prevalence of pure paraseptal emphysema was 3% in the FHS

Paraseptal emphysema: Prevalence and distribution on CT and association with interstitial lung abnormalities

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Araki, Tetsuro, E-mail: taraki@partners.org [Department of Radiology, Center for Pulmonary Functional Imaging, Brigham and Women' s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02215 (United States); Department of Radiology, Kinki University Faculty of Medicine, Osaka-Sayama (Japan); Nishino, Mizuki [Department of Radiology, Center for Pulmonary Functional Imaging, Brigham and Women' s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02215 (United States); Zazueta, Oscar E. [The Pulmonary and Critical Care Division, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Gao, Wei [Department of Biostatistics, Boston University School of Public Health, Boston, MA (United States); Dupuis, Josée [Department of Biostatistics, Boston University School of Public Health, Boston, MA (United States); The National Heart Lung and Blood Institute' s Framingham Heart Study, Framingham, MA (United States); Okajima, Yuka [Department of Radiology, Center for Pulmonary Functional Imaging, Brigham and Women' s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02215 (United States); Latourelle, Jeanne C. [Department of Medicine and Neurology, Boston University School of Medicine, Boston, MA (United States); Rosas, Ivan O. [The Pulmonary and Critical Care Division, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Murakami, Takamichi [Department of Radiology, Kinki University Faculty of Medicine, Osaka-Sayama (Japan); O’Connor, George T. [The National Heart Lung and Blood Institute' s Framingham Heart Study, Framingham, MA (United States); Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA (United States); Washko, George R.; Hunninghake, Gary M. [The Pulmonary and Critical Care Division, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); and others

2015-07-15

Highlights: • The prevalence of pure paraseptal emphysema was 3% (85/2633) in the Framingham Heart Study population, predominantly affects the upper lung zone, and contributes to slightly decreased pulmonary function. • There was significant association between paraseptal emphysema and interstitial lung abnormalities, which is a novel finding. • Prevalence of paraseptal emphysema and its impact on pulmonary function could have been underestimated in the previous reports. - Abstract: Objective: To investigate the prevalence and distribution of paraseptal emphysema on chest CT images in the Framingham Heart Study (FHS) population, and assess its impact on pulmonary function. Also pursued was the association with interstitial lung abnormalities. Materials and methods: We assessed 2633 participants in the FHS for paraseptal emphysema on chest CT. Characteristics of the participants, including age, sex, smoking status, clinical symptoms, and results of pulmonary function tests, were compared between those with and without paraseptal emphysema. The association between paraseptal emphysema and interstitial lung abnormalities was investigated. Results: Of the 2633 participants, 86 (3%) had pure paraseptal emphysema (defined as paraseptal emphysema with no other subtypes of emphysema other than paraseptal emphysema or a very few centrilobular emphysema involved) in at least one lung zone. The upper zone of the lungs was almost always involved. Compared to the participants without paraseptal emphysema, those with pure paraseptal emphysema were significantly older, and were more frequently male and smokers (mean 64 years, 71% male, mean 36 pack-years, P < 0.001) and had significantly decreased FEV{sub 1}/FVC% (P = 0.002), and diffusion capacity of carbon monoxide (DLCO) (P = 0.002). There was a significant association between pure paraseptal emphysema and interstitial lung abnormalities (P < 0.001). Conclusions: The prevalence of pure paraseptal emphysema was 3% in the

Evaluation of pulmonary artery flow in acute massive pulmonary thromboembolism with MRI

International Nuclear Information System (INIS)

Li Yongzhong; Li Kuncheng; Zhao Xigang; Zhao Hong

2004-01-01

Objective: To probe into the value of MR imaging in evaluating the pulmonary artery hemodynamics and pulmonary artery pressure in acute massive pulmonary embolism. Methods: MR studies were performed in 21 patients with acute massive pulmonary embolism (diagnosed by contrast enhanced MR pulmonary angiography) and 20 healthy volunteers. The pulmonary artery hemodynamic parameters, such as the diameters of main and right pulmonary artery, peak velocity, average velocity, flow volume, flow patterns, and ejection acceleration time in main pulmonary artery were measured. The findings in patients and volunteers were compared. The hemodynamic parameters in patients were correlated with mean pulmonary artery pressure acquired with right heart catheterization. Results: The diameters of main pulmonary artery (2.93 vs 2.52 cm) and right pulmonary artery (2.49 vs 1.92 cm) in patients and volunteers showed significant differences (t=3.55, P<0.01 and t=4.19, P<0.01, respectively); Peak velocity (85.29 vs 100.63 cm/s), average velocity (11.00 vs 17.12 cm/s), flow volume (89.15 vs 98.96 ml/s), and ejection acceleration time (105.09 vs 163.85 ms) in main pulmonary artery were significantly different between patients and volunteers (t values were 2.89, 6.37, 2.21, and 9.46, respectively; P values were 0.01, <0.01, 0.03, and <0.01, respectively). The peak velocity-time curve of main pulmonary artery acquired with velocity encoded cine of MR in patients demonstrated earlier and lower peak velocity as well as abnormal retrograde flow. In addition, linear correlations were seen between the mean pulmonary pressure and the diameter of main pulmonary artery (r=0.62, P=0.001), diameter of right pulmonary artery (r=0.63, P=0.001), and ejection acceleration time (r=-0.55, P=0.005). Conclusion: MR imaging is a promising technique not only for the detection of pulmonary thromboemboli but also for the evaluation of hemodynamic parameters in pulmonary hypertension. (author)

Yersinia pestis subverts the dermal neutrophil response in a mouse model of bubonic plague.

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Shannon, Jeffrey G; Hasenkrug, Aaron M; Dorward, David W; Nair, Vinod; Carmody, Aaron B; Hinnebusch, B Joseph

2013-08-27

The majority of human Yersinia pestis infections result from introduction of bacteria into the skin by the bite of an infected flea. Once in the dermis, Y. pestis can evade the host's innate immune response and subsequently disseminate to the draining lymph node (dLN). There, the pathogen replicates to large numbers, causing the pathognomonic bubo of bubonic plague. In this study, several cytometric and microscopic techniques were used to characterize the early host response to intradermal (i.d.) Y. pestis infection. Mice were infected i.d. with fully virulent or attenuated strains of dsRed-expressing Y. pestis, and tissues were analyzed by flow cytometry. By 4 h postinfection, there were large numbers of neutrophils in the infected dermis and the majority of cell-associated bacteria were associated with neutrophils. We observed a significant effect of the virulence plasmid (pCD1) on bacterial survival and neutrophil activation in the dermis. Intravital microscopy of i.d. Y. pestis infection revealed dynamic interactions between recruited neutrophils and bacteria. In contrast, very few bacteria interacted with dendritic cells (DCs), indicating that this cell type may not play a major role early in Y. pestis infection. Experiments using neutrophil depletion and a CCR7 knockout mouse suggest that dissemination of Y. pestis from the dermis to the dLN is not dependent on neutrophils or DCs. Taken together, the results of this study show a very rapid, robust neutrophil response to Y. pestis in the dermis and that the virulence plasmid pCD1 is important for the evasion of this response. Yersinia pestis remains a public health concern today because of sporadic plague outbreaks that occur throughout the world and the potential for its illegitimate use as a bioterrorism weapon. Since bubonic plague pathogenesis is initiated by the introduction of Y. pestis into the skin, we sought to characterize the response of the host's innate immune cells to bacteria early after

Visceral leishmaniasis patients display altered composition and maturity of neutrophils as well as impaired neutrophil effector functions

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Endalew Yizengaw

2016-11-01

Full Text Available Immunologically, active visceral leishmaniasis (VL is characterised by profound immunosuppression, severe systemic inflammatory responses and an impaired capacity to control parasite replication. Neutrophils are highly versatile cells, which play a crucial role in the induction as well as the resolution of inflammation, the control of pathogen replication and the regulation of immune responses. Neutrophil functions have been investigated in human cutaneous leishmaniasis, however, their role in human visceral leishmaniasis is poorly understood.In the present study we evaluated the activation status and effector functions of neutrophils in patients with active VL and after successful anti-leishmanial treatment. Our results show that neutrophils are highly activated and have degranulated; high levels of arginase, myeloperoxidase and elastase, all contained in neutrophils’ granules, were found in the plasma of VL patients. In addition, we show that a large proportion of these cells are immature. We also analysed effector functions of neutrophils that are essential for pathogen clearance and show that neutrophils have an impaired capacity to release neutrophil extracellular traps, produce reactive oxygen species and phagocytose bacterial particles, but not Leishmania parasites.Our results suggest that impaired effector functions, increased activation and immaturity of neutrophils play a key role in the pathogenesis of VL.

Cytoplasmic lipid bodies of human neutrophilic leukocytes

International Nuclear Information System (INIS)

Weller, P.F.; Ackerman, S.J.; Nicholson-Weller, A.; Dvorak, A.M.

1989-01-01

The morphology and function of cytoplasmic lipid bodies in human neutrophils were evaluated. By transmission electron microscopy, neutrophil lipid bodies were cytoplasmic inclusions, usually several microns in diameter, that occasionally coalesced to attain a diameter up to 7 microM. Neutrophil lipid bodies were not enveloped by membrane but were often surrounded by a more electron-dense shell at their periphery. Normal peripheral blood neutrophils contained an average of approximately one lipid body per cell. Lipid bodies appeared in greater numbers in neutrophils from inflammatory lesions. Perturbation of neutrophils during conventional methods of cell isolation and purification modestly increased lipid body numbers in neutrophils, whereas incubation of neutrophils with 1 microM oleic acid rapidly induced lipid body formation over 30 to 60 minutes. After granulocytes were incubated for 2 hours with 3H-fatty acids, including arachidonic, oleic, and palmitic acids, electron microscopic autoradiography demonstrated that lipid bodies represented the predominant intracellular sites of localization of each of the three 3H-fatty acids. There was lesser labeling noted in the perinuclear cisterna, but not in cell membranes. Virtually all of each of the three 3H-fatty acids incorporated by the neutrophils were esterified into chromatographically resolved classes of neutral lipids or phospholipids. These findings indicate that cytoplasmic lipid bodies are more prominent in neutrophils in vivo engaged in inflammatory responses and that these organelles in human neutrophils function as sites of deposition of esterified, incorporated fatty acids

CD177 modulates human neutrophil migration through activation-mediated integrin and chemoreceptor regulation.

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Bai, Ming; Grieshaber-Bouyer, Ricardo; Wang, Junxia; Schmider, Angela B; Wilson, Zachary S; Zeng, Liling; Halyabar, Olha; Godin, Matthew D; Nguyen, Hung N; Levescot, Anaïs; Cunin, Pierre; Lefort, Craig T; Soberman, Roy J; Nigrovic, Peter A

2017-11-09

CD177 is a glycosylphosphatidylinositol (GPI)-anchored protein expressed by a variable proportion of human neutrophils that mediates surface expression of the antineutrophil cytoplasmic antibody antigen proteinase 3. CD177 associates with β2 integrins and recognizes platelet endothelial cell adhesion molecule 1 (PECAM-1), suggesting a role in neutrophil migration. However, CD177 pos neutrophils exhibit no clear migratory advantage in vivo, despite interruption of in vitro transendothelial migration by CD177 ligation. We sought to understand this paradox. Using a PECAM-1-independent transwell system, we found that CD177 pos and CD177 neg neutrophils migrated comparably. CD177 ligation selectively impaired migration of CD177 pos neutrophils, an effect mediated through immobilization and cellular spreading on the transwell membrane. Correspondingly, CD177 ligation enhanced its interaction with β2 integrins, as revealed by fluorescence lifetime imaging microscopy, leading to integrin-mediated phosphorylation of Src and extracellular signal-regulated kinase (ERK). CD177-driven cell activation enhanced surface β2 integrin expression and affinity, impaired internalization of integrin attachments, and resulted in ERK-mediated attenuation of chemokine signaling. We conclude that CD177 signals in a β2 integrin-dependent manner to orchestrate a set of activation-mediated mechanisms that impair human neutrophil migration. © 2017 by The American Society of Hematology.

Role of LTB4 in the pathogenesis of elastase-induced murine pulmonary emphysema

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Paige, Mikell; Hanna, Halim; Kim, Su H.; Burdick, Marie D.; Strieter, Robert M.

2010-01-01

Exaggerated levels of the leukotriene B4 (LTB4) frequently coexist at sites of inflammation and tissue remodeling. Therefore, we hypothesize that the LTB4 pathway plays an important role in the pathogenesis of neutrophilic inflammation that contributes to pulmonary emphysema. In this study, significant levels of LTB4 were detected in human lung tissues with emphysema compared with lungs without emphysema (9,497 ± 2,839 vs. 4,142 ± 1,173 pg/ml, n = 9 vs. 10, P = 0.04). To further determine the biological role of LTB4 in the pathogenesis of emphysema, we compared the lungs of wild-type (WT) and LTA4 hydrolase−/− mice (LTB4 deficient, LTA4H−/−) exposed to intranasal elastase or vehicle control. We found that intranasal elastase induced accumulation of LTB4 in the lungs and caused progressively worsening emphysema between 14 and 28 days after elastase exposure in WT mice but not in LTA4H−/− mice. Premortem physiology documented increased lung compliance in elastase-exposed WT mice compared with elastase-exposed LTA4H−/− mice as measured by Flexivent (0.058 ± 0.005 vs. 0.041 ± 0.002 ml/cmH2O pressure). Postmortem morphometry documented increased total lung volume and alveolar sizes in elastase-exposed WT mice compared with elastase-exposed LTA4H−/− mice as measured by volume displacement and alveolar chord length assessment. Furthermore, elastase-exposed LTA4H−/− mice were found to have significantly delayed influx of the CD45highCD11bhighLy6Ghigh leukocytes compatible with neutrophils compared with elastase-exposed WT mice. Mechanistic insights to these phenotypes were provided by demonstrating protection from elastase-induced murine emphysema with neutrophil depletion in the elastase-exposed WT mice and by demonstrating time-dependent modulation of cysteinyl leukotriene biosynthesis in the elastase-exposed LTA4H−/− mice compared with elastase-exposed WT mice. Together, these findings demonstrated that LTB4 played an important role in

Perfusion abnormalities in congenital and neoplastic pulmonary disease: comparison of MR perfusion and multislice CT imaging

International Nuclear Information System (INIS)

Boll, Daniel T.; Lewin, Jonathan S.; Young, Philip; Gilkeson, Robert C.; Siwik, Ernest S.

2005-01-01

The aim of this work was to assess magnetic resonance (MR) perfusion patterns of chronic, nonembolic pulmonary diseases of congenital and neoplastic origin and to compare the findings with results obtained with pulmonary, contrast-enhanced multislice computed tomography (CT) imaging to prove that congenital and neoplastic pulmonary conditions require MR imaging over the pulmonary perfusion cycle to successfully and directly detect changes in lung perfusion patterns. Twenty-five patients underwent concurrent CT and MR evaluation of chronic pulmonary diseases of congenital (n=15) or neoplastic (n=10) origin. Analysis of MR perfusion and contrast-enhanced CT datasets was realized by defining pulmonary and vascular regions of interest in corresponding positions. MR perfusion calculated time-to-peak enhancement, maximal enhancement and the area under the perfusion curve. CT datasets provided pulmonary signal-to-noise ratio measurements. Vessel centerlines of bronchial arteries were determined. Underlying perfusion type, such as pulmonary arterial or systemic arterial supply, as well as regions with significant variations in perfusion were determined statistically. Analysis of the pulmonary perfusion pattern detected pulmonary arterial supply in 19 patients; six patients showed systemic arterial supply. In pulmonary arterial perfusion, MR and multislice CT imaging consistently detected the perfusion type and regions with altered perfusion patterns. In bronchial arterial supply, MR perfusion and CT imaging showed significant perfusion differences. Patients with bronchial arterial supply had bronchial arteries ranging from 2.0 to 3.6 mm compared with submillimeter diameters in pulmonary arterial perfusion. Dynamic MR imaging of congenital and neoplastic pulmonary conditions allowed characterization of the pulmonary perfusion type. CT imaging suggested the presence of systemic arterial perfusion by visualizing hypertrophied bronchial arteries. (orig.)

Fibrosis of Two: Epithelial Cell-Fibroblast Interactions in Pulmonary Fibrosis

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Sakai, Norihiko; Tager, Andrew M.

2013-01-01

Idiopathic pulmonary fibrosis (IPF) is characterized by the progressive and ultimately fatal accumulation of fibroblasts and extracellular matrix in the lung that distorts its architecture and compromises its function. IPF is now thought to result from wound-healing processes that, although initiated to protect the host from injurious environmental stimuli, lead to pathological fibrosis due to these processes becoming aberrant or over-exuberant. Although the environmental stimuli that trigger IPF remain to be identified, recent evidence suggests that they initially injure the alveolar epithelium. Repetitive cycles of epithelial injury and resultant alveolar epithelial cell death provoke the migration, proliferation, activation and myofibroblast differentiation of fibroblasts, causing the accumulation of these cells and the extracellular matrix that they synthesize. In turn, these activated fibroblasts induce further alveolar epithelial cell injury and death, thereby creating a vicious cycle of pro-fibrotic epithelial cell-fibroblast interactions. Though other cell types certainly make important contributions, we focus here on the “pas de deux” (steps of two), or perhaps more appropriate to IPF pathogenesis, the “folie à deux” (madness of two) of epithelial cells and fibroblasts that drives the progression of pulmonary fibrosis. We describe the signaling molecules that mediate the interactions of these cell types in their “fibrosis of two”, including transforming growth factor-β, connective tissue growth factor, sonic hedgehog, prostaglandin E2, angiotensin II and reactive oxygen species. PMID:23499992

Leukotriene B4-Neutrophil Elastase Axis Drives Neutrophil Reverse Transendothelial Cell Migration In Vivo.

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Colom, Bartomeu; Bodkin, Jennifer V; Beyrau, Martina; Woodfin, Abigail; Ody, Christiane; Rourke, Claire; Chavakis, Triantafyllos; Brohi, Karim; Imhof, Beat A; Nourshargh, Sussan

2015-06-16

Breaching endothelial cells (ECs) is a decisive step in the migration of leukocytes from the vascular lumen to the extravascular tissue, but fundamental aspects of this response remain largely unknown. We have previously shown that neutrophils can exhibit abluminal-to-luminal migration through EC junctions within mouse cremasteric venules and that this response is elicited following reduced expression and/or functionality of the EC junctional adhesion molecule-C (JAM-C). Here we demonstrate that the lipid chemoattractant leukotriene B4 (LTB4) was efficacious at causing loss of venular JAM-C and promoting neutrophil reverse transendothelial cell migration (rTEM) in vivo. Local proteolytic cleavage of EC JAM-C by neutrophil elastase (NE) drove this cascade of events as supported by presentation of NE to JAM-C via the neutrophil adhesion molecule Mac-1. The results identify local LTB4-NE axis as a promoter of neutrophil rTEM and provide evidence that this pathway can propagate a local sterile inflammatory response to become systemic. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

N-Formyl-Perosamine Surface Homopolysaccharides Hinder the Recognition of Brucella abortus by Mouse Neutrophils.

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Mora-Cartín, Ricardo; Chacón-Díaz, Carlos; Gutiérrez-Jiménez, Cristina; Gurdián-Murillo, Stephany; Lomonte, Bruno; Chaves-Olarte, Esteban; Barquero-Calvo, Elías; Moreno, Edgardo

2016-06-01

Brucella abortus is an intracellular pathogen of monocytes, macrophages, dendritic cells, and placental trophoblasts. This bacterium causes a chronic disease in bovines and in humans. In these hosts, the bacterium also invades neutrophils; however, it fails to replicate and just resists the killing action of these leukocytes without inducing significant activation or neutrophilia. Moreover, B. abortus causes the premature cell death of human neutrophils. In the murine model, the bacterium is found within macrophages and dendritic cells at early times of infection but seldom in neutrophils. Based on this observation, we explored the interaction of mouse neutrophils with B. abortus In contrast to human, dog, and bovine neutrophils, naive mouse neutrophils fail to recognize smooth B. abortus bacteria at early stages of infection. Murine normal serum components do not opsonize smooth Brucella strains, and neutrophil phagocytosis is achieved only after the appearance of antibodies. Alternatively, mouse normal serum is capable of opsonizing rough Brucella mutants. Despite this, neutrophils still fail to kill Brucella, and the bacterium induces cell death of murine leukocytes. In addition, mouse serum does not opsonize Yersinia enterocolitica O:9, a bacterium displaying the same surface polysaccharide antigen as smooth B. abortus Therefore, the lack of murine serum opsonization and absence of murine neutrophil recognition are specific, and the molecules responsible for the Brucella camouflage are N-formyl-perosamine surface homopolysaccharides. Although the mouse is a valuable model for understanding the immunobiology of brucellosis, direct extrapolation from one animal system to another has to be undertaken with caution. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Ensemble models of neutrophil trafficking in severe sepsis.

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Sang Ok Song

Full Text Available A hallmark of severe sepsis is systemic inflammation which activates leukocytes and can result in their misdirection. This leads to both impaired migration to the locus of infection and increased infiltration into healthy tissues. In order to better understand the pathophysiologic mechanisms involved, we developed a coarse-grained phenomenological model of the acute inflammatory response in CLP (cecal ligation and puncture-induced sepsis in rats. This model incorporates distinct neutrophil kinetic responses to the inflammatory stimulus and the dynamic interactions between components of a compartmentalized inflammatory response. Ensembles of model parameter sets consistent with experimental observations were statistically generated using a Markov-Chain Monte Carlo sampling. Prediction uncertainty in the model states was quantified over the resulting ensemble parameter sets. Forward simulation of the parameter ensembles successfully captured experimental features and predicted that systemically activated circulating neutrophils display impaired migration to the tissue and neutrophil sequestration in the lung, consequently contributing to tissue damage and mortality. Principal component and multiple regression analyses of the parameter ensembles estimated from survivor and non-survivor cohorts provide insight into pathologic mechanisms dictating outcome in sepsis. Furthermore, the model was extended to incorporate hypothetical mechanisms by which immune modulation using extracorporeal blood purification results in improved outcome in septic rats. Simulations identified a sub-population (about 18% of the treated population that benefited from blood purification. Survivors displayed enhanced neutrophil migration to tissue and reduced sequestration of lung neutrophils, contributing to improved outcome. The model ensemble presented herein provides a platform for generating and testing hypotheses in silico, as well as motivating further experimental

Patho-radiologic correlation of invasive pulmonary aspergillosis in the compromised host.

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Orr, D P; Myerowitz, R L; Dubois, P J

1978-05-01

The autopsy findings and antemortem radiographic abnormalities were correlated in 20 patients with invasive pulmonary aspergillosis to define typical radiographic patterns, their progression and anatomic basis. Sixteen (80%) patients had radiographic abnormalities due to aspergillosis. Fifty-nine percent of the specific radiographic abnormalities seen in these patients were caused by anatomic lesions of asperigillosis and 67% of such anatomic lesions were radiographically definable. The most common initial radiographic pattern was a patchy density (single or multifocal) or a well defined nodule. The densities remained stable in half the patients but progressed, over several weeks to either diffuse consolidation or cavitation in the others. Most anatomic lesions were categorized as either nodular ("target") lesions (1-3 cm in diameter) or hemorrhagic infarctions (5-10 cm in diameter), both due to vascular invasion causing thrombosis and ischemic necrosis. Unlike pulmonary candidiasis, which is usually radiographically undetectable, invasive pulmonary asperigillosis frequently caused radiographically visible lesions.

Dermal neutrophil, macrophage and dendritic cell responses to Yersinia pestis transmitted by fleas.

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Jeffrey G Shannon

2015-03-01

Full Text Available Yersinia pestis, the causative agent of plague, is typically transmitted by the bite of an infected flea. Many aspects of mammalian innate immune response early after Y. pestis infection remain poorly understood. A previous study by our lab showed that neutrophils are the most prominent cell type recruited to the injection site after intradermal needle inoculation of Y. pestis, suggesting that neutrophil interactions with Y. pestis may be important in bubonic plague pathogenesis. In the present study, we developed new tools allowing for intravital microscopy of Y. pestis in the dermis of an infected mouse after transmission by its natural route of infection, the bite of an infected flea. We found that uninfected flea bites typically induced minimal neutrophil recruitment. The magnitude of neutrophil response to flea-transmitted Y. pestis varied considerably and appeared to correspond to the number of bacteria deposited at the bite site. Macrophages migrated towards flea bite sites and interacted with small numbers of flea-transmitted bacteria. Consistent with a previous study, we observed minimal interaction between Y. pestis and dendritic cells; however, dendritic cells did consistently migrate towards flea bite sites containing Y. pestis. Interestingly, we often recovered viable Y. pestis from the draining lymph node (dLN 1 h after flea feeding, indicating that the migration of bacteria from the dermis to the dLN may be more rapid than previously reported. Overall, the innate cellular host responses to flea-transmitted Y. pestis differed from and were more variable than responses to needle-inoculated bacteria. This work highlights the importance of studying the interactions between fleas, Y. pestis and the mammalian host to gain a better understanding of the early events in plague pathogenesis.

Neither eosinophils nor neutrophils require ATG5-dependent autophagy for extracellular DNA trap formation.

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Germic, Nina; Stojkov, Darko; Oberson, Kevin; Yousefi, Shida; Simon, Hans-Uwe

2017-11-01

The importance of extracellular traps (ETs) in innate immunity is well established, but the molecular mechanisms responsible for their formation remain unclear and in scientific dispute. ETs have been defined as extracellular DNA scaffolds associated with the granule proteins of eosinophils or neutrophils. They are capable of killing bacteria extracellularly. Based mainly on results with phosphoinositide 3-kinase (PI3K) inhibitors such as 3-methyladenine (3-MA) and wortmannin, which are commonly used to inhibit autophagy, several groups have reported that autophagy is required for neutrophil extracellular trap (NET) formation. We decided to investigate this apparent dependence on autophagy for ET release and generated genetically modified mice that lack, specifically in eosinophils or neutrophils, autophagy-related 5 (Atg5), a gene encoding a protein essential for autophagosome formation. Interestingly, neither eosinophils nor neutrophils from Atg5-deficient mice exhibited abnormalities in ET formation upon physiological activation or exposure to low concentrations of PMA, although we could confirm that human and mouse eosinophils and neutrophils, after pre-treatment with inhibitors of class III PI3K, show a block both in reactive oxygen species (ROS) production and in ET formation. The so-called late autophagy inhibitors bafilomycin A1 and chloroquine, on the other hand, were without effect. These data indicate that ET formation occurs independently of autophagy and that the inhibition of ROS production and ET formation in the presence of 3-MA and wortmannin is probably owing to their additional ability to block the class I PI3Ks, which are involved in signalling cascades initiated by triggers of ET formation. © 2017 John Wiley & Sons Ltd.

Mitochondria in neutrophil apoptosis

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van Raam, B. J.; Verhoeven, A. J.; Kuijpers, T. W.

2006-01-01

Central in the regulation of the short life span of neutrophils are their mitochondria. These organelles hardly contribute to the energy status of neutrophils but play a vital role in the apoptotic process. Not only do the mitochondria contain cytotoxic proteins that are released during apoptosis

Neutrophil Responses to Sterile Implant Materials.

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Siddharth Jhunjhunwala

Full Text Available In vivo implantation of sterile materials and devices results in a foreign body immune response leading to fibrosis of implanted material. Neutrophils, one of the first immune cells to be recruited to implantation sites, have been suggested to contribute to the establishment of the inflammatory microenvironment that initiates the fibrotic response. However, the precise numbers and roles of neutrophils in response to implanted devices remains unclear. Using a mouse model of peritoneal microcapsule implantation, we show 30-500 fold increased neutrophil presence in the peritoneal exudates in response to implants. We demonstrate that these neutrophils secrete increased amounts of a variety of inflammatory cytokines and chemokines. Further, we observe that they participate in the foreign body response through the formation of neutrophil extracellular traps (NETs on implant surfaces. Our results provide new insight into neutrophil function during a foreign body response to peritoneal implants which has implications for the development of biologically compatible medical devices.

Neutrophil elastase processing of Gelatinase A is mediated by extracellular matrix

Energy Technology Data Exchange (ETDEWEB)

Rice, A.; Banda, M.J. [Univ. of California, San Franciso, CA (United States)

1995-07-18

Gelatinase A (72-kDa type IV collagenase) is a metalloproteinase that is expressed by many cells in culture and is overexpressed by some tumor cells. It has been suggested that the serine proteinase neutrophil elastase might play a role iii the posttranslational processing of gelatinase A and that noncatalytic interactions between gelatinase A and components of the extracellular matrix might alter potential processing pathways. These questions were addressed with the use of gelatin substrate zymography, gelatinolytic activity assays, and amino acid sequence analysis. We found that neutrophil elastase does proteolytically modify gelatinase A by cleaving at a number of sites within gelatinase A. Sequential treatment of gelatinase A with 4-aminophenylmercuric acetate (APMA) and neutrophil elastase yielded an active gelatinase with a 4-fold increase in gelatinolytic activity. The increased gelatinolytic activity correlated with that of a 40-kDa fragment of gelatinase A. Matrix components altered the proteolytic modifications in gelatinase A that were mediated by neutrophil elastase. In the absence of gelatin, neutrophil elastase destructively degraded gelatinase A by hydrolyzing at least two bonds within the fibronectin-like gelatin-binding domain of gelatinase A. In the presence of gelatin, these two inactivating cleavage sites were protected, and cleavage at a site within the hemopexin-like carboxyl-terminal domain resulted in a truncated yet active gelatinase. The results suggest a regulatory role for extracellular matrix molecules in stabilizing gelatinase A fragments and in altering the availability of sites susceptible to destructive proteolysis by neutrophil elastase. 32 refs., 10 figs.

Pulmonary hypertension in patients with chronic pulmonary thromboembolism: chest radiograph and CT evaluation before and after surgery

International Nuclear Information System (INIS)

Schmidt, H.C.; Kauczor, H.U.; Schild, H.H.; Renner, C.; Kirchhoff, E.; Lang, P.; Iversen, S.; Thelen, M.

1996-01-01

The purpose of this study was to assess the value of morphometric data on conventional radiography and CT predicting the presence and degree of pulmonary hypertension and to assess the reversibility after surgery. On preoperative X-ray films and CT scans of 50 patients with pulmonary hypertension secondary to chronic thromboembolism, we measured the cardiothoracic ratio, basal diameter, length of cardiac contact to sternum, pulmonary trunk, right and left descending pulmonary artery, and the septum angle. These data were correlated with pulmonary arterial pressure. In 14 X-ray patients and 18 CT patients, with follow-up after surgical thromboendarterectomy the reversibility of these changes was assessed. A dilated pulmonary trunk was the most common abnormality (96% each on X-ray and CT). Pulmonary arteries were dilated on X-ray in 40% (right) and 14% (left), and on CT in 92% (right) and 96% (left). The best correlation with mean arterial pressure was found measuring the pulmonary trunk on CT (r=0.43, p<0.01). After surgery, reversibility was most significant for the pulmonary trunk on CT (p<0.0001). In patients with chronic pulmonary embolism, pulmonary hypertension can best be predicted by assessing the diameter of the pulmonary trunk both on X-ray and CT. No close correlation is present between the extent of any parameter and the level of the pulmonary pressure. (orig.)

Tumor Associated Neutrophils in Human Lung Cancer

Science.gov (United States)

2016-10-01

tumor innate immune response. anti-tumor adaptive immune response, neutrophil and T cell interaction. ACCOMPLISHMENTS There were no significant...and by producing factors to recruit and acti- vate cells of the innate and adaptive immune system (Mantovani et al., 2011). Given these varying effects...vivo effects on neutro- phil activation (Figure 2, A and B) and cleavage of myeloid and lymphoid cell markers (Supplemental Figure 1, C–G). Once opti

Pulmonary Vascular Congestion: A Mechanism for Distal Lung Unit Dysfunction in Obesity.

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Oppenheimer, Beno W; Berger, Kenneth I; Ali, Saleem; Segal, Leopoldo N; Donnino, Robert; Katz, Stuart; Parikh, Manish; Goldring, Roberta M

2016-01-01

Obesity is characterized by increased systemic and pulmonary blood volumes (pulmonary vascular congestion). Concomitant abnormal alveolar membrane diffusion suggests subclinical interstitial edema. In this setting, functional abnormalities should encompass the entire distal lung including the airways. We hypothesize that in obesity: 1) pulmonary vascular congestion will affect the distal lung unit with concordant alveolar membrane and distal airway abnormalities; and 2) the degree of pulmonary congestion and membrane dysfunction will relate to the cardiac response. 54 non-smoking obese subjects underwent spirometry, impulse oscillometry (IOS), diffusion capacity (DLCO) with partition into membrane diffusion (DM) and capillary blood volume (VC), and cardiac MRI (n = 24). Alveolar-capillary membrane efficiency was assessed by calculation of DM/VC. Mean age was 45±12 years; mean BMI was 44.8±7 kg/m2. Vital capacity was 88±13% predicted with reduction in functional residual capacity (58±12% predicted). Despite normal DLCO (98±18% predicted), VC was elevated (135±31% predicted) while DM averaged 94±22% predicted. DM/VC varied from 0.4 to 1.4 with high values reflecting recruitment of alveolar membrane and low values indicating alveolar membrane dysfunction. The most abnormal IOS (R5 and X5) occurred in subjects with lowest DM/VC (r2 = 0.31, ppulmonary vascular congestion and failure to achieve the high output state of obesity. Pulmonary vascular congestion and consequent fluid transudation and/or alterations in the structure of the alveolar capillary membrane may be considered often unrecognized causes of airway dysfunction in obesity.

Pulmonary fibrosis in rheumatoid arthritis: a review of clinical features and therapy.

Science.gov (United States)

Roschmann, R A; Rothenberg, R J

1987-02-01

During the past four decades there has been a growing appreciation of the frequency of pulmonary abnormalities associated with RA. Approximately 30% to 40% of patients with RA demonstrate either radiographic or pulmonary function abnormalities indicative of interstitial fibrosis or restrictive lung disease. The severity of pulmonary fibrosis is not associated with rheumatologic symptoms or the duration of the associated RA, nor is there any clear relation to the extraarticular features of RA or serologic findings. Survival rates in patients with coexisting RA and pulmonary fibrosis are similar to those of patients with idiopathic pulmonary fibrosis. However, the spectrum of disease activity is quite variable. The majority of patients with progressive pulmonary symptomatology, when treated with corticosteroids, will have equivocal results. Some patients appear to respond to immunosuppressive or cytotoxic medications. The role of macrophages may be central to the injury to lung. Recent studies suggest a potential treatment role for cyclosporine, which may be able to interrupt lymphocyte-stimulated macrophage activation, and thus, fibroblast-mediated fibrosis in patients with pulmonary interstitial fibrosis. Bronchoalveolar lavage studies may delineate subgroups of patients who are more likely to respond to immunosuppressive agents, especially when treatment is started early.

A new direction in the pathogenesis of idiopathic pulmonary fibrosis?

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Kolb Martin

2002-01-01

Full Text Available Abstract A recent review article suggested that idiopathic pulmonary fibrosis (IPF is a disease that is associated more with abnormal wound healing than with inflammation. Data derived from transgenic and gene transfer rodent models suggest that lung inflammation may be a necessary but insufficient component of IPF, and that at some point in the natural history of the disease IPF becomes no longer dependent on the inflammatory response for propagation. Altered microenvironment and involvement of epithelial cell/mesenchymal cell interaction are the most likely contributors to the pathogenesis of this chronic progressive disorder.

Correlation of grading of pulmonary emphysema by computed tomography to pulmonary function

International Nuclear Information System (INIS)

Yamagishi, Masahiko; Mori, Masaki; Hirai, Hideyuki; Mori, Yuji; Koba, Hiroyuki; Suzuki, Akira

1988-01-01

We studied the CT findings of 17 emphysema patients with special reference to the extent of emphysematous changes. Characteristic CT findings were low-attenuation area (LAA) and vascular abnormality and the appearance of various images on CT. To assess the extent of emphysematous changes, we classified the CT images into 4 grades based on the distribution and size of LAAs. As the grades progressed, the distribution and size of LAAs became wider and larger and vascular abnormalities were clearly evident. Although this CT-grading is a semiquantitative method, it is simple to use and gives information on the approximate extent of disease. This CT-grading was also used to show pulmonary function. The RV/TLC and expiratory flow showed a tendency to be impaired in Grade IV and the diffusion capacity was impaired parallel to CT-grading. CT is able to demonstrate the presence and distribution of LAAs noninvasively. Therefore it is considered that CT is useful for clinical diagnosis and the assessment of the extent of pulmonary emphysema. (author)

Targeting Neutrophilic Inflammation Using Polymersome-Mediated Cellular Delivery.

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Robertson, James D; Ward, Jon R; Avila-Olias, Milagros; Battaglia, Giuseppe; Renshaw, Stephen A

2017-05-01

Neutrophils are key effector cells in inflammation and play an important role in neutralizing invading pathogens. During inflammation resolution, neutrophils undergo apoptosis before they are removed by macrophages, but if apoptosis is delayed, neutrophils can cause extensive tissue damage and chronic disease. Promotion of neutrophil apoptosis is a potential therapeutic approach for treating persistent inflammation, yet neutrophils have proven difficult cells to manipulate experimentally. In this study, we deliver therapeutic compounds to neutrophils using biocompatible, nanometer-sized synthetic vesicles, or polymersomes, which are internalized by binding to scavenger receptors and subsequently escape the early endosome through a pH-triggered disassembly mechanism. This allows polymersomes to deliver molecules into the cell cytosol of neutrophils without causing cellular activation. After optimizing polymersome size, we show that polymersomes can deliver the cyclin-dependent kinase inhibitor (R)-roscovitine into human neutrophils to promote apoptosis in vitro. Finally, using a transgenic zebrafish model, we show that encapsulated (R)-roscovitine can speed up inflammation resolution in vivo more efficiently than the free drug. These results show that polymersomes are effective intracellular carriers for drug delivery into neutrophils. This has important consequences for the study of neutrophil biology and the development of neutrophil-targeted therapeutics. Copyright © 2017 The Authors.

Neutrophil Reverse Migration Becomes Transparent with Zebrafish

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Taylor W. Starnes

2012-01-01

Full Text Available The precise control of neutrophil-mediated inflammation is critical for both host defense and the prevention of immunopathology. In vivo imaging studies in zebrafish, and more recently in mice, have made the novel observation that neutrophils leave a site of inflammation through a process called neutrophil reverse migration. The application of advanced imaging techniques to the genetically tractable, optically transparent zebrafish larvae was critical for these advances. Still, the mechanisms underlying neutrophil reverse migration and its effects on the resolution or priming of immune responses remain unclear. Here, we review the current knowledge of neutrophil reverse migration, its potential roles in host immunity, and the live imaging tools that make zebrafish a valuable model for increasing our knowledge of neutrophil behavior in vivo.

Inhaled corticosteroids for abnormal pulmonary function in children with a history of Chronic Lung Disease of Infancy: study protocol [ISRCTN55153521

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Sauve Reginald

2005-04-01

Full Text Available Abstract Background There is considerable evidence from the literature that children with chronic lung disease of infancy (CLD have abnormal pulmonary function in childhood and this could have an impact on their life quality and overall health. There are similarities between CLD and asthma, and corticosteroids are the mainstay treatment for asthma. Many physicians use inhaled corticosteroids in children with CLD with no evidence. Therefore we wish to conduct a randomized double-blinded placebo controlled trial to test for the role of inhaled corticosteroids in children aged from3 to 9 years with a history of CLD. Our primary hypothesis will be that inhaled corticosteroids are beneficial in children with CLD. Methods Our primary hypothesis is that using inhaled steroids; Beclomethasone Dipropionate (QVAR 100 mcg 2 puffs 2 times a day for 6 weeks will improve the respiratory system resistance and the quality of life in children with CLD. Discussion We propose that Beclomethasone Dipropionate (QVAR will affect the pulmonary function after 6 weeks of treatment. In summary we think that our study will highlight knowledge on whether the use of inhaled steroids is clinically effective for CLD.

Neutrophils Contribute to the Protection Conferred by ArtinM against Intracellular Pathogens: A Study on Leishmania major.

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Ricci-Azevedo, Rafael; Oliveira, Aline Ferreira; Conrado, Marina C A V; Carvalho, Fernanda Caroline; Roque-Barreira, Maria Cristina

2016-04-01

ArtinM, a D-mannose binding lectin from Artocarpus heterophyllus, has immunomodulatory activities through its interaction with N-glycans of immune cells, culminating with the establishment of T helper type 1 (Th1) immunity. This interaction protects mice against intracellular pathogens, including Leishmania major and Leishmania amazonensis. ArtinM induces neutrophils activation, which is known to account for both resistance to pathogens and host tissue injury. Although exacerbated inflammation was not observed in ArtinM-treated animals, assessment of neutrophil responses to ArtinM is required to envisage its possible application to design a novel immunomodulatory agent based on carbohydrate recognition. Herein, we focus on the mechanisms through which neutrophils contribute to ArtinM-induced protection against Leishmania, without exacerbating inflammation. For this purpose, human neutrophils treated with ArtinM and infected with Leishmania major were analyzed together with untreated and uninfected controls, based on their ability to eliminate the parasite, release cytokines, degranulate, produce reactive oxygen species (ROS), form neutrophil extracellular traps (NETs) and change life span. We demonstrate that ArtinM-stimulated neutrophils enhanced L. major clearance and at least duplicated tumor necrosis factor (TNF) and interleukin-1beta (IL-1β) release; otherwise, transforming growth factor-beta (TGF-β) production was reduced by half. Furthermore, ROS production and cell degranulation were augmented. The life span of ArtinM-stimulated neutrophils decreased and they did not form NETs when infected with L. major. We postulate that the enhanced leishmanicidal ability of ArtinM-stimulated neutrophils is due to augmented release of inflammatory cytokines, ROS production, and cell degranulation, whereas host tissue integrity is favored by their shortened life span and the absence of NET formation. Our results reinforce the idea that ArtinM may be considered an

Neutrophils Contribute to the Protection Conferred by ArtinM against Intracellular Pathogens: A Study on Leishmania major.

Directory of Open Access Journals (Sweden)

Rafael Ricci-Azevedo

2016-04-01

Full Text Available ArtinM, a D-mannose binding lectin from Artocarpus heterophyllus, has immunomodulatory activities through its interaction with N-glycans of immune cells, culminating with the establishment of T helper type 1 (Th1 immunity. This interaction protects mice against intracellular pathogens, including Leishmania major and Leishmania amazonensis. ArtinM induces neutrophils activation, which is known to account for both resistance to pathogens and host tissue injury. Although exacerbated inflammation was not observed in ArtinM-treated animals, assessment of neutrophil responses to ArtinM is required to envisage its possible application to design a novel immunomodulatory agent based on carbohydrate recognition. Herein, we focus on the mechanisms through which neutrophils contribute to ArtinM-induced protection against Leishmania, without exacerbating inflammation. For this purpose, human neutrophils treated with ArtinM and infected with Leishmania major were analyzed together with untreated and uninfected controls, based on their ability to eliminate the parasite, release cytokines, degranulate, produce reactive oxygen species (ROS, form neutrophil extracellular traps (NETs and change life span. We demonstrate that ArtinM-stimulated neutrophils enhanced L. major clearance and at least duplicated tumor necrosis factor (TNF and interleukin-1beta (IL-1β release; otherwise, transforming growth factor-beta (TGF-β production was reduced by half. Furthermore, ROS production and cell degranulation were augmented. The life span of ArtinM-stimulated neutrophils decreased and they did not form NETs when infected with L. major. We postulate that the enhanced leishmanicidal ability of ArtinM-stimulated neutrophils is due to augmented release of inflammatory cytokines, ROS production, and cell degranulation, whereas host tissue integrity is favored by their shortened life span and the absence of NET formation. Our results reinforce the idea that ArtinM may be

MR-based assessment of pulmonary ventilation-perfusion in animal models

International Nuclear Information System (INIS)

Yang Jian; Wan Mingxi; Guo Youmin

2003-01-01

Objective: To show the feasibility and value in the diagnosis of airway obstruction and pulmonary embolism with MR oxygen-enhanced ventilation combined with pulmonary perfusion imaging. Methods: Eight canines were implemented for peripheral pulmonary embolism by intravenous injection of gelfoam granules at pulmonary segmental arterial level, and five of them were formed airway obstruction models by inserting self-made balloon catheter at second-bronchia. The oxygen-enhanced MR ventilation imaging was introduced by subtracting the images of pre- and post- inhaled pure oxygen. The MR pulmonary perfusion imaging was achieved by the first-pass contrast agent method. Moreover, the manifestation of MR ventilation and perfusion imaging was observed and contradistinguished with that of general pathologic anatomy, ventilation-perfusion scintigraphy, and pulmonary angiography. Results: The manifestations of airway obstruction regions in MR ventilation and perfusion imaging were matched, but those of pulmonary embolism regions were dismatched. The defect range of airway obstruction in MR ventilation image was smaller than that in ventilation scintigraphy. The abnormal perfusion regions of pulmonary embolism were divided into defect regions and reduce regions based on the time courses of signal intensity changes. The sensitivity and specificity of diagnosis on pulmonary embolism by MR ventilation combined with perfusion technique were 75.0% and 98.1%. The diagnostic results were in good coherence with ventilation-perfusion scintigraphy and pulmonary angiography (K=0.743, 0.899). Conclusion: The MR oxygen-enhanced ventilation combined with pulmonary perfusion imaging can be used to diagnose the airway and vascular abnormity in lung. This technique resembles the ventilation-perfusion scintigraphy. It can provide quantitative functional information and better spatial and temporal resolution, and possesses the value of clinical application

Pulmonary hypertension due to left heart disease.

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Berthelot, Emmanuelle; Bailly, Minh Tam; Hatimi, Safwane El; Robard, Ingrid; Rezgui, Hatem; Bouchachi, Amir; Montani, David; Sitbon, Olivier; Chemla, Denis; Assayag, Patrick

Pulmonary hypertension due to left heart disease, also known as group 2 pulmonary hypertension according to the European Society of Cardiology/European Respiratory Society classification, is the most common cause of pulmonary hypertension. In patients with left heart disease, the development of pulmonary hypertension favours right heart dysfunction, which has a major impact on disease severity and outcome. Over the past few years, this condition has been considered more frequently. However, epidemiological studies of group 2 pulmonary hypertension are less exhaustive than studies of other causes of pulmonary hypertension. In group 2 patients, pulmonary hypertension may be caused by an isolated increase in left-sided filling pressures or by a combination of this condition with increased pulmonary vascular resistance, with an abnormally high pressure gradient between arteries and pulmonary veins. A better understanding of the conditions underlying pulmonary hypertension is of key importance to establish a comprehensive diagnosis, leading to an adapted treatment to reduce heart failure morbidity and mortality. In this review, epidemiology, mechanisms and diagnostic approaches are reviewed; then, treatment options and future approaches are considered. Copyright © 2017. Published by Elsevier Masson SAS.

Neutrophil-endothelial cell interactions on endothelial monolayers grown on micropore filters.

Science.gov (United States)

Taylor, R F; Price, T H; Schwartz, S M; Dale, D C

1981-01-01

We have developed a technique for growing endothelial monolayers on micropore filters. These monolayers demonstrate confluence by phase and electron microscopy and provide a functional barrier to passage of radiolabeled albumin. Neutrophils readily penetrate the monolayer in response to chemotaxin, whereas there is little movement in the absence of chemotaxin. This system offers unique advantages over available chemotaxis assays and may have wider applications in the study of endothelial function. Images PMID:7007441

Echocardiographic Evaluation of Indices of Right Ventricle Dysfunction in Pulmonary Hypertension

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Homayounfar Sh

2017-03-01

Full Text Available Introduction: Echocardiography is usually the fist modalities of imaging to evaluate the structural and functional disorders of the heart and great vessels, and colored flw and Doppler images are able to perform hemodynamic and bloodstream evaluations. Th goal of this study was the investigation of right ventricular function using echocardiography in patients with pulmonary artery hypertension. Methods: In this cross-sectional study, the study population included all the patients with pulmonary artery hypertension for any reason, and their diagnoses using echocardiography and measurement of pulmonary artery pressure were confimed, which were higher than 25. Th number of samples was 80 and patients underwent echocardiography with twodimensional and tissue doppler imaging. Data were analyzed using SPSS softare version 16 and Chi-squared test, Pearson’s correlation coeffient and t-test. Th signifiance level was considered less than 0.05. Results: Th results of statistical tests showed that the means of FAC, TAPSE, and TIE indexes in the group with PVR less than 2 were signifiantly higher than the means of FAC (P = 0.006, TAPSE (P = 0.04, and TIE (P = 0.01 indexes in the group with more PVR, and were equal to 2 in this study. Also, the diffrences between the mean of normal and abnormal values of FAC, SWAVE, and TIE indexes in patients with normal PVR were not signifiant, while these diffrences were signifiant in patients with abnormal PVRs. Conclusion: In echocardiography investigations of right ventricular function in patients with pulmonary artery hypertension, the values obtained from FAC, SWAVE and TIE indexes and TAPSE had high diagnostic confiences in these patients. Threfore, these items were disturbed as a result of increase in the degree of resistance of pulmonary bed, and were good criteria to evaluate the right ventricular function in these patients. In the meantime, FAC values were more sensitive to the abnormal values of PVR due to

Radiological aspects in pulmonary involvement of Behcet disease

International Nuclear Information System (INIS)

Kim, Jae Hyoung; Im, Jung Gi; Kim, Hyung Jin; Park, Jae Hyung

1988-01-01

To evaluate the pulmonary manifestations of Behcet disease, authors reviewed the chest radiographs of 130 cases of Behcet disease diagnosed at Seoul National University Hospital from January 1980 to December 1987 retrospectively. Of the 130 cases, 6 cases (4.6%) showed pulmonary abnormalities that were considered as a manifestation of Behcet disease. Two cases showed round masses near the hila on chest radiographs which were confirmed as pulmonary artery aneurysms on angiographies. Two cases showed pulmonary infiltrates due to pulmonary infarcts. Others were a case of unilateral pulmonary edema due to compression og the contralateral pulmonary artery by aortic aneurysm and a case of lung abscess due to esophagobronchial fistula as a compulmonary artery by aortic aneurysm and a case of lung abscess due to esophagobronchial fistula as a complication of esophageal ulcer. Though its occurrence is rare, nodular and/or infiltrative pulmonary lesions in patients with Behcet disease should be suspected as a vascular involvement of the disease itself until proven otherwise.

Radiological aspects in pulmonary involvement of Behcet disease

Energy Technology Data Exchange (ETDEWEB)

Kim, Jae Hyoung; Im, Jung Gi; Kim, Hyung Jin; Park, Jae Hyung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1988-08-15

To evaluate the pulmonary manifestations of Behcet disease, authors reviewed the chest radiographs of 130 cases of Behcet disease diagnosed at Seoul National University Hospital from January 1980 to December 1987 retrospectively. Of the 130 cases, 6 cases (4.6%) showed pulmonary abnormalities that were considered as a manifestation of Behcet disease. Two cases showed round masses near the hila on chest radiographs which were confirmed as pulmonary artery aneurysms on angiographies. Two cases showed pulmonary infiltrates due to pulmonary infarcts. Others were a case of unilateral pulmonary edema due to compression og the contralateral pulmonary artery by aortic aneurysm and a case of lung abscess due to esophagobronchial fistula as a compulmonary artery by aortic aneurysm and a case of lung abscess due to esophagobronchial fistula as a complication of esophageal ulcer. Though its occurrence is rare, nodular and/or infiltrative pulmonary lesions in patients with Behcet disease should be suspected as a vascular involvement of the disease itself until proven otherwise.

Novel mechanisms of sildenafil in pulmonary hypertension involving cytokines/chemokines, MAP kinases and Akt.

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Tamas Kiss

Full Text Available Pulmonary arterial hypertension (PH is associated with high mortality due to right ventricular failure and hypoxia, therefore to understand the mechanism by which pulmonary vascular remodeling initiates these processes is very important. We used a well-characterized monocrotaline (MCT-induced rat PH model, and analyzed lung morphology, expression of cytokines, mitogen-activated protein kinase (MAPK phosphorylation, and phosphatidylinositol 3-kinase-Akt (PI-3k-Akt pathway and nuclear factor (NF-κB activation in order to elucidate the mechanisms by which sildenafil's protective effect in PH is exerted. Besides its protective effect on lung morphology, sildenafil suppressed multiple cytokines involved in neutrophil and mononuclear cells recruitment including cytokine-induced neutrophil chemoattractant (CINC-1, CINC-2α/β, tissue inhibitor of metalloproteinase (TIMP-1, interleukin (IL-1α, lipopolysaccharide induced CXC chemokine (LIX, monokine induced by gamma interferon (MIG, macrophage inflammatory protein (MIP-1α, and MIP-3α. NF-κB activation and phosphorylation were also attenuated by sildenafil. Furthermore, sildenafil reduced extracellular signal-regulated kinase (ERK1/2 and p38 MAPK activation while enhanced activation of the cytoprotective Akt pathway in PH. These data suggest a beneficial effect of sildenafil on inflammatory and kinase signaling mechanisms that substantially contribute to its protective effects, and may have potential implications in designing future therapeutic strategies in the treatment of pulmonary hypertension.

Targeting Neutrophilic Inflammation using Polymersome-Mediated Cellular Delivery

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Robertson, J.D.; Ward, J.R.; Avila-Olias, M.; Battaglia, G.; Renshaw, S.A.

2017-01-01

Neutrophils are key effector cells in inflammation and play an important role in neutralizing invading pathogens. During inflammation resolution, neutrophils undergo apoptosis before they are removed by macrophages, but if apoptosis is delayed, neutrophils can cause extensive tissue damage and chronic disease. Promotion of neutrophil apoptosis is a potential therapeutic approach for treating persistent inflammation, yet neutrophils have proven difficult cells to manipulate experimentally. In ...

Leukotriene B4-Neutrophil Elastase Axis Drives Neutrophil Reverse Transendothelial Cell Migration In Vivo

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Colom, Bartomeu; Bodkin, Jennifer V.; Beyrau, Martina; Woodfin, Abigail; Ody, Christiane; Rourke, Claire; Chavakis, Triantafyllos; Brohi, Karim; Imhof, Beat A.; Nourshargh, Sussan

2015-01-01

Summary Breaching endothelial cells (ECs) is a decisive step in the migration of leukocytes from the vascular lumen to the extravascular tissue, but fundamental aspects of this response remain largely unknown. We have previously shown that neutrophils can exhibit abluminal-to-luminal migration through EC junctions within mouse cremasteric venules and that this response is elicited following reduced expression and/or functionality of the EC junctional adhesion molecule-C (JAM-C). Here we demonstrate that the lipid chemoattractant leukotriene B4 (LTB4) was efficacious at causing loss of venular JAM-C and promoting neutrophil reverse transendothelial cell migration (rTEM) in vivo. Local proteolytic cleavage of EC JAM-C by neutrophil elastase (NE) drove this cascade of events as supported by presentation of NE to JAM-C via the neutrophil adhesion molecule Mac-1. The results identify local LTB4-NE axis as a promoter of neutrophil rTEM and provide evidence that this pathway can propagate a local sterile inflammatory response to become systemic. PMID:26047922

Abnormal biodistribution of radiogallium in persons treated with phenytoin

International Nuclear Information System (INIS)

Lentle, B.C.; Starreveld, Elout; Catz, Zolly; Penney, Heather; Turner, A.R.

1983-01-01

After incidentally observing a patient in whom abnormal uptake of gallium-67 citrate appeared to be explained by treatment with phenytoin, we have conducted a prospective study. Of sixteen persons with a seizure disorder treated with phenytoin, five (31 percent) had abnormal uptake of radiogallium either in the mediastinum, pulmonary hilum or both. Of nineteen historical control patients only one had such abnormal uptake. Phenytoin may thus cause the false-positive uptake of radiogallium in lymph nodes; this finding may also prove to have nosological importance in identifying patients at particular risk of the side-effects of this drug

The expression of Mirc1/Mir17-92 cluster in sputum samples correlates with pulmonary exacerbations in cystic fibrosis patients.

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Krause, Kathrin; Kopp, Benjamin T; Tazi, Mia F; Caution, Kyle; Hamilton, Kaitlin; Badr, Asmaa; Shrestha, Chandra; Tumin, Dmitry; Hayes, Don; Robledo-Avila, Frank; Hall-Stoodley, Luanne; Klamer, Brett G; Zhang, Xiaoli; Partida-Sanchez, Santiago; Parinandi, Narasimham L; Kirkby, Stephen E; Dakhlallah, Duaa; McCoy, Karen S; Cormet-Boyaka, Estelle; Amer, Amal O

2017-12-11

Cystic fibrosis (CF) is a multi-organ disorder characterized by chronic sino-pulmonary infections and inflammation. Many patients with CF suffer from repeated pulmonary exacerbations that are predictors of worsened long-term morbidity and mortality. There are no reliable markers that associate with the onset or progression of an exacerbation or pulmonary deterioration. Previously, we found that the Mirc1/Mir17-92a cluster which is comprised of 6 microRNAs (Mirs) is highly expressed in CF mice and negatively regulates autophagy which in turn improves CF transmembrane conductance regulator (CFTR) function. Therefore, here we sought to examine the expression of individual Mirs within the Mirc1/Mir17-92 cluster in human cells and biological fluids and determine their role as biomarkers of pulmonary exacerbations and response to treatment. Mirc1/Mir17-92 cluster expression was measured in human CF and non-CF plasma, blood-derived neutrophils, and sputum samples. Values were correlated with pulmonary function, exacerbations and use of CFTR modulators. Mirc1/Mir17-92 cluster expression was not significantly elevated in CF neutrophils nor plasma when compared to the non-CF cohort. Cluster expression in CF sputum was significantly higher than its expression in plasma. Elevated CF sputum Mirc1/Mir17-92 cluster expression positively correlated with pulmonary exacerbations and negatively correlated with lung function. Patients with CF undergoing treatment with the CFTR modulator Ivacaftor/Lumacaftor did not demonstrate significant change in the expression Mirc1/Mir17-92 cluster after six months of treatment. Mirc1/Mir17-92 cluster expression is a promising biomarker of respiratory status in patients with CF including pulmonary exacerbation. Published by Elsevier B.V.

GROUP B STREPTOCOCCUS CIRCUMVENTS NEUTROPHILS AND NEUTROPHIL EXTRACELLULAR TRAPS DURING AMNIOTIC CAVITY INVASION AND PRETERM LABOR

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Boldenow, Erica; Gendrin, Claire; Ngo, Lisa; Bierle, Craig; Vornhagen, Jay; Coleman, Michelle; Merillat, Sean; Armistead, Blair; Whidbey, Christopher; Alishetti, Varchita; Santana-Ufret, Veronica; Ogle, Jason; Gough, Michael; Srinouanprachanh, Sengkeo; MacDonald, James W; Bammler, Theo K; Bansal, Aasthaa; Liggitt, H. Denny; Rajagopal, Lakshmi; Waldorf, Kristina M Adams

2016-01-01

Preterm birth is a leading cause of neonatal morbidity and mortality. Although microbial invasion of the amniotic cavity (MIAC) is associated with the majority of early preterm births, the temporal events that occur during MIAC and preterm labor are not known. Group B Streptococci (GBS) are β-hemolytic, gram-positive bacteria, which commonly colonize the vagina but have been recovered from the amniotic fluid in preterm birth cases. To understand temporal events that occur during MIAC, we utilized a unique chronically catheterized nonhuman primate model that closely emulates human pregnancy. This model allows monitoring of uterine contractions, timing of MIAC and immune responses during pregnancy-associated infections. Here, we show that adverse outcomes such as preterm labor, MIAC, and fetal sepsis were observed more frequently during infection with hemolytic GBS when compared to nonhemolytic GBS. Although MIAC was associated with systematic progression in chorioamnionitis beginning with chorionic vasculitis and progressing to neutrophilic infiltration, the ability of the GBS hemolytic pigment toxin to induce neutrophil cell death and subvert killing by neutrophil extracellular traps (NETs) in placental membranes in vivo facilitated MIAC and fetal injury. Furthermore, compared to maternal neutrophils, fetal neutrophils exhibit decreased neutrophil elastase activity and impaired phagocytic functions to GBS. Collectively, our studies demonstrate how a unique bacterial hemolytic lipid toxin enables GBS to circumvent neutrophils and NETs in placental membranes to induce fetal injury and preterm labor. PMID:27819066

Prognostic value of neutrophil to lymphocyte ratio in patients with acute pulmonary embolism: a restrospective study.

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Kayrak, Mehmet; Erdoğan, Halil Ibrahim; Solak, Yalcin; Akilli, Hakan; Gül, Enes Elvin; Yildirim, Oğuzhan; Erer, Murat; Akilli, Nezire Belgin; Bekci, Taha Tahir; Aribaş, Alpay; Yazici, Mehmet

2014-01-01

Acute pulmonary embolism (PE) is a serious clinical condition characterised by a high mortality rate. Previous studies showed that leukocytosis was associated with recurrences of venous thromboemboli, major bleeding and increased mortality. The aim of the present study was to investigate the prognostic value of neutrophil to lymphocyte ratio (NLR) in patients with acute PE during short term follow-up. A total of 640 patients were screened by I26 code of ICD-9 and 359 patients were included as cases of confirmed acute PE. Admission blood counts and clinical data were obtained from medical charts. The predictors of 30-day mortality were examined. Fifty-one out of 359 patients (14.2%) included in the study died during 30 days follow-up. In multivariate Cox regression analysis systolic blood pressure (HR:0.97 (0.94-0.99 CI95%), p=0.019), diabetes mellitus (HR:3.3 (1.30-8.39 CI95%), p=0.012), CK-MB(HR:1.03 (1.01-1.06 CI95%), p=0.024) and NLR (HR:1.03 (1.01-1.06 CI95%), p=0.008) were predictors of 30-day mortality. An optimal cut-off value of NLR was determined as 9.2 by using ROC curve. Hazards ratio of NLR>9.2 was found to be 3.60 (1.44-9.18 CI95%, p=0.006). NLR>9.2 had a sensitivity, specificity, negative predictive value, and positive predictive value of 68.6%, 80.5%, 93.9% and 36.5%, respectively. NLR on hospital admission may be a predictor of 30-day mortality in acute PE. Since complete blood count is a part of the routine laboratory investigation in the most hospitalised patients use and preliminary promising results of this study, NLR should be investigated in future prospective randomised trials regarding prognostic value in acute PE. Copyright © 2013 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Neutrophil labeling with [99mTc]-technetium stannous colloid is complement receptor 3-mediated and increases the neutrophil priming response to lipopolysaccharide

International Nuclear Information System (INIS)

Gallagher, Hayley; Ramsay, Stuart C.; Barnes, Jodie; Maggs, Jacqueline; Cassidy, Nathan; Ketheesan, Natkunam

2006-01-01

Introduction: [ 99m Tc]-technetium stannous colloid (TcSnC)-labeled white cells are used to image inflammation. Neutrophil labeling with TcSnC is probably phagocytic, but the phagocytic receptor involved is not known. We hypothesised that complement receptor 3 (CR3) plays a key role. Phagocytic labeling could theoretically result in neutrophil activation or priming, affecting the behaviour of labeled cells. Fluorescence-activated cell sorter (FACS) analysis side scatter measurements can assess neutrophil activation and priming. Methods: We tested whether TcSnC neutrophil labeling is CR3-mediated by assessing if neutrophil uptake of TcSnC was inhibited by a monoclonal antibody (mAb) directed at the CD11b component of CR3. We tested if TcSnC-labeled neutrophils show altered activation or priming status, comparing FACS side scatter in labeled and unlabeled neutrophils and examining the effect of lipopolysaccharide (LPS), a known priming agent. Results: Anti-CD11b mAb reduced neutrophil uptake of TcSnC in a dose-dependent fashion. Labeled neutrophils did not show significantly increased side scatter compared to controls. LPS significantly increased side scatter in control cells and labeled neutrophils. However, the increase was significantly greater in labeled neutrophils than unlabeled cells. Conclusions: Neutrophil labeling with TcSnC is related to the function of CR3, a receptor which plays a central role in phagocytosis. TcSnC labeling did not significantly activate or prime neutrophils. However, labeled neutrophils showed a greater priming response to LPS. This could result in labeled neutrophils demonstrating increased adhesion on activated endothelium at sites of infection

Radiographic features of pleural effusions in pulmonary embolism

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Bynum, L.J.; Wilson, J.E.

1978-01-01

A prospective analysis of 155 patients with pulmonary embolism was undertaken to describe the radiographic characteristics of associated pleural effusions and related abnormalities. Approximately one half of these patients had pleural effusions. Patients with other potential causes of effusion, such as heart failure, pneumonia, or cancer, were eliminated from further analysis. In the remaining 62 patients, radiographic evidence of pulmonary infarction accompanied pleural effusions in one half of the cases. One third of patients with parenchymal consolidation had no evidence of effusion. Atelectasis and other nonspecific radiographic abnormalities occurred in less than one fifth of the cases. Typically, pleural effusions were small and unilateral, appeared soon after symptoms of thromboembolism began, and tended to reach their maximal size very early in the course of the disorder. Pulmonary infarction was associated with larger effusions that cleared more slowly and were more often bloody in appearance on thoracentesis. Chest pain occurred in all but one patient and was a valuable diagnostic clue. Pain and pleural effusions were always ipsilateral and almost always unilateral, but neither correlated well with the presence or time course of infarction. Effusions that were delayed in onset or that enlarged late in the course were associated with recurrent pulmonary embolism or superinfection. These radiographic features may be helpful in the diagnosis and management of pulmonary embolism

Sexy again: the renaissance of neutrophils in psoriasis.

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Schön, Michael P; Broekaert, Sigrid M C; Erpenbeck, Luise

2017-04-01

Notwithstanding their prominent presence in psoriatic skin, the functional role of neutrophilic granulocytes still remains somewhat enigmatic. Sparked by exciting scientific discoveries regarding neutrophil functions within the last years, the interest in these short-lived cells of the innate immune system has been boosted recently. While it had been known for some time that neutrophils produce and respond to a number of inflammatory mediators, recent research has linked neutrophils with the pathogenic functions of IL-17, possibly in conjunction with the formation of NETs (neutrophil extracellular traps). Antipsoriatic therapies exert their effects, at least in part, through interference with neutrophils. Neutrophils also appear to connect psoriasis with comorbid diseases. However, directly tampering with neutrophil functions is not trivial as evinced by the failure of therapeutic approaches targeting redundantly regulated cellular communication networks. It has also become apparent that neutrophils link important pathogenic functions of the innate and the adaptive immune system and that they are intricately involved in regulatory networks underlying the pathophysiology of psoriasis. In order to advocate intensified research into the role of this interesting cell population, we here highlight some features of neutrophils and put them into perspective with our current view of the pathophysiology of psoriasis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Paraseptal Emphysema: Prevalence and Distribution on CT and Association with Interstitial Lung Abnormalities

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Araki, Tetsuro; Nishino, Mizuki; Zazueta, Oscar E.; Gao, Wei; Dupuis, Josée; Okajima, Yuka; Latourelle, Jeanne C.; Rosas, Ivan O.; Murakami, Takamichi; O’Connor, George T.; Washko, George R.; Hunninghake, Gary M.; Hatabu, Hiroto

2015-01-01

Objective To investigate the prevalence and distribution of paraseptal emphysema on chest CT images in the Framingham Heart Study (FHS) population, and assess its impact on pulmonary function. Also pursued was the association with interstitial lung abnormalities. Materials and Methods We assessed 2633 participants in the FHS for paraseptal emphysema on chest CT. Characteristics of participants, including age, sex, smoking status, clinical symptoms, and results of pulmonary function tests, were compared between those with and without paraseptal emphysema. The association between paraseptal emphysema and interstitial lung abnormalities was investigated. Results Of the 2633 participants, 86 (3%) had pure paraseptal emphysema (defined as paraseptal emphysema with no other subtypes of emphysema other than paraseptal emphysema or a very few centrilobular emphysema involved) in at least one lung zone. The upper zone of the lungs was almost always involved. Compared to the participants without paraseptal emphysema, those with pure paraseptal emphysema were significantly older, and were more frequently male and smokers (mean 64 years, 71% male, mean 36 pack-years, pemphysema and interstitial lung abnormalities (pemphysema was 3% in the FHS population, predominantly affects the upper lung zone, and contributes to decreased pulmonary function. Cigarette smoking, aging, and male gender were the factors associated with the presence of paraseptal emphysema. Significant association between paraseptal emphysema and interstitial lung abnormalities was observed. PMID:25868675

Rapid lung MRI in children with pulmonary infections: Time to change our diagnostic algorithms.

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Sodhi, Kushaljit Singh; Khandelwal, Niranjan; Saxena, Akshay Kumar; Singh, Meenu; Agarwal, Ritesh; Bhatia, Anmol; Lee, Edward Y

2016-05-01

To determine the diagnostic utility of a new rapid MRI protocol, as compared with computed tomography (CT) for the detection of various pulmonary and mediastinal abnormalities in children with suspected pulmonary infections. Seventy-five children (age range of 5 to 15 years) with clinically suspected pulmonary infections were enrolled in this prospective study, which was approved by the institutional ethics committee. All patients underwent thoracic MRI (1.5T) and CT (64 detector) scan within 48 h of each other. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MRI were evaluated with CT as a standard of reference. Inter-observer agreement was measured with the kappa coefficient. MRI with a new rapid MRI protocol demonstrated sensitivity, specificity, PPV, and NPV of 100% for detecting pulmonary consolidation, nodules (>3 mm), cyst/cavity, hyperinflation, pleural effusion, and lymph nodes. The kappa-test showed almost perfect agreement between MRI and multidetector CT (MDCT) in detecting thoracic abnormalities (k = 0.9). No statistically significant difference was observed between MRI and MDCT for detecting thoracic abnormalities by the McNemar test (P = 0.125). Rapid lung MRI was found to be comparable to MDCT for detecting thoracic abnormalities in pediatric patients with clinically suspected pulmonary infections. It has a great potential as the first line cross-sectional imaging modality of choice in this patient population. However, further studies will be helpful for confirmation of our findings. © 2015 Wiley Periodicals, Inc.

Familial Interstitial Pulmonary Fibrosis: A Large Family with Atypical Clinical Features

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Ranji Chibbar

2010-01-01

Full Text Available A large kindred of familial pulmonary fibrosis is reported. Six members from the first two generations of this particular kindred were described more than 40 years previously; six more individuals from the third and fourth generations have also been evaluated. The proband, now 23 years of age, has mild disease; the other 11 documented affected family members all died from their disease at an average age of 37 years (range 25 to 50 years. The pathology was that of usual interstitial pneumonia, as is typical in idiopathic pulmonary fibrosis. However, the initial radiographic pattern in many of these individuals was upper lobe and nodular and, along with the young age, was atypical for idiopathic pulmonary fibrosis. Several genetic abnormalities have been associated with familial pulmonary fibrosis. The present study examined the genes coding for surfactant protein-C, ATP-binding cassette protein A3 and telomerase, and found no abnormalities.

Severe Impairments of Social Interaction and Associated Abnormalities in Children: Epidemiology and Classification.

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Wing, Lorna; Gould, Judith

1979-01-01

The prevalence of severe impairments of social interaction, language abnormalities, and repetitive stereotyped behaviors was investigated in a group of 132 children under 15 years old, consisting of a socially impaired group (more than half of whom were severely retarded) and a comparison group of sociable severely mentally retarded. Author/DLS)

Neutrophils in Cancer: Two Sides of the Same Coin.

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Uribe-Querol, Eileen; Rosales, Carlos

2015-01-01

Neutrophils are the most abundant leukocytes in blood and are considered to be the first line of defense during inflammation and infections. In addition, neutrophils are also found infiltrating many types of tumors. Tumor-associated neutrophils (TANs) have relevant roles in malignant disease. Indeed neutrophils may be potent antitumor effector cells. However, increasing clinical evidence shows TANs correlate with poor prognosis. The tumor microenvironment controls neutrophil recruitment and in turn TANs help tumor progression. Hence, TANs can be beneficial or detrimental to the host. It is the purpose of this review to highlight these two sides of the neutrophil coin in cancer and to describe recent studies that provide some light on the mechanisms for neutrophil recruitment to the tumor, for neutrophils supporting tumor progression, and for neutrophil activation to enhance their antitumor functions.

Interleukin-17 Promotes Neutrophil-Mediated Immunity by Activating Microvascular Pericytes and Not Endothelium

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Liu, Rebecca; Lauridsen, Holly M.; Amezquita, Robert A.; Pierce, Richard W.; Jane-wit, Dan; Fang, Caodi; Pellowe, Amanda S.; Kirkiles-Smith, Nancy C.; Gonzalez, Anjelica L.; Pober, Jordan S.

2016-01-01

A classical hallmark of acute inflammation is neutrophil infiltration of tissues, a multi-step process that involves sequential cell-cell interactions of circulating leukocytes with interleukin (IL)-1- or tumor necrosis factor-α (TNF)-activated microvascular endothelial cells (ECs) and pericytes (PCs) that form the wall of the postcapillary venules. The initial infiltrating cells accumulate perivascularly in close proximity to PCs. IL-17, a pro-inflammatory cytokine that acts on target cells via a heterodimeric receptor formed by IL-17RA and IL-17RC subunits, also promotes neutrophilic inflammation but its effects on vascular cells are less clear. We report that both cultured human ECs and PCs strongly express IL-17RC and, while neither cell type expresses much IL-17RA, PCs express significantly more than ECs. IL-17, alone or synergistically with TNF, significantly alters inflammatory gene expression in cultured human PCs but not ECs. RNA-seq analysis identifies many IL-17-induced transcripts in PCs encoding proteins known to stimulate neutrophil-mediated immunity. Conditioned media (CM) from IL-17-activated PCs, but not ECs, induce pertussis toxin-sensitive neutrophil polarization, likely mediated by PC-secreted chemokines, and also stimulate neutrophil production of pro-inflammatory molecules, including TNF, IL-1α, IL-1β, and IL-8. Furthermore, IL-17-activated PCs but not ECs can prolong neutrophil survival by producing G-CSF and GM-CSF, delaying the mitochondria outer membrane permeabilization and caspase 9 activation. Importantly, neutrophils exhibit enhanced phagocytic capacity after activation by CM from IL-17-treated PCs. We conclude that PCs, not ECs, are the major target of IL-17 within the microvessel wall and that IL-17-activated PCs can modulate neutrophil functions within the perivascular tissue space. PMID:27534549

Inflammatory Response Mechanisms Exacerbating Hypoxemia in Coexistent Pulmonary Fibrosis and Sleep Apnea

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Ayodeji Adegunsoye

2015-01-01

Full Text Available Mediators of inflammation, oxidative stress, and chemoattractants drive the hypoxemic mechanisms that accompany pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis commonly have obstructive sleep apnea, which potentiates the hypoxic stimuli for oxidative stress, culminating in systemic inflammation and generalized vascular endothelial damage. Comorbidities like pulmonary hypertension, obesity, gastroesophageal reflux disease, and hypoxic pulmonary vasoconstriction contribute to chronic hypoxemia leading to the release of proinflammatory cytokines that may propagate clinical deterioration and alter the pulmonary fibrotic pathway. Tissue inhibitor of metalloproteinase (TIMP-1, interleukin- (IL- 1α, cytokine-induced neutrophil chemoattractant (CINC-1, CINC-2α/β, lipopolysaccharide induced CXC chemokine (LIX, monokine induced by gamma interferon (MIG-1, macrophage inflammatory protein- (MIP- 1α, MIP-3α, and nuclear factor- (NF- κB appear to mediate disease progression. Adipocytes may induce hypoxia inducible factor (HIF 1α production; GERD is associated with increased levels of lactate dehydrogenase (LDH, alkaline phosphatase (ALP, and tumor necrosis factor alpha (TNF-α; pulmonary artery myocytes often exhibit increased cytosolic free Ca2+. Protein kinase C (PKC mediated upregulation of TNF-α and IL-1β also occurs in the pulmonary arteries. Increased understanding of the inflammatory mechanisms driving hypoxemia in pulmonary fibrosis and obstructive sleep apnea may potentiate the identification of appropriate therapeutic targets for developing effective therapies.

Chest radiographic pulmonary changes reflecting extrapulmonary involvement in paediatric HIV disease

International Nuclear Information System (INIS)

Pitcher, Richard D.; Goddard, Elizabeth; Hendricks, Marc; Lawrenson, John

2009-01-01

Respiratory infections are the commonest cause of pulmonary change on chest radiographs of HIV-infected children. However, HIV-related neurological, oropharyngeal, oesophageal, cardiac and haematological abnormalities may also manifest with pulmonary changes and must be considered in the interpretation of the chest radiograph in HIV-infected children. (orig.)

Regulation of neutrophil senescence by microRNAs.

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Jon R Ward

2011-01-01

Full Text Available Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease.

Melatonin Decreases Pulmonary Vascular Remodeling and Oxygen Sensitivity in Pulmonary Hypertensive Newborn Lambs

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Cristian R. Astorga

2018-03-01

Full Text Available Background: Chronic hypoxia and oxidative stress during gestation lead to pulmonary hypertension of the neonate (PHN, a condition characterized by abnormal pulmonary arterial reactivity and remodeling. Melatonin has strong antioxidant properties and improves pulmonary vascular function. Here, we aimed to study the effects of melatonin on the function and structure of pulmonary arteries from PHN lambs.Methods: Twelve lambs (Ovis aries gestated and born at highlands (3,600 m were instrumented with systemic and pulmonary catheters. Six of them were assigned to the control group (CN, oral vehicle and 6 were treated with melatonin (MN, 1 mg.kg−1.d−1 during 10 days. At the end of treatment, we performed a graded oxygenation protocol to assess cardiopulmonary responses to inspired oxygen variations. Further, we obtained lung and pulmonary trunk samples for histology, molecular biology, and immunohistochemistry determinations.Results: Melatonin reduced the in vivo pulmonary pressor response to oxygenation changes. In addition, melatonin decreased cellular density of the media and diminished the proliferation marker KI67 in resistance vessels and pulmonary trunk (p < 0.05. This was associated with a decreased in the remodeling markers α-actin (CN 1.28 ± 0.18 vs. MN 0.77 ± 0.04, p < 0.05 and smoothelin-B (CN 2.13 ± 0.31 vs. MN 0.88 ± 0.27, p < 0.05. Further, melatonin increased vascular density by 134% and vascular luminal surface by 173% (p < 0.05. Finally, melatonin decreased nitrotyrosine, an oxidative stress marker, in small pulmonary vessels (CN 5.12 ± 0.84 vs. MN 1.14 ± 0.34, p < 0.05.Conclusion: Postnatal administration of melatonin blunts the cardiopulmonary response to hypoxia, reduces the pathological vascular remodeling, and increases angiogenesis in pulmonary hypertensive neonatal lambs.These effects improve the pulmonary vascular structure and function in the neonatal period under chronic hypoxia.

Melatonin Decreases Pulmonary Vascular Remodeling and Oxygen Sensitivity in Pulmonary Hypertensive Newborn Lambs

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Astorga, Cristian R.; González-Candia, Alejandro; Candia, Alejandro A.; Figueroa, Esteban G.; Cañas, Daniel; Ebensperger, Germán; Reyes, Roberto V.; Llanos, Aníbal J.; Herrera, Emilio A.

2018-01-01

Background: Chronic hypoxia and oxidative stress during gestation lead to pulmonary hypertension of the neonate (PHN), a condition characterized by abnormal pulmonary arterial reactivity and remodeling. Melatonin has strong antioxidant properties and improves pulmonary vascular function. Here, we aimed to study the effects of melatonin on the function and structure of pulmonary arteries from PHN lambs. Methods: Twelve lambs (Ovis aries) gestated and born at highlands (3,600 m) were instrumented with systemic and pulmonary catheters. Six of them were assigned to the control group (CN, oral vehicle) and 6 were treated with melatonin (MN, 1 mg.kg−1.d−1) during 10 days. At the end of treatment, we performed a graded oxygenation protocol to assess cardiopulmonary responses to inspired oxygen variations. Further, we obtained lung and pulmonary trunk samples for histology, molecular biology, and immunohistochemistry determinations. Results: Melatonin reduced the in vivo pulmonary pressor response to oxygenation changes. In addition, melatonin decreased cellular density of the media and diminished the proliferation marker KI67 in resistance vessels and pulmonary trunk (p < 0.05). This was associated with a decreased in the remodeling markers α-actin (CN 1.28 ± 0.18 vs. MN 0.77 ± 0.04, p < 0.05) and smoothelin-B (CN 2.13 ± 0.31 vs. MN 0.88 ± 0.27, p < 0.05). Further, melatonin increased vascular density by 134% and vascular luminal surface by 173% (p < 0.05). Finally, melatonin decreased nitrotyrosine, an oxidative stress marker, in small pulmonary vessels (CN 5.12 ± 0.84 vs. MN 1.14 ± 0.34, p < 0.05). Conclusion: Postnatal administration of melatonin blunts the cardiopulmonary response to hypoxia, reduces the pathological vascular remodeling, and increases angiogenesis in pulmonary hypertensive neonatal lambs.These effects improve the pulmonary vascular structure and function in the neonatal period under chronic hypoxia. PMID:29559926

Neutrophils in Cancer: Two Sides of the Same Coin

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Eileen Uribe-Querol

2015-01-01

Full Text Available Neutrophils are the most abundant leukocytes in blood and are considered to be the first line of defense during inflammation and infections. In addition, neutrophils are also found infiltrating many types of tumors. Tumor-associated neutrophils (TANs have relevant roles in malignant disease. Indeed neutrophils may be potent antitumor effector cells. However, increasing clinical evidence shows TANs correlate with poor prognosis. The tumor microenvironment controls neutrophil recruitment and in turn TANs help tumor progression. Hence, TANs can be beneficial or detrimental to the host. It is the purpose of this review to highlight these two sides of the neutrophil coin in cancer and to describe recent studies that provide some light on the mechanisms for neutrophil recruitment to the tumor, for neutrophils supporting tumor progression, and for neutrophil activation to enhance their antitumor functions.

Radiospirometry and perfusion scintigraphy in cases of limited pulmonary fibrosis

International Nuclear Information System (INIS)

Tarkowska, A.; Smajkiewicz, L.; Szarewicz-Adamczyk, W.; Zaorska-Rajca, J.; Woytowicz, A.; Patyra, S.

1981-01-01

In 60 cases of limited pulmonary fibrosis radiospirometric investigation was performed using 133 Xe and a four-channel set. Perfusion scintigraphy was done as well after administration of labelled molecules. In all patients abnormalities were found in the results of both isotope methods suggesting presence of disturbances in the regional pulmonary functions. These disturbances included impairment of perfusion as well as ventilation, with evidence of obturation, increased volume of residual air, and decreased vital and total capasity of the lungs. These abnormalities occurred exclusively or most intensively in the areas corresponding to the location of the anatomical change, and in a considerable proportion of cases they were more extensive than the radiological changes. In about 40% of the patients in the contralateral lung diffuse changes of perfusion and ventilation were present, although much less intense, suggesting concomitant chronic obturative disease. The authors think that perfusion scintigraphy and radiospirometry owing to their value as a method of assessing pulmonary function are useful in cases of pulmonary fibrosis for establishing treatment methods and for evaluating disability to work. (author)

Radiation-induced muscositis and neutrophil granulocytes in oral mucosa; Strahleninduzierte Mukositis und neutrophile Granulozyten in der Mundschleimhaut

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Schmidberger, H.; Rave-Fraenk, M.; Kim, S.; Hille, A.; Pradier, O.; Hess, C.F. [Klinik fuer Strahlentherapie und Radioonkologie, Univ. Goettingen (Germany)

2003-10-01

Background: Chemotherapy-induced mucositis can be related to a decrease in oral neutrophils. We tested the relationship between radiation-induced mucositis and oral neutrophil counts. Patients and Methods: Oral neutrophil counts were obtained for ten patients with head and neck cancer who received radiotherapy of the pharynx and oral cavity. Four patients received additional chemotherapy (5-FU, Mitomycin). Counts were obtained before and during treatment; four healthy volunteers were included in the study as well. For evaluation, a quantitative mouth rinse assay, including neutrophil-staining with acridin-orange, was applied. Results: We observed large inter-individual variations with respect to neutrophil counts for patients and control persons (Table 1). During treatment (irradiation or chemoirradiation), large intra-individual variations were seen additionally (Figure 1). We found a correlation between neutrophil counts and clinical reaction grade. Neutrophil counts increased with increasing mucositis (Figure 2). This increase was more pronounced for patients treated with chemoirradiation compared to radiation alone. Treatment breaks at weekends had no clear influence on neutrophil counts. Conclusions: We observed a weak correlation between neutrophil counts and clinical reaction grade. However, the variations in neutrophil counts are too large to utilize this parameter as a surrogate for clinical mucositis grading. The assumption that a decrease in oral neutrophils is associated with radiation-induced mucositis was clearly negated. (orig.) [German] Hintergrund: Die chemotherapieinduzierte Mukositis kann mit einer Verarmung der Mundschleimhaut an neutrophilen Granulozyten vergesellschaftet sein. Wir ueberprueften den Zusammenhang zwischen der radiogenen Mukositis und der Anzahl neutrophiler Granulozyten. Patienten und Methoden: Bei zehn Patienten mit Tumoren der Kopf-Hals-Region, die sich einer Strahlentherapie unterzogen, wurde die Anzahl enoraler neutrophiler

IFN-γ protects from lethal IL-17 mediated viral encephalomyelitis independent of neutrophils

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Savarin Carine

2012-05-01

Full Text Available Abstract Background The interplay between IFN-γ, IL-17 and neutrophils during CNS inflammatory disease is complex due to cross-regulatory factors affecting both positive and negative feedback loops. These interactions have hindered the ability to distinguish the relative contributions of neutrophils, Th1 and Th17 cell-derived effector molecules from secondary mediators to tissue damage and morbidity. Methods Encephalitis induced by a gliatropic murine coronavirus was used as a model to assess the direct contributions of neutrophils, IFN-γ and IL-17 to virus-induced mortality. CNS inflammatory conditions were selectively manipulated by adoptive transfer of virus-primed wild-type (WT or IFN-γ deficient (GKO memory CD4+ T cells into infected SCID mice, coupled with antibody-mediated neutrophil depletion and cytokine blockade. Results Transfer of GKO memory CD4+ T cells into infected SCID mice induced rapid mortality compared to recipients of WT memory CD4+ T cells, despite similar virus control and demyelination. In contrast to recipients of WT CD4+ T cells, extensive neutrophil infiltration and IL-17 expression within the CNS in recipients of GKO CD4+ T cells provided a model to directly assess their contribution(s to disease. Recipients of WT CD4+ T cells depleted of IFN-γ did not express IL-17 and were spared from mortality despite abundant CNS neutrophil infiltration, indicating that mortality was not mediated by excessive CNS neutrophil accumulation. By contrast, IL-17 depletion rescued recipients of GKO CD4+ T cells from rapid mortality without diminishing neutrophils or reducing GM-CSF, associated with pathogenic Th17 cells in CNS autoimmune models. Furthermore, co-transfer of WT and GKO CD4+ T cells prolonged survival in an IFN-γ dependent manner, although IL-17 transcription was not reduced. Conclusions These data demonstrate that IL-17 mediates detrimental clinical consequences in an IFN-γ-deprived environment, independent of

Neutrophil labeling with [{sup 99m}Tc]-technetium stannous colloid is complement receptor 3-mediated and increases the neutrophil priming response to lipopolysaccharide

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Gallagher, Hayley [School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811 (Australia); Ramsay, Stuart C. [School of Medicine, James Cook University, Townsville, Queensland (Australia) and Townsville Nuclear Medicine, Mater Hospital, Townsville, Queensland 4812 (Australia)]. E-mail: stuart.ramsey@jcu.edu.au; Barnes, Jodie [School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811 (Australia); Maggs, Jacqueline [Department of Nuclear Medicine, Townsville Hospital, Townsville, Queensland 4814 (Australia); Cassidy, Nathan [Townsville Nuclear Medicine, Mater Hospital, Townsville, Queensland 4812 (Australia); Ketheesan, Natkunam [School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811 (Australia); School of Medicine, James Cook University, Townsville, Queensland (Australia)

2006-04-15

Introduction: [{sup 99m}Tc]-technetium stannous colloid (TcSnC)-labeled white cells are used to image inflammation. Neutrophil labeling with TcSnC is probably phagocytic, but the phagocytic receptor involved is not known. We hypothesised that complement receptor 3 (CR3) plays a key role. Phagocytic labeling could theoretically result in neutrophil activation or priming, affecting the behaviour of labeled cells. Fluorescence-activated cell sorter (FACS) analysis side scatter measurements can assess neutrophil activation and priming. Methods: We tested whether TcSnC neutrophil labeling is CR3-mediated by assessing if neutrophil uptake of TcSnC was inhibited by a monoclonal antibody (mAb) directed at the CD11b component of CR3. We tested if TcSnC-labeled neutrophils show altered activation or priming status, comparing FACS side scatter in labeled and unlabeled neutrophils and examining the effect of lipopolysaccharide (LPS), a known priming agent. Results: Anti-CD11b mAb reduced neutrophil uptake of TcSnC in a dose-dependent fashion. Labeled neutrophils did not show significantly increased side scatter compared to controls. LPS significantly increased side scatter in control cells and labeled neutrophils. However, the increase was significantly greater in labeled neutrophils than unlabeled cells. Conclusions: Neutrophil labeling with TcSnC is related to the function of CR3, a receptor which plays a central role in phagocytosis. TcSnC labeling did not significantly activate or prime neutrophils. However, labeled neutrophils showed a greater priming response to LPS. This could result in labeled neutrophils demonstrating increased adhesion on activated endothelium at sites of infection.

Differential pulmonary and cardiac effects of pulmonary exposure to a panel of particulate matter-associated metals

International Nuclear Information System (INIS)

Wallenborn, J. Grace; Schladweiler, Mette J.; Richards, Judy H.; Kodavanti, Urmila P.

2009-01-01

Biological mechanisms underlying the association between particulate matter (PM) exposure and increased cardiovascular health effects are under investigation. Water-soluble metals reaching systemic circulation following pulmonary exposure are likely exerting a direct effect. However, it is unclear whether specific PM-associated metals may be driving this. We hypothesized that exposure to equimolar amounts of five individual PM-associated metals would cause differential pulmonary and cardiac effects. We exposed male WKY rats (14 weeks old) via a single intratracheal instillation (IT) to saline or 1 μmol/kg body weight of zinc, nickel, vanadium, copper, or iron in sulfate form. Responses were analyzed 4, 24, 48, or 96 h after exposure. Pulmonary effects were assessed by bronchoalveolar lavage fluid levels of total cells, macrophages, neutrophils, protein, albumin, and activities of lactate dehydrogenase, γ-glutamyl transferase, and n-acetyl glucosaminidase. Copper induced earlier pulmonary injury/inflammation, while zinc and nickel produced later effects. Vanadium or iron exposure induced minimal pulmonary injury/inflammation. Zinc, nickel, or copper increased serum cholesterol, red blood cells, and white blood cells at different time points. IT of nickel and copper increased expression of metallothionein-1 (MT-1) in the lung. Zinc, nickel, vanadium, and iron increased hepatic MT-1 expression. No significant changes in zinc transporter-1 (ZnT-1) expression were noted in the lung or liver; however, zinc increased cardiac ZnT-1 at 24 h, indicating a possible zinc-specific cardiac effect. Nickel exposure induced an increase in cardiac ferritin 96 h after IT. This data set demonstrating metal-specific cardiotoxicity is important in linking metal-enriched anthropogenic PM sources with adverse health effects.

Correlation of tomographic findings with pulmonary function parameters in nonsmoking patients with idiopathic pulmonary fibrosis

International Nuclear Information System (INIS)

Lopes, Agnaldo Jose; Capone, Domenico; Mogami, Roberto; Jansen, Jose Manoel .E mail: phel.lop@uol.com.br; Cunha, Daniel Leme da; Melo, Pedro Lopes de

2007-01-01

Objective: To correlate tomographic findings with pulmonary function parameters in patients with idiopathic pulmonary fibrosis (IPF). Methods: A cross-sectional study was carried out, in which 30 nonsmoking patients with IPF were evaluated. Using a semiquantitative scoring system, the following high-resolution computerized tomography findings were quantified: total interstitial disease (TID), reticular abnormality/honeycombing, and ground-glass opacity (GGO). The functional variables were measured by spirometry, forced oscillation technique (FOT), helium dilution method, as well as the single-breath method of measuring diffusion capacity of the lung for carbon monoxide (DLCO). Results: Of the 30 patients studied, 18 were female, and 12 were male, with a mean age of 70.9 years. We found that TID and reticular abnormality and honeycombing correlated significantly (negative correlations) with the measurements of forced vital capacity (FVC), total lung capacity (TLC), DLCO, and dynamic respiratory compliance were found, as well as that GGO correlated significantly (and positively) with residual volume/TLC. The ratio of forced expiratory flow between 25 and 75% of FVC to FVC (FEF25-75%/FVC) correlated positively with TID, reticular abnormality/honeycombing, and GGO. Conclusion: In IPF patients, the measurements of volume, diffusion, and dynamic compliance are the physiological variables which best reflect the extent of the interstitial disease on HRCT scans. (author)

Correlation of tomographic findings with pulmonary function parameters in nonsmoking patients with idiopathic pulmonary fibrosis

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Lopes, Agnaldo Jose; Capone, Domenico; Mogami, Roberto; Jansen, Jose Manoel [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). School of Medical Sciences].E mail: phel.lop@uol.com.br; Cunha, Daniel Leme da [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Pedro Ernesto University Hospital. Dept. of Radiology and Diagnostic Imaging; Melo, Pedro Lopes de [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Inst. of Biology

2007-11-15

Objective: To correlate tomographic findings with pulmonary function parameters in patients with idiopathic pulmonary fibrosis (IPF). Methods: A cross-sectional study was carried out, in which 30 nonsmoking patients with IPF were evaluated. Using a semiquantitative scoring system, the following high-resolution computerized tomography findings were quantified: total interstitial disease (TID), reticular abnormality/honeycombing, and ground-glass opacity (GGO). The functional variables were measured by spirometry, forced oscillation technique (FOT), helium dilution method, as well as the single-breath method of measuring diffusion capacity of the lung for carbon monoxide (DLCO). Results: Of the 30 patients studied, 18 were female, and 12 were male, with a mean age of 70.9 years. We found that TID and reticular abnormality and honeycombing correlated significantly (negative correlations) with the measurements of forced vital capacity (FVC), total lung capacity (TLC), DLCO, and dynamic respiratory compliance were found, as well as that GGO correlated significantly (and positively) with residual volume/TLC. The ratio of forced expiratory flow between 25 and 75% of FVC to FVC (FEF25-75%/FVC) correlated positively with TID, reticular abnormality/honeycombing, and GGO. Conclusion: In IPF patients, the measurements of volume, diffusion, and dynamic compliance are the physiological variables which best reflect the extent of the interstitial disease on HRCT scans. (author)

Neutrophils in Tuberculosis: Heterogeneity Shapes the Way?

Science.gov (United States)

2017-01-01

Infection with M. tuberculosis remains one of the most common infections in the world. The outcome of the infection depends on host ability to mount effective protection and balance inflammatory responses. Neutrophils are innate immune cells implicated in both processes. Accordingly, during M. tuberculosis infection, they play a dual role. Particularly, they contribute to the generation of effector T cells, participate in the formation of granuloma, and are directly involved in tissue necrosis, destruction, and infection dissemination. Neutrophils have a high bactericidal potential. However, data on their ability to eliminate M. tuberculosis are controversial, and the results of neutrophil depletion experiments are not uniform. Thus, the overall roles of neutrophils during M. tuberculosis infection and factors that determine these roles are not fully understood. This review analyzes data on neutrophil defensive and pathological functions during tuberculosis and considers hypotheses explaining the dualism of neutrophils during M. tuberculosis infection and tuberculosis disease. PMID:28626346

Detection of pulmonary aspiration in children with gastroesophageal reflux

International Nuclear Information System (INIS)

Orellana, P.; Olea, E.; Pino, C.; Rossel, M.; Ceresa, S.; Gonzalez, P.; Otarola, S.; Astudillo, S.

1985-01-01

The presence of pulmonary aspiration (PA) should be suspected in two groups of patients; those with symptoms of gastroesophageal reflux (GER) and pulmonary disease and patient's with pulmonary symptoms without signs of GER in whom other etiologies of pulmonary disease have been excluded. To determine if PA could be diagnosed in children using radionuclides 114 patients aged 3-12 months drank 500 μCi of Tc-99m sulfur colloid mixed with infant formula and an additional 1.5 mCi was administered in the evening. All medicine was suspended 24 hours before. Images of the chest in supine position (ant, post views) were acquired on computer in 32 x 32 (byte mode) during 5 min each view at 2 and 18 hours. No outside pressure was applied. None of the patients with digestive symptomatology alone had positive exam. Of 88 patients with bronchopulmonary symptomatology 35 had abnormal examination 35% with moderate symptom were (Abn) and 55% with severe disease were abnormal. The radionuclide method appears to be the ideal study in patients where PA is suspected. The positivity of the method depends on the group of patients selected. The sensitivity is highest in patients with marked symptomatology

Radiological abnormalities associated with Aspergillus colonization in a cystic fibrosis population

International Nuclear Information System (INIS)

McMahon, Michelle A.; Chotirmall, Sanjay Haresh; McCullagh, Brian; Branagan, Peter; McElvaney, N.G.; Logan, P.M.

2012-01-01

Objective: To determine if sputum colonization with Aspergillus species in patients with cystic fibrosis (PWCF) correlates with radiological abnormalities and/or a reduction in pulmonary function (FEV1). Methods: We prospectively evaluated 32 PWCF utilizing high resolution computed tomography (HRCT) of the thorax and pulmonary function testing (PFT). The cohort was assessed as two groups: Aspergillus positive (n = 16) and Aspergillus negative (n = 16) based on sputum culture for Aspergillus species. A modified Bhalla scoring system was applied to each HRCT scan by two blinded radiologists. Results: Aspergillus positive patients had more severe and significant bronchiectasis compared to those Aspergillus negative (p < 0.05). This was most marked in the right upper and lower lobes (RUL, RLL). Total Bhalla score was clinically significant in both groups and approached statistical significance between groups (p = 0.063). No difference in pulmonary function between the groups was detected. Conclusion: PWCF colonized by Aspergillus species have greater radiological abnormalities undetectable by PFTs. Early radiological evaluation of Aspergillus colonized PWCF is therefore warranted.

Clinical signs and clinicopathologic abnormalities in dogs with clinical spirocercosis: 39 cases (1996-2004).

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Mylonakis, Mathios E; Rallis, Tim; Koutinas, Alexander F; Leontides, Leonidas S; Patsikas, Michail; Florou, Marianna; Papadopoulos, Elias; Fytianou, Anna

2006-04-01

To determine clinical signs and clinicopathologic abnormalities in dogs with naturally occurring clinical spirocercosis. Retrospective case series. 39 dogs with spirocercosis. Medical records were reviewed, and information on signalment, residence (rural vs urban), owner complaints, physical examination findings, clinicopathologic abnormalities, radiographic and endoscopic findings, and concurrent systemic diseases was recorded. Hellenic hounds and mixed-breed dogs were overrepresented, compared with a group of 117 control dogs without spirocercosis that were examined because of gastrointestinal tract disease, and mean body weight of dogs with spirocercosis was significantly higher than mean body weight of control dogs. Odynophagia (34 [87%]), regurgitation (24 [62%]), and excessive salivation (14 [36%]) were the most common clinical findings. The most common radiographic abnormalities were a mass in the caudodorsal aspect of the mediastinum (15/35 [43%]) and spondylitis of the caudal thoracic vertebrae (10 [29%]). Parasitic nodules were seen during esophagoscopy in all 39 dogs. Normocytic, normochromic, nonregenerative anemia; neutrophilic leukocytosis; hyperproteinemia; and high alkaline phosphatase activity were significantly more common in dogs with spirocercosis than in a control group of 56 healthy dogs. Concurrent systemic diseases, mainly leishmaniosis, dirofilariosis, and monocytic ehrlichiosis, were documented in 14 (36%) dogs. Results suggest that clinical spirocercosis occurs more often in young-adult, large-breed dogs. Nonregenerative anemia, neutrophilic leukocytosis, hyperproteinemia, and high alkaline phosphatase activity may be useful clinicopathologic indicators of this disease.

A new method for quantification of pulmonary thallium uptake in myocardial SPECT studies

International Nuclear Information System (INIS)

Mannting, F.

1990-01-01

Quantified pulmonary thallium 201 (Tl) uptake was assessed in 32 normal people and 66 patients with suspected coronary artery disease (CAD) by a new method utilizing SPECT acquisition data. In 26 subjects pulmonary uptake was assessed with both SPECT and planar techniques. Pulmonary/myocardial (PM) ratios for the whole right lung (PM1) and for the upper left lung (PM2) were computed and compared with stress test, coronary angiography, radionuclide angiography (ERNA), and quantified Tl SPECT results. Excellent correlation between pulmonary uptake assessed by planar and SPECT technique was disclosed (r=0.92). The PM ratio (PM1/PM2) sensitivity and specificity in patients with CAD was 88%/92% and 60%/70%, for predicting perfusion abnormalities 90%/87% and 88%/88%, and an inverse correlation to LVEF was found (r=-0.40/r=-0.37, P<0.01). Significant correlations to coronary angiography findings (r=0.54/r=0.49, P<0.001) and to number of vessel territories with abnormal perfusion (r=0.70/r=0.69, P<0.001) were seen. Thus, pulmonary Tl uptake can be assessed in SPECT studies. The new method's discriminative ability seems higher than that of the standard planar technique currently employed. Positive correlations to coronary angiography findings and even stronger ones to perfusion abnormalities were observed. (orig.)

Cardiac MRI in pulmonary artery hypertension: correlations between morphological and functional parameters and invasive measurements

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Alunni, Jean-Philippe; Otal, Philippe; Rousseau, Herve; Chabbert, Valerie [CHU Rangueil, Department of Radiology, Toulouse (France); Degano, Bruno; Tetu, Laurent; Didier, Alain [CHU Larrey, Department of Pneumology, Toulouse (France); Arnaud, Catherine [CHU Rangueil, Department of Methods in Clinical Research, Toulouse (France); Blot-Souletie, Nathalie [CHU Rangueil, Department of Cardiology, Toulouse (France)

2010-05-15

To compare cardiac MRI with right heart catheterisation in patients with pulmonary hypertension (PH) and to evaluate its ability to assess PH severity. Forty patients were included. MRI included cine and phase-contrast sequences, study of ventricular function, cardiac cavity areas and ratios, position of the interventricular septum (IVS) in systole and diastole, and flow measurements. We defined four groups according to the severity of PH and three groups according to IVS position: A, normal position; B, abnormal in diastole; C, abnormal in diastole and systole. IVS position was correlated with pulmonary artery pressures and PVR (pulmonary vascular resistance). Median pulmonary artery pressures and resistance were significantly higher in patients with an abnormal septal position compared with those with a normal position. Correlations were good between the right ventricular ejection fraction and PVR, right ventricular end-systolic volume and PAP, percentage of right ventricular area change and PVR, and diastolic and systolic ventricular area ratio and PVR. These parameters were significantly associated with PH severity. Cardiac MRI can help to assess the severity of PH. (orig.)

Flow Cytometric Evaluation of Human Neutrophil Apoptosis During Nitric Oxide Generation In Vitro: The Role of Exogenous Antioxidants

Directory of Open Access Journals (Sweden)

Zofia Sulowska

2005-01-01

in vitro. The effect of exogenous supply of NO donors such as SNP, SIN-1, and GEA-3162 on the course of human neutrophil apoptosis and the role of extracellular antioxidants in this process was investigated. Isolated from peripheral blood, neutrophils were cultured in the presence or absence of NO donor compounds and antioxidants for 8, 12, and 20 hours. Apoptosis of neutrophils was determined in vitro by flow cytometric analysis of cellular DNA content and Annexin V protein binding to the cell surface. Exposure of human neutrophils to GEA-3162 and SIN-1 significantly accelerates and enhances their apoptosis in vitro in a time-dependent fashion. In the presence of SNP, intensification of apoptosis has not been revealed until 12 hours after the culture. The inhibition of GEA-3162- and SIN-1-mediated neutrophil apoptosis by superoxide dismutase (SOD but not by catalase (CAT was observed. Our results show that SOD and CAT can protect neutrophils against NO-donors-induced apoptosis and suggest that the interaction of NO and oxygen metabolites signals may determine the destructive or protective role of NO donor compounds during apoptotic neutrophil death.

Allelic interaction of F1 pollen sterility loci and abnormal chromosome behaviour caused pollen sterility in intersubspecific autotetraploid rice hybrids.

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He, J H; Shahid, M Q; Li, Y J; Guo, H B; Cheng, X A; Liu, X D; Lu, Y G

2011-08-01

The intersubspecific hybrids of autotetraploid rice has many features that increase rice yield, but lower seed set is a major hindrance in its utilization. Pollen sterility is one of the most important factors which cause intersubspecific hybrid sterility. The hybrids with greater variation in seed set were used to study how the F(1) pollen sterile loci (S-a, S-b, and S-c) interact with each other and how abnormal chromosome behaviour and allelic interaction of F(1) sterility loci affect pollen fertility and seed set of intersubspecific autotetraploid rice hybrids. The results showed that interaction between pollen sterility loci have significant effects on the pollen fertility of autotetraploid hybrids, and pollen fertility further decreased with an increase in the allelic interaction of F(1) pollen sterility loci. Abnormal ultra-structure and microtubule distribution patterns during pollen mother cell (PMC) meiosis were found in the hybrids with low pollen fertility in interphase and leptotene, suggesting that the effect-time of pollen sterility loci interaction was very early. There were highly significant differences in the number of quadrivalents and bivalents, and in chromosome configuration among all the hybrids, and quadrivalents decreased with an increase in the seed set of autotetraploid hybrids. Many different kinds of chromosomal abnormalities, such as chromosome straggling, chromosome lagging, asynchrony of chromosome disjunction, and tri-fission were found during the various developmental stages of PMC meiosis. All these abnormalities were significantly higher in sterile hybrids than in fertile hybrids, suggesting that pollen sterility gene interactions tend to increase the chromosomal abnormalities which cause the partial abortion of male gametes and leads to the decline in the seed set of the autotetraploid rice hybrids. © 2011 The Author(s).

Activation of bovine neutrophils by Brucella spp.

Science.gov (United States)

Keleher, Lauren L; Skyberg, Jerod A

2016-09-01

Brucellosis is a globally important zoonotic infectious disease caused by gram negative bacteria of the genus Brucella. While many species of Brucella exist, Brucella melitensis, Brucella abortus, and Brucella suis are the most common pathogens of humans and livestock. The virulence of Brucella is largely influenced by its ability to evade host factors, including phagocytic killing mechanisms, which are critical for the host response to infection. The aim of this study was to characterize the bovine neutrophil response to virulent Brucella spp. Here, we found that virulent strains of smooth B. abortus, B. melitensis, B. suis, and virulent, rough, strains of Brucella canis possess similar abilities to resist killing by resting, or IFN-γ-activated, bovine neutrophils. Bovine neutrophils responded to infection with a time-dependent oxidative burst that varied little between Brucella spp. Inhibition of TAK1, or SYK kinase blunted the oxidative burst of neutrophils in response to Brucella infection. Interestingly, Brucella spp. did not induce robust death of bovine neutrophils. These results indicate that bovine neutrophils respond similarly to virulent Brucella spp. In addition, virulent Brucella spp., including naturally rough strains of B. canis, have a conserved ability to resist killing by bovine neutrophils. Copyright © 2016 Elsevier B.V. All rights reserved.

Surface area-dependence of gas-particle interactions influences pulmonary and neuroinflammatory outcomes

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Tyler, Christina R.; Zychowski, Katherine E.; Sanchez, Bethany N.; Rivero, Valeria; Lucas, Selita; Herbert, Guy; Liu, June; Irshad, Hammad; McDonald, Jacob D.; Bleske, Barry E.; Campen, Matthew J.

2016-01-01

Background Deleterious consequences of exposure to traffic emissions may derive from interactions between carbonaceous particulate matter (PM) and gaseous components in a manner that is dependent on the surface area or complexity of the particles. To determine the validity of this hypothesis, we examined pulmonary and neurological inflammatory outcomes in C57BL/6 and apolipoprotein E knockout (ApoE?/?) male mice after acute and chronic exposure to vehicle engine-derived particulate matter, ge...

Right-sided phase abnormalities on gated blood pool ventriculography: Demonstration of six different patterns

International Nuclear Information System (INIS)

Bahar, R.H.; Abdel-Dayem, H.M.; Ziada, G.; Al-Suhali, A.; Constantinides, C.; Nair, K.M.

1986-01-01

Phase pattern abnormalities on multiple gated blood pool ventriculography are better reported for the left ventricle (LV) than for the right side of the heart. In a study of 92 patients who also underwent contrast ventriculography, the authors identified six different patterns of right-sided phase abnormalities and their causes: right bundle-branch block, causing delayed phase in the entire right ventricle (RV); ischemic right coronary artery disease, causing delayed phase in the inferior RV wall; pericardial effusion, causing an L-shaped area of delayed phase to the right of the septum and below the LV; pulmonary hypertension, causing delayed phase in the pulmonary infundibulum; tricuspid regurgitation, causing a crescentic area of delayed phase around and below the right RV and extending below the LV as well, and atrial septal defect causing an abnormally large auricular phase

The complex interplay between neutrophils and cancer.

Science.gov (United States)

Rakic, Andrea; Beaudry, Paul; Mahoney, Douglas J

2018-03-01

Neutrophils are the most abundant type of white blood cell, and are an essential component of the innate immune system. They characteristically arrive rapidly at sites of infection and injury, and release a variety of cytokines and toxic molecules to eliminate pathogens and elicit an acute inflammatory response. Research into the function of neutrophils in cancer suggest they have divergent roles. Indeed, while most studies have found neutrophils to be associated with cancer progression, others have also documented anticancer effects. In this review, we describe the investigations into neutrophil populations that have been implicated in promoting tumor growth and metastasis as well those demonstrating antitumor functions. The collective research suggests a complex role for neutrophils in cancer biology, which raises the prospect of their targeting for the treatment of cancer.

Spontaneous neutrophil migration patterns during sepsis after major burns.

Science.gov (United States)

Jones, Caroline N; Moore, Molly; Dimisko, Laurie; Alexander, Andrew; Ibrahim, Amir; Hassell, Bryan A; Warren, H Shaw; Tompkins, Ronald G; Fagan, Shawn P; Irimia, Daniel

2014-01-01

Finely tuned to respond quickly to infections, neutrophils have amazing abilities to migrate fast and efficiently towards sites of infection and inflammation. Although neutrophils ability to migrate is perturbed in patients after major burns, no correlations have yet been demonstrated between altered migration and higher rate of infections and sepsis in these patients when compared to healthy individuals. To probe if such correlations exist, we designed microfluidic devices to quantify the neutrophil migration phenotype with high precision. Inside these devices, moving neutrophils are confined in channels smaller than the neutrophils and forced to make directional decisions at bifurcations and around posts. We employed these devices to quantify neutrophil migration across 18 independent parameters in 74 blood samples from 13 patients with major burns and 3 healthy subjects. Blinded, retrospective analysis of clinical data and neutrophil migration parameters revealed that neutrophils isolated from blood samples collected during sepsis migrate spontaneously inside the microfluidic channels. The spontaneous neutrophil migration is a unique phenotype, typical for patients with major burns during sepsis and often observed one or two days before the diagnosis of sepsis is confirmed. The spontaneous neutrophil migration phenotype is rare in patients with major burns in the absence of sepsis, and is not encountered in healthy individuals. Our findings warrant further studies of neutrophils and their utility for early diagnosing and monitoring sepsis in patients after major burns.

Dynamic (4D) CT perfusion offers simultaneous functional and anatomical insights into pulmonary embolism resolution

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Mirsadraee, Saeed, E-mail: saeed.mirsadraee@ed.ac.uk [Clinical Research Imaging Centre, Queen' s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ (United Kingdom); Reid, John H.; Connell, Martin [Clinical Research Imaging Centre, Queen' s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ (United Kingdom); MacNee, William; Hirani, Nikhil [The Queen' s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ (United Kingdom); Murchison, John T. [Department of Radiology, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA (United Kingdom); Beek, Edwin J. van [Clinical Research Imaging Centre, Queen' s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ (United Kingdom)

2016-10-15

Objective: Resolution and long-term functional effects of pulmonary emboli are unpredictable. This study was carried out to assess persisting vascular bed perfusion abnormalities and resolution of arterial thrombus in patients with recent pulmonary embolism (PE). Methods and materials: 26 Patients were prospectively evaluated by dynamic (4D) contrast enhanced CT perfusion dynamic pulmonary CT perfusion. Intermittent volume imaging was performed every 1.5–1.7 s during breath-hold and perfusion values were calculated by maximum-slope technique. Thrombus load (modified Miller score; MMS) and ventricular diameter were determined. Perfusion maps were visually scored and correlated with residual endoluminal filling defects. Results: The mean initial thrombus load was 13.1 ± 4.6 MMS (3–16), and 1.2 ± 2.1 MMS (0–8) at follow up. From the 24 CTPs with diagnostic quality perfusion studies, normal perfusion was observed in 7 (29%), and mildly-severely abnormal in 17 (71%). In 15 patients with no residual thrombus on follow up CTPA, normal perfusion was observed in 6, and abnormal perfusion in 9. Perfusion was abnormal in all patients with residual thrombus on follow up CTPA. Pulmonary perfusion changes were classified as reduced (n = 4), delayed (systemic circulation pattern; n = 5), and absent (no-flow; n = 5). The right ventricle was dilated in 12/25 (48%) at presentation, and normal in all 26 follow up scans. Weak correlation was found between initial ventricular dilatation and perfusion abnormality at follow up (r = 0.15). Conclusions: Most patients had substantial perfusion abnormality at 3–6 months post PE. Abnormal perfusion patterns were frequently observed in patients and in regions with no corresponding evidence of residual thrombus on CTPA. Some defects exhibit delayed, presumed systemic, enhancement (which we have termed ‘stunned’ lung). CT perfusion provides combined anatomical and functional information about PE resolution.

Cardiorespiratory Interactions in Paediatrics: 'It's (almost always) the circulation stupid!'

Science.gov (United States)

Rigby, M L; Rosenthal, M

2017-03-01

The interaction of the heart and lungs is probably the most important aspect of life and survival. Fortunately, it is not difficult to understand the fundamentals. The purpose of the lungs and their ventilation is to present oxygen to the circulation via the alveoli and to receive carbon dioxide from the circulation and then expel it. The relations of the heart and lungs and the matching of blood flow to the various organs with ventilation and lung perfusion may be disrupted by a variety of congenital or acquired heart malformations. They include those giving rise to an increased or reduced pulmonary blood flow, elevated pulmonary venous pressure or external physical pressure on the airways or lung parenchyma. Respiratory disorders which compromise cardiac function include states with reduced alveolar ventilation, those with a barrier to ventilation or perfusion, ventilation/perfusion mismatch and pulmonary vascular disease. There is also a fascinating group in which congenital disorders of the heart and lung co-exist to produce very particular modes of abnormal cardiopulmonary interaction. Copyright © 2016. Published by Elsevier Ltd.

Pathophysiology of neutrophil-mediated extracellular redox reactions.

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Jaganjac, Morana; Cipak, Ana; Schaur, Rudolf Joerg; Zarkovic, Neven

2016-01-01

Neutrophil granulocyte leukocytes (neutrophils) play fundamental role in the innate immune response. In the presence of adequate stimuli, neutrophils release excessive amount of reactive oxygen species (ROS) that may induce cell and tissue injury. Oxidative burst of neutrophils acts as a double-edged sword. It may contribute to the pathology of atherosclerosis and brain injury but is also necessary in resolving infections. Moreover, neutrophil-derived ROS may also have both a tumor promoting and tumor suppressing role. ROS have a specific activities and diffusion distance, which is related to their short lifetime. Therefore, the manner in which ROS will act depends on the cells targeted and the intra- and extracellular levels of individual ROS, which can further cause production of reactive aldehydes like 4-hydroxynonenal (HNE) that act as a second messengers of ROS. In this review we discuss the influence of neutrophil mediated extracellular redox reactions in ischemia reperfusion injury, transplant rejection and chronic diseases (atherosclerosis, inflammatory bowel diseases and cancer). At the end a brief overview of cellular mechanisms to maintain ROS homeostasis is given.

Localization and Functionality of the Inflammasome in Neutrophils

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Bakele, Martina; Joos, Melanie; Burdi, Sofia

2014-01-01

Neutrophils represent the major fraction of circulating immune cells and are rapidly recruited to sites of infection and inflammation. The inflammasome is a multiprotein complex that regulates the generation of IL-1 family proteins. The precise subcellular localization and functionality...... of the inflammasome in human neutrophils are poorly defined. Here we demonstrate that highly purified human neutrophils express key components of the NOD-like receptor family, pyrin domain containing 3 (NLRP3), and absent in melanoma 2 (AIM2) inflammasomes, particularly apoptosis-associated speck-like protein...... and released as protein, highly purified neutrophils neither expressed nor released IL-1α at baseline or upon stimulation. Upon inflammasome activation, highly purified neutrophils released substantially lower levels of IL-1β protein compared with partially purified neutrophils. Serine proteases and caspases...

CYFRA 21.1 in bronchoalveolar lavage of idiopathic pulmonary fibrosis patients.

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Vercauteren, Inge M; Verleden, Stijn E; McDonough, John E; Vandermeulen, Elly; Ruttens, David; Lammertyn, Elise J; Bellon, Hannelore; De Dycker, Els; Dooms, Christophe; Yserbyt, Jonas; Verleden, Geert M; Vanaudenaerde, Bart M; Wuyts, Wim A

2015-01-01

Idiopathic pulmonary fibrosis (IPF) is one of the most aggressive forms of interstitial lung diseases, however, clinically relevant biomarkers of diagnosis or prognosis are lacking. In this study, we investigated the levels of a fragment of Cytokeratin 19 (CYFRA 21.1) in bronchoalveolar lavage (BAL) of IPF patients at time of diagnosis. We further evaluated associations between CYFRA 21.1, pulmonary function evolution, mortality, and BAL cell count. Using the Lumipulse® G1200, CYFRA 21.1 was measured in BAL samples of 81 IPF patients and 9 controls. Based upon the median detected level (1.2 ng/mL) of CYFRA 21.1 in IPF patients, they were subdivided into an IPF CYFRA 21.1 low group (≤ 1.2 ng/mL) and IPF CYFRA 21.1 high group (> 1.2 ng/mL). The CYFRA 21.1 levels were significantly higher in BAL of IPF patients compared to controls (P = .0015).Worse survival was observed, but no changes in pulmonary function, for IPF patients with high CYFRA 21.1 levels versus patients with low CYFRA 21.1 levels [P = .030, HR: 0.41, (0.18-0.92)[. The CYFRA 21.1 level correlated with both neutrophils (%: R = 0.60, P < .0001; #: R = 0.47, P < .0001) and eosinophils (%: R = 0.38, P = .0005; #: R = 0.30, P < .0072). CYFRA 21.1 is increased in BAL of IPF patients. IPF patients with a high CYFRA 21.1 concentration have a worse survival. CYFRA 21.1 levels correlate with eosinophils and neutrophils. Further studies are warranted in using CYFRA 21.1 as a biomarker for IPF prognosis.

Treatment with Rutin - A Therapeutic Strategy for Neutrophil-Mediated Inflammatory and Autoimmune Diseases - Anti-inflammatory Effects of Rutin on Neutrophils -

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Bahareh Abd Nikfarjam

2017-03-01

Full Text Available Objectives: Neutrophils represent the front line of human defense against infections. Immediately after stimulation, neutrophilic enzymes are activated and produce toxic mediators such as pro-inflammatory cytokines, nitric oxide (NO and myeloperoxidase (MPO. These mediators can be toxic not only to infectious agents but also to host tissues. Because flavonoids exhibit antioxidant and anti-inflammatory effects, they are subjects of interest for pharmacological modulation of inflammation. In the present study, the effects of rutin on stimulus-induced NO and tumor necrosis factor (TNF-α productions and MPO activity in human neutrophils were investigated. Methods: Human peripheral blood neutrophils were isolated using Ficoll-Hypaque density gradient centrifugation coupled with dextran T500 sedimentation. The cell preparations containing > 98% granulocytes were determined by morphological examination through Giemsa staining. Neutrophils were cultured in complete Roswell Park Memorial Institute (RPMI medium, pre-incubated with or without rutin (25 μM for 45 minutes, and stimulated with phorbol 12-myristate 13-acetate (PMA. Then, the TNF-α, NO and MPO productions were analyzed using enzyme-linked immunosorbent assay (ELISA, Griess Reagent, and MPO assay kits, respectively. Also, the viability of human neutrophils was assessed using tetrazolium salt 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT, and neutrophils were treated with various concentrations of rutin (1 - 100 μM, after which MTT was appended and incubated at 37ºC for 4 hour. Results: Rutin at concentrations up to 100 μM did not affect neutrophil viability during the 4-hour incubation period. Rutin significantly decreased the NO and TNF-α productions in human peripheral blood neutrophils compared to PMA-control cells (P < 0.001. Also, MPO activity was significantly reduced by rutin (P < 0.001. Conclusion: In this in vitro study, rutin had an anti-inflammatory effect

Inspiratory and expiratory HRCT findings in Behcet's disease and correlation with pulmonary function tests

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Oezer, Caner [Department of Radiology, Mersin University, Faculty of Medicine, Mersin (Turkey)]. E-mail: cozer@mersin.edu.tr; Duce, Meltem Nass [Department of Radiology, Mersin University, Faculty of Medicine, Mersin (Turkey); Ulubas, Bahar [Department of Respiratory Disease, Mersin University, Faculty of Medicine, Mersin (Turkey); Bicer, Ali [Department of Physical Medicine and Rehabilitation, Mersin University, Faculty of Medicine, Mersin (Turkey); Tuersen, Uemit [Department of Dermatology, Mersin University, Faculty of Medicine, Mersin (Turkey); Apaydin, F. Demir [Department of Radiology, Mersin University, Faculty of Medicine, Mersin (Turkey); Yildiz, Altan [Department of Radiology, Mersin University, Faculty of Medicine, Mersin (Turkey); Camdeviren, Handan [Department of Biostatistics, Mersin University, Faculty of Medicine, Mersin (Turkey)

2005-10-01

Purpose: The purpose of our study was to describe the pulmonary parenchymal changes of Behcet's disease using high-resolution computed tomography and to correlate them with pulmonary function tests. Materials and methods: Thirty-four patients with Behcet's disease (18 men, 16 women), 3 of whom were symptomatic, were included as the study group. Four of 34 patients were smokers. Twenty asymptomatic volunteers (12 men, 8 women), 4 of whom were smokers, constituted the control group. The pulmonary function tests and high-resolution computed tomography were performed for both groups. Results: Inspiratory high-resolution computed tomography findings were abnormal in nine patients (26.5%) of the study group. In eight patients, there were multiple abnormalities, whereas one patient had only one abnormality. Pleural thickening and irregularities, major fissure thickening, emphysematous changes, bronchiectasis, parenchymal bands, and irregular densities, and parenchymal nodules were the encountered abnormalities. Inspiratory high-resolution computed tomography scans were normal in the control group. On expiratory scans, there was statistically significant difference between study group and control group when air trapping, especially grades 3 and 4, was compared (P < 0.01). Pulmonary function tests of both the study and the control groups were in normal ranges, and there was no statistically significant difference between the two groups according to pulmonary function tests (P > 0.05). Discussion and conclusion: High-resolution computed tomography is sensitive in the demonstration of pulmonary changes in patients with Behcet's disease. End-expiratory high-resolution computed tomography examination is very useful and necessary to show the presence of air trapping, thus the presence of small airway disease, even if the patient is asymptomatic or has normal pulmonary function tests.

Neutrophil transmigration mediated by the neutrophil-specific antigen CD177 is influenced by the endothelial S536N dimorphism of platelet endothelial cell adhesion molecule-1.

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Bayat, Behnaz; Werth, Silke; Sachs, Ulrich J H; Newman, Debra K; Newman, Peter J; Santoso, Sentot

2010-04-01

The human neutrophil-specific adhesion molecule CD177 (also known as the NB1 alloantigen) becomes upregulated on the cell surface in a number of inflammatory settings. We recently showed that CD177 functions as a novel heterophilic counterreceptor for the endothelial junctional protein PECAM-1 (CD31), an interaction that is mediated by membrane-proximal PECAM-1 IgD 6, which is known to harbor an S(536)N single nucleotide polymorphism of two major isoforms V(98)N(536)G(643) and L(98)S(536)R(643) and a yet-to-be-determined region on CD177. In vitro transendothelial migration experiments revealed that CD177(+) neutrophils migrated significantly faster through HUVECs expressing the LSR, compared with the VNG, allelic variant of PECAM-1 and that this correlated with the decreased ability of anti-PECAM-1 Ab of ITIM tyrosine phosphorylation in HUVECs expressing the LSR allelic variant relative to the VNG allelic variant. Moreover, engagement of PECAM-1 with rCD177-Fc (to mimic heterophilic CD177 binding) suppressed Ab-induced tyrosine phosphorylation to a greater extent in cells expressing the LSR isoform compared with the VNG isoform, with a corresponding increased higher level of beta-catenin phosphorylation. These data suggest that heterophilic PECAM-1/CD177 interactions affect the phosphorylation state of PECAM-1 and endothelial cell junctional integrity in such a way as to facilitate neutrophil transmigration in a previously unrecognized allele-specific manner.

Out of proportion pulmonary hypertension in obstructive lung diseases.

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Chatterjee, Kshitij; Tarawneh, Ahmad R; Alam, Shoaib

2018-03-01

Pulmonary hypertension is common (25-90%) in chronic obstructive pulmonary diseases (COPDs). Severe pulmonary hypertension, however, is quite rare (1-3%). The term 'out of proportion' pulmonary hypertension is still widely used. New guidelines instead propose to use the term 'Severe pulmonary hypertension' if mean pulmonary arterial pressure at least 35 mmHg or cardiac index (CI) is less than 2.0 l/min/m on right heart catheterization (RHC). Why only a minority of COPD patients develop severe pulmonary hypertension is unclear. When present, severe pulmonary hypertension in COPD is associated with increased dyspnea and decreased survival and often does not closely correlate with degree of obstructive abnormality on pulmonary function testing. COPD patients with severe pulmonary hypertension experience circulatory limitation at maximum exercise, and not ventilatory limitation, which is typical for moderate-to-severe COPD patients with no or moderate pulmonary hypertension. There is no conclusive evidence to support or completely reject the possibility of the use of specific pulmonary arterial hypertension (PAH) therapies in pulmonary hypertension associated with COPD. In mild-to-moderate COPD patients who have severe and progressive symptoms, and have evidence of severe pulmonary hypertension on RHC, specific PAH therapies may be used similar to WHO group-I PAH guidelines.

The contribution of pulmonary nuclear medicine

International Nuclear Information System (INIS)

Kawakami, Kenji

1991-01-01

The contribution of pulmonary nuclear medicine was evaluated in 115 patients with interstitial pulmonary diseases (IPD). Ventilation study (V) with 81m Kr or 133 Xe, distribution of compliance in thoraco-pulmonary system (C) by 81m Kr gas bolus inhalation method, perfusion study (Q) with 99m Tc-MAA, 67 Ga scintigraphy and an assessment of pulmonary epithelial permeability with 99m Tc-DTPA aerosol were performed as nuclear medicine procedures. Pulmonary function test (%DLco, vital capacity, and functional residual capacity) and blood gas analysis were also examined. Abnormalities in V were larger than that in Q, which was high V/Q mismatch finding, in interstitial pneumonia. Correlation between V/Q mismatch and PaO 2 was, therefore, not significant. %DLco was decreased in cases with larger V/Q mismatches. 67 Ga accumulated in the early stage of interstitial pneumonia when CT or chest X-ray did not show any finding. %DLco was decreased in cases with strong accumulation of 67 Ga. 67 Ga might be useful to evaluate activity of the disease. Pulmonary epithelial permeability was assessed by 99m Tc-DTPA inhalation study. This permeability became accelerated in idiopathic interstitial fibrosis and sarcoidosis. Pulmonary epithelial permeability may be useful as an indicator for epithelial cell injury. (author)

Pulmonary disease in patients with human immunodeficiency virus infection

DEFF Research Database (Denmark)

Lundgren, J D; Orholm, Marianne; Lundgren, B

1989-01-01

cause pulmonary disease alone or in combination. Bilateral interstitial infiltrates are the most frequent chest x-ray abnormality and are most frequently caused by infection with Pneumocystis carinii. Cytomegalovirus, Mycobacterium tuberculosis, nonspecific interstitial pneumonitis and pulmonary Kaposi......Pulmonary disease is the most important cause of morbidity and mortality in patients infected with human immunodeficiency virus (HIV). All parts of the hospital system are expected to be involved in the diagnosis and treatment of HIV infected patients in the coming years. Many different processes......'s sarcoma are the most important parts of the differential diagnosis. An aggressive approach to the diagnosis of pulmonary disease in this patient population is indicated in order to provide optimal care and assess new therapies....

Age is the work of art? Impact of neutrophil and organism age on neutrophil extracellular trap formation.

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Ortmann, Weronika; Kolaczkowska, Elzbieta

2018-03-01

Neutrophil extracellular traps or NETs are released by highly activated neutrophils in response to infectious agents, sterile inflammation, autoimmune stimuli and cancer. In the cells, the nuclear envelop disintegrates and decondensation of chromatin occurs that depends on peptidylarginine deiminase 4 (PAD4) and neutrophil elastase (NE). Subsequently, proteins from neutrophil granules (e.g., NE, lactoferrin and myeloperoxidase) and the nucleus (histones) bind to decondensed DNA and the whole structure is ejected from the cell. The DNA decorated with potent antimicrobials and proteases can act to contain dissemination of infection and in sterile inflammation NETs were shown to degrade cytokines and chemokines via serine proteases. On the other hand, overproduction of NETs, or their inadequate removal and prolonged presence in vasculature or tissues, can lead to bystander damage or even initiation of diseases. Considering the pros and cons of NET formation, it is of relevance if the stage of neutrophil maturation (immature, mature and senescent cells) affects the capacity to produce NETs as the cells of different age-related phenotypes dominate in given (pathological) conditions. Moreover, the immune system of neonates and elderly individuals is weaker than in adulthood. Is the same pattern followed when it comes to NETs? The overall importance of individual and neutrophil age on the capacity to release NETs is reviewed in detail and the significance of these facts is discussed.

Neutrophil Interactions with Epithelial Expressed ICAM-1 Enhances Intestinal Mucosal Wound Healing

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Sumagin, R; Brazil, JC; Nava, P; Nishio, H; Alam, A; Luissint, AC; Weber, DA; Neish, AS; Nusrat, A; Parkos, CA

2015-01-01

A characteristic feature of gastrointestinal tract inflammatory disorders, such as inflammatory bowel disease, is polymorphonuclear neutrophil (PMN) transepithelial migration (TEM) and accumulation in the gut lumen. PMN accumulation within the intestinal mucosa contributes to tissue injury. While epithelial infiltration by large numbers of PMNs results in mucosal injury, we found that PMN interactions with luminal epithelial membrane receptors may also play a role in wound healing. Intercellular adhesion molecule-1 (ICAM-1) is a PMN ligand that is upregulated on apical surfaces of intestinal epithelial cells under inflammatory conditions. In our study, increased expression of ICAM-1 resulted in enhanced PMN binding to the apical epithelium, which was associated with reduced PMN apoptosis. Following TEM, PMN adhesion to ICAM-1 resulted in activation of Akt and β-catenin signaling, increased epithelial-cell proliferation, and wound healing. Such responses were ICAM-1 dependent as engagement of epithelial ICAM-1 by antibody-mediated cross-linking yielded similar results. Furthermore, using an in-vivo biopsy-based, colonic-mucosal-injury model, we demonstrated epithelial ICAM-1 plays an important role in activation of epithelial Akt and β-catenin signaling and wound healing. These findings suggest that post-migrated PMNs within the intestinal lumen can regulate epithelial homeostasis, thereby identifying ICAM-1 as a potential therapeutic target for promoting mucosal wound healing. PMID:26732677

Neutrophil interactions with epithelial-expressed ICAM-1 enhances intestinal mucosal wound healing.

Science.gov (United States)

Sumagin, R; Brazil, J C; Nava, P; Nishio, H; Alam, A; Luissint, A C; Weber, D A; Neish, A S; Nusrat, A; Parkos, C A

2016-09-01

A characteristic feature of gastrointestinal tract inflammatory disorders, such as inflammatory bowel disease, is polymorphonuclear neutrophil (PMN) transepithelial migration (TEM) and accumulation in the gut lumen. PMN accumulation within the intestinal mucosa contributes to tissue injury. Although epithelial infiltration by large numbers of PMNs results in mucosal injury, we found that PMN interactions with luminal epithelial membrane receptors may also play a role in wound healing. Intercellular adhesion molecule-1 (ICAM-1) is a PMN ligand that is upregulated on apical surfaces of intestinal epithelial cells under inflammatory conditions. In our study, increased expression of ICAM-1 resulted in enhanced PMN binding to the apical epithelium, which was associated with reduced PMN apoptosis. Following TEM, PMN adhesion to ICAM-1 resulted in activation of Akt and β-catenin signaling, increased epithelial-cell proliferation, and wound healing. Such responses were ICAM-1 dependent as engagement of epithelial ICAM-1 by antibody-mediated cross-linking yielded similar results. Furthermore, using an in-vivo biopsy-based, colonic-mucosal-injury model, we demonstrated epithelial ICAM-1 has an important role in activation of epithelial Akt and β-catenin signaling and wound healing. These findings suggest that post-migrated PMNs within the intestinal lumen can regulate epithelial homeostasis, thereby identifying ICAM-1 as a potential therapeutic target for promoting mucosal wound healing.

[Early diagnosis and therapy in pulmonary hypertension--aspects of a vision].

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Ewert, R; Olschewski, H; Ghofrani, H A; Opitz, C F

2013-07-01

In patients with pulmonary hypertension progressive vascular changes in the lung precede the clinical and hemodynamic manifestations of the disease. Therefore, early diagnosis and timely treatment of the disease are crucial. This has been the topic of an expert meeting in Greifswald, Germany in June 2012. The current definition of pulmonary hypertension requires a mean pulmonary artery pressure ≥ 25 mmHg at rest, a hemodynamic abnormality already reflecting pulmonary vascular changes beyond early disease. There is increasing evidence supporting the concept that a lower pressure threshold at rest or an abnormal pressure response with exercise better characterize early disease. While right heart catheterization at rest remains the diagnostic gold standard other methods for detecting early disease are explored with echocardiography being the most frequently used technique. Targeted therapy has been approved for patients with pulmonary arterial hypertension (PAH, WHO-group I) in functional class II-IV. Preliminary data in functional class I patients suggest therapeutic potential of theses drugs in early disease as well. Current guidelines propose therapeutic goals based on parameters with prognostic importance. However, these recommendations are based on mostly retrospective analyses of pre-treatment data obtained in patients with pulmonary hypertension in functional class II-IV. Therefore, evidence-based therapeutic goals for early interventions in functional class I patients are lacking. © Georg Thieme Verlag KG Stuttgart · New York.

Cryptococcus neoformans modulates extracellular killing by neutrophils

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Asfia eQureshi

2011-09-01

Full Text Available We recently established a key role for host sphingomyelin synthase (SMS in the regulation of the killing activity of neutrophils against Cryptococcus neoformans. In this work, we studied the effect of C. neoformans on the killing activity of neutrophils and whether SMS would still be a player against C. neoformans in immunocompromised mice lacking T and NK cells (Tgε26 mice. To this end, we analyzed whether C. neoformans would have any effect on neutrophil survival and killing in vitro and in vivo. We show that unlike C. albicans, neither the presence nor the capsule size of C. neoformans cells have any effect on neutrophil viability. Interestingly, melanized C. neoformans cells totally abrogated the killing activity of neutrophils. Next, we monitored how exposure of neutrophils to C. neoformans cells would interfere with any further killing activity of the medium and found that pre-incubation with live but not heat-killed fungal cells significantly inhibits further killing activity of the medium. We next studied whether activation of SMS at the site of C. neoformans infection is dependent on T and NK cells. Using matrix-assisted laser desorption-ionization (MALDI tissue imaging in infected lung we found that similarly to previous observations in the isogenic wild type CBA/J mice, SM 16:0 levels are significantly elevated at the site of infection in mice lacking T and NK cells but only at early time points. This study highlights that C. neoformans may negatively regulate the killing activity of neutrophils and that SMS activation in neutrophils appears to be partially independent of T and/or NK cells.

Pulmonary function in children and adolescents with sickle cell disease: have we paid proper attention to this problem?

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Ana Karine Vieira

Full Text Available ABSTRACT Objective: To evaluate pulmonary function and functional capacity in children and adolescents with sickle cell disease. Methods: This was a cross-sectional study involving 70 children and adolescents (8-15 years of age with sickle cell disease who underwent pulmonary function tests (spirometry and functional capacity testing (six-minute walk test. The results of the pulmonary function tests were compared with variables related to the severity of sickle cell disease and history of asthma and of acute chest syndrome. Results: Of the 64 patients who underwent spirometry, 15 (23.4% showed abnormal results: restrictive lung disease, in 8 (12.5%; and obstructive lung disease, in 7 (10.9%. Of the 69 patients who underwent the six-minute walk test, 18 (26.1% showed abnormal results regarding the six-minute walk distance as a percentage of the predicted value for age, and there was a ≥ 3% decrease in SpO2 in 36 patients (52.2%. Abnormal pulmonary function was not significantly associated with any of the other variables studied, except for hypoxemia and restrictive lung disease. Conclusions: In this sample of children and adolescents with sickle cell disease, there was a significant prevalence of abnormal pulmonary function. The high prevalence of respiratory disorders suggests the need for a closer look at the lung function of this population, in childhood and thereafter.

Pituitary and pulmonary abnormalities in an adult patient with Langerhans cell histiocytosis

International Nuclear Information System (INIS)

Perez, Adrian; Castro, Ricardo; Pantuso, Silvina

2003-01-01

Pulmonary histiocytosis is an uncommon interstitial lung disease, which is infrequent in adults and is part of a spectrum of disorders characterized by monoclonal proliferation and infiltration of organs by Langerhans cells. Histiocytosis X affects only the lungs in more than 85% of the cases. We report a case of a 21-years-old male patient with Diabetes Insipidus (DI) and respiratory symptoms due to a spontaneous pneumothorax with favorable clinical evolution. High-resolution CT demonstrated bilateral nodular and cystic pulmonary lesions. MRI revealed a nodular widening of the pituitary stalk. An endoscopic trans bronchial biopsy was negative for Langerhans cells. After thoracoscopy with surgical biopsy of the lung the diagnosis of Langerhans' cell histiocytosis was confirmed. (author)

Contribution of neutrophils to acute lung injury.

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Grommes, Jochen; Soehnlein, Oliver

2011-01-01

Treatment of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), remain unsolved problems of intensive care medicine. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. Lung edema, endothelial and epithelial injury are accompanied by an influx of neutrophils into the interstitium and broncheoalveolar space. Hence, activation and recruitment of neutrophils are regarded to play a key role in progression of ALI/ARDS. Neutrophils are the first cells to be recruited to the site of inflammation and have a potent antimicrobial armour that includes oxidants, proteinases and cationic peptides. Under pathological circumstances, however, unregulated release of these microbicidal compounds into the extracellular space paradoxically can damage host tissues. This review focuses on the mechanisms of neutrophil recruitment into the lung and on the contribution of neutrophils to tissue damage in ALI.

Phenotypic Diversity and Plasticity in Circulating Neutrophil Subpopulations in Cancer

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Jitka Y. Sagiv

2015-02-01

Full Text Available Controversy surrounds neutrophil function in cancer because neutrophils were shown to provide both pro- and antitumor functions. We identified a heterogeneous subset of low-density neutrophils (LDNs that appear transiently in self-resolving inflammation but accumulate continuously with cancer progression. LDNs display impaired neutrophil function and immunosuppressive properties, characteristics that are in stark contrast to those of mature, high-density neutrophils (HDNs. LDNs consist of both immature myeloid-derived suppressor cells (MDSCs and mature cells that are derived from HDNs in a TGF-β-dependent mechanism. Our findings identify three distinct populations of circulating neutrophils and challenge the concept that mature neutrophils have limited plasticity. Furthermore, our findings provide a mechanistic explanation to mitigate the controversy surrounding neutrophil function in cancer.

Ventilation abnormalities in obstructive airways disorder. Detection with pulmonary dynamic densitometry by means of spinal CT versus dynamic Xe-133 SPECT

International Nuclear Information System (INIS)

Suga, Kazuyoshi; Nishigauchi, Kazuya; Kume, Norihiko; Takana, Katsuyuki; Koike, Shinji; Shimizu, Kensaku; Matsunaga, Naofumi

1999-01-01

The usefulness of pulmonary dynamic densitometry (PDD) acquired by spiral computed tomography (CT) to detect ventilation abnormalities in obstructive airway disorders was evaluated in comparison with dynamic xenon-133 (Xe-133) SPECT. Eight-second, continuous spiral CT scan was performed over 2-3 respiratory cycles in six healthy volunteers, 19 patients with airways disorder, and six patients with restrictive lung disease. The data set were reconstructed as 36 one-second temporally overlapping images at 0.2-second intervals, and regional PDD curves were displayed. Regional ventilation was assessed by Xe-133 clearance-time on Xe-133 SPECT. Normal lungs showed smooth, sinusoidal PDD curves with maximal amplitude in lung attenuation change (MALAC) of 54.9+24.5 HU; whereas, obstructive airways disorders with prolonged Xe-133 clearance showed significantly diminished MALAC (31.6+20.1 HU, P<0.0001), accompanied by irregularity, asynchronous phase, and deterioration of normal ventral-to-dorsal gradients in MALAC and lung attenuation. Restrictive diseases without prolonged Xe-133 clearance did not show statistically significant reduction in MALAC. In total 251 lung regions, regional MALAC correlated inversely with Xe-133 clearance-time (r=842). PDD acquired by spiral CT is acceptable for detecting ventilation abnormalities in obstructive airways disorder. (author)

Detection of pulmonary aspiration in children with gastroesophageal reflux

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Orellana, P.; Olea, E.; Pino, C.; Rossel, M.; Ceresa, S.; Gonzalez, P.; Otarola, S.; Astudillo, S.

1985-05-01

The presence of pulmonary aspiration (PA) should be suspected in two groups of patients; those with symptoms of gastroesophageal reflux (GER) and pulmonary disease and patient's with pulmonary symptoms without signs of GER in whom other etiologies of pulmonary disease have been excluded. To determine if PA could be diagnosed in children using radionuclides 114 patients aged 3-12 months drank 500 ..mu..Ci of Tc-99m sulfur colloid mixed with infant formula and an additional 1.5 mCi was administered in the evening. All medicine was suspended 24 hours before. Images of the chest in supine position (ant, post views) were acquired on computer in 32 x 32 (byte mode) during 5 min each view at 2 and 18 hours. No outside pressure was applied. None of the patients with digestive symptomatology alone had positive exam. Of 88 patients with bronchopulmonary symptomatology 35 had abnormal examination 35% with moderate symptom were (Abn) and 55% with severe disease were abnormal. The radionuclide method appears to be the ideal study in patients where PA is suspected. The positivity of the method depends on the group of patients selected. The sensitivity is highest in patients with marked symptomatology.

CXC-chemokine regulation and neutrophil trafficking in hepatic ischemia-reperfusion injury in P-selectin/ICAM-1 deficient mice

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Crockett Elahé T

2007-05-01

Full Text Available Abstract Background Neutrophil adhesion and migration are critical in hepatic ischemia and reperfusion injury (I/R. P-selectin and the intercellular adhesion molecule (ICAM-1 can mediate neutrophil-endothelial cell interactions, neutrophil migration, and the interactions of neutrophils with hepatocytes in the liver. Despite very strong preclinical data, recent clinical trials failed to show a protective effect of anti-adhesion therapy in reperfusion injury, indicating that the length of injury might be a critical factor in neutrophil infiltration. Therefore, the aim of this study was to assess the role of P-selectin and ICAM-1 in neutrophil infiltration and liver injury during early and late phases of liver I/R. Methods Adult male wild-type and P-selectin/ICAM-1-deficient (P/I null mice underwent 90 minutes of partial liver ischemia followed by various periods of reperfusion (6, 15 h, and a survival study. Liver injury was assessed by plasma level of alanine aminotransferase (ALT and histopathology. The plasma cytokines, TNF-α, IL-6, MIP-2 and KC, were measured by ELISA. Results Reperfusion caused significant hepatocellular injury in both wild-type and P/I null mice as was determined by plasma ALT levels and liver histopathology. The injury was associated with a marked neutrophil infiltration into the ischemic livers of both wild-type and P/I null mice. Although the levels of ALT and neutrophil infiltration were slightly lower in the P/I null mice compared with the wild-type mice the differences were not statistically significant. The plasma cytokine data of TNF-α and IL-6 followed a similar pattern to ALT data, and no significant difference was found between the wild-type and P/I null groups. In contrast, a significant difference in KC and MIP-2 chemokine levels was observed between the wild-type and P/I null mice. Additionally, the survival study showed a trend towards increased survival in the P/I null group. Conclusion While ICAM-1 and P

Radiological profile of pulmonary tuberculosis in HIV: concerning 171 observations in Kinshasa

International Nuclear Information System (INIS)

Djamba, O.N.; Mukaya, J.; Kayembe, J.M.

2011-01-01

This prospective descriptive study was conducted in Depistage center of the Tuberculosis treatment of Kabinda during a period of three months, had as objectives to study the radiological profile of pulmonary tuberculosis in HIV and HIV- patients, then to compare the frequency of different radiological abnormalities between the two groups to determine some characteristics of co-infection HIV/TP+. Among 171 patients with contagious pulmonary tuberculosis, 50 patients had positive serology for HIV, a prevalence of 29,2%. The intrathoracic lymph nodes, localized lesions only in the lower field were more observed in HIV, as well as pleurisy and the absence of radiological abnormality. The only one case of miliary was HIV positive. By contrast, excavations and localized lesions in the upper field were predominant in HIV-. Atypical radiological manifestations of pulmonary tuberculosis were more common in patients with HIV infection.

Multifactor dimensionality reduction reveals a three-locus epistatic interaction associated with susceptibility to pulmonary tuberculosis

DEFF Research Database (Denmark)

Collins, Ryan L; Hu, Ting; Wejse, Christian

2013-01-01

for this problem. The goal of the present study was to apply MDR to mining high-order epistatic interactions in a population-based genetic study of tuberculosis (TB). Results The study used a previously published data set consisting of 19 candidate single-nucleotide polymorphisms (SNPs) in 321 pulmonary TB cases...

Hidden truth of circulating neutrophils (polymorphonuclear neutrophil function in periodontally healthy smoker subjects

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Chitra Agarwal

2016-01-01

Full Text Available Context: Tobacco smoking is considered to be a major risk factor associated with periodontal disease. Smoking exerts a major effect on the protective elements of the immune response, resulting in an increase in the extent and severity of periodontal destruction. Aims: The aim of the present study was to assess viability and phagocytic function of neutrophils in circulating blood of the smokers and nonsmokers who are periodontally healthy. Settings and Design: Two hundred subjects in the mean range of 20–30 years of age were included in the study population. It was a retrospective study carried out for 6 months. Materials and Methods: Two hundred subjects were divided into four groups: 50 nonsmokers, 50 light smokers (15 cigarettes/day. Full mouth plaque index, sulcus bleeding index, and probing depths were measured. Percentage viability of circulating neutrophils and average number of phagocytosed Candida albicans were recorded. Statistical Analysis Used: Means and standard deviations were calculated from data obtained within the groups. Comparison between the smokers and nonsmokers was performed by Kruskal–Wallis ANOVA analysis. Comparison between smoker groups was performed using Mann–Whitney–Wilcoxon test. Results: Percentage viability of neutrophils was significantly less in heavy smokers (66.9 ± 4.0, moderate (76.6 ± 4.2, light smokers (83.1 ± 2.5 as compared to nonsmokers (92.3 ± 2.6 (P < 0.01. The ability of neutrophils to phagocytose, i.e., mean particle number was significantly less in light smokers (3.5 ± 0.5, moderate smokers (2.3 ± 0.5, and heavy smokers (1.4 ± 0.5 compared to nonsmokers (4.9 ± 0.7 (P < 0.01 with evidence of dose-response effect. Conclusions: Smoking significantly affects neutrophils viability and phagocytic function in periodontally healthy population.

Biomaterial-induced alterations of neutrophil superoxide production.

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Kaplan, S S; Basford, R E; Mora, E; Jeong, M H; Simmons, R L

1992-08-01

Because periprosthetic infection remains a vexing problem for patients receiving implanted devices, we evaluated the effect of several materials on neutrophil free radical production. Human peripheral blood neutrophils were incubated with several sterile, lipopolysaccharide (LPS)-free biomaterials used in surgically implantable prosthetic devices: polyurethane, woven dacron, and velcro. Free radical formation as the superoxide (O2-) anion was evaluated by cytochrome c reduction in neutrophils that were exposed to the materials and then removed and in neutrophils allowed to remain in association with the materials. Neutrophils exposed to polyurethane or woven dacron for 30 or 60 min and then removed consistently exhibited an enhanced release of O2- after simulation via receptor engagement with formyl methionyl-leucyl-phenylalanine. Enhanced reactivity to stimulation via protein kinase C with phorbol myristate acetate, however, was not consistently observed. The cells evaluated for O2- release during continuous association with the biomaterials showed enhanced metabolic activity during short periods of association (especially with polyurethane and woven dacron). Although O2- release by neutrophils in association with these materials decreased with longer periods of incubation, it was not obliterated. These studies, therefore, show that several commonly used biomaterials activate neutrophils soon after exposure and that this activated state diminishes with prolonged exposure but nevertheless remains measurable. The diminishing level of activity with prolonged exposure, however, suggests that ultimately a depletion of reactivity may occur and may result in increased susceptibility to periprosthetic infection.

Spontaneous regression of pulmonary bullae

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Satoh, H.; Ishikawa, H.; Ohtsuka, M.; Sekizawa, K.

2002-01-01

The natural history of pulmonary bullae is often characterized by gradual, progressive enlargement. Spontaneous regression of bullae is, however, very rare. We report a case in which complete resolution of pulmonary bullae in the left upper lung occurred spontaneously. The management of pulmonary bullae is occasionally made difficult because of gradual progressive enlargement associated with abnormal pulmonary function. Some patients have multiple bulla in both lungs and/or have a history of pulmonary emphysema. Others have a giant bulla without emphysematous change in the lungs. Our present case had treated lung cancer with no evidence of local recurrence. He had no emphysematous change in lung function test and had no complaints, although the high resolution CT scan shows evidence of underlying minimal changes of emphysema. Ortin and Gurney presented three cases of spontaneous reduction in size of bulla. Interestingly, one of them had a marked decrease in the size of a bulla in association with thickening of the wall of the bulla, which was observed in our patient. This case we describe is of interest, not only because of the rarity with which regression of pulmonary bulla has been reported in the literature, but also because of the spontaneous improvements in the radiological picture in the absence of overt infection or tumor. Copyright (2002) Blackwell Science Pty Ltd

Superoxide anion production by human neutrophils activated by Trichomonas vaginalis.

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Song, Hyun-Ouk; Ryu, Jae-Sook

2013-08-01

Neutrophils are the predominant inflammatory cells found in vaginal discharges of patients infected with Trichomonas vaginalis. In this study, we examined superoxide anion (O2 (.-)) production by neutrophils activated by T. vaginalis. Human neutrophils produced superoxide anions when stimulated with either a lysate of T. vaginalis, its membrane component (MC), or excretory-secretory product (ESP). To assess the role of trichomonad protease in production of superoxide anions by neutrophils, T. vaginalis lysate, ESP, and MC were each pretreated with a protease inhibitor cocktail before incubation with neutrophils. Superoxide anion production was significantly decreased by this treatment. Trichomonad growth was inhibited by preincubation with supernatants of neutrophils incubated for 3 hr with T. vaginalis lysate. Furthermore, myeloperoxidase (MPO) production by neutrophils was stimulated by live trichomonads. These results indicate that the production of superoxide anions and MPO by neutrophils stimulated with T. vaginalis may be a part of defense mechanisms of neutrophils in trichomoniasis.

The relationship between tumor markers and pulmonary embolism in lung cancer.

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Xiong, Wei; Zhao, Yunfeng; Xu, Mei; Guo, Jian; Pudasaini, Bigyan; Wu, Xueling; Liu, Jinming

2017-06-20

Tumor markers (TMs) and D-Dimer are both hallmarks of severity and prognosis of lung cancer. Tumor markers could be related to pulmonary embolism (PE) in lung cancer. The number of abnormal tumor markers of lung cancer patients with pulmonary embolism (3.9 ± 1.1vs1.6 ± 0.6,P 0.005) was more than that in patients without pulmonary embolism. TMs panel (P trend tumor markers, TMs panel (OR5.98, P Tumor markers were compared between lung cancer patients complicated with pulmonary embolism and those without pulmonary embolism Then the correlation between each tumor marker as well as panel of combined TMs and D-Dimer as well as pulmonary embolism were analyzed for patients with pulmonary embolism. There is a relationship between tumor markers and pulmonary embolism in patients with lung cancer. The panel of combined tumor markers is a valuable diagnostic marker for pulmonary embolism in lung cancer.

Computer-aided pulmonary image analysis in small animal models

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Xu, Ziyue; Mansoor, Awais; Mollura, Daniel J. [Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, National Institutes of Health (NIH), Bethesda, Maryland 32892 (United States); Bagci, Ulas, E-mail: ulasbagci@gmail.com [Center for Research in Computer Vision (CRCV), University of Central Florida (UCF), Orlando, Florida 32816 (United States); Kramer-Marek, Gabriela [The Institute of Cancer Research, London SW7 3RP (United Kingdom); Luna, Brian [Microfluidic Laboratory Automation, University of California-Irvine, Irvine, California 92697-2715 (United States); Kubler, Andre [Department of Medicine, Imperial College London, London SW7 2AZ (United Kingdom); Dey, Bappaditya; Jain, Sanjay [Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231 (United States); Foster, Brent [Department of Biomedical Engineering, University of California-Davis, Davis, California 95817 (United States); Papadakis, Georgios Z. [Radiology and Imaging Sciences, National Institutes of Health (NIH), Bethesda, Maryland 32892 (United States); Camp, Jeremy V. [Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky 40202 (United States); Jonsson, Colleen B. [National Institute for Mathematical and Biological Synthesis, University of Tennessee, Knoxville, Tennessee 37996 (United States); Bishai, William R. [Howard Hughes Medical Institute, Chevy Chase, Maryland 20815 and Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231 (United States); Udupa, Jayaram K. [Medical Image Processing Group, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States)

2015-07-15

Purpose: To develop an automated pulmonary image analysis framework for infectious lung diseases in small animal models. Methods: The authors describe a novel pathological lung and airway segmentation method for small animals. The proposed framework includes identification of abnormal imaging patterns pertaining to infectious lung diseases. First, the authors’ system estimates an expected lung volume by utilizing a regression function between total lung capacity and approximated rib cage volume. A significant difference between the expected lung volume and the initial lung segmentation indicates the presence of severe pathology, and invokes a machine learning based abnormal imaging pattern detection system next. The final stage of the proposed framework is the automatic extraction of airway tree for which new affinity relationships within the fuzzy connectedness image segmentation framework are proposed by combining Hessian and gray-scale morphological reconstruction filters. Results: 133 CT scans were collected from four different studies encompassing a wide spectrum of pulmonary abnormalities pertaining to two commonly used small animal models (ferret and rabbit). Sensitivity and specificity were greater than 90% for pathological lung segmentation (average dice similarity coefficient > 0.9). While qualitative visual assessments of airway tree extraction were performed by the participating expert radiologists, for quantitative evaluation the authors validated the proposed airway extraction method by using publicly available EXACT’09 data set. Conclusions: The authors developed a comprehensive computer-aided pulmonary image analysis framework for preclinical research applications. The proposed framework consists of automatic pathological lung segmentation and accurate airway tree extraction. The framework has high sensitivity and specificity; therefore, it can contribute advances in preclinical research in pulmonary diseases.

Neutrophil extracellular trap formation in supragingival biofilms.

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Hirschfeld, Josefine; Dommisch, Henrik; Skora, Philipp; Horvath, Gabor; Latz, Eicke; Hoerauf, Achim; Waller, Tobias; Kawai, Toshihisa; Jepsen, Søren; Deschner, James; Bekeredjian-Ding, Isabelle

2015-01-01

Oral biofilms are the causative agents of the highly prevalent oral diseases periodontitis and caries. Additionally, the host immune response is thought to play a critical role in disease onset. Neutrophils are known to be a key host response factor to bacterial challenge on host surfaces. Release of neutrophil extracellular traps (NETs) as a novel antimicrobial defense strategy has gained increasing attention in the past years. Here, we investigated the influx of neutrophils into the dental plaque and the ability of oral bacteria to trigger intra-biofilm release of NETs and intracellular proteins. Supragingival biofilms and whole saliva were sampled from systemically healthy subjects participating in an experimental gingivitis study. Biofilms were analysed by immunofluorescence followed by confocal and fluorescence microscopy. Moreover, concentrations of cytokines and immune-associated proteins in biofilm suspensions and saliva were assessed by ELISA. Neutrophils obtained from blood were stimulated with twelve bacterial species isolated from cultured biofilms or with lipopolysaccharide to monitor NET formation. Neutrophils, NETs, neutrophil-associated proteins (myeloperoxidase, elastase-2, cathepsin G, cathelicidin LL-37), interleukin-8, interleukin-1β and tumor necrosis factor were detected within plaque samples and saliva. All tested bacterial species as well as the polymicrobial samples isolated from the plaque of each donor induced release of NETs and interleukin-8. The degree of NET formation varied among different subjects and did not correlate with plaque scores or clinical signs of local inflammation. Our findings indicate that neutrophils are attracted towards dental biofilms, in which they become incorporated and where they are stimulated by microbes to release NETs and immunostimulatory proteins. Thus, neutrophils and NETs may be involved in host biofilm control, although their specific role needs to be further elucidated. Moreover, inter

Antagonism of CD11b with neutrophil inhibitory factor (NIF) inhibits vascular lesions in diabetic retinopathy.

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Veenstra, Alexander A; Tang, Jie; Kern, Timothy S

2013-01-01

Leukocytes and proteins that govern leukocyte adhesion to endothelial cells play a causal role in retinal abnormalities characteristic of the early stages of diabetic retinopathy, including diabetes-induced degeneration of retinal capillaries. Leukocyte integrin αmβ2 (CD11b/CD18, MAC1), a protein mediating adhesion, has been shown to mediate damage to endothelial cells by activated leukocytes in vitro. We hypothesized that Neutrophil Inhibitory Factor (NIF), a selective antagonist of integrin αmβ2, would inhibit the diabetes-induced degeneration of retinal capillaries by inhibiting the excessive interaction between leukocytes and retinal endothelial cells in diabetes. Wild type animals and transgenic animals expressing NIF were made diabetic with streptozotocin and assessed for diabetes-induced retinal vascular abnormalities and leukocyte activation. To assess if the leukocyte blocking therapy compromised the immune system, animals were challenged with bacteria. Retinal superoxide production, leukostasis and leukocyte superoxide production were increased in wild type mice diabetic for 10 weeks, as was the ability of leukocytes isolated from diabetic animals to kill retinal endothelial cells in vitro. Retinal capillary degeneration was significantly increased in wild type mice diabetic 40 weeks. In contrast, mice expressing NIF did not develop any of these abnormalities, with the exception that non-diabetic and diabetic mice expressing NIF generated greater amounts of superoxide than did similar mice not expressing NIF. Importantly, NIF did not significantly impair the ability of mice to clear an opportunistic bacterial challenge, suggesting that NIF did not compromise immune surveillance. We conclude that antagonism of CD11b (integrin αmβ2) by NIF is sufficient to inhibit early stages of diabetic retinopathy, while not compromising the basic immune response.

Aircraft Abnormal Conditions Detection, Identification, and Evaluation Using Innate and Adaptive Immune Systems Interaction

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Al Azzawi, Dia

Abnormal flight conditions play a major role in aircraft accidents frequently causing loss of control. To ensure aircraft operation safety in all situations, intelligent system monitoring and adaptation must rely on accurately detecting the presence of abnormal conditions as soon as they take place, identifying their root cause(s), estimating their nature and severity, and predicting their impact on the flight envelope. Due to the complexity and multidimensionality of the aircraft system under abnormal conditions, these requirements are extremely difficult to satisfy using existing analytical and/or statistical approaches. Moreover, current methodologies have addressed only isolated classes of abnormal conditions and a reduced number of aircraft dynamic parameters within a limited region of the flight envelope. This research effort aims at developing an integrated and comprehensive framework for the aircraft abnormal conditions detection, identification, and evaluation based on the artificial immune systems paradigm, which has the capability to address the complexity and multidimensionality issues related to aircraft systems. Within the proposed framework, a novel algorithm was developed for the abnormal conditions detection problem and extended to the abnormal conditions identification and evaluation. The algorithm and its extensions were inspired from the functionality of the biological dendritic cells (an important part of the innate immune system) and their interaction with the different components of the adaptive immune system. Immunity-based methodologies for re-assessing the flight envelope at post-failure and predicting the impact of the abnormal conditions on the performance and handling qualities are also proposed and investigated in this study. The generality of the approach makes it applicable to any system. Data for artificial immune system development were collected from flight tests of a supersonic research aircraft within a motion-based flight

Gβ1 is required for neutrophil migration in zebrafish.

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Ke, Wenfan; Ye, Ding; Mersch, Kacey; Xu, Hui; Chen, Songhai; Lin, Fang

2017-08-01

Signaling mediated by G protein-coupled receptors (GPCRs) is essential for the migration of cells toward chemoattractants. The recruitment of neutrophils to injured tissues in zebrafish larvae is a useful model for studying neutrophil migration and trafficking in vivo. Indeed, the study of this process led to the discovery that PI3Kγ is required for the polarity and motility of neutrophils, features that are necessary for the directed migration of these cells to wounds. However, the mechanism by which PI3Kγ is activated remains to be determined. Here we show that signaling by specifically the heterotrimeric G protein subunit Gβ1 is critical for neutrophil migration in response to wounding. In embryos treated with small-molecule inhibitors of Gβγ signaling, neutrophils failed to migrate to wound sites. Although both the Gβ1 and Gβ4 isoforms are expressed in migrating neutrophils, only deficiency for the former (morpholino-based knockdown) interfered with the directed migration of neutrophils towards wounds. The Gβ1 deficiency also impaired the ability of cells to change cell shape and reduced their general motility, defects that are similar to those in neutrophils deficient for PI3Kγ. Transplantation assays showed that the requirement for Gβ1 in neutrophil migration is cell autonomous. Finally, live imaging revealed that Gβ1 is required for polarized activation of PI3K, and for the actin dynamics that enable neutrophil migration. Collectively, our data indicate that Gβ1 signaling controls proper neutrophil migration by activating PI3K and modulating actin dynamics. Moreover, they illustrate a role for a specific Gβ isoform in chemotaxis in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

Radiologic findings of pulmonary endometriosis

International Nuclear Information System (INIS)

Kim, Seon Bok; Lee, Eil Seong; Jung, Hae Kyoung; Kim, Uk Jung; Yi, Jeong Geun; Kang, Ik Won; Kook, Shin Ho; Park, Jae Sung; Ryu, Dae Sik

1998-01-01

To describe the radiologic findings of pulmonary endometriosis. This study involved five patients with catamenial hemoptysis diagnosed as pulmonary endometriosis. All cases were diagnosed on the basis of bronchoscopic abnormalities. In one patient, endometrial glandular cells were seen on transthoracic fine needle aspiration biopsy. In three, hemoptysis ceased after Danazol treatment. The pattern, location and number of parenchymal abnormalities and the presence or absence of pleural lesion were analyzed retrospectively on plain chest radiographs (n=3D5) and CT scans(n=3D5). Follow-up study for each menstrual period was performed in two cases and changes from the initial lesion were assessed. Plain chest radiographic findings showed focal ground-glass opacity in three cases;two were in the right lung and one in the left. CT findings included ground-glass attenuation (n=3D3) and a mixed pattern of ground-glass attenuations and consolidations(n=3D2). Sites were single in four cases, and in one case, there were two; thus there were in all six lesions. Five of these were located in the right lung and subpleural region, continving to the pleura. Pleural lesion was not detected on either chest radiographs or CT scans. Follow-up CT scans (n=3D2) showed a similar lesion at the same site. In patient with repeated catamenial hemoptysis, CT may be helpful for the diagnosis of pulmonary endometriosis by exclusion of other diseases.=20

Radiologic findings of pulmonary endometriosis

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Kim, Seon Bok; Lee, Eil Seong; Jung, Hae Kyoung; Kim, Uk Jung; Yi, Jeong Geun; Kang, Ik Won [Hallym Univ. College of Medicine, Seoul (Korea, Republic of); Kook, Shin Ho [Kangbuk Samsung Hospital, Seoul (Korea, Republic of); Park, Jae Sung [Soonchunhyang Univ. College of Medicine, Seoul (Korea, Republic of); Ryu, Dae Sik [Kangnung Hospital, Kangnung (Korea, Republic of)

1998-12-01

To describe the radiologic findings of pulmonary endometriosis. This study involved five patients with catamenial hemoptysis diagnosed as pulmonary endometriosis. All cases were diagnosed on the basis of bronchoscopic abnormalities. In one patient, endometrial glandular cells were seen on transthoracic fine needle aspiration biopsy. In three, hemoptysis ceased after Danazol treatment. The pattern, location and number of parenchymal abnormalities and the presence or absence of pleural lesion were analyzed retrospectively on plain chest radiographs (n=3D5) and CT scans(n=3D5). Follow-up study for each menstrual period was performed in two cases and changes from the initial lesion were assessed. Plain chest radiographic findings showed focal ground-glass opacity in three cases;two were in the right lung and one in the left. CT findings included ground-glass attenuation (n=3D3) and a mixed pattern of ground-glass attenuations and consolidations(n=3D2). Sites were single in four cases, and in one case, there were two; thus there were in all six lesions. Five of these were located in the right lung and subpleural region, continving to the pleura. Pleural lesion was not detected on either chest radiographs or CT scans. Follow-up CT scans (n=3D2) showed a similar lesion at the same site. In patient with repeated catamenial hemoptysis, CT may be helpful for the diagnosis of pulmonary endometriosis by exclusion of other diseases.=20.

The Evaluation of Interstitial Abnormalities in Group B of the 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Classification of Chronic Obstructive Pulmonary Disease (COPD).

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Ohgiya, Masahiro; Matsui, Hirotoshi; Tamura, Atsuhisa; Kato, Takafumi; Akagawa, Shinobu; Ohta, Ken

2017-10-15

Objective In 2011, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification categorized chronic obstructive pulmonary disease (COPD) patients into 4 groups. A report demonstrated that the mortality in Group B was higher than that in Group C. Ischemic heart disease and cancer were suggested to be the cause. The aim of the present study was to test the hypothesis that interstitial lung abnormalities (ILAs) are more prevalent in Group B than Group C and that they may be responsible for the higher mortality in Group B. Methods Patients were selected based on their pulmonary function test results. The inclusion criterion was a forced expiratory volume in 1 second (FEV 1 )/forced vital capacity (FVC) of COPD patients, ILAs were detected in 10.3% of the patients in Group A, 22.5% of the patients in Group B, 5.6% of the patients in Group C, and 23.1% of the patients in Group D. In Group B, the frequency of ILAs was significantly higher and the area affected by the ILAs was significantly greater in comparison to Group C. Among the patterns of interstitial abnormalities, the area of honeycombing in Group B was significantly greater than that in Group C. Furthermore, among the patients in Group B, the LAA in the ILA-positive patients was significantly greater than that in the ILA-negative patients. Conclusion In Group B, the area occupied by ILAs-especially honeycombing-was greater than that in Group C. This contributed to the preserved %FEV 1 and possibly to the poorer prognosis of the patients in Group B.

Nicotinamide exacerbates hypoxemia in ventilator-induced lung injury independent of neutrophil infiltration.

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Heather D Jones

Full Text Available Ventilator-induced lung injury is a form of acute lung injury that develops in critically ill patients on mechanical ventilation and has a high degree of mortality. Nicotinamide phosphoribosyltransferase is an enzyme that is highly upregulated in ventilator-induced lung injury and exacerbates the injury when given exogenously. Nicotinamide (vitamin B3 directly inhibits downstream pathways activated by Nicotinamide phosphoribosyltransferase and is protective in other models of acute lung injury.We administered nicotinamide i.p. to mice undergoing mechanical ventilation with high tidal volumes to study the effects of nicotinamide on ventilator-induced lung injury. Measures of injury included oxygen saturations and bronchoalveolar lavage neutrophil counts, protein, and cytokine levels. We also measured expression of nicotinamide phosophoribosyltransferase, and its downstream effectors Sirt1 and Cebpa, Cebpb, Cebpe. We assessed the effect of nicotinamide on the production of nitric oxide during ventilator-induced lung injury. We also studied the effects of ventilator-induced lung injury in mice deficient in C/EBPε.Nicotinamide treatment significantly inhibited neutrophil infiltration into the lungs during ventilator-induced lung injury, but did not affect protein leakage or cytokine production. Surprisingly, mice treated with nicotinamide developed significantly worse hypoxemia during mechanical ventilation. This effect was not linked to increases in nitric oxide production or alterations in expression of Nicotinamide phosphoribosyl transferase, Sirt1, or Cebpa and Cebpb. Cebpe mRNA levels were decreased with either nicotinamide treatment or mechanical ventilation, but mice lacking C/EBPε developed the same degree of hypoxemia and ventilator-induced lung injury as wild-type mice.Nicotinamide treatment during VILI inhibits neutrophil infiltration of the lungs consistent with a strong anti-inflammatory effect, but paradoxically also leads to the

Comparison of acute ozone-induced nasal and pulmonary inflammatory responses

International Nuclear Information System (INIS)

Hotchkiss, J.A.; Harkema, J.R.; Sun, J.D.; Henderson, R.F.

1988-01-01

The present study was designed to compare the effects of acute ozone exposure in the nose and lungs of rats. Rats were exposed to 0.0, 0.12, 0.80, or 1.5 ppm O 3 for 6 h and were sacrificed immediately, 3,18, 42, or 66 h after exposure. Cellular inflammatory responses were assessed by quantitating polymorphonuclear neutrophils (PMN) recovered by nasal lavage (NL) and bronchoalveolar lavage (BAL) and morphometric quantitation of PMN within the nasal mucosa and pulmonary centriacinar region. Rats exposed to 0.12 ppm O 3 had a transient nasal PMN response 18 h after exposure but no increase in pulmonary PMN. Rats exposed to 0.8 ppm O 3 had a marked increase in nasal PMN immediately after exposure but the number of PMN within the nasal cavity decreased as the number of pulmonary PMN increased with time after exposure. Rats exposed to 1.5 ppm O 3 had an increase in pulmonary PMN beginning 3 h post-exposure, but no increase in nasal PMN at any time. Our results suggest that at high O 3 concentrations, the acute nasal inflammatory response is attenuated by a simultaneous, competing, inflammatory response within the lung. (author)

Comparison of acute ozone-induced nasal and pulmonary inflammatory responses

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Hotchkiss, J A; Harkema, J R; Sun, J D; Henderson, R F

1988-12-01

The present study was designed to compare the effects of acute ozone exposure in the nose and lungs of rats. Rats were exposed to 0.0, 0.12, 0.80, or 1.5 ppm O{sub 3} for 6 h and were sacrificed immediately, 3,18, 42, or 66 h after exposure. Cellular inflammatory responses were assessed by quantitating polymorphonuclear neutrophils (PMN) recovered by nasal lavage (NL) and bronchoalveolar lavage (BAL) and morphometric quantitation of PMN within the nasal mucosa and pulmonary centriacinar region. Rats exposed to 0.12 ppm O{sub 3} had a transient nasal PMN response 18 h after exposure but no increase in pulmonary PMN. Rats exposed to 0.8 ppm O{sub 3} had a marked increase in nasal PMN immediately after exposure but the number of PMN within the nasal cavity decreased as the number of pulmonary PMN increased with time after exposure. Rats exposed to 1.5 ppm O{sub 3} had an increase in pulmonary PMN beginning 3 h post-exposure, but no increase in nasal PMN at any time. Our results suggest that at high O{sub 3} concentrations, the acute nasal inflammatory response is attenuated by a simultaneous, competing, inflammatory response within the lung. (author)

Prevention of vascular inflammation by nanoparticle targeting of adherent neutrophils

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Wang, Zhenjia; Li, Jing; Cho, Jaehyung; Malik, Asrar B.

2014-03-01

Inflammatory diseases such as acute lung injury and ischaemic tissue injury are caused by the adhesion of a type of white blood cell--polymorphonuclear neutrophils--to the lining of the circulatory system or vascular endothelium and unchecked neutrophil transmigration. Nanoparticle-mediated targeting of activated neutrophils on vascular endothelial cells at the site of injury may be a useful means of directly inactivating neutrophil transmigration and hence mitigating vascular inflammation. Here, we report a method employing drug-loaded albumin nanoparticles, which efficiently deliver drugs into neutrophils adherent to the surface of the inflamed endothelium. Using intravital microscopy of tumour necrosis factor-α-challenged mouse cremaster post-capillary venules, we demonstrate that fluorescently tagged albumin nanoparticles are largely internalized by neutrophils adherent to the activated endothelium via cell surface Fcɣ receptors. Administration of albumin nanoparticles loaded with the spleen tyrosine kinase inhibitor, piceatannol, which blocks `outside-in' β2 integrin signalling in leukocytes, detached the adherent neutrophils and elicited their release into the circulation. Thus, internalization of drug-loaded albumin nanoparticles into neutrophils inactivates the pro-inflammatory function of activated neutrophils, thereby offering a promising approach for treating inflammatory diseases resulting from inappropriate neutrophil sequestration and activation.

Pulmonary capillary wedge pressure, as inferred from lung areas in gated blood-pool scintigrams: concise communication

International Nuclear Information System (INIS)

Urbina, A.; Okada, R.D.; Palacios, I.; Osbakken, M.; Strauss, H.W.

1981-01-01

To determine whether the apex-to-base distribution of pulmonary blood volume, as obtained from gated cardiac blood-pool scans, could be used as a noninvasive method to estimate mean pulmonary capillary wedge pressure (PCWP), gated blood-pool scans were analyzed in 77 patients who also had PCWP measurements at cardiac catheterization. Ten of these patients had gated cardiac blood-pool scans and PCWP measurements both at rest and during exercise. The apex-to-base distribution of pulmonary blood volume was determined from the end-systolic frame of the left anterior oblique view by placing equal-sized regions of interest over the apex and base of the right lung. The ratio of apex counts over base counts (A/B ratio) was considered abnormal if greater than unity. The mean A/B ratio was 1.15 +/- 0.27 (1 s.d.) for the 32 studies associated with an abnormal mean PCWP (greater than 12 mm Hg). The mean A/B ratio was 0.85 +/- 0.23 for the 55 studies associated with a normal mean PCWP (p less than 0.01 comparing normal group with abnormal). The sensitivity of the A/B ratio for a mean PCWP greater than 12 mm Hg was 81%R (26/32). The specificity of the A/B ratio for a mean PCWP greater than or equal to 12 mm Hg was 89% (49/55). Thus, noninvasive determination of the pulmonary apex-to-base ratio from gated cardiac blood-pool scans appears to differentiate subjects with normal and abnormal mean pulmonary capillary wedge pressures

Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice

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Suidan, Georgette L.; Demers, Melanie; Herr, Nadine; Carbo, Carla; Brill, Alexander; Cifuni, Stephen M.; Mauler, Maximilian; Cicko, Sanja; Bader, Michael; Idzko, Marco; Bode, Christoph

2013-01-01

The majority of peripheral serotonin is stored in platelets, which secrete it on activation. Serotonin releases Weibel-Palade bodies (WPBs) and we asked whether absence of platelet serotonin affects neutrophil recruitment in inflammatory responses. Tryptophan hydroxylase (Tph)1–deficient mice, lacking non-neuronal serotonin, showed mild leukocytosis compared with wild-type (WT), primarily driven by an elevated neutrophil count. Despite this, 50% fewer leukocytes rolled on unstimulated mesenteric venous endothelium of Tph1−/− mice. The velocity of rolling leukocytes was higher in Tph1−/− mice, indicating fewer selectin-mediated interactions with endothelium. Stimulation of endothelium with histamine, a secretagogue of WPBs, or injection of serotonin normalized the rolling in Tph1−/− mice. Diminished rolling in Tph1−/− mice resulted in reduced firm adhesion of leukocytes after lipopolysaccharide treatment. Blocking platelet serotonin uptake with fluoxetine in WT mice reduced serum serotonin by > 80% and similarly reduced leukocyte rolling and adhesion. Four hours after inflammatory stimulation, neutrophil extravasation into lung, peritoneum, and skin wounds was reduced in Tph1−/− mice, whereas in vitro neutrophil chemotaxis was independent of serotonin. Survival of lipopolysaccharide-induced endotoxic shock was improved in Tph1−/− mice. In conclusion, platelet serotonin promotes the recruitment of neutrophils in acute inflammation, supporting an important role for platelet serotonin in innate immunity. PMID:23243271

Effect of occupational silica exposure on pulmonary function.

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Hertzberg, Vicki Stover; Rosenman, Kenneth D; Reilly, Mary Jo; Rice, Carol H

2002-08-01

To assess the effect of occupational silica exposure on pulmonary function. Epidemiologic evaluation based on employee interview, plant walk-through, and information abstracted from company medical records, employment records, and industrial hygiene measurements. Drawn from 1,072 current and former hourly wage workers employed before January 1, 1986. Thirty-six individuals with radiographic evidence of parenchymal changes consistent with asbestosis or silicosis were excluded. In addition, eight individuals whose race was listed as other than white or black were excluded. Analysis of spirometry data (FVC, FEV1, FEV1/FVC) only using the test results that met American Thoracic Society criteria for reproducibility and acceptability shows decreasing percent-predicted FVC and FEV1 and decreasing FEV1/FVC in relationship to increasing silica exposure among smokers. Logistic regression analyses of abnormal FVC and abnormal FEV1 values (where abnormal is defined as OSHA)-allowable level of 0.1 mg/m3. Longitudinal analyses of FVC and FEV1 measurements show a 1.6 mL/yr and 1.1 mL/yr, respectively, decline per milligram/cubic meter mean silica exposure (p = 0.011 and p = 0.001, respectively). All analyses were adjusted for weight, height, age, ethnicity, smoking status, and other silica exposures. Systematic problems leading to measurement error were possible, but would have been nondifferential in effect and not related to silica measurements. There is a consistent association between increased pulmonary function abnormalities and estimated measures of cumulative silica exposure within the current allowable OSHA regulatory level. Despite concerns about the quality control of the pulmonary function measurements use in these analyses, our results support the need to lower allowable air levels of silica and increase efforts to encourage cessation of cigarette smoking among silica-exposed workers.

Differential Use of Human Neutrophil Fcγ Receptors for Inducing Neutrophil Extracellular Trap Formation.

Science.gov (United States)

Alemán, Omar Rafael; Mora, Nancy; Cortes-Vieyra, Ricarda; Uribe-Querol, Eileen; Rosales, Carlos

2016-01-01

Neutrophils (PMN) are the most abundant leukocytes in the blood. PMN migrate from the circulation to sites of infection, where they are responsible for antimicrobial functions. PMN use phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs) to kill microbes. NETs are fibers composed of chromatin and neutrophil-granule proteins. Several pathogens, including bacteria, fungi, and parasites, and also some pharmacological stimuli such as phorbol 12-myristate 13-acetate (PMA) are efficient inducers of NETs. Antigen-antibody complexes are also capable of inducing NET formation. However the particular Fcγ receptor involved in triggering this function is a matter of controversy. In order to provide some insight into what Fcγ receptor is responsible for NET formation, each of the two human Fcγ receptors was stimulated individually by specific monoclonal antibodies and NET formation was evaluated. FcγRIIa cross-linking did not promote NET formation. Cross-linking other receptors such as integrins also did not promote NET formation. In contrast FcγRIIIb cross-linking induced NET formation similarly to PMA stimulation. NET formation was dependent on NADPH-oxidase, PKC, and ERK activation. These data show that cross-linking FcγRIIIb is responsible for NET formation by the human neutrophil.

Differential Use of Human Neutrophil Fcγ Receptors for Inducing Neutrophil Extracellular Trap Formation

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Omar Rafael Alemán

2016-01-01

Full Text Available Neutrophils (PMN are the most abundant leukocytes in the blood. PMN migrate from the circulation to sites of infection, where they are responsible for antimicrobial functions. PMN use phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs to kill microbes. NETs are fibers composed of chromatin and neutrophil-granule proteins. Several pathogens, including bacteria, fungi, and parasites, and also some pharmacological stimuli such as phorbol 12-myristate 13-acetate (PMA are efficient inducers of NETs. Antigen-antibody complexes are also capable of inducing NET formation. However the particular Fcγ receptor involved in triggering this function is a matter of controversy. In order to provide some insight into what Fcγ receptor is responsible for NET formation, each of the two human Fcγ receptors was stimulated individually by specific monoclonal antibodies and NET formation was evaluated. FcγRIIa cross-linking did not promote NET formation. Cross-linking other receptors such as integrins also did not promote NET formation. In contrast FcγRIIIb cross-linking induced NET formation similarly to PMA stimulation. NET formation was dependent on NADPH-oxidase, PKC, and ERK activation. These data show that cross-linking FcγRIIIb is responsible for NET formation by the human neutrophil.

Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats

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Suzuki, Chihiro; Takahashi, Masafumi; Morimoto, Hajime; Izawa, Atsushi; Ise, Hirohiko; Hongo, Minoru; Hoshikawa, Yasushi; Ito, Takayuki; Miyashita, Hiroshi; Kobayashi, Eiji; Shimada, Kazuyuki; Ikeda, Uichi

2006-01-01

Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation of smooth muscle cells (SMCs), leading to occlusion of pulmonary arterioles, right ventricular (RV) hypertrophy, and death. We investigated whether mycophenolate mofetil (MMF), a potent immunosuppresssant, prevents the development of monocrotaline (MCT)-induced PAH in rats. MMF effectively decreased RV systolic pressure and RV hypertrophy, and reduced the medial thickness of pulmonary arteries. MMF significantly inhibited the number of proliferating cell nuclear antigen (PCNA)-positive cells, infiltration of macrophages, and expression of P-selectin and interleukin-6 on the endothelium of pulmonary arteries. The infiltration of T cells and mast cells was not affected by MMF. In vitro experiments revealed that mycophenolic acid (MPA), an active metabolite of MMF, dose-dependently inhibited proliferation of human pulmonary arterial SMCs. MMF attenuated the development of PAH through its anti-inflammatory and anti-proliferative properties. These findings provide new insight into the potential role of immunosuppressants in the treatment of PAH

Pulmonary sarcoidosis : CT findings and correlation with sACE level and PFT

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Ji, Eun Kyung; Song, Koun Sik; Lee, Jin Seong; Kwon, Jin Sook; Park, Kwang Bo; Lim, Tae Whan

1997-01-01

To assess CT findings of pulmonary sarcoidosis and correlate these with sACE level and PFT Between 1989 and 1995, 14 patients (4 men and 10 women, aged between 28 and 55 years) with histologically confirmed pulmonary sarcoidosis were consecutively selected. HRCT scans were performed in 12 patients and conventional CT scans in two. CT findings were reviewed by three radiologists, and were correlated with the index of disease activity based on sACE level and pulmonary function test. Pulmonary parenchymal abnormalities were seen in all patients;small nodules of less than 3mm in diameter were seen in eight. Other abnormalities were nodules of more than 3mm in diameter (n=7), confluent nodules (n=5), ground glass opacity (n=5), patchy areas of consolidation with air bronchogram (n=5), and architectural distortion (n=3). The upper lung zone was more frequently involved than the middle or lower zone. In ten patients, the paripheral interstitum was predominantly involved, while only three patients showed predominant peribronchovascular involvement. Lymphadenopathy was noted in 13. There was no correlation between sACE level, the results of a pulmonary function test and the extent of parenchymal involvement. HRCT is valuable for the identification, characterization, and determination of the extent to which parenchymal lung is involved in sarcoidosis. The extent of this involvement does not correlate with sACE level and pulmonary function test results

Hypoxia upregulates neutrophil degranulation and potential for tissue injury

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Hoenderdos, Kim; Lodge, Katharine M; Hirst, Robert A; Chen, Cheng; Palazzo, Stefano G C; Emerenciana, Annette; Summers, Charlotte; Angyal, Adri; Porter, Linsey; Juss, Jatinder K; O'Callaghan, Christopher; Chilvers, Edwin R

2016-01-01

Background The inflamed bronchial mucosal surface is a profoundly hypoxic environment. Neutrophilic airway inflammation and neutrophil-derived proteases have been linked to disease progression in conditions such as COPD and cystic fibrosis, but the effects of hypoxia on potentially harmful neutrophil functional responses such as degranulation are unknown. Methods and results Following exposure to hypoxia (0.8% oxygen, 3 kPa for 4 h), neutrophils stimulated with inflammatory agonists (granulocyte-macrophage colony stimulating factor or platelet-activating factor and formylated peptide) displayed a markedly augmented (twofold to sixfold) release of azurophilic (neutrophil elastase, myeloperoxidase), specific (lactoferrin) and gelatinase (matrix metalloproteinase-9) granule contents. Neutrophil supernatants derived under hypoxic but not normoxic conditions induced extensive airway epithelial cell detachment and death, which was prevented by coincubation with the antiprotease α-1 antitrypsin; both normoxic and hypoxic supernatants impaired ciliary function. Surprisingly, the hypoxic upregulation of neutrophil degranulation was not dependent on hypoxia-inducible factor (HIF), nor was it fully reversed by inhibition of phospholipase C signalling. Hypoxia augmented the resting and cytokine-stimulated phosphorylation of AKT, and inhibition of phosphoinositide 3-kinase (PI3K)γ (but not other PI3K isoforms) prevented the hypoxic upregulation of neutrophil elastase release. Conclusion Hypoxia augments neutrophil degranulation and confers enhanced potential for damage to respiratory airway epithelial cells in a HIF-independent but PI3Kγ-dependent fashion. PMID:27581620

Pulmonary drug toxicity. FDG-PET findings in patients with lymphoma

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Kazama, Toshiki; Faria, S.C.; Macapinlac, H.A.; Uchida, Yoshitaka; Ito, Hisao

2008-01-01

The objective of this study was to evaluate the prevalence and positron emission tomography (PET) imaging features of pulmonary drug toxicity in patients with lymphoma during or just following chemotherapy. A total of 677 PET scans on 460 patients with lymphoma (351 non-Hodgkin's lymphoma, 92 Hodgkin's disease, and 17 both Hodgkin's and non-Hodgkin's lymphoma) were performed for the evaluation of chemotherapy response. In 51 patients, abnormal accumulation on both sides of the chest was reported. A review of medical records, 18 fluorodeoxyglucose ( 18 FDG)-PET scans, and chest computed tomography (CT) was performed, and cases with probable drug toxicity were identified. Inclusion criteria of probable drug toxicity were abnormal but symmetrical FDG accumulation in both lungs seen during or just following the completion of chemotherapy, the abnormal accumulation or corresponding abnormal CT findings resolved on subsequent studies, exclusion of clinical diagnosis of pneumonia, radiation pneumonitis, or lymphoma involvement. In 10 patients (six men and four women, average age 47.3), 2.2% of cases, probable drug toxicity was identified. In all 10 cases, diffuse and subpleural-dominant FDG accumulation was seen on FDG-PET scans, and scattered or diffuse ground-glass opacities were observed on chest CT. Four patients reported symptoms, and six patients did not report any symptoms. Diffuse and peripheral-dominant FDG accumulation in the lung, which may represent pulmonary drug toxicity, was not uncommon in patients with lymphoma who underwent chemotherapy. FDG-PET scan might be able to detect pulmonary drug toxicity in asymptomatic patients. (author)

Neutrophilic dermatoses in a patient with collagenous colitis

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Didac Barco

2010-01-01

Full Text Available We report the case of a 75-year old woman with collagenous colitis who presented with erythematous and edematous plaques on the periorbital and eyelid regions, accompanied by oral ulcers. Histopathology showed a dermal neutrophilic infiltrate plus mild septal and lobular panniculitis with lymphocytes, neutrophils and eosinophils. Five years earlier she had presented a flare of papules and vesicles on the trunk, together with oral ulcers; a skin biopsy revealed a neutrophilic dermal infiltrate and Sweet’s syndrome was diagnosed. Both the neutrophilic panniculitis and the Sweet’s syndrome were accompanied by fever, malaise and diarrhea. Cutaneous and intestinal symptoms disappeared with corticoid therapy. The two types of neutrophilic dermatoses that appeared in periods of colitis activity suggest that intestinal and cutaneous manifestations may be related.

Pediatric Pulmonary Abscess

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Kyle Barbour

2018-04-01

Full Text Available History of present illness: A 6-year-old previously healthy male presented to the emergency department with three days of left upper quadrant abdominal pain. Family endorsed one week of fevers, cough productive of yellow sputum, and non-bilious, non-bloody emesis. He denied shortness of breath and chest pain. On exam, the patient was febrile with otherwise normal vital signs. He had diffuse tenderness to his abdomen but clear lungs. Laboratory studies revealed leukocytosis to 25,000/mm3 with a left shift. Significant findings: Upright posterior-anterior plain chest films show a left lower lobe consolidation with an air-fluid level and a single septation consistent with a pulmonary abscess (white arrows. A small left pleural effusion was also present, seen as blunting of the left costophrenic angle and obscuration of the left hemidiaphragm (black arrows. Discussion: Pediatric pulmonary abscesses are rare, most commonly caused by aspiration, and the majority consequently arise in dependent portions of the lung.1 The most common pathogens in children are Streptococcus pneumoniaeand Staphylococcus aureus.1 Immunocompromised patients and those with existing pulmonary disease more commonly contract Pseudomonas aeruginosaor Bacteroides, and fungal pathogens are possible.1 Common symptoms include tachypnea, fever, and cough. Imaging is necessary to distinguish pulmonary abscesses from pneumonia, empyema, pneumatocele, and other etiologies. Plain film radiography may miss up to 18% of pulmonary abscesses yet is often the first modality to visualize an intrathoracic abnormality.2 If seen, pulmonary abscesses most often appear as consolidations with air-fluid levels. Generally, pulmonary abscesses are round with irregular, thick walls, whereas empyemas are elliptical with smooth, thin walls.3 However, these characteristics cannot definitively distinguish these processes.2 Advantages of plain films include being low cost and easily obtained. Computed

Role of Proteases in Chronic Obstructive Pulmonary Disease

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Kailash C. Pandey

2017-08-01

Full Text Available Chronic obstructive pulmonary disease (COPD is generally associated with progressive destruction of airways and lung parenchyma. Various factors play an important role in the development and progression of COPD, like imbalance of proteases, environmental and genetic factors and oxidative stress. This review is specifically focused on the role of proteases and their imbalance in COPD. There are three classes (serine, mettalo, and cysteine of proteases involved in COPD. In serine proteases, neutrophil elastase, cathepsin G, and proteinase-3 are involved in destruction of alveolar tissue. Matrix-mettaloproteinase-9, 12, 13, plays an influential role in severity of COPD. Among cysteine proteases, caspase-3, caspases-8 and caspase-9 play an important role in controlling apoptosis. These proteases activities can be regulated by inhibitors like α-1-antitrypsin, neutrophil elastase inhibitor, and leukocyte protease inhibitor. Studies suggest that neutrophil elastase may be a therapeutic target for COPD, and specific inhibitor against this enzyme has potential role to control the disease. Current study suggests that Dipeptidyl Peptidase IV is a potential marker for COPD. Since the expression of proteases and its inhibitors play an important role in COPD pathogenesis, therefore, it is worth investigating the role of proteases and their regulation. Understanding the biochemical basis of COPD pathogenesis using advanced tools in protease biochemistry and aiming toward translational research from bench-to-bedside will have great impact to deal with this health problem.

Neutrophil and macrophage apoptosis in bronchoalveolar lavage fluid from healthy horses and horses with recurrent airway obstruction (RAO)

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2014-01-01

Background Dysregulation of apoptosis has been implicated in a range of diseases including tumors, neurodegenerative and autoimmine diseases, as well as allergic asthma and chronic obstructive pulmonary disease (COPD) in humans. Although it has a different pathophysiology, delayed apoptosis of various inflammatory cells may play a pivotal role in the development of recurrent airway obstruction (RAO) in horses. Reduction of inflammatory cell apoptosis or a dysregulation of this process could lead to chronic inflammation and tissue injury. Therefore, the aim of this study was to investigate the rate of apoptosis and necrosis of neutrophils and macrophages in bronchoalveolar lavage fluid obtained from seven horses suffering from RAO (study group) and seven control horses. Results We demonstrated that neutrophil/macrophage apoptosis is altered in RAO-affected horses compared with the control group in the BAL fluid. We found a significant difference between the median percentage of early and late apoptosis of neutrophils between the study and control group of horses. Moreover, we found a positive correlation between the rate of apoptosis and the median percentage of macrophages in RAO-affected horses. Conclusion The findings suggest that apoptosis dysregulation may play a significant role in the pathogenesis of RAO. However, further studies are needed to clarify the role of altered apoptosis in the course of equine recurrent airway obstruction. PMID:24460911

Chemotactic Activity on Human Neutrophils to Streptococcus mutans

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Tetiana Haniastuti

2013-07-01

Full Text Available Objective: The aim of this study was to evaluate chemotactic activity o neutrophil to S. mutans. Chemotaxis assay was performed in blind well chambers. Materials and Methods: Hanks balanced salt solution (HBSS containing 106 S. mutans,  108 S. mutans, 10-8 M fMLP, or HBSS alone were placed in the lower wells of the chamber and covered with polycorbonate membrane filter. Neutrophils suspension (2x105 cells was then placed in the upper compartment. After incubation for 60 mins at 37ºC in a humidified atmosphere with 5% CO2, the filters were removed and stained with Giemsa. Result: ANOVA revealed statistically significant differences among groups (p<0.05, indicating that S. mutans induced neutrophils chemotaxis. The number of neutrophils migration in response to 108 S. mutans and 106 S. mutans were signifiantly greater compared to fMLP (p<0.05. Conclusion: S. mutans may activate human neutrophils, resulting in the chemotaxis of the neutrophils.DOI: 10.14693/jdi.v16i2.99

Epithelial to mesenchymal transition-related proteins ZEB1, β-catenin, and β-tubulin-III in idiopathic pulmonary fibrosis.

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Chilosi, Marco; Caliò, Anna; Rossi, Andrea; Gilioli, Eliana; Pedica, Federica; Montagna, Licia; Pedron, Serena; Confalonieri, Marco; Doglioni, Claudio; Ziesche, Rolf; Grubinger, Markus; Mikulits, Wolfgang; Poletti, Venerino

2017-01-01

Epithelial to mesenchymal transition has been suggested as a relevant contributor to pulmonary fibrosis, but how and where this complex process is triggered in idiopathic pulmonary fibrosis is not fully understood. Beta-tubulin-III (Tubβ3), ZEB1, and β-catenin are partially under the negative control of miR-200, a family of micro-RNAs playing a major role in epithelial to mesenchymal transition, that are reduced in experimental lung fibrosis and idiopathic pulmonary fibrosis. We wonder whether in situ expression of these proteins is increased in idiopathic pulmonary fibrosis, to better understand the significance of miR-200 feedback loop and epithelial to mesenchymal transition. We investigated the immunohistochemical and immunofluorescent expression and precise location of ZEB1, Tubβ3, and β-catenin in tissue samples from 34 idiopathic pulmonary fibrosis cases and 21 controls (5 normal lungs and 16 other interstitial lung diseases). In 100% idiopathic pulmonary fibrosis samples, the three proteins were concurrently expressed in fibroblastic foci, as well in damaged epithelial cells overlying these lesions and in pericytes within neo-angiogenesis areas. These results were also confirmed by immunofluorescence assay. In controls the abnormal expression of the three proteins was absent or limited. This is the first study that relates concurrent expression of Tubβ3, ZEB1, and β-catenin to abnormal epithelial and myofibroblast differentiation in idiopathic pulmonary fibrosis, providing indirect but robust evidence of miR-200 deregulation and epithelial to mesenchymal transition activation in idiopathic pulmonary fibrosis. The abnormal expression and localization of these proteins in bronchiolar fibro-proliferative lesions are unique for idiopathic pulmonary fibrosis, and might represent a disease-specific marker in challenging lung biopsies.