TAM receptors in apoptotic cell clearance, autoimmunity, and cancer.

Science.gov (United States)

Nguyen, Khanh-Quynh; Tsou, Wen-I; Kotenko, Sergei; Birge, Raymond B

2013-08-01

Receptor tyrosine kinases, Tyro-3, Axl and Mer, collectively designated as TAM, are involved in the clearance of apoptotic cells. TAM ligands, Gas6 and Protein S, bind to the surfaces of apoptotic cells, and at the same time, interact directly with TAM expressed on phagocytes, impacting the engulfment and clearance of apoptotic cells and debris. The well-tuned and balanced actions of TAM may affect a variety of human pathologies including autoimmunity, retinal degeneration, and cancer. This article emphasizes some of the emerging findings and mechanistic insights into TAM functions that are clinically relevant and possibly therapeutically targeted.

Macrophage Clearance of Apoptotic Cells: A Critical Assessment

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Siamon Gordon

2018-01-01

Full Text Available As the body continues to grow and age, it becomes essential to maintain a balance between living and dying cells. Macrophages and dendritic cells play a central role in discriminating among viable, apoptotic, and necrotic cells, as selective and efficient phagocytes, without inducing inappropriate inflammation or immune responses. A great deal has been learnt concerning clearance receptors for modified and non-self-ligands on potential targets, mediating their eventual uptake, disposal, and replacement. In this essay, we assess current understanding of the phagocytic recognition of apoptotic cells within their tissue environment; we conclude that efferocytosis constitutes a more complex process than simply removal of corpses, with regulatory interactions between the target and effector cells, which determine the outcome of this homeostatic process.

Computer simulations and the use of radiolabelled sulphur colloid to measure the efficiency of the mononuclear phagocyte system

International Nuclear Information System (INIS)

Saad, A.H.; Rutishauser, S.C.B.; Williams, A.R.

1985-01-01

Techniques are described whereby the clearance of the radiolabelled blood borne colloid can be continuously and reproducibly measured non-invasively from the same animal in vivo or from the isolated perfused intact liver in vitro. Using these techniques, the rate of removal of radiolabelled sulphur colloid by the mononuclear phagocytes in vivo and in vitro was shown to be biexponential. The pattern of clearance of colloid and the factors contributing to this were analysed with the aid of a computer program which mimicked the in vitro liver perfusion. (Auth.)

Increased dependence of leucine in posttraumatic sepsis: leucine/tyrosine clearance ratio as an indicator of hepatic impairment in septic multiple organ failure syndrome.

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Pittiruti, M; Siegel, J H; Sganga, G; Coleman, B; Wiles, C E; Belzberg, H; Wedel, S; Placko, R

1985-09-01

The body clearance of 10 plasma amino acids (AA) was determined from the rate of compared muscle-released AA and AA administered by infusion of total parenteral nutrition (TPN) compared to their estimated extracellular (ECW) pool in patients with multiple trauma with (n = 10) or without (n = 16) sepsis at 8-hour intervals. In both nonseptic and septic trauma, increasing TPN increased the mean clearance rate of all infused AA. When the individual AA clearance rates were normalized by the total AA infusion rate, regression-covariance analysis revealed that patients with sepsis had relatively impaired clearances of alanine (p less than 0.01) and methionine, proline, phenylalanine, and tyrosine p less than 0.05 for all). In contrast, the clearances of branched-chain AA (BCAA) valine and isoleucine were maintained, and the clearance of leucine was higher (p less than 0.05) in trauma patients with sepsis than in those without. At any AA infusion rate, compared with surviving patients with sepsis (p less than 0.05), patients who developed fatal multiple organ failure syndrome (MOFS) showed increased clearances of all BCAA with further impaired clearance of tyrosine. The clearance ratio of leucine/tyrosine was increased in MOFS at any AA infusion rate (p less than 0.0001), was an indicator of severity, and, if persistent, was a manifestation of a fatal outcome. Because tyrosine metabolism occurs almost entirely in the liver while leucine can be utilized by viscera and muscle, these data suggest early and progressive septic impairment of the pattern of hepatic uptake and oxidation of AA with a greater body dependence on BCAA, especially leucine, as septic MOFS develops.

Scan Manifestations and Blood Clearance Rates in Typhoid Liver

International Nuclear Information System (INIS)

Bahk, Yong Whee; Ahn, Jae Sung; Kim, Soon Hi

1970-01-01

Fourteen patients with typhoid fever studied by scanning and clearance-rate measurements of subcritical dose colloidal radiogold ( 198 Au). Mild to moderate enlargement of the liver and spleen was noted in 78.6 and 64.3 percent of patients, respectively; and splenic and spinal bone-marrow uptake was seen in 78.6 and 57.1 percent of cases, respectively. Typically, these scan changes occurred concomitantly (57.1%) and are considered to represent increased phagocytic activity of the RE cells which is characteristic of typhoid fever. The half clearance-time was significantly shortened during the first 10-day period of the illness indicating an increase in the hepatic blood in the early phase of typhoid infection. Hepatomegaly, splenomegaly and extrahepatic uptakes along with an accelerated (or less a normal) clearance time are characteristic of typhoid fever.

Chloride flux in phagocytes.

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Wang, Guoshun

2016-09-01

Phagocytes, such as neutrophils and macrophages, engulf microbes into phagosomes and launch chemical attacks to kill and degrade them. Such a critical innate immune function necessitates ion participation. Chloride, the most abundant anion in the human body, is an indispensable constituent of the myeloperoxidase (MPO)-H2 O2 -halide system that produces the potent microbicide hypochlorous acid (HOCl). It also serves as a balancing ion to set membrane potentials, optimize cytosolic and phagosomal pH, and regulate phagosomal enzymatic activities. Deficient supply of this anion to or defective attainment of this anion by phagocytes is linked to innate immune defects. However, how phagocytes acquire chloride from their residing environment especially when they are deployed to epithelium-lined lumens, and how chloride is intracellularly transported to phagosomes remain largely unknown. This review article will provide an overview of chloride protein carriers, potential mechanisms for phagocytic chloride preservation and acquisition, intracellular chloride supply to phagosomes for oxidant production, and methods to measure chloride levels in phagocytes and their phagosomes. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hyperglycemia Impairs Neutrophil-Mediated Bacterial Clearance in Mice Infected with the Lyme Disease Pathogen.

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Ashkan Javid

Full Text Available Insulin-insufficient type 1 diabetes is associated with attenuated bactericidal function of neutrophils, which are key mediators of innate immune responses to microbes as well as pathological inflammatory processes. Neutrophils are central to immune responses to the Lyme pathogen Borrelia burgdorferi. The effect of hyperglycemia on host susceptibility to and outcomes of B. burgdorferi infection has not been examined. The present study investigated the impact of sustained obesity-independent hyperglycemia in mice on bacterial clearance, inflammatory pathology and neutrophil responses to B. burgdorferi. Hyperglycemia was associated with reduced arthritis incidence but more widespread tissue colonization and reduced clearance of bacterial DNA in multiple tissues including brain, heart, liver, lung and knee joint. B. burgdorferi uptake and killing were impaired in neutrophils isolated from hyperglycemic mice. Thus, attenuated neutrophil function in insulin-insufficient hyperglycemia was associated with reduced B. burgdorferi clearance in target organs. These data suggest that investigating the effects of comorbid conditions such as diabetes on outcomes of B. burgdorferi infections in humans may be warranted.

Scan Manifestations and Blood Clearance Rates in Typhoid Liver

Energy Technology Data Exchange (ETDEWEB)

Bahk, Yong Whee; Ahn, Jae Sung; Kim, Soon Hi [St. Mary' s Hospital, Catholic Medical College, Seoul (Korea, Republic of)

1970-09-15

Fourteen patients with typhoid fever studied by scanning and clearance-rate measurements of subcritical dose colloidal radiogold ({sup 198}Au). Mild to moderate enlargement of the liver and spleen was noted in 78.6 and 64.3 percent of patients, respectively; and splenic and spinal bone-marrow uptake was seen in 78.6 and 57.1 percent of cases, respectively. Typically, these scan changes occurred concomitantly (57.1%) and are considered to represent increased phagocytic activity of the RE cells which is characteristic of typhoid fever. The half clearance-time was significantly shortened during the first 10-day period of the illness indicating an increase in the hepatic blood in the early phase of typhoid infection. Hepatomegaly, splenomegaly and extrahepatic uptakes along with an accelerated (or less a normal) clearance time are characteristic of typhoid fever.

Blood phagocyte activity after race training sessions in Thoroughbred and Arabian horses.

Science.gov (United States)

Cywinska, Anna; Szarska, Ewa; Degorski, Andrzej; Guzera, Maciej; Gorecka, Renata; Strzelec, Katarzyna; Kowalik, Sylwester; Schollenberger, Antoni; Winnicka, Anna

2013-10-01

Intensive exercise and exertion during competition promote many changes that may result in the impairment of immunity and increased susceptibility to infections. The aim of this study was to evaluate the activity of "the first line of defense": neutrophils and monocytes in racing Thoroughbred and Arabian horses after routine training sessions. Twenty-three (12 Thoroughbred and 11 Arabian) horses were examined. Routine haematological (number of red blood cells - RBC, haemoglobin concentration - HGB, haematocrit - HCT, total number of white blood cells - WBC), biochemical (creatine phosphokinase activity - CPK and total protein concentration - TP) parameters, cortisol concentration as well as phagocytic and oxidative burst activity of neutrophils and monocytes were determined. The values of basic parameters and the activity of phagocytes differed between breeds and distinct patterns of exercise-induced changes were observed. The training sessions did not produce the decrease in phagocyte activity that might lead to the suppression of immunity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cigarette Smoke Exposure Inhibits Bacterial Killing via TFEB-Mediated Autophagy Impairment and Resulting Phagocytosis Defect

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Garrett Pehote

2017-01-01

Full Text Available Introduction. Cigarette smoke (CS exposure is the leading risk factor for COPD-emphysema pathogenesis. A common characteristic of COPD is impaired phagocytosis that causes frequent exacerbations in patients leading to increased morbidity. However, the underlying mechanism is unclear. Hence, we investigated if CS exposure causes autophagy impairment as a mechanism for diminished bacterial clearance via phagocytosis by utilizing murine macrophages (RAW264.7 cells and Pseudomonas aeruginosa (PA01-GFP as an experimental model. Methods. Briefly, RAW cells were treated with cigarette smoke extract (CSE, chloroquine (autophagy inhibitor, TFEB-shRNA, CFTR(inh-172, and/or fisetin prior to bacterial infection for functional analysis. Results. Bacterial clearance of PA01-GFP was significantly impaired while its survival was promoted by CSE (p<0.01, autophagy inhibition (p<0.05; p<0.01, TFEB knockdown (p<0.01; p<0.001, and inhibition of CFTR function (p<0.001; p<0.01 in comparison to the control group(s that was significantly recovered by autophagy-inducing antioxidant drug, fisetin, treatment (p<0.05; p<0.01; and p<0.001. Moreover, investigations into other pharmacological properties of fisetin show that it has significant mucolytic and bactericidal activities (p<0.01; p<0.001, which warrants further investigation. Conclusions. Our data suggests that CS-mediated autophagy impairment as a critical mechanism involved in the resulting phagocytic defect, as well as the therapeutic potential of autophagy-inducing drugs in restoring is CS-impaired phagocytosis.

In Vivo Hemozoin Kinetics after Clearance of Plasmodium berghei Infection in Mice

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Rosangela Frita

2012-01-01

Full Text Available Hemozoin (Hz is released into the blood stream after rupture of infected red blood cells (iRBCs at the end of each parasite replication cycle. This free Hz is ingested by circulating and resident phagocytes. The presence of Hz in tissues after clearance of infection has been previously reported. Still, little is known about the kinetics of Hz in vivo, during and after Plasmodium infection. It is particularly important to understand Hz kinetics after malaria infections as it has been reported that Hz is associated with impairment of immune functions, including possible consequences for coinfections. Indeed, if Hz remains biologically active for prolonged periods of time inside immunocompetent cells, the potential consequences of such accumulation and presence to the immune system should be clarified. Here, using several independent methods to assess the presence of Hz, we report the long-term in vivo kinetics of Hz in diverse organs in a murine model of malaria infection.

Esophageal chemical clearance is impaired in gastro-esophageal reflux disease--a 24-h impedance-pH monitoring assessment.

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Frazzoni, M; Manta, R; Mirante, V G; Conigliaro, R; Frazzoni, L; Melotti, G

2013-05-01

Impedance-pH monitoring allows assessment of retrograde and antegrade intra-esophageal movement of fluids and gas. Reflux is followed by volume clearance and chemical clearance, elicited by secondary and swallow-induced peristalsis, respectively. We aimed to assess whether chemical clearance is impaired in gastro-esophageal reflux disease (GERD). Blinded retrospective review of impedance-pH tracings from patients with erosive reflux disease (ERD) and non-erosive reflux disease (NERD), and from proton pump inhibitor (PPI)-refractory patients before and after laparoscopic fundoplication. The number of refluxes followed within 30 s by swallow-induced peristaltic waves was divided by the number of total refluxes to obtain a parameter representing chemical clearance namely the postreflux swallow-induced peristaltic wave (PSPW) index. The PSPW index was significantly lower in 31 ERD (15%) and in 44 NERD (33%) off-PPI patients than in 30 controls (75%), as well as in 18 ERD (16%) and in 48 NERD (31%) on-PPI patients than in 26 on-PPI functional heartburn (FH) cases (67%) (P < 0.05 for all comparisons). In 29 PPI-refractory patients, the median PSPW index was unaltered by otherwise effective antireflux surgery (20% postoperatively, 21% preoperatively). The overall sensitivity, specificity, positive, and negative predictive values of the PSPW index in identifying GERD patients were 97%, 89%, 96%, and 93%. Impairment of chemical clearance is a primary pathophysiological mechanism specific to GERD: it is unaffected by medical/surgical therapy, is not found in FH, and is more pronounced in ERD than in NERD. Using the PSPW index could improve the diagnostic efficacy of impedance-pH monitoring. © 2013 Blackwell Publishing Ltd.

2A4 binds soluble and insoluble light chain aggregates from AL amyloidosis patients and promotes clearance of amyloid deposits by phagocytosis †.

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Renz, Mark; Torres, Ronald; Dolan, Philip J; Tam, Stephen J; Tapia, Jose R; Li, Lauri; Salmans, Joshua R; Barbour, Robin M; Shughrue, Paul J; Nijjar, Tarlochan; Schenk, Dale; Kinney, Gene G; Zago, Wagner

2016-09-01

Amyloid light chain (AL) amyloidosis is characterized by misfolded light chain (LC) (amyloid) deposition in various peripheral organs, leading to progressive dysfunction and death. There are no regulatory agency-approved treatments for AL amyloidosis, and none of the available standard of care approaches directly targets the LC protein that constitutes the amyloid. NEOD001, currently in late-stage clinical trials, is a conformation-specific, anti-LC antibody designed to specifically target misfolded LC aggregates and promote phagocytic clearance of AL amyloid deposits. The present study demonstrated that the monoclonal antibody 2A4, the murine form of NEOD001, binds to patient-derived soluble and insoluble LC aggregates and induces phagocytic clearance of AL amyloid in vitro. 2A4 specifically labeled all 21 fresh-frozen organ samples studied, which were derived from 10 patients representing both κ and λ LC amyloidosis subtypes. 2A4 immunoreactivity largely overlapped with thioflavin T-positive labeling, and 2A4 bound both soluble and insoluble LC aggregates extracted from patient tissue. Finally, 2A4 induced macrophage engagement and phagocytic clearance of AL amyloid deposits in vitro. These findings provide further evidence that 2A4/NEOD001 can effectively clear and remove human AL-amyloid from tissue and further support the rationale for the evaluation of NEOD001 in patients with AL amyloidosis.

2A4 binds soluble and insoluble light chain aggregates from AL amyloidosis patients and promotes clearance of amyloid deposits by phagocytosis †

Science.gov (United States)

Renz, Mark; Torres, Ronald; Dolan, Philip J.; Tam, Stephen J.; Tapia, Jose R.; Li, Lauri; Salmans, Joshua R.; Barbour, Robin M.; Shughrue, Paul J.; Nijjar, Tarlochan; Schenk, Dale; Kinney, Gene G.; Zago, Wagner

2016-01-01

Abstract Amyloid light chain (AL) amyloidosis is characterized by misfolded light chain (LC) (amyloid) deposition in various peripheral organs, leading to progressive dysfunction and death. There are no regulatory agency–approved treatments for AL amyloidosis, and none of the available standard of care approaches directly targets the LC protein that constitutes the amyloid. NEOD001, currently in late-stage clinical trials, is a conformation-specific, anti-LC antibody designed to specifically target misfolded LC aggregates and promote phagocytic clearance of AL amyloid deposits. The present study demonstrated that the monoclonal antibody 2A4, the murine form of NEOD001, binds to patient-derived soluble and insoluble LC aggregates and induces phagocytic clearance of AL amyloid in vitro. 2A4 specifically labeled all 21 fresh-frozen organ samples studied, which were derived from 10 patients representing both κ and λ LC amyloidosis subtypes. 2A4 immunoreactivity largely overlapped with thioflavin T–positive labeling, and 2A4 bound both soluble and insoluble LC aggregates extracted from patient tissue. Finally, 2A4 induced macrophage engagement and phagocytic clearance of AL amyloid deposits in vitro. These findings provide further evidence that 2A4/NEOD001 can effectively clear and remove human AL-amyloid from tissue and further support the rationale for the evaluation of NEOD001 in patients with AL amyloidosis. PMID:27494229

One-year follow-up of the phagocytic activity of leukocytes after exposure of rats to asbestos and basalt fibers.

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Hurbánková, M

1994-01-01

The phagocytic activity of leukocytes in peripheral blood was investigated after 2, 24, and 48 hr; 1, 2, 4, and 8 weeks; and 6 and 12 months following intraperitoneal administration of asbestos and basalt fibers to Wistar rats. Asbestos and basalt fibers differed in their effects on the parameters studied. Both granulocyte count and phagocytic activity of leukocytes during the 1-year dynamic follow-up in both dust-exposed groups of animals changed in two phases, characterized by the initial stimulation of the acute phase I, followed by the suppression of the parameters in the chronic phase II. Exposure to asbestos and basalt fibers led, in phase II, to impairment of the phagocytic activity of granulocytes. Asbestos fibers also significantly decreased phagocytic activity of monocytes. Exposure to basalt fibers did not affect the phagocytic activity of monocytes in phase II. Results suggest that the monocytic component of leukocytes plays an important role in the development of diseases caused by exposure to fibrous dusts, but basalt fibers have lesser biological effects than asbestos fibers. PMID:7882931

PAH clearance after renal ischemia and reperfusion is a function of impaired expression of basolateral Oat1 and Oat3

OpenAIRE

Bischoff, Ariane; Bucher, Michael; Gekle, Michael; Sauvant, Christoph

2014-01-01

Abstract Determination of renal plasma flow (RPF) by para‐aminohippurate (PAH) clearance leads to gross underestimation of this respective parameter due to impaired renal extraction of PAH after renal ischemia and reperfusion injury. However, no mechanistic explanation for this phenomenon is available. Based on our own previous studies we hypothesized that this may be due to impairment of expression of the basolateral rate limiting organic anion transporters Oat1 and Oat3. Thus, we investigat...

Mice lacking prostaglandin E receptor subtype 4 manifest disrupted lipid metabolism attributable to impaired triglyceride clearance.

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Cai, Yin; Ying, Fan; Song, Erfei; Wang, Yu; Xu, Aimin; Vanhoutte, Paul M; Tang, Eva Hoi-Ching

2015-12-01

Upon high-fat feeding, prostaglandin E receptor subtype 4 (EP4)-knockout mice gain less body weight than their EP4(+/+) littermates. We investigated the cause of the lean phenotype. The mice showed a 68.8% reduction in weight gain with diminished fat mass that was not attributable to reduced food intake, fat malabsorption, or increased energy expenditure. Plasma triglycerides in the mice were elevated by 244.9%. The increase in plasma triglycerides was independent of changes in hepatic very low density lipoprotein (VLDL)-triglyceride production or intestinal chylomicron-triglyceride synthesis. However, VLDL-triglyceride clearance was drastically impaired in the EP4-knockout mice. The absence of EP4 in mice compromised the activation of lipoprotein lipase (LPL), the key enzyme responsible for trafficking of plasma triglycerides into peripheral tissues. Deficiency in EP4 reduced hepatic mRNA expression of the transcriptional factor cAMP response element binding protein H (by 36.8%) and LPL activators, including apolipoprotein (Apo)a5 (by 40.2%) and Apoc2 (by 61.3%). In summary, the lean phenotype of EP4-deficient mice resulted from reduction in adipose tissue and accretion of other peripheral organs caused by impaired triglyceride clearance. The findings identify a new metabolic dimension in the physiologic role played by endogenous EP4. © FASEB.

Uptake, localization and clearance of quantum dots in ciliated protozoa Tetrahymena thermophila

International Nuclear Information System (INIS)

Mortimer, Monika; Kahru, Anne; Slaveykova, Vera I.

2014-01-01

Protozoa as phagocytizing cells have been shown to integrate engineered nanoparticles (NPs), while the mechanism, dynamics and extent of such uptake are unclear. Here our fluorescence microscopy data showed that CdSe/ZnS quantum dots (QDs) with primary size of 12 nm were readily phagocytized into the food vacuoles of Tetrahymena thermophila in a time- and dose-dependent manner. Twenty hours after the exposure to QDs in sublethal concentration the clearance of the QDs from the cells was incomplete suggesting that phagocytosis of QDs into food vacuoles was not the only pathway of uptake by T. thermophila. This was further proven by the results that the inhibition of phagocytosis did not block the internalization of QDs into protozoans. This study provides a new insight into uptake and cellular trafficking of subtoxic concentrations of nanoparticles that may, due to prolonged retention times in the cells, pose risks by potentially becoming available to higher trophic levels. - Highlights: • Tetrahymena thermophila internalized QDs in a dose- and time-dependent manner. • The egested QDs were not significantly biodegraded in the food vacuoles. • In addition to phagocytosis QDs entered protozoa by alternative uptake pathways. • The clearance of the QDs from the cells was incomplete after 20 h in fresh medium. • The prolonged retention time of nontoxic NPs in protozoa could increase their transfer in food chain. - In addition to phagocytosis, quantum dots (QDs) entered protozoans by alternative pathways which did not lead to complete clearance of the QDs from the cells

Decreased Fc receptor expression on innate immune cells is associated with impaired antibody-mediated cellular phagocytic activity in chronically HIV-1 infected individuals.

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Dugast, Anne-Sophie; Tonelli, Andrew; Berger, Christoph T; Ackerman, Margaret E; Sciaranghella, Gaia; Liu, Qingquan; Sips, Magdalena; Toth, Ildiko; Piechocka-Trocha, Alicja; Ghebremichael, Musie; Alter, Galit

2011-07-05

In addition to neutralization, antibodies mediate other antiviral activities including antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular cytotoxicity (ADCC), as well as complement deposition. While it is established that progressive HIV infection is associated with reduced ADCC and ADCP, the underlying mechanism for this loss of function is unknown. Here we report considerable changes in FcR expression over the course of HIV infection on both mDCs and monocytes, including elevated FcγRI expression in acute HIV infection and reduced expression of FcγRII and FcγRIIIa in chronic HIV infection. Furthermore, selective blockade of FcγRII alone was associated with a loss in ADCP activity, suggesting that FcγRII plays a central role in modulating ADCP. Overall, HIV infection is associated with a number of changes in FcR expression on phagocytic cells that are associated with changes in their ability to respond to antibody-opsonized targets, potentially contributing to a failure in viral clearance in progressive HIV-1 infection. Copyright © 2011 Elsevier Inc. All rights reserved.

Decreased Fc-Receptor expression on innate immune cells is associated with impaired antibody mediated cellular phagocytic activity in chronically HIV-1 infected individuals

Science.gov (United States)

Dugast, Anne-Sophie; Tonelli, Andrew; Berger, Christoph T.; Ackerman, Margaret E.; Sciaranghella, Gaia; Liu, Qingquan; Sips, Magdalena; Toth, Ildiko; Piechocka-Trocha, Alicja; Ghebremichael, Musie; Alter, Galit

2011-01-01

In addition to neutralization, antibodies mediate other antiviral activities including antibody-dependent cellular-phagocytosis (ADCP), antibody dependent cellular-cytotoxicity (ADCC), as well as complement deposition. While it is established that progressive HIV infection is associated with reduced ADCC and ADCP, the underlying mechanism for this loss of function is unknown. Here we report considerable changes in FcR expression over the course of HIV infection on both mDCs and monocytes, including elevated FcγRI expression in acute HIV infection and reduced expression of FcγRII and FcγRIIIa in chronic HIV infection. Furthermore, selective blockade of FcγRII alone was associated with a loss in ADCP activity, suggesting that FcγRII plays a central role in modulating ADCP. Overall, HIV infection is associated with a number of changes in FcR expression on phagocytic cells that are associated with changes in their ability to respond to antibody-opsonized targets, potentially contributing to a failure in viral clearance in progressive HIV-1 infection. PMID:21565376

The effect of core and lanthanide ion dopants in sodium fluoride-based nanocrystals on phagocytic activity of human blood leukocytes

Science.gov (United States)

Sojka, Bartlomiej; Liskova, Aurelia; Kuricova, Miroslava; Banski, Mateusz; Misiewicz, Jan; Dusinska, Maria; Horvathova, Mira; Ilavska, Silvia; Szabova, Michaela; Rollerova, Eva; Podhorodecki, Artur; Tulinska, Jana

2017-02-01

Sodium fluoride-based β-NaLnF4 nanoparticles (NPs) doped with lanthanide ions are promising materials for application as luminescent markers in bio-imaging. In this work, the effect of NPs doped with yttrium (Y), gadolinium (Gd), europium (Eu), thulium (Tm), ytterbium (Yb) and terbium (Tb) ions on phagocytic activity of monocytes and granulocytes and the respiratory burst was examined. The surface functionalization of toxic with respect to conducted test; however, some cause toxic effects (they have statistically significant deviations compared to reference) in some selected doses tested. Both core types of NPs (Y-core and Gd-core) impaired the phagocytic activity of monocytes the strongest, having minimal or none whatsoever influence on granulocytes and respiratory burst of phagocytic cells. The lowest toxicity was observed in Gd-core, Yb, Tm dopants and near-infrared nanoparticles. Clear dose-dependent effect of NPs on phagocytic activity of leukocytes and respiratory burst of cells was observed for limited number of samples.

Effect of prior immobilization on muscular glucose clearance in resting and running rats

International Nuclear Information System (INIS)

Vissing, J.; Ohkuwa, Tetsuo; Ploug, T.; Galbo, H.

1988-01-01

In vitro studies have shown that prior disuse impairs the glucose clearance of red skeletal muscle because of a developed insensitivity to insulin. We studied whether an impaired glucose clearance is present in vivo in 42-h immobilized muscles of resting rats and, furthermore, whether the exercise-induced increase in glucose clearance of red muscles is affected by prior immobilization. The 2-[ 3 H]deoxy-D-glucose (2DG) bolus injection method was used to determine glucose clearance of individual muscles. At rest, glucose clearance was markedly impaired in rats with previously immobilized red muscles compared with nonimmobilized control rats. During running, glucose clearance did not differ between muscles in previously immobilized and control rats. Insulin levels were always similar in the two groups and decreased during exercise. Intracellular nonphosphorylated 2DG was present in tissues with high glucose clearances. In conclusion, 42 h of immobilization markedly impairs glucose clearance of resting red muscle fibers in vivo. Apparently, physical inactivity in particular affects steps involved in insulin-mediated action that are not part of contraction-induced glucose uptake and metabolism. Presence of intracellular 2DG shows that separate determination of phosphorylated 2DG is necessary for accurate estimates of glucose metabolism and that accumulation of phosphorylated 2DG does not accurately reflect glucose transport

Impairment of chemical clearance and mucosal integrity distinguishes hypersensitive esophagus from functional heartburn.

Science.gov (United States)

Frazzoni, Marzio; de Bortoli, Nicola; Frazzoni, Leonardo; Furnari, Manuele; Martinucci, Irene; Tolone, Salvatore; Farioli, Andrea; Marchi, Santino; Fuccio, Lorenzo; Savarino, Vincenzo; Savarino, Edoardo

2017-04-01

Hypersensitive esophagus (HE) is defined by endoscopy-negative heartburn with a normal acid exposure time but positive symptom association probability (SAP) and/or symptom index (SI) on impedance-pH monitoring, and proton pump inhibitor (PPI) responsiveness. Functional heartburn (FH) is distinguished by negative SAP/SI and PPI refractoriness. The clinical value of SAP and SI has been questioned. We aimed to investigate whether impairment of chemical clearance and of mucosal integrity, expressed by the postreflux swallow-induced peristaltic wave (PSPW) index and the mean nocturnal baseline impedance (MNBI), characterize HE independently of SAP and SI. Impedance-pH tracings from PPI-responsive endoscopy-negative patients, 125 with nonerosive reflux disease and 108 with HE, distinguished by an abnormal and a normal acid exposure time, and from 70 patients with FH were retrospectively selected and blindly reviewed. The mean PSPW index and MNBI were significantly lower in nonerosive reflux disease (30 %, 1378 Ω) than in HE (51 %; 2274 Ω) and in both of them as compared with FH (76 %; 3445 Ω) (P = 0.0001). Both the PSPW index (adjusted odds ratio 0.863, P = 0.001) and the MNBI (adjusted odds ratio 0.998, P = 0.001) were independent predictors of HE; with their combined assessment, the area under the curve on receiver operating characteristic analysis was 0.957. SAP and/or SI was positive in 67 of the 108 HE patients (62 %), whereas the PSPW index and/or MNBI was abnormal in 99 of the 108 HE patients (92 %; P < 0.0001). HE is characterized by impairment of chemical clearance and mucosal integrity, which explains the increased reflux perception. When SAP and SI afford uncertain results, the PSPW index and MNBI should be analyzed.

Effect of prior immobilization on muscular glucose clearance in resting and running rats

DEFF Research Database (Denmark)

Vissing, J; Ohkuwa, T; Ploug, Thorkil

1988-01-01

with nonimmobilized control rats (red gastrocnemius 0.46 +/- 0.02 vs. 0.99 +/- 0.08 and soleus 1.10 +/- 0.30 vs. 3.97 +/- 0.54 ml.min-1.100 g-1, P less than 0.005). During running (18 m/min), glucose clearance did not differ between muscles in previously immobilized and control rats. Insulin levels were always......In vitro studies have shown that prior disuse impairs the glucose clearance of red skeletal muscle because of a developed insensitivity to insulin. We studied whether an impaired glucose clearance is present in vivo in 42-h immobilized muscles of resting rats and, furthermore, whether the exercise......-induced increase in glucose clearance of red muscles is affected by prior immobilization. The 2-[3H]deoxy-D-glucose (2DG) bolus injection method was used to determine glucose clearance of individual muscles. At rest, glucose clearance was markedly impaired in rats with previously immobilized red muscles compared...

Arctigenin effectively ameliorates memory impairment in Alzheimer's disease model mice targeting both β-amyloid production and clearance.

Science.gov (United States)

Zhu, Zhiyuan; Yan, Jianming; Jiang, Wei; Yao, Xin-gang; Chen, Jing; Chen, Lili; Li, Chenjing; Hu, Lihong; Jiang, Hualiang; Shen, Xu

2013-08-07

Alzheimer's disease (AD) chiefly characterizes a progressively neurodegenerative disorder of the brain, and eventually leads to irreversible loss of intellectual abilities. The β-amyloid (Aβ)-induced neurodegeneration is believed to be the main pathological mechanism of AD, and Aβ production inhibition or its clearance promotion is one of the promising therapeutic strategies for anti-AD research. Here, we report that the natural product arctigenin from Arctium lappa (L.) can both inhibit Aβ production by suppressing β-site amyloid precursor protein cleavage enzyme 1 expression and promote Aβ clearance by enhancing autophagy through AKT/mTOR signaling inhibition and AMPK/Raptor pathway activation as investigated in cells and APP/PS1 transgenic AD model mice. Moreover, the results showing that treatment of arctigenin in mice highly decreased Aβ formation and senile plaques and efficiently ameliorated AD mouse memory impairment strongly highlight the potential of arctigenin in anti-AD drug discovery.

Hypoglycemic depression of RES function.

Science.gov (United States)

Buchanan, B J; Filkins, J P

1976-07-01

The intravascular removal rates of colloidal carbon and of biologically active endotoxin by the reticuloendothelial system (RES) were evaluated as a function of blood-glucose levels. There was a significant negative correlation of carbon clearance half time on blood glucose in both saline-treated and insulin-treated rats. Insulin hypoglycemia depressed RES carbon clearance with the maximal effect occurring at blood glucose values below 30 mg/dl. Insulin hypoglycemia also severely impaired the intravascular removal of endotoxin as evaluated by lethality bioassay in lead-sensitized rats. It is concluded that blood glucose may modulate RES phagocytic function and that the hypoglycemia of endotoxin shock may augment the shock state due to impairment of RES host defense clearance functions.

Cross-talk between miR-471-5p and autophagy component proteins regulates LC3-associated phagocytosis (LAP) of apoptotic germ cells.

Science.gov (United States)

Panneerdoss, Subbarayalu; Viswanadhapalli, Suryavathi; Abdelfattah, Nourhan; Onyeagucha, Benjamin C; Timilsina, Santosh; Mohammad, Tabrez A; Chen, Yidong; Drake, Michael; Vuori, Kristiina; Kumar, T Rajendra; Rao, Manjeet K

2017-09-19

Phagocytic clearance of apoptotic germ cells by Sertoli cells is vital for germ cell development and differentiation. Here, using a tissue-specific miRNA transgenic mouse model, we show that interaction between miR-471-5p and autophagy member proteins regulates clearance of apoptotic germ cells via LC3-associated phagocytosis (LAP). Transgenic mice expressing miR-471-5p in Sertoli cells show increased germ cell apoptosis and compromised male fertility. Those effects are due to defective engulfment and impaired LAP-mediated clearance of apoptotic germ cells as miR-471-5p transgenic mice show lower levels of Dock180, LC3, Atg12, Becn1, Rab5 and Rubicon in Sertoli cells. Our results reveal that Dock180 interacts with autophagy member proteins to constitute a functional LC3-dependent phagocytic complex. We find that androgen regulates Sertoli cell phagocytosis by controlling expression of miR-471-5p and its target proteins. These findings suggest that recruitment of autophagy machinery is essential for efficient clearance of apoptotic germ cells by Sertoli cells using LAP.Although phagocytic clearance of apoptotic germ cells by Sertoli cells is essential for spermatogenesis, little of the mechanism is known. Here the authors show that Sertoli cells employ LC3-associated phagocytosis (LAP) by recruiting autophagy member proteins to clear apoptotic germ cells.

Impairment of Release Site Clearance within the Active Zone by Reduced SCAMP5 Expression Causes Short-Term Depression of Synaptic Release

Directory of Open Access Journals (Sweden)

Daehun Park

2018-03-01

Full Text Available Summary: Despite being a highly enriched synaptic vesicle (SV protein and a candidate gene for autism, the physiological function of SCAMP5 remains mostly enigmatic. Here, using optical imaging and electrophysiological experiments, we demonstrate that SCAMP5 plays a critical role in release site clearance at the active zone. Truncation analysis revealed that the 2/3 loop domain of SCAMP5 directly interacts with adaptor protein 2, and this interaction is critical for its role in release site clearance. Knockdown (KD of SCAMP5 exhibited pronounced synaptic depression accompanied by a slower recovery of the SV pool. Moreover, it induced a strong frequency-dependent short-term depression of synaptic release, even under the condition of sufficient release-ready SVs. Super-resolution microscopy further proved the defects in SV protein clearance induced by KD. Thus, reduced expression of SCAMP5 may impair the efficiency of SV clearance at the active zone, and this might relate to the synaptic dysfunction observed in autism. : Park et al. show that SCAMP5 plays an important role in release site clearance during intense neuronal activity. Loss of SCAMP5 results in a traffic jam at release sites, causing aberrant short-term synaptic depression that might be associated with the synaptic dysfunction observed in autism. Keywords: secretory carrier membrane protein, SCAMP5, autism spectrum disorder, adaptor protein 2, release site clearance, presynaptic active zone, short-term depression, endocytosis, super-resolution microscopy

Comparative anatomy of phagocytic and immunological synapses

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Florence eNiedergang

2016-01-01

Full Text Available The generation of phagocytic cups and immunological synapses are crucial events of the innate and adaptive immune responses, respectively. They are triggered by distinct immune receptors and performed by different cell types. However, growing experimental evidence shows that a very close series of molecular and cellular events control these two processes. Thus, the tight and dynamic interplay between receptor signaling, actin and microtubule cytoskeleton, and targeted vesicle traffic are all critical features to build functional phagosomes and immunological synapses. Interestingly, both phagocytic cups and immunological synapses display particular spatial and temporal patterns of receptors and signaling molecules, leading to the notion of phagocytic synapse. Here we discuss both types of structures, their organization and the mechanisms by which they are generated and regulated.

Distinct innate immune phagocyte responses to Aspergillus fumigatus conidia and hyphae in zebrafish larvae.

Science.gov (United States)

Knox, Benjamin P; Deng, Qing; Rood, Mary; Eickhoff, Jens C; Keller, Nancy P; Huttenlocher, Anna

2014-10-01

Aspergillus fumigatus is the most common filamentous fungal pathogen of immunocompromised hosts, resulting in invasive aspergillosis (IA) and high mortality rates. Innate immunity is known to be the predominant host defense against A. fumigatus; however, innate phagocyte responses to A. fumigatus in an intact host and their contributions to host survival remain unclear. Here, we describe a larval zebrafish A. fumigatus infection model amenable to real-time imaging of host-fungal interactions in live animals. Following infection with A. fumigatus, innate phagocyte populations exhibit clear preferences for different fungal morphologies: macrophages rapidly phagocytose conidia and form aggregates around hyphae, while the neutrophil response is dependent upon the presence of hyphae. Depletion of macrophages rendered host larvae susceptible to invasive disease. Moreover, a zebrafish model of human leukocyte adhesion deficiency with impaired neutrophil function also resulted in invasive disease and impaired host survival. In contrast, macrophage-deficient but not neutrophil-deficient larvae exhibited attenuated disease following challenge with a less virulent (ΔlaeA) strain of A. fumigatus, which has defects in secondary metabolite production. Taking these results together, we have established a new vertebrate model for studying innate immune responses to A. fumigatus that reveals distinct roles for neutrophils and macrophages in mediating host defense against IA. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Effects of Enrofloxacin on Porcine Phagocytic Function

OpenAIRE

Schoevers, E. J.; van Leengoed, L. A. M. G.; Verheijden, J. H. M.; Niewold, T. A.

1999-01-01

The interaction between enrofloxacin and porcine phagocytes was studied with clinically relevant concentrations of enrofloxacin. Enrofloxacin accumulated in phagocytes, with cellular concentration/extracellular concentration ratios of 9 for polymorphonuclear leukocytes (PMNs) and 5 for alveolar macrophages (AMs). Cells with accumulated enrofloxacin brought into enrofloxacin-free medium released approximately 80% (AMs) to 90% (PMNs) of their enrofloxacin within the first 10 min, after which no...

Survival and function of phagocytes in blood culture media

DEFF Research Database (Denmark)

Fischer, T K; Prag, J; Kharazmi, A

1999-01-01

The survival and function of human phagocytes in sterile aerobic and anaerobic blood culture media were investigated using neutrophil morphology, white blood cell count in a haemoanalyser, flow cytometry, oxidative burst response, and bactericidal effect in Colorbact and Septi-Chek blood culture...... media and Bact/Alert. When comparing agitation to stationary incubation no difference in phagocytic activity was found. The methods showed the same trends demonstrating that the phagocytes' viability and activity were prolonged by oxygen and shortened by anaerobic conditions and sodium polyethanol...... sulfonate (SPS). Best preserved activity and viability were found in the aerobic media containing less than 0.5 g/l SPS, in which significant phagocyte oxidative burst and bactericidal activity were found up to 4 days after inoculation. Considering that the majority of bacteremias are due to aerobic...

Chronic cerebral hypoperfusion-induced impairment of Aβ clearance requires HB-EGF-dependent sequential activation of HIF1α and MMP9.

Science.gov (United States)

Ashok, Anushruti; Rai, Nagendra Kumar; Raza, Waseem; Pandey, Rukmani; Bandyopadhyay, Sanghamitra

2016-11-01

Chronic cerebral hypoperfusion (CCH) manifests Alzheimer's Disease (AD) neuropathology, marked by increased amyloid beta (Aβ). Besides, hypoxia stimulates Heparin-binding EGF-like growth factor (HB-EGF) mRNA expression in the hippocampus. However, involvement of HB-EGF in CCH-induced Aβ pathology remains unidentified. Here, using Bilateral Common Carotid Artery Occlusion mouse model, we explored the mechanism of HB-EGF regulated Aβ induction in CCH. We found that HB-EGF inhibition suppressed, while exogenous-HB-EGF triggered hippocampal Aβ, proving HB-EGF-dependent Aβ increase. We also detected that HB-EGF affected the expression of primary Aβ transporters, receptor for advanced glycation end-products (RAGE) and lipoprotein receptor-related protein-1 (LRP-1), indicating impaired Aβ clearance across the blood-brain barrier (BBB). An HB-EGF-dependent loss in BBB integrity supported impaired Aβ clearance. The effect of HB-EGF on Amyloid Precursor Protein pathway was relatively insignificant, suggesting a lesser effect on Aβ generation. Delving into BBB disruption mechanism demonstrated HB-EGF-mediated stimulation of Matrix metalloprotease-9 (MMP9), which affected BBB via HB-EGF-ectodomain shedding and epidermal growth factor receptor activation. Examining the intersection of HB-EGF-regulated pathway and hypoxia revealed HB-EGF-dependent increase in transcription factor, Hypoxia-inducible factor-1alpha (HIF1α). Further, via binding to hypoxia-responsive elements in MMP9 gene, HIF1α stimulated MMP9 expression, and therefore appeared as a prominent intermediary in HB-EGF-induced BBB damage. Overall, our study reveals the essential role of HB-EGF in triggering CCH-mediated Aβ accumulation. The proposed mechanism involves an HB-EGF-dependent HIF1α increase, generating MMP9 that stimulates soluble-HB-EGF/EGFR-induced BBB disintegration. Consequently, CCH-mediated hippocampal RAGE and LRP-1 deregulation together with BBB damage impair Aβ transport and clearance

Iron inhibits respiratory burst of peritoneal phagocytes in vitro

DEFF Research Database (Denmark)

Gotfryd, Kamil; Jurek, Aleksandra; Kubit, Piotr

2011-01-01

Objective. This study examines the effects of iron ions Fe(3+) on the respiratory burst of phagocytes isolated from peritoneal effluents of continuous ambulatory peritoneal dialysis (CAPD) patients, as an in vitro model of iron overload in end-stage renal disease (ESRD). Material and Methods....... Respiratory burst of peritoneal phagocytes was measured by chemiluminescence method. Results. At the highest used concentration of iron ions Fe(3+) (100 µM), free radicals production by peritoneal phagocytes was reduced by 90% compared to control. Conclusions. Iron overload may increase the risk of infectious...

Impaired bolus clearance in combined high-resolution esophageal manometry and impedance measurement helps to differentiate between esophagogastric junction outflow obstruction and achalasia.

Science.gov (United States)

Zizer, Eugen; Seufferlein, Thomas; Hänle, Mark Martin

2017-02-01

Introduction and aims  High-resolution esophageal manometry (HRM) has improved the diagnostic work-up of esophageal motility disorders. Simultaneous evaluation of bolus clearance delivers useful information about the function of tubular esophagus. We assessed bolus clearance in a combined HRM-impedance examination for esophagogastric junction outflow obstruction (EGJOO) in comparison to achalasia patients. The collected data were assessed in a retrospective analysis. Patients and methods  After gastroscopy excluded a mechanical esophageal or gastric obstruction, 142 consecutive patients underwent combined HRM-impedance examination. The assessment and interpretation of the manometry results were done according to the Chicago Classification of esophageal motility disorders v3.0. After classifying the motility disorder, the evaluation of bolus clearance was done according to published studies. Results  All patients with achalasia (n = 24) showed a significantly impaired bolus clearance (achalasia cases. This might be helpful as an additional tool to differentiate between achalasia and EGJOO patients. Furthermore, the role of the combined impedance-HRM investigation for early diagnosis of achalasia in "pre-achalasia" condition or in evaluation of potential progress of EGJOO to achalasia should be evaluated in a prospective study. © Georg Thieme Verlag KG Stuttgart · New York.

High content analysis of phagocytic activity and cell morphology with PuntoMorph

DEFF Research Database (Denmark)

Al-Ali, Hassan; Gao, Han; Dalby-Hansen, Camilla

2017-01-01

methods for quantifying phagocytic activity in multiple dimensions including speed, accuracy, and resolution. Conclusions We provide a framework to facilitate the development of high content assays suitable for drug screening. For convenience, we implemented our algorithm in a standalone software package...... with image-based quantification of phagocytic activity. New method We present a robust algorithm and cell-based assay system for high content analysis of phagocytic activity. The method utilizes fluorescently labeled beads as a phagocytic substrate with defined physical properties. The algorithm employs...... content screening. Results We tested our assay system using microglial cultures. Our results recapitulated previous findings on the effects of microglial stimulation on cell morphology and phagocytic activity. Moreover, our cell-level analysis revealed that the two phenotypes associated with microglial...

Assessment of renal function with the Tc-99m-MAG3 clearance

International Nuclear Information System (INIS)

Keske, U.; Corcles, M.; Andreessen, R.; Wilfling, M.; Roll, D.; Gahl, G.; Felix, R.

1990-01-01

This paper evaluates the applicability of the 99m-Tc-mercaptoacetyle-triglycine (MAG3) clearance for the documentation of renal function. Renal clearance was measured with the method of Tauxe in 699 patients during routine renal scintigraphy with 80 MBq of 99mTc-MAG3. Serum creatinine level and MAG3 clearance show an inverse correlation. Patients with an elevated serum creatinine level constantly have a lowered MAG3 clearance and vice versa. For creatinine values lower than 1.8 mg/dL, minor changes in creatinine level are accompanied by large changes in MAG3 clearance. Age (in years) dependence of MAG3 clearance was evaluated in 487 patients who showed no evidence of impaired renal function

Mechanisms underlying the redistribution of particles among the lung's alveolar macrophages during alveolar phase clearance

Energy Technology Data Exchange (ETDEWEB)

Lehnert, B.E.; Oritz, J.B.; Steinkamp, J.A.; Tietjen, G.L.; Sebring, R.J. (Los Alamos National Lab., NM (United States)); Oberdorster, G. (Rochester Univ., NY (United States))

1991-01-01

In order to obtain information about the particle redistribution phenomenon following the deposition of inhaled particles, as well as to obtain information about some of the mechanisms that may be operable in the redistribution of particles, lavaged lung free cell analyses and transmission electron microscopic (TEM) analyses of lung tissue and were performed using lungs from rats after they were subchronically exposed to aerosolized dioxide (TiO{sub 2}). TEM analyses indicated that the in situ autolysis of particle-containing Alveolar Macropages (AM) is one important mechanism involved in the redistribution of particles. Evidence was also obtained that indicated that the engulfment of one particle-containing phagocyte by another phagocyte also occurs. Another prominent mechanism of the particle redistribution phenomenon may be the in situ proliferation of particle-laden AM. We used the macrophage cell line J774A.1 as a surrogate for AM to investigate how different particulate loads in macrophages may affect their abilities to proliferate. These in vitro investigations indicated that the normal rate of proliferation of macrophages is essentially unaffected by the containment of relatively high particulate burdens. Overall, the results of our investigations suggest that in situ autolysis of particle-containing AM and the rephagocytosis of freed particles by other phagocytes, the phagocytosis of effete and disintegrating particle-containing phagocytes by other AM, and the in situ division of particle-containing AM are likely mechanisms that underlie the post-depositional redistribution of particles among the lung's AM during alveolar phase clearance. 19 refs., 8 figs., 2 tabs.

A radiolabel release microassay for phagocytic killing of Candida albicans

International Nuclear Information System (INIS)

Bistoni, F.; Baccarini, M.; Blasi, E.; Marconi, P.; Puccetti, P.

1982-01-01

The chromium-51 release technique for quantifying intracellular killing of radiolabelled Candida albicans particles was exploited in a microassay in which murine and human phagocytes acted as effectors under peculiarly simple conditions. At appropriate effector: target ratios and with a 4 h incubation, up to 50% specific chromium release could be detected in the supernatant with no need for opsonization or lysis of phagocytes. This simple microassay permits easy-to-perform, simultaneous testing of a variety of different phagocytes even if only available in limited amounts, and provides an objective measurement of intracellular killing of Candida albicans. (Auth.)

Human and mouse mononuclear phagocyte networks: a tale of two species?

Directory of Open Access Journals (Sweden)

Gary eReynolds

2015-06-01

Full Text Available Dendritic cells (DCs, monocytes and macrophages are a heterogeneous population of mononuclear phagocytes that are involved in antigen processing and presentation to initiate and regulate immune responses to pathogens, vaccines, tumour and tolerance to self. In addition to their afferent sentinel function, DCs and macrophages are also critical as effectors and coordinators of inflammation and homeostasis in peripheral tissues. Harnessing DCs and macrophages for therapeutic purposes has major implications for infectious disease, vaccination, transplantation, tolerance induction, inflammation and cancer immunotherapy. There has been a paradigm shift in our understanding of the developmental origin and function of the cellular constituents of the mononuclear phagocyte system. Significant progress has been made in tandem in both human and mouse mononuclear phagocyte biology. This progress has been accelerated by comparative biology analysis between mouse and human, which has proved to be an exceptionally fruitful strategy to harmonise findings across species. Such analyses have provided unexpected insights and facilitated productive reciprocal and iterative processes to inform our understanding of human and mouse mononuclear phagocytes. In this review, we discuss the strategies, power and utility of comparative biology approaches to integrate recent advances in human and mouse mononuclear phagocyte biology and its potential to drive forward clinical translation of this knowledge. We also present a functional framework on the parallel organisation of human and mouse mononuclear phagocyte networks.

Nanoparticles of barium induce apoptosis in human phagocytes.

Science.gov (United States)

Mores, Luana; França, Eduardo Luzia; Silva, Núbia Andrade; Suchara, Eliane Aparecida; Honorio-França, Adenilda Cristina

2015-01-01

Nutrients and immunological factors of breast milk are essential for newborn growth and the development of their immune system, but this secretion can contain organic and inorganic toxins such as barium. Colostrum contamination with barium is an important issue to investigate because this naturally occurring element is also associated with human activity and industrial pollution. The study evaluated the administration of barium nanoparticles to colostrum, assessing the viability and functional activity of colostral mononuclear phagocytes. Colostrum was collected from 24 clinically healthy women (aged 18-35 years). Cell viability, superoxide release, intracellular Ca(2+) release, and phagocyte apoptosis were analyzed in the samples. Treatment with barium lowered mononuclear phagocyte viability, increased superoxide release, and reduced intracellular calcium release. In addition, barium increased cell death by apoptosis. These data suggest that nanoparticles of barium in colostrum are toxic to cells, showing the importance of avoiding exposure to this element.

The effect of core and lanthanide ion dopants in sodium fluoride-based nanocrystals on phagocytic activity of human blood leukocytes

Energy Technology Data Exchange (ETDEWEB)

Sojka, Bartlomiej [Wroclaw University of Science and Technology, Department of Experimental Physics (Poland); Liskova, Aurelia; Kuricova, Miroslava [Slovak Medical University, Medical Faculty, Department of Immunology and Immunotoxicology (Slovakia); Banski, Mateusz; Misiewicz, Jan [Wroclaw University of Science and Technology, Department of Experimental Physics (Poland); Dusinska, Maria [Norwegian Institute for Air Research, Health Effects Laboratory, Department of Environmental Chemistry (Norway); Horvathova, Mira; Ilavska, Silvia; Szabova, Michaela [Slovak Medical University, Medical Faculty, Department of Immunology and Immunotoxicology (Slovakia); Rollerova, Eva [Slovak Medical University, Faculty of Public Health, Department of Toxicology (Slovakia); Podhorodecki, Artur, E-mail: artur.p.podhorodecki@pwr.edu.pl [Wroclaw University of Science and Technology, Department of Experimental Physics (Poland); Tulinska, Jana, E-mail: jana.tulinska@szu.sk [Slovak Medical University, Medical Faculty, Department of Immunology and Immunotoxicology (Slovakia)

2017-02-15

Sodium fluoride-based β-NaLnF4 nanoparticles (NPs) doped with lanthanide ions are promising materials for application as luminescent markers in bio-imaging. In this work, the effect of NPs doped with yttrium (Y), gadolinium (Gd), europium (Eu), thulium (Tm), ytterbium (Yb) and terbium (Tb) ions on phagocytic activity of monocytes and granulocytes and the respiratory burst was examined. The surface functionalization of <10-nm NPs was performed according to our variation of patent pending ligand exchange method that resulted in meso-2,3-dimercaptosuccinic acid (DMSA) molecules on their surface. Y-core-based NCs were doped with Eu ions, which enabled them to be excited with UV light wavelengths. Cultures of human peripheral blood (n = 8) were in vitro treated with five different concentrations of eight NPs for 24 h. In summary, neither type of nanoparticles is found toxic with respect to conducted test; however, some cause toxic effects (they have statistically significant deviations compared to reference) in some selected doses tested. Both core types of NPs (Y-core and Gd-core) impaired the phagocytic activity of monocytes the strongest, having minimal or none whatsoever influence on granulocytes and respiratory burst of phagocytic cells. The lowest toxicity was observed in Gd-core, Yb, Tm dopants and near-infrared nanoparticles. Clear dose-dependent effect of NPs on phagocytic activity of leukocytes and respiratory burst of cells was observed for limited number of samples.

The effect of core and lanthanide ion dopants in sodium fluoride-based nanocrystals on phagocytic activity of human blood leukocytes

International Nuclear Information System (INIS)

Sojka, Bartlomiej; Liskova, Aurelia; Kuricova, Miroslava; Banski, Mateusz; Misiewicz, Jan; Dusinska, Maria; Horvathova, Mira; Ilavska, Silvia; Szabova, Michaela; Rollerova, Eva; Podhorodecki, Artur; Tulinska, Jana

2017-01-01

Sodium fluoride-based β-NaLnF4 nanoparticles (NPs) doped with lanthanide ions are promising materials for application as luminescent markers in bio-imaging. In this work, the effect of NPs doped with yttrium (Y), gadolinium (Gd), europium (Eu), thulium (Tm), ytterbium (Yb) and terbium (Tb) ions on phagocytic activity of monocytes and granulocytes and the respiratory burst was examined. The surface functionalization of <10-nm NPs was performed according to our variation of patent pending ligand exchange method that resulted in meso-2,3-dimercaptosuccinic acid (DMSA) molecules on their surface. Y-core-based NCs were doped with Eu ions, which enabled them to be excited with UV light wavelengths. Cultures of human peripheral blood (n = 8) were in vitro treated with five different concentrations of eight NPs for 24 h. In summary, neither type of nanoparticles is found toxic with respect to conducted test; however, some cause toxic effects (they have statistically significant deviations compared to reference) in some selected doses tested. Both core types of NPs (Y-core and Gd-core) impaired the phagocytic activity of monocytes the strongest, having minimal or none whatsoever influence on granulocytes and respiratory burst of phagocytic cells. The lowest toxicity was observed in Gd-core, Yb, Tm dopants and near-infrared nanoparticles. Clear dose-dependent effect of NPs on phagocytic activity of leukocytes and respiratory burst of cells was observed for limited number of samples.

Dying cell clearance and its impact on the outcome of tumor radiotherapy

International Nuclear Information System (INIS)

Lauber, Kirsten; Ernst, Anne; Orth, Michael; Herrmann, Martin; Belka, Claus

2012-01-01

The induction of tumor cell death is one of the major goals of radiotherapy and has been considered to be the central determinant of its therapeutic outcome for a long time. However, accumulating evidence suggests that the success of radiotherapy does not only derive from direct cytotoxic effects on the tumor cells alone, but instead might also depend – at least in part – on innate as well as adaptive immune responses, which can particularly target tumor cells that survive local irradiation. The clearance of dying tumor cells by phagocytic cells of the innate immune system represents a crucial step in this scenario. Dendritic cells and macrophages, which engulf, process and present dying tumor cell material to adaptive immune cells, can trigger, skew, or inhibit adaptive immune responses, respectively. In this review we summarize the current knowledge of different forms of cell death induced by ionizing radiation, the multi-step process of dying cell clearance, and its immunological consequences with special regard toward the potential exploitation of these mechanisms for the improvement of tumor radiotherapy.

p85α recruitment by the CD300f phosphatidylserine receptor mediates apoptotic cell clearance required for autoimmunity suppression

Science.gov (United States)

Tian, Linjie; Choi, Seung-Chul; Murakami, Yousuke; Allen, Joselyn; Morse, Herbert C., III; Qi, Chen-Feng; Krzewski, Konrad; Coligan, John E.

2014-01-01

Apoptotic cell (AC) clearance is essential for immune homeostasis. Here we show that mouse CD300f (CLM-1) recognizes outer membrane-exposed phosphatidylserine, and regulates the phagocytosis of ACs. CD300f accumulates in phagocytic cups at AC contact sites. Phosphorylation within CD300f cytoplasmic tail tyrosine-based motifs initiates signals that positively or negatively regulate AC phagocytosis. Y276 phosphorylation is necessary for enhanced CD300f-mediated phagocytosis through the recruitment of the p85α regulatory subunit of phosphatidylinositol-3-kinase (PI3K). CD300f-PI3K association leads to activation of downstream Rac/Cdc42 GTPase and mediates changes of F-actin that drive AC engulfment. Importantly, primary macrophages from CD300f-deficient mice have impaired phagocytosis of ACs. The biological consequence of CD300f deficiency is predisposition to autoimmune disease development, as FcγRIIB-deficient mice develop a systemic lupus erythematosus-like disease at a markedly accelerated rate if CD300f is absent. In this report we identify the mechanism and role of CD300f in AC phagocytosis and maintenance of immune homeostasis.

Clearance systems in the brain—implications for Alzheimer disease

Science.gov (United States)

Tarasoff-Conway, Jenna M.; Carare, Roxana O.; Osorio, Ricardo S.; Glodzik, Lidia; Butler, Tracy; Fieremans, Els; Axel, Leon; Rusinek, Henry; Nicholson, Charles; Zlokovic, Berislav V.; Frangione, Blas; Blennow, Kaj; Ménard, Joël; Zetterberg, Henrik; Wisniewski, Thomas; de Leon, Mony J.

2015-01-01

Accumulation of toxic protein aggregates—amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles—is the pathological hallmark of Alzheimer disease (AD). Aβ accumulation has been hypothesized to result from an imbalance between Aβ production and clearance; indeed, Aβ clearance seems to be impaired in both early and late forms of AD. To develop efficient strategies to slow down or halt AD, it is critical to understand how Aβ is cleared from the brain. Extracellular Aβ deposits can be removed from the brain by various clearance systems, most importantly, transport across the blood–brain barrier. Findings from the past few years suggest that astroglial-mediated interstitial fluid (ISF) bulk flow, known as the glymphatic system, might contribute to a larger portion of extracellular Aβ (eAβ) clearance than previously thought. The meningeal lymphatic vessels, discovered in 2015, might provide another clearance route. Because these clearance systems act together to drive eAβ from the brain, any alteration to their function could contribute to AD. An understanding of Aβ clearance might provide strategies to reduce excess Aβ deposits and delay, or even prevent, disease onset. In this Review, we describe the clearance systems of the brain as they relate to proteins implicated in AD pathology, with the main focus on Aβ. PMID:26195256

Clearance systems in the brain-implications for Alzheimer disease.

Science.gov (United States)

Tarasoff-Conway, Jenna M; Carare, Roxana O; Osorio, Ricardo S; Glodzik, Lidia; Butler, Tracy; Fieremans, Els; Axel, Leon; Rusinek, Henry; Nicholson, Charles; Zlokovic, Berislav V; Frangione, Blas; Blennow, Kaj; Ménard, Joël; Zetterberg, Henrik; Wisniewski, Thomas; de Leon, Mony J

2015-08-01

Accumulation of toxic protein aggregates-amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles-is the pathological hallmark of Alzheimer disease (AD). Aβ accumulation has been hypothesized to result from an imbalance between Aβ production and clearance; indeed, Aβ clearance seems to be impaired in both early and late forms of AD. To develop efficient strategies to slow down or halt AD, it is critical to understand how Aβ is cleared from the brain. Extracellular Aβ deposits can be removed from the brain by various clearance systems, most importantly, transport across the blood-brain barrier. Findings from the past few years suggest that astroglial-mediated interstitial fluid (ISF) bulk flow, known as the glymphatic system, might contribute to a larger portion of extracellular Aβ (eAβ) clearance than previously thought. The meningeal lymphatic vessels, discovered in 2015, might provide another clearance route. Because these clearance systems act together to drive eAβ from the brain, any alteration to their function could contribute to AD. An understanding of Aβ clearance might provide strategies to reduce excess Aβ deposits and delay, or even prevent, disease onset. In this Review, we describe the clearance systems of the brain as they relate to proteins implicated in AD pathology, with the main focus on Aβ.

The perivascular phagocyte of the mouse pineal gland: An antigen-presenting cell

DEFF Research Database (Denmark)

Møller, Morten; Rath, Martin F; Klein, David C

2006-01-01

The perivascular space of the rat pineal gland is known to contain phagocytic cells that are immunoreactive for leukocyte antigens, and thus they appear to belong to the macrophage/microglial cell line. These cells also contain MHC class II proteins. We investigated this cell type in the pineal g...... for MHC class II protein and for CD68, a marker of monocytes/phagocytes. This study verifies that perivascular phagocytes with antigen-presenting properties are present in the mouse pineal gland....

Impairment of the glymphatic system after diabetes

DEFF Research Database (Denmark)

Jiang, Quan; Zhang, Li; Ding, Guangliang

2017-01-01

diabetes affects the glymphatic system. The current study is the first investigation of the effect of diabetes on the glymphatic system and the link between alteration of glymphatic clearance and cognitive impairment in Type-2 diabetes mellitus rats. MRI analysis revealed that clearance of cerebrospinal...... to the retention of Gd-DTPA contrast and fluorescent tracer in the hippocampus of Type-2 diabetes mellitus rats. Type-2 diabetes mellitus suppresses clearance of interstitial fluid in the hippocampus and hypothalamus, suggesting that an impairment of the glymphatic system contributes to Type-2 diabetes mellitus......The glymphatic system has recently been shown to clear brain extracellular solutes and abnormalities in glymphatic clearance system may contribute to both initiation and progression of neurological diseases. Despite that diabetes is known as a risk factor for vascular diseases, little is known how...

Body Mass Index Is Associated with Increased Creatinine Clearance by a Mechanism Independent of Body Fat Distribution

Science.gov (United States)

Gerchman, Fernando; Tong, Jenny; Utzschneider, Kristina M.; Zraika, Sakeneh; Udayasankar, Jayalakshmi; McNeely, Marguerite J.; Carr, Darcy B.; Leonetti, Donna L.; Young, Bessie A.; de Boer, Ian H.; Boyko, Edward J.; Fujimoto, Wilfred Y.; Kahn, Steven E.

2009-01-01

Context: Although obesity has been, in general, associated with glomerular hyperfiltration, visceral adiposity has been suggested to be associated with reduced glomerular filtration. Objective: The aim of the study was to evaluate the differential effects of obesity and body fat distribution on glomerular filtration. Design and Setting: We conducted a cross-sectional study of the Japanese-American community in Seattle, Washington. Participants: We studied a representative sample of second-generation Japanese-American men and women with normal glucose tolerance (n = 124) and impaired glucose metabolism (impaired fasting glucose and/or impaired glucose tolerance) (n = 144) residing in King County, Washington. Main Outcome Measures: Glomerular filtration rate was estimated by 24-h urinary creatinine clearance, body size by body mass index (BMI), and intra-abdominal fat (IAF), sc fat (SCF), and lean thigh areas by CT scan. Results: Creatinine clearance was positively correlated with BMI (r = 0.429; P creatinine clearance and BMI remained significant after adjustments for IAF, SCF areas, and fasting insulin levels (r = 0.337; P creatinine clearance after adjusting for BMI. Creatinine clearance increased with increasing BMI after adjusting for fasting insulin, fasting glucose, IAF and SCF areas in subjects with normal glucose tolerance (r = 0.432; P metabolism (r = 0.471; P creatinine clearance in nondiabetic subjects. Lean body mass, rather than adiposity, may explain this association. PMID:19584179

Effect of influenza infection on the phagocytic and bactericidal activities of pulmonary macrophages

International Nuclear Information System (INIS)

Nugent, K.M.; Pesanti, E.L.

1979-01-01

The effect of mouse-adapted influenza A/PR/8/34 virus on pulmonary macrophage function was evaluated by using an in vitro system which allowed direct virus interaction with macrophages and then separate analysis of the steps required for bacterial clearance by macrophages. Infection of macrophages with this virus resulted in the appearance of a hemagglutinating activity on the macrophage surface; expression of this activity was inhibited by amantadine, 2-deoxyglucose, and cycloheximide and by pretreatment of the virus inoculum with with ultraviolet light and specific antiserum. After influenza infection, net ingestion of viable Staphylococcus aureus by macrophage monolayers was unaltered and there was no change in the fraction of the monolayer which ingested cocci over a wide range of bacterial inputs. Influenza-infected microphages also inactivated intracellular S. aureus at a rate indistinguishable from controls. Therefore, these in vitro studies do not support the hypothesis that the defect in pulmonary antibacterial mechanisms associated with influenza infections results from a direct effect of virus infection on either the phagocytic or bactericidal activity of resistant pulmonary macarophages

Protein clearance from the air spaces and lungs of unanesthetized sheep over 144 h

International Nuclear Information System (INIS)

Berthiaume, Y.; Albertine, K.H.; Grady, M.; Fick, G.; Matthay, M.A.

1989-01-01

We studied the rate, the routes, and the mechanisms for protein clearance from the air spaces and lungs of 20 unanesthetized sheep over 144 h. We instilled 100 ml of autologous serum labeled with 125I-albumin into one lung. At the end of 24, 48, 96, or 144 h, the lungs were removed and the residual native protein and 125I-albumin in the air spaces were determined by bronchoalveolar lavage. Also the fraction of the instilled 125I-albumin remaining in the rest of the lung was measured in the lung homogenate. Clearance of the 125I-albumin from the lung into the plasma, lymph, thyroid, urine, and feces was also determined. The removal of both the 125I-albumin and the native protein from the air spaces was slow, following a monoexponential decline. The removal rate of the 125I-albumin from the air spaces was slightly but significantly faster (1.6%/h) than the clearance rate of the native protein (0.9%/h). Clearance of the 125I-albumin from the lung also followed a slow monoexponential decline at a rate of 1.4%/h. At all time periods, 75% of the 125I-albumin remaining in the lung was located in the air spaces, thus indicating that the pulmonary epithelium is the principal barrier to protein clearance from the normal lung. Macrophages appeared to play a minor role in alveolar protein clearance because the quantity of 125I-albumin present in the phagocytic cells in the air spaces was less than 1% of the instilled 125I-albumin at all time periods. However, macrophages may play some role in protein clearance after 48 h because we visualized phagolysosomes in macrophages, and there was an increase in free iodine in lung lavage, urine, thyroid, and feces after 48 h. However, gel electrophoretic studies showed that most of the 125I-albumin was cleared from the lung as an intact molecule, although only 24.7 +/- 4.7% of the 125I-albumin was cleared by the lymphatics

Effects of Levamisole on Phagocytic Activity of Rainbow Trout (Oncorhynchus mykiss W.

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U. Ispir

2007-01-01

Full Text Available In this study, activation of phagocytic cells was examined in rainbow trout (Oncorhynchus mykiss W. exposed to 1, 5 and 10 μg ml-1 concentrations of levamisole solution. For this purpose, blood samples were taken from fish on days 1, 7 and 14 of exposure. Potential killing activity was determined by measuring oxidative radical production and phagocytic activity of neutrophils and superoxide anion production of phagocytic cells against Y. ruckeri. The activity of phagocytic cells in fish exposed to each of three concentrations was found higher than that in controls and the differences were statistically significant (p p -1 concentration of levamisole solution was determined on day 7, it was observed that all indicators increased on day 14 of exposure. The present results suggest that the application of levamisole in fish farms could increase non-specific immunity and resistance to infection of fish and offer economics benefits.

Phagocytic response of astrocytes to damaged neighboring cells.

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Nicole M Wakida

Full Text Available This study aims to understand the phagocytic response of astrocytes to the injury of neurons or other astrocytes at the single cell level. Laser nanosurgery was used to damage individual cells in both primary mouse cortical astrocytes and an established astrocyte cell line. In both cases, the release of material/substances from laser-irradiated astrocytes or neurons induced a phagocytic response in near-by astrocytes. Propidium iodide stained DNA originating from irradiated cells was visible in vesicles of neighboring cells, confirming phagocytosis of material from damaged cortical cells. In the presence of an intracellular pH indicator dye, newly formed vesicles correspond to acidic pH fluorescence, thus suggesting lysosome bound degradation of cellular debris. Cells with shared membrane connections prior to laser damage had a significantly higher frequency of induced phagocytosis compared to isolated cells with no shared membrane. The increase in phagocytic response of cells with a shared membrane occurred regardless of the extent of shared membrane (a thin filopodial connection vs. a cell cluster with significant shared membrane. In addition to the presence (or lack of a membrane connection, variation in phagocytic ability was also observed with differences in injury location within the cell and distance separating isolated astrocytes. These results demonstrate the ability of an astrocyte to respond to the damage of a single cell, be it another astrocyte, or a neuron. This single-cell level of analysis results in a better understanding of the role of astrocytes to maintain homeostasis in the CNS, particularly in the sensing and removal of debris in damaged or pathologic nervous tissue.

High content analysis of phagocytic activity and cell morphology with PuntoMorph.

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Al-Ali, Hassan; Gao, Han; Dalby-Hansen, Camilla; Peters, Vanessa Ann; Shi, Yan; Brambilla, Roberta

2017-11-01

Phagocytosis is essential for maintenance of normal homeostasis and healthy tissue. As such, it is a therapeutic target for a wide range of clinical applications. The development of phenotypic screens targeting phagocytosis has lagged behind, however, due to the difficulties associated with image-based quantification of phagocytic activity. We present a robust algorithm and cell-based assay system for high content analysis of phagocytic activity. The method utilizes fluorescently labeled beads as a phagocytic substrate with defined physical properties. The algorithm employs statistical modeling to determine the mean fluorescence of individual beads within each image, and uses the information to conduct an accurate count of phagocytosed beads. In addition, the algorithm conducts detailed and sophisticated analysis of cellular morphology, making it a standalone tool for high content screening. We tested our assay system using microglial cultures. Our results recapitulated previous findings on the effects of microglial stimulation on cell morphology and phagocytic activity. Moreover, our cell-level analysis revealed that the two phenotypes associated with microglial activation, specifically cell body hypertrophy and increased phagocytic activity, are not highly correlated. This novel finding suggests the two phenotypes may be under the control of distinct signaling pathways. We demonstrate that our assay system outperforms preexisting methods for quantifying phagocytic activity in multiple dimensions including speed, accuracy, and resolution. We provide a framework to facilitate the development of high content assays suitable for drug screening. For convenience, we implemented our algorithm in a standalone software package, PuntoMorph. Copyright © 2017 Elsevier B.V. All rights reserved.

Adenylate Cyclase Toxin promotes bacterial internalisation into non phagocytic cells.

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Martín, César; Etxaniz, Asier; Uribe, Kepa B; Etxebarria, Aitor; González-Bullón, David; Arlucea, Jon; Goñi, Félix M; Aréchaga, Juan; Ostolaza, Helena

2015-09-08

Bordetella pertussis causes whooping cough, a respiratory infectious disease that is the fifth largest cause of vaccine-preventable death in infants. Though historically considered an extracellular pathogen, this bacterium has been detected both in vitro and in vivo inside phagocytic and non-phagocytic cells. However the precise mechanism used by B. pertussis for cell entry, or the putative bacterial factors involved, are not fully elucidated. Here we find that adenylate cyclase toxin (ACT), one of the important toxins of B. pertussis, is sufficient to promote bacterial internalisation into non-phagocytic cells. After characterization of the entry route we show that uptake of "toxin-coated bacteria" proceeds via a clathrin-independent, caveolae-dependent entry pathway, allowing the internalised bacteria to survive within the cells. Intracellular bacteria were found inside non-acidic endosomes with high sphingomyelin and cholesterol content, or "free" in the cytosol of the invaded cells, suggesting that the ACT-induced bacterial uptake may not proceed through formation of late endolysosomes. Activation of Tyr kinases and toxin-induced Ca(2+)-influx are essential for the entry process. We hypothesize that B. pertussis might use ACT to activate the endocytic machinery of non-phagocytic cells and gain entry into these cells, in this way evading the host immune system.

The effect of loss of O-antigen ligase on phagocytic susceptibility of motile and non-motile Pseudomonas aeruginosa.

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Demirdjian, Sally; Schutz, Kristin; Wargo, Matthew J; Lam, Joseph S; Berwin, Brent

2017-12-01

The bacterial pathogen Pseudomonas aeruginosa undergoes adaptation and selection over the course of chronic respiratory tract infections which results in repeatedly-observed phenotypic changes that are proposed to enable its persistence. Two of the clinically significant P. aeruginosa phenotypic changes are loss of flagellar motility and modifications to LPS structure, including loss of O-antigen expression. The effect of loss of O-antigen, frequently described as conversion from smooth to rough LPS, and the combined effect of loss of motility and O-antigen on phagocytic susceptibility by immune cells remain unknown. To address this, we generated genetic deletion mutants of waaL, which encodes the O-antigen ligase responsible for linking O-antigen to lipid A-core oligosaccharide, in both motile and non-motile P. aeruginosa strains. With the use of these bacterial strains we provide the first demonstration that, despite a progressive selection for P. aeruginosa with rough LPS during chronic pulmonary infections, loss of the LPS O-antigen does not confer phagocytic resistance in vitro. However, use of the waaLmotABmotCD mutant revealed that loss of motility confers resistance to phagocytosis regardless of the smooth or rough LPS phenotype. These findings reveal how the O-antigen of P. aeruginosa can influence bacterial clearance during infection and expand our current knowledge about the impact of bacterial phenotypic changes during chronic infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Diversity and functions of intestinal mononuclear phagocytes

DEFF Research Database (Denmark)

Joeris, Thorsten; Müller-Luda, K; Agace, William Winston

2017-01-01

The intestinal lamina propria (LP) contains a diverse array of mononuclear phagocyte (MNP) subsets, including conventional dendritic cells (cDC), monocytes and tissue-resident macrophages (mφ) that collectively play an essential role in mucosal homeostasis, infection and inflammation. In the curr......The intestinal lamina propria (LP) contains a diverse array of mononuclear phagocyte (MNP) subsets, including conventional dendritic cells (cDC), monocytes and tissue-resident macrophages (mφ) that collectively play an essential role in mucosal homeostasis, infection and inflammation....... In the current review we discuss the function of intestinal cDC and monocyte-derived MNP, highlighting how these subsets play several non-redundant roles in the regulation of intestinal immune responses. While much remains to be learnt, recent findings also underline how the various populations of MNP adapt...

DMPD: Regulation of phagocyte migration and recruitment by Src-family kinases. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 18385944 Regulation of phagocyte migration and recruitment by Src-family kinases. B...how Regulation of phagocyte migration and recruitment by Src-family kinases. PubmedID 18385944 Title Regulat...ion of phagocyte migration and recruitment by Src-family kinases. Authors Baruzzi

Suppression and recovery of the alveolar macrophage phagocytic system during continuous exposure to 0. 5 ppm ozone

Energy Technology Data Exchange (ETDEWEB)

Gilmour, M.I.; Hmieleski, R.R.; Stafford, E.A.; Jakab, G.J. (Johns Hopkins University, School of Hygiene and Public Health, Baltimore, MD (USA))

1991-05-01

Short-term exposures to ozone (O3) are known to impair pulmonary antibacterial defenses and alveolar macrophage (AM) phagocytosis in a dose-related manner. To determine the effect of prolonged O3 exposure, Swiss mice were exposed continuously to 0.5 ppm O3. At 1, 3, 7, and 14 days, intrapulmonary killing was assessed by inhalation challenge with Staphylococcus aureus or Proteus mirabilis and by comparing the number of viable bacteria remaining in the lungs at 4 h between O3-exposed and control animals. To evaluate the effects of O3 on the functional capacity of the AMs, Fc-receptor mediated phagocytosis was assessed. Ozone exposure impaired the intrapulmonary killing of S. aureus at 1 and 3 days; however, with prolonged exposure, the bactericidal capacity of the lungs returned to normal. This trend of an initial suppression followed by recovery was reflected in the phagocytic capacity of the AMs. In contrast to S. aureus, when P. mirabilis was used as the challenge organism, O3 exposure had no suppressive effect on pulmonary bactericidal activity, which correlated with an increase in the phagocytic cell population in the lungs. Morphologic examination of the lavaged macrophages showed that after 1 day of O3 exposure, the AMs were more foamy, and contained significantly more vacuoles. There was also a significant increase in binucleated cells at 3 days. These studies demonstrate that continuous exposure to O3 modulates AM-dependent lung defenses and points to the importance of the challenge organism and exposure protocol in establishing the adverse effect of O3.

Hepatic drug clearance following traumatic injury.

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Slaughter, R L; Hassett, J M

1985-11-01

Trauma is a complex disease state associated with physiologic changes that have the potential to alter hepatic drug clearance mechanisms. These responses include alterations in hepatic blood flow, reduction in hepatic microsomal activity, reduction in hepatic excretion processes, and changes in protein binding. Hepatic blood flow is influenced by sympathomimetic activity. Both animal and human studies demonstrate an initial reduction and subsequent increase in hepatic blood flow, which coincides with an observed increase and subsequent return to normal in serum catecholamine concentrations. Unfortunately, there are no human studies that address the importance these findings may have to the clearance processes of high intrinsic clearance compounds. Animal studies of trauma indicate that hepatic microsomal activity is depressed during the post-traumatic period. Reduction in the hepatic clearance of antipyrine, a model low intrinsic compound, has also been demonstrated in animal models of trauma. In addition to these effects, hepatic excretion of substances such as indocyanine green and bilirubin have been demonstrated to be impaired in both traumatized animals and humans. Finally, substantial increases in the serum concentration of the binding protein alpha 1-acid glycoprotein occur in trauma patients. This has been reported to be associated with subsequent decreases in the free fraction of lidocaine and quinidine. In addition to changing serum drug concentration/response relationships, the pharmacokinetic behavior of drugs bound to alpha 1-acid glycoprotein should also change. Preliminary observations in our laboratory in a dog model of surgically-induced trauma have shown a reduction in the total clearance of lidocaine and reduction in free lidocaine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

133 xenon muscle clearance as a test parameter in the diagnosis of peripheral diabetic angiopathies

International Nuclear Information System (INIS)

Kuhlmann, J.E.

1980-01-01

In 100 patients with manifest diabetes mellitus the irrigation in both legs at rest and in radioactive hyperemia after ischemic muscle work was measured by means of the 133-xenon muscle clearance. The clearance values measured ranged between 0.8 and 3.5 ml/100 g/60 s at rest and between 3.3 and 40.0 ml/100 gl/60 s during radioactive hyperemia. In 96 pc of the probands the irrigation of the legs was impaired. For the relation between glucose level and irrigation at rest a significant negative correlation was found. The difference between the clearance values for the right and left lower extremity was significant. For the relation between glucose level and reactive hyperemia, too, a significant negative correlation was found. The difference between the clearance values for the right and left lower extremities was significant. The measurement of the irrigation at rest showed no significant correlation between the period of manifestation of the diabetes and the clearance values. By contrast, the irrigation values during reactive hyperemia were shown to be in significantly negative correlation to the duration of the diabetes. No connection was found between the frequency of diabetic gangrene and impaired irrigation at rest. By contrast, there was a relation between decreasing hyperemia values and increased frequency of gangrene. A collection of case histories shows how the measuring results of the xenon clearance fit into the overall clinical picture. A comparison of xenon clearance with other methods of irrigation measurement confirmed obvious advantages of xenon clearance for the detection of diabetic microangiopathies. (orig./MG) [de

LRP1 in Brain Vascular Smooth Muscle Cells Mediates Local Clearance of Alzheimer's Amyloid-β

OpenAIRE

Kanekiyo, Takahisa; Liu, Chia-Chen; Shinohara, Mitsuru; Li, Jie; Bu, Guojun

2012-01-01

Impaired clearance of amyloid-β (Aβ) is a major pathogenic event for Alzheimer’s disease (AD). Aβ depositions in brain parenchyma as senile plaques and along cerebrovasculature as cerebral amyloid angiopathy (CAA) are hallmarks of AD. A major pathway that mediates brain Aβ clearance is the cerebrovascular system where Aβ is eliminated through the blood-brain barrier (BBB) and/or degraded by cerebrovascular cells along the interstitial fluid drainage pathway. An Aβ clearance receptor, the low-...

Fungal invasion of normally non-phagocytic host cells.

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Scott G Filler

2006-12-01

Full Text Available Many fungi that cause invasive disease invade host epithelial cells during mucosal and respiratory infection, and subsequently invade endothelial cells during hematogenous infection. Most fungi invade these normally non-phagocytic host cells by inducing their own uptake. Candida albicans hyphae interact with endothelial cells in vitro by binding to N-cadherin on the endothelial cell surface. This binding induces rearrangement of endothelial cell microfilaments, which results in the endocytosis of the organism. The capsule of Cryptococcus neoformans is composed of glucuronoxylomannan, which binds specifically to brain endothelial cells, and appears to mediate both adherence and induction of endocytosis. The mechanisms by which other fungal pathogens induce their own uptake are largely unknown. Some angioinvasive fungi, such as Aspergillus species and the Zygomycetes, invade endothelial cells from the abluminal surface during the initiation of invasive disease, and subsequently invade the luminal surface of endothelial cells during hematogenous dissemination. Invasion of normally non-phagocytic host cells has different consequences, depending on the type of invading fungus. Aspergillus fumigatus blocks apoptosis of pulmonary epithelial cells, whereas Paracoccidioides brasiliensis induces apoptosis of epithelial cells. This review summarizes the mechanisms by which diverse fungal pathogens invade normally non-phagocytic host cells and discusses gaps in our knowledge that provide opportunities for future research.

Autophagy Proteins in Phagocyte Endocytosis and Exocytosis

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Christian Münz

2017-09-01

Full Text Available Autophagy was initially described as a catabolic pathway that recycles nutrients of cytoplasmic constituents after lysosomal degradation during starvation. Since the immune system monitors products of lysosomal degradation via major histocompatibility complex (MHC class II restricted antigen presentation, autophagy was found to process intracellular antigens for display on MHC class II molecules. In recent years, however, it has become apparent that the molecular machinery of autophagy serves phagocytes in many more membrane trafficking pathways, thereby regulating immunity to infectious disease agents. In this minireview, we will summarize the recent evidence that autophagy proteins regulate phagocyte endocytosis and exocytosis for myeloid cell activation, pathogen replication, and MHC class I and II restricted antigen presentation. Selective stimulation and inhibition of the respective functional modules of the autophagy machinery might constitute valid therapeutic options in the discussed disease settings.

Insulin resistance and delayed clearance of peptide hormones in cirrhotic rat liver

International Nuclear Information System (INIS)

Shankar, T.P.; Drake, S.; Solomon, S.S.

1987-01-01

Clearance of porcine insulin, glucagon, and human growth hormone was measured in intact perfused cirrhotic and normal rat livers. Binding and degradation of 125 I-insulin by hepatocytes isolated from cirrhotic and normal livers were also studied. The half-lives (t/sub 1/2/) of immunoreactive insulin and glucagon were 14.0 +/- 3.1 and 9.6 +/- 2.1 min in normal livers and 26.0 +/- 6.1 and 25.0 +/- 7.1 min in cirrhotic livers. Insulin binding and degradation by hepatocytes from control and cirrhotic livers showed no significant differences. Intraportal insulin infusion in perfusion studies suppressed glucagon-stimulated increases in glucose output from control livers but failed to suppress glucose production by cirrhotic livers, suggesting the presence of hepatic insulin resistance in cirrhosis. Impaired clearance of insulin and glucagon by the intact cirrhotic liver and normal binding and degradation of insulin by isolated hepatocytes suggest that factors such as intrahepatic fibrosis and shunting and postbinding defects may be responsible for the impaired hormone clearance and hepatic insulin resistance

Hepatic macrophage complement receptor clearance function following injury.

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Cuddy, B G; Loegering, D J; Blumenstock, F A; Shah, D M

1986-03-01

Previous work has demonstrated that in vivo hepatic macrophage complement receptor clearance function is depressed following thermal injury. The present study was carried out to determine if complement receptor function depression is associated with other states of depressed host defense. Hepatic complement receptor clearance function was determined from the hepatic uptake of rat erythrocytes coated with antierythrocyte IgM (EIgM) in rats. Receptor function was determined following cannulation of a carotid artery, laparotomy plus enterotomy, hemorrhagic shock, trauma, thermal injury, acute bacteremia, acute endotoxemia, and injection of erythrocyte stroma, gelatinized lipid emulsion, or colloidal carbon. Hepatic uptake of EIgM was depressed following each of these experimental interventions except arterial cannulation. This effect was shown not to be due to a decrease in hepatic blood flow or depletion of complement and was therefore due to a depression in hepatic macrophage complement receptor clearance function. Thus, impairment of hepatic macrophage complement receptor function is associated with several states of depressed host defense.

[Effect of general magnetotherapy on specific activity of blood phagocytes in patients with ischemic heart disease].

Science.gov (United States)

Ishutin, I S; Klemenkov, S V; Lesovskaia, M I; Spiridonova, M S; Krotova, T K; Ishutin, E I; Tsyganova, O B

2007-01-01

In general magnetotherapy for patients with hyporeactive phagocytes (less than 67% from the level of normal chelicoluminescent response) the adequate level of magnetic induction is 1 mT, for patients with normoreactive phagocytes--0.5 mT and for patients with hyperreactive phagocytes (more than 133% from the level of normal chelicoluminescent response)--0.75 mT daily.

Effects of Enrofloxacin on Porcine Phagocytic Function

Science.gov (United States)

Schoevers, E. J.; van Leengoed, L. A. M. G.; Verheijden, J. H. M.; Niewold, T. A.

1999-01-01

The interaction between enrofloxacin and porcine phagocytes was studied with clinically relevant concentrations of enrofloxacin. Enrofloxacin accumulated in phagocytes, with cellular concentration/extracellular concentration ratios of 9 for polymorphonuclear leukocytes (PMNs) and 5 for alveolar macrophages (AMs). Cells with accumulated enrofloxacin brought into enrofloxacin-free medium released approximately 80% (AMs) to 90% (PMNs) of their enrofloxacin within the first 10 min, after which no further release was seen. Enrofloxacin affected neither the viability of PMNs and AMs nor the chemotaxis of PMNs at concentrations ranging from 0 to 10 μg/ml. Enrofloxacin (0.5 μg/ml) did not alter the capability of PMNs and AMs to phagocytize fluorescent microparticles or Actinobacillus pleuropneumoniae, Pasteurella multocida, and Staphylococcus aureus. Significant differences in intracellular killing were seen with enrofloxacin at 5× the MIC compared with that for controls not treated with enrofloxacin. PMNs killed all S. aureus isolates in 3 h with or without enrofloxacin. Intracellular S. aureus isolates in AMs were less susceptible than extracellular S. aureus isolates to the bactericidal effect of enrofloxacin. P. multocida was not phagocytosed by PMNs. AMs did not kill P. multocida, and similar intra- and extracellular reductions of P. multocida isolates by enrofloxacin were found. Intraphagocytic killing of A. pleuropneumoniae was significantly enhanced by enrofloxacin at 5× the MIC in both PMNs and AMs. AMs are very susceptible to the A. pleuropneumoniae cytotoxin. This suggests that in serologically naive pigs the enhancing effect of enrofloxacin on the bactericidal action of PMNs may have clinical relevance. PMID:10471554

Impaired clearance of influenza A virus in obese, leptin receptor deficient mice is independent of leptin signaling in the lung epithelium and macrophages.

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Kathryn A Radigan

Full Text Available During the recent H1N1 outbreak, obese patients had worsened lung injury and increased mortality. We used a murine model of influenza A pneumonia to test the hypothesis that leptin receptor deficiency might explain the enhanced mortality in obese patients.We infected wild-type, obese mice globally deficient in the leptin receptor (db/db and non-obese mice with tissue specific deletion of the leptin receptor in the lung epithelium (SPC-Cre/LepR fl/fl or macrophages and alveolar type II cells (LysM-Cre/Lepr fl/fl with influenza A virus (A/WSN/33 [H1N1] (500 and 1500 pfu/mouse and measured mortality, viral clearance and several markers of lung injury severity.The clearance of influenza A virus from the lungs of mice was impaired in obese mice globally deficient in the leptin receptor (db/db compared to normal weight wild-type mice. In contrast, non-obese, SP-C-Cre+/+/LepR fl/fl and LysM-Cre+/+/LepR fl/fl had improved viral clearance after influenza A infection. In obese mice, mortality was increased compared with wild-type mice, while the SP-C-Cre+/+/LepR fl/fl and LysM-Cre+/+/LepR fl/fl mice exhibited improved survival.Global loss of the leptin receptor results in reduced viral clearance and worse outcomes following influenza A infection. These findings are not the result of the loss of leptin signaling in lung epithelial cells or macrophages. Our results suggest that factors associated with obesity or with leptin signaling in non-myeloid populations such as natural killer and T cells may be associated with worsened outcomes following influenza A infection.

Impairment of innate immune responses in cirrhotic patients and treatment by branched-chain amino acids

Science.gov (United States)

Nakamura, Ikuo

2014-01-01

It has been reported that host defense responses, such as phagocytic function of neutrophils and natural killer (NK) cell activity of lymphocytes, are impaired in cirrhotic patients. This review will concentrate on the impairment of innate immune responses in decompensated cirrhotic patients and the effect of the treatment by branched-chain amino acids (BCAA) on innate immune responses. We already reported that phagocytic function of neutrophils was significantly improved by 3-mo BCAA supplementation. In addition, the changes of NK activity were also significant at 3 mo of supplementation compared with before supplementation. Also, Fisher’s ratios were reported to be significantly increased at 3 mo of BCAA supplementation compared with those before oral supplementation. Therefore, administration of BCAA could reduce the risk of bacterial and viral infection in patients with decompensated cirrhosis by restoring impaired innate immune responses of the host. In addition, it was also revealed that BCAA oral supplementation could reduce the risk of development of hepatocellular carcinoma in cirrhotic patients. The mechanisms of the effects will also be discussed in this review article. PMID:24966600

Reciprocal upregulation of scavenger receptors complicates interpretation of nanoparticle uptake in non-phagocytic cells

NARCIS (Netherlands)

Prapainop, Kanlaya; Miao, Rong; Åberg, Christoffer; Salvati, Anna; Dawson, Kenneth A

2017-01-01

Nanoparticles have great potential as drug delivery vehicles or as imaging agents for treatment and diagnosis of various diseases. It is therefore crucial to understand how nanoparticles are taken up by cells, both phagocytic and non-phagocytic. Small interference RNA has previously been used to

Plasminogen activator inhibitor type 1 regulates microglial motility and phagocytic activity

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Jeon Hyejin

2012-06-01

Full Text Available Abstract Background Plasminogen activator inhibitor type 1 (PAI-1 is the primary inhibitor of urokinase type plasminogen activators (uPA and tissue type plasminogen activators (tPA, which mediate fibrinolysis. PAI-1 is also involved in the innate immunity by regulating cell migration and phagocytosis. However, little is known about the role of PAI-1 in the central nervous system. Methods In this study, we identified PAI-1 in the culture medium of mouse mixed glial cells by liquid chromatography and tandem mass spectrometry. Secretion of PAI-1 from glial cultures was detected by ELISA and western blotting analysis. Cell migration was evaluated by in vitro scratch-wound healing assay or Boyden chamber assay and an in vivo stab wound injury model. Phagocytic activity was measured by uptake of zymosan particles. Results The levels of PAI-1 mRNA and protein expression were increased by lipopolysaccharide and interferon-γ stimulation in both microglia and astrocytes. PAI-1 promoted the migration of microglial cells in culture via the low-density lipoprotein receptor-related protein (LRP 1/Janus kinase (JAK/signal transducer and activator of transcription (STAT1 axis. PAI-1 also increased microglial migration in vivo when injected into mouse brain. PAI-1-mediated microglial migration was independent of protease inhibition, because an R346A mutant of PAI-1 with impaired PA inhibitory activity also promoted microglial migration. Moreover, PAI-1 was able to modulate microglial phagocytic activity. PAI-1 inhibited microglial engulfment of zymosan particles in a vitronectin- and Toll-like receptor 2/6-dependent manner. Conclusion Our results indicate that glia-derived PAI-1 may regulate microglial migration and phagocytosis in an autocrine or paracrine manner. This may have important implications in the regulation of brain microglial activities in health and disease.

Effect of ovarian hormones on the phagocytic response of ovariectomized mares.

Science.gov (United States)

Ganjam, V K; McLeod, C; Klesius, P H; Washburn, S M; Kwapien, R; Brown, B; Fazeli, M H

1982-01-01

The reaction between ovarian hormones and experimental uterine infection (Streptococcus zooepidemicus) was investigated in 3 groups, each containing 6 ovariectomized mares. Group 1 served as controls ('anoestrus'), Group 2 mares were injected with oestrogen ('oestrus') and Group 3 with progesterone ('dioestrus') over a period of 5 weeks. All mares received an intrauterine inoculation of the bacteria 1 week after the start of hormonal treatment, and the results of the challenge were examined by endometrial biopsy and swabs once weekly. At the end of Week 1 no bacteria were recovered from the mares in Group 2. Group 1 mares were free of bacteria at the end of Week 2 but all Group 3 mares remained infected at least for the total period examined. Streptococcal phagocytosis was quantitated by chemiluminescence. Before the challenge-inoculation, phagocytosis was not significantly different in the 3 groups of mares. Bacterial cultures were negative for all three groups. However, within 48 h after infection, there was a significant increase (P less than 0.01) in phagocytosis in Group 2 and a significant suppression (P less than 0.05) in Group 3 mares. Patterns of streptococcal clearance from the uterus closely paralleled the changes in the magnitude of chemiluminescence response. The results suggest that ovarian hormonal status can modulate the phagocytic response in episodes of streptococcal-induced endometritus in mares.

Dysregulation of Nutrient Sensing and CLEARance in Presenilin Deficiency

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Kavya Reddy

2016-03-01

Full Text Available Attenuated auto-lysosomal system has been associated with Alzheimer disease (AD, yet all underlying molecular mechanisms leading to this impairment are unknown. We show that the amino acid sensing of mechanistic target of rapamycin complex 1 (mTORC1 is dysregulated in cells deficient in presenilin, a protein associated with AD. In these cells, mTORC1 is constitutively tethered to lysosomal membranes, unresponsive to starvation, and inhibitory to TFEB-mediated clearance due to a reduction in Sestrin2 expression. Normalization of Sestrin2 levels through overexpression or elevation of nuclear calcium rescued mTORC1 tethering and initiated clearance. While CLEAR network attenuation in vivo results in buildup of amyloid, phospho-Tau, and neurodegeneration, presenilin-knockout fibroblasts and iPSC-derived AD human neurons fail to effectively initiate autophagy. These results propose an altered mechanism for nutrient sensing in presenilin deficiency and underline an importance of clearance pathways in the onset of AD.

Value of phagocyte function screening for immunotoxicity of nanoparticles in vivo

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Fröhlich E

2015-05-01

Full Text Available Eleonore Fröhlich Center for Medical Research, Medical University of Graz, Graz, Austria Abstract: Nanoparticles (NPs present in the environment and in consumer products can cause immunotoxic effects. The immune system is very complex, and in vivo studies are the gold standard for evaluation. Due to the increased amount of NPs that are being developed, cellular screening assays to decrease the amount of NPs that have to be tested in vivo are highly needed. Effects on the unspecific immune system, such as effects on phagocytes, might be suitable for screening for immunotoxicity because these cells mediate unspecific and specific immune responses. They are present at epithelial barriers, in the blood, and in almost all organs. This review summarizes the effects of carbon, metal, and metal oxide NPs used in consumer and medical applications (gold, silver, titanium dioxide, silica dioxide, zinc oxide, and carbon nanotubes and polystyrene NPs on the immune system. Effects in animal exposures through different routes are compared to the effects on isolated phagocytes. In addition, general problems in the testing of NPs, such as unknown exposure doses, as well as interference with assays are mentioned. NPs appear to induce a specific immunotoxic pattern consisting of the induction of inflammation in normal animals and aggravation of pathologies in disease models. The evaluation of particle action on several phagocyte functions in vitro may provide an indication on the potency of the particles to induce immunotoxicity in vivo. In combination with information on realistic exposure levels, in vitro studies on phagocytes may provide useful information on the health risks of NPs. Keywords: immunotoxicity, phagocytes, cytokines, respiratory burst, nitric oxide generation, phagocytosis

Value of phagocyte function screening for immunotoxicity of nanoparticles in vivo.

Science.gov (United States)

Fröhlich, Eleonore

2015-01-01

Nanoparticles (NPs) present in the environment and in consumer products can cause immunotoxic effects. The immune system is very complex, and in vivo studies are the gold standard for evaluation. Due to the increased amount of NPs that are being developed, cellular screening assays to decrease the amount of NPs that have to be tested in vivo are highly needed. Effects on the unspecific immune system, such as effects on phagocytes, might be suitable for screening for immunotoxicity because these cells mediate unspecific and specific immune responses. They are present at epithelial barriers, in the blood, and in almost all organs. This review summarizes the effects of carbon, metal, and metal oxide NPs used in consumer and medical applications (gold, silver, titanium dioxide, silica dioxide, zinc oxide, and carbon nanotubes) and polystyrene NPs on the immune system. Effects in animal exposures through different routes are compared to the effects on isolated phagocytes. In addition, general problems in the testing of NPs, such as unknown exposure doses, as well as interference with assays are mentioned. NPs appear to induce a specific immunotoxic pattern consisting of the induction of inflammation in normal animals and aggravation of pathologies in disease models. The evaluation of particle action on several phagocyte functions in vitro may provide an indication on the potency of the particles to induce immunotoxicity in vivo. In combination with information on realistic exposure levels, in vitro studies on phagocytes may provide useful information on the health risks of NPs.

Ultrastuctural study of the phagocytic activities of splenic ...

African Journals Online (AJOL)

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Direct phagocytic reaction of cells in the presence of an antigen is therefore very important in immunity. Key words: ... The main lymphoid organs of fish are the thymus, the ... The innate (non-specific) immunity is thought to have a major role in ...

Plasmodium and mononuclear phagocytes.

Science.gov (United States)

Mac-Daniel, Laura; Ménard, Robert

2015-01-01

Plasmodium, the causative agent of malaria, initially multiplies inside liver cells and then in successive cycles inside erythrocytes, causing the symptoms of the disease. In this review, we discuss interactions between the extracellular and intracellular forms of the Plasmodium parasite and innate immune cells in the mammalian host, with a special emphasis on mononuclear phagocytes. We overview here what is known about the innate immune cells that interact with parasites, mechanisms used by the parasite to evade them, and the protective or detrimental contribution of these interactions on parasite progression through its life cycle and pathology in the host. Copyright © 2014 Elsevier Ltd. All rights reserved.

Lung mucociliary clearance

International Nuclear Information System (INIS)

Mortensen, J.; Lange, P.; Nyboe, J.; Groth, S.

1994-01-01

The aim of this study was to establish reference values for mucociliary clearance and mucociliary clearance reserve capacity as determined by β 2 -adrenergic agonist-induced increase in mucociliary clearance. We studied 62 healthy females (n=33) and males (n=29). Their ages ranged evenly between 18 and 84 years. Fifty-three of the subjects were life-long non-smokers, while nine were ex-smokers. Multiple linear regression analyses showed that mucociliary clearance was significantly faster when the radioaerosol was deposited in the central airways than when it was deposited in the peripheral airways, and faster in life-long non-smokers than in ex-smokers. There was no influence of age, and no convincing association with sex. The variation was less within than between subjects. Mean mucociliary clearance reserve capacity was 21.3% (SD: 10.0%, P 2 agonist-induced increase in lung mucociliary clearance was significantly larger (P<0.05) than the stimulation which has previously been reported in patients with asthma, bronchiectasis or cystic fibrosis. The signal-to-noise ratio of the mucociliary clearance reserve capacity in relation to measurement of baseline mucociliary clearance indicates that measurement of mucociliary clearance reserve capacity may be a more efficient means of distinguishing between ''normal'' and ''abnormal'' mucociliary clearance than single measurement of baseline mucociliary clearance. (orig.)

Phagocytic and bactericidal activities of leukocytes in whole blood from atomic bomb survivors

International Nuclear Information System (INIS)

Sasagawa, S.; Yoshimoto, Y.; Toyota, E.; Neriishi, S.; Yamakido, M.; Matsuo, M.; Hosoda, Y.; Finch, S.C.

1990-01-01

This study evaluated the phagocytic and bactericidal activities of peripheral blood leukocytes from Hiroshima and Nagasaki atomic bomb survivors for Staphylococcus aureus. The data were analyzed by multiple linear regression for age, sex, radiation exposure, city of exposure, and neutrophil counts. No significant radiation effect was observed for either blood phagocytic or bactericidal activities. The only significant variable for these functions was the neutrophil count

Isotope determinations of renal clearance equivalent with physiological clearance measurements

International Nuclear Information System (INIS)

Junges, R.

1983-01-01

The concept of renal clearance in nuclear medicine describes the tubular secretion and glomerular filtration of a substance being removed from the blood plasma. The concept of clearance as used physiologically is rather wider and includes consideration of the outflow of the substances remained back in the kidneys. The present paper discusses clearance measurements as seen from a thermodynamic point of view, in which isotope clearances become equivalent with the physiological concept of clearance. In addition, it is possible to quantify each single step of the excretory function of each kidney separately. (orig.) [de

Activating transcription factor 4 underlies the pathogenesis of arsenic trioxide-mediated impairment of macrophage innate immune functions

Energy Technology Data Exchange (ETDEWEB)

Srivastava, Ritesh K.; Li, Changzhao [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Wang, Yong [Department of Medicine, University of Alabama at Birmingham, Birmingham, AL (United States); Weng, Zhiping; Elmets, Craig A. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Harrod, Kevin S. [Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL (United States); Deshane, Jessy S., E-mail: treena@uab.edu [Department of Medicine, University of Alabama at Birmingham, Birmingham, AL (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States)

2016-10-01

Chronic arsenic exposure to humans is considered immunosuppressive with augmented susceptibility to several infectious diseases. The exact molecular mechanisms, however, remain unknown. Earlier, we showed the involvement of unfolded protein response (UPR) signaling in arsenic-mediated impairment of macrophage functions. Here, we show that activating transcription factor 4 (ATF4), a UPR transcription factor, regulates arsenic trioxide (ATO)-mediated dysregulation of macrophage functions. In ATO-treated ATF4{sup +/+} wild-type mice, a significant down-regulation of CD11b expression was associated with the reduced phagocytic functions of peritoneal and lung macrophages. This severe immuno-toxicity phenotype was not observed in ATO-treated ATF4{sup +/−} heterozygous mice. To confirm these observations, we demonstrated in Raw 264.7 cells that ATF4 knock-down rescues ATO-mediated impairment of macrophage functions including cytokine production, bacterial engulfment and clearance of engulfed bacteria. Sustained activation of ATF4 by ATO in macrophages induces apoptosis, while diminution of ATF4 expression protects against ATO-induced apoptotic cell death. Raw 264.7 cells treated with ATO also manifest dysregulated Ca{sup ++} homeostasis. ATO induces Ca{sup ++}-dependent calpain-1 and caspase-12 expression which together regulated macrophage apoptosis. Additionally, apoptosis was also induced by mitochondria-regulated pathway. Restoring ATO-impaired Ca{sup ++} homeostasis in ER/mitochondria by treatments with the inhibitors of inositol 1,4,5-trisphosphate receptor (IP3R) and voltage-dependent anion channel (VDAC) attenuate innate immune functions of macrophages. These studies identify a novel role for ATF4 in underlying pathogenesis of macrophage dysregulation and immuno-toxicity of arsenic. - Highlights: • ATF4 regulates arsenic-mediated impairment in macrophage functions. • Arsenic-mediated alterations in pulmonary macrophage are diminished in ATF4{sup +/−} mice

Activating transcription factor 4 underlies the pathogenesis of arsenic trioxide-mediated impairment of macrophage innate immune functions

International Nuclear Information System (INIS)

Srivastava, Ritesh K.; Li, Changzhao; Wang, Yong; Weng, Zhiping; Elmets, Craig A.; Harrod, Kevin S.; Deshane, Jessy S.; Athar, Mohammad

2016-01-01

Chronic arsenic exposure to humans is considered immunosuppressive with augmented susceptibility to several infectious diseases. The exact molecular mechanisms, however, remain unknown. Earlier, we showed the involvement of unfolded protein response (UPR) signaling in arsenic-mediated impairment of macrophage functions. Here, we show that activating transcription factor 4 (ATF4), a UPR transcription factor, regulates arsenic trioxide (ATO)-mediated dysregulation of macrophage functions. In ATO-treated ATF4 +/+ wild-type mice, a significant down-regulation of CD11b expression was associated with the reduced phagocytic functions of peritoneal and lung macrophages. This severe immuno-toxicity phenotype was not observed in ATO-treated ATF4 +/− heterozygous mice. To confirm these observations, we demonstrated in Raw 264.7 cells that ATF4 knock-down rescues ATO-mediated impairment of macrophage functions including cytokine production, bacterial engulfment and clearance of engulfed bacteria. Sustained activation of ATF4 by ATO in macrophages induces apoptosis, while diminution of ATF4 expression protects against ATO-induced apoptotic cell death. Raw 264.7 cells treated with ATO also manifest dysregulated Ca ++ homeostasis. ATO induces Ca ++ -dependent calpain-1 and caspase-12 expression which together regulated macrophage apoptosis. Additionally, apoptosis was also induced by mitochondria-regulated pathway. Restoring ATO-impaired Ca ++ homeostasis in ER/mitochondria by treatments with the inhibitors of inositol 1,4,5-trisphosphate receptor (IP3R) and voltage-dependent anion channel (VDAC) attenuate innate immune functions of macrophages. These studies identify a novel role for ATF4 in underlying pathogenesis of macrophage dysregulation and immuno-toxicity of arsenic. - Highlights: • ATF4 regulates arsenic-mediated impairment in macrophage functions. • Arsenic-mediated alterations in pulmonary macrophage are diminished in ATF4 +/− mice. • Changes in macrophage

Macrophage migration inhibitory factor deficiency is associated with impaired killing of gram-negative bacteria by macrophages and increased susceptibility to Klebsiella pneumoniae sepsis.

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Roger, Thierry; Delaloye, Julie; Chanson, Anne-Laure; Giddey, Marlyse; Le Roy, Didier; Calandra, Thierry

2013-01-15

The cytokine macrophage migration inhibitory factor (MIF) is an important component of the early proinflammatory response of the innate immune system. However, the antimicrobial defense mechanisms mediated by MIF remain fairly mysterious. In the present study, we examined whether MIF controls bacterial uptake and clearance by professional phagocytes, using wild-type and MIF-deficient macrophages. MIF deficiency did not affect bacterial phagocytosis, but it strongly impaired the killing of gram-negative bacteria by macrophages and host defenses against gram-negative bacterial infection, as shown by increased mortality in a Klebsiella pneumonia model. Consistent with MIF's regulatory role of Toll-like 4 expression in macrophages, MIF-deficient cells stimulated with lipopolysaccharide or Escherichia coli exhibited reduced nuclear factor κB activity and tumor necrosis factor (TNF) production. Addition of recombinant MIF or TNF corrected the killing defect of MIF-deficient macrophages. Together, these data show that MIF is a key mediator of host responses against gram-negative bacteria, acting in part via a modulation of bacterial killing by macrophages.

Myelin down-regulates myelin phagocytosis by microglia and macrophages through interactions between CD47 on myelin and SIRPα (signal regulatory protein-α on phagocytes

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Reichert Fanny

2011-03-01

. Unexpectedly, phagocytosis of CD47-/- myelin by SIRPα-KD phagocytes, which is not altered from normal when tested in serum-free medium, is augmented when serum is present. Therefore, both myelin CD47 and serum may each promote SIRPα-dependent down-regulation of myelin phagocytosis irrespective of the other. Conclusions Myelin down-regulates its own phagocytosis through CD47-SIRPα interactions. It may further be argued that CD47 functions normally as a marker of "self" that helps protect intact myelin and myelin-forming oligodendrocytes and Schwann cells from activated microglia and macrophages. However, the very same mechanism that impedes phagocytosis may turn disadvantageous when rapid clearance of degenerated myelin is helpful.

Soluble Receptor for Advanced Glycation End-Products Predicts Impaired Alveolar Fluid Clearance in Acute Respiratory Distress Syndrome.

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Jabaudon, Matthieu; Blondonnet, Raiko; Roszyk, Laurence; Bouvier, Damien; Audard, Jules; Clairefond, Gael; Fournier, Mathilde; Marceau, Geoffroy; Déchelotte, Pierre; Pereira, Bruno; Sapin, Vincent; Constantin, Jean-Michel

2015-07-15

Levels of the soluble form of the receptor for advanced glycation end-products (sRAGE) are elevated during acute respiratory distress syndrome (ARDS) and correlate with severity and prognosis. Alveolar fluid clearance (AFC) is necessary for the resolution of lung edema but is impaired in most patients with ARDS. No reliable marker of this process has been investigated to date. To verify whether sRAGE could predict AFC during ARDS. Anesthetized CD-1 mice underwent orotracheal instillation of hydrochloric acid. At specified time points, lung injury was assessed by analysis of blood gases, alveolar permeability, lung histology, AFC, and plasma/bronchoalveolar fluid measurements of proinflammatory cytokines and sRAGE. Plasma sRAGE and AFC rates were also prospectively assessed in 30 patients with ARDS. The rate of AFC was inversely correlated with sRAGE levels in the plasma and the bronchoalveolar fluid of acid-injured mice (Spearman's ρ = -0.73 and -0.69, respectively; P < 10(-3)), and plasma sRAGE correlated with AFC in patients with ARDS (Spearman's ρ = -0.59; P < 10(-3)). Similarly, sRAGE levels were significantly associated with lung injury severity, and decreased over time in mice, whereas AFC was restored and lung injury resolved. Our results indicate that sRAGE levels could be a reliable predictor of impaired AFC during ARDS, and should stimulate further studies on the pathophysiologic implications of RAGE axis in the mechanisms leading to edema resolution. Clinical trial registered with www.clinicaltrials.gov (NCT 00811629).

In Vivo Evidence for Lysosome Depletion and Impaired Autophagic Clearance in Hereditary Spastic Paraplegia Type SPG11.

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Rita-Eva Varga

2015-08-01

Full Text Available Hereditary spastic paraplegia (HSP is characterized by a dying back degeneration of corticospinal axons which leads to progressive weakness and spasticity of the legs. SPG11 is the most common autosomal-recessive form of HSPs and is caused by mutations in SPG11. A recent in vitro study suggested that Spatacsin, the respective gene product, is needed for the recycling of lysosomes from autolysosomes, a process known as autophagic lysosome reformation. The relevance of this observation for hereditary spastic paraplegia, however, has remained unclear. Here, we report that disruption of Spatacsin in mice indeed causes hereditary spastic paraplegia-like phenotypes with loss of cortical neurons and Purkinje cells. Degenerating neurons accumulate autofluorescent material, which stains for the lysosomal protein Lamp1 and for p62, a marker of substrate destined to be degraded by autophagy, and hence appears to be related to autolysosomes. Supporting a more generalized defect of autophagy, levels of lipidated LC3 are increased in Spatacsin knockout mouse embryonic fibrobasts (MEFs. Though distinct parameters of lysosomal function like processing of cathepsin D and lysosomal pH are preserved, lysosome numbers are reduced in knockout MEFs and the recovery of lysosomes during sustained starvation impaired consistent with a defect of autophagic lysosome reformation. Because lysosomes are reduced in cortical neurons and Purkinje cells in vivo, we propose that the decreased number of lysosomes available for fusion with autophagosomes impairs autolysosomal clearance, results in the accumulation of undegraded material and finally causes death of particularly sensitive neurons like cortical motoneurons and Purkinje cells in knockout mice.

High glucose impairs superoxide production from isolated blood neutrophils

DEFF Research Database (Denmark)

Perner, A; Nielsen, S E; Rask-Madsen, J

2003-01-01

Superoxide (O(2)(-)), a key antimicrobial agent in phagocytes, is produced by the activity of NADPH oxidase. High glucose concentrations may, however, impair the production of O(2)(-) through inhibition of glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the formation of NADPH. This study...... measured the acute effects of high glucose or the G6PD inhibitor dehydroepiandrosterone (DHEA) on the production of O(2)(-) from isolated human neutrophils....

Comparison of the endogenous creatinine clearance, the creatinin clearance calculated without urine collection and the isotope clearance

International Nuclear Information System (INIS)

Mohacsi, Gabor; Lang, Jenoe; Csernay, Laszlo; Sonkodi, Sandor; Orvostudomanyi Egyetem, Szeged

1987-01-01

Observations are reported relating to the endogenous creatinine clearance, the Tc-99m-EDTA-complex clearance and the creatinine clearance estimated via a selected mathematical formula, with special regard to the problems of renal insufficiency and the nephrotic syndrome. The activity applied was in the range of 3.7-7.4 MBq. It was observed that measurement of the isotope clearance can also be applied to determine the endogeneous creatinine clearance in otherwise less suitable patients. A reliable result is obtained even if the renal function is restricted, but the accuracy of the method may be reduced in nephrotic syndrome cases. (author) 24 refs

Zebrafish kidney phagocytes utilize macropinocytosis and Ca+-dependent endocytic mechanisms.

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Claudia Hohn

Full Text Available BACKGROUND: The innate immune response constitutes the first line of defense against invading pathogens and consists of a variety of immune defense mechanisms including active endocytosis by macrophages and granulocytes. Endocytosis can be used as a reliable measure of selective and non-selective mechanisms of antigen uptake in the early phase of an immune response. Numerous assays have been developed to measure this response in a variety of mammalian and fish species. The small size of the zebrafish has prevented the large-scale collection of monocytes/macrophages and granulocytes for these endocytic assays. METHODOLOGY/PRINCIPAL FINDINGS: Pooled zebrafish kidney hematopoietic tissues were used as a source of phagocytic cells for flow-cytometry based endocytic assays. FITC-Dextran, Lucifer Yellow and FITC-Edwardsiella ictaluri were used to evaluate selective and non-selective mechanisms of uptake in zebrafish phagocytes. CONCLUSIONS/SIGNIFICANCE: Zebrafish kidney phagocytes characterized as monocytes/macrophages, neutrophils and lymphocytes utilize macropinocytosis and Ca(2+-dependant endocytosis mechanisms of antigen uptake. These cells do not appear to utilize a mannose receptor. Heat-killed Edwardsiella ictaluri induces cytoskeletal interactions for internalization in zebrafish kidney monocytes/macrophages and granulocytes. The proposed method is easy to implement and should prove especially useful in immunological, toxicological and epidemiological research.

Efferocytosis of Pathogen-Infected Cells

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Niloofar Karaji

2017-12-01

Full Text Available The prompt and efficient clearance of unwanted and abnormal cells by phagocytes is termed efferocytosis and is crucial for organism development, maintenance of tissue homeostasis, and regulation of the immune system. Dying cells are recognized by phagocytes through pathways initiated via “find me” signals, recognition via “eat me” signals and down-modulation of regulatory “don’t eat me” signals. Pathogen infection may trigger cell death that drives phagocytic clearance in an immunologically silent, or pro-inflammatory manner, depending on the mode of cell death. In many cases, efferocytosis is a mechanism for eliminating pathogens and pathogen-infected cells; however, some pathogens have subverted this process and use efferocytic mechanisms to avoid innate immune detection and assist phagocyte infection. In parallel, phagocytes can integrate signals received from infected dying cells to elicit the most appropriate effector response against the infecting pathogen. This review focuses on pathogen-induced cell death signals that drive infected cell recognition and uptake by phagocytes, and the outcomes for the infected target cell, the phagocyte, the pathogen and the host.

Creatinine clearance test

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Serum creatinine clearance; Kidney function - creatinine clearance; Renal function - creatinine clearance ... Creatinine is a chemical waste product of creatine. Creatine is a chemical the body makes to supply ...

Clearance of the cervical spine in clinically unevaluable trauma patients.

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Halpern, Casey H; Milby, Andrew H; Guo, Wensheng; Schuster, James M; Gracias, Vicente H; Stein, Sherman C

2010-08-15

Meta-analytic costeffectiveness analysis. Our goal was to compare the results of different management strategies for trauma patients in whom the cervical spine was not clinically evaluable due to impaired consciousness, endotracheal intubation, or painful distracting injuries. We performed a structured literature review related to cervical spine trauma, radiographic clearance techniques (plain radiography, flexion/extension, CT, and MRI), and complications associated with semirigid collar use. Meta-analytic techniques were used to pool data from multiple sources to calculate pooled mean estimates of sensitivities and specificities of imaging techniques for cervical spinal clearance, rates of complications from various clearance strategies and from empirical use of semirigid collars. A decision analysis model was used to compare outcomes and costs among these strategies. Slightly more than 7.5% of patients who are clinically unevaluable have cervical spine injuries, and 42% of these injuries are associated with spinal instability. Sensitivity of plain radiography or fluoroscopy for spinal clearance was 57% (95% CI: 57%-60%). Sensitivities for CT and MRI alone were 83% (82%-84%) and 87% (84%-89%), respectively. Complications associated with collar use ranged from 1.3% (2 days) to 7.1% (10 days) but were usually minor and short-lived. Quadriplegia resulting from spinal instability missed by a clearance test had enormous impacts on longevity, quality of life, and costs. These impacts overshadowed the effects of prolonged collar application, even when the incidence of quadriplegia was extremely low. As currently used, neuroimaging studies for cervical spinal clearance in clinically unevaluable patients are not cost-effective compared with empirical immobilization in a semirigid collar.

Mucociliary clearance, airway inflammation and nasal symptoms in urban motorcyclists

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Tereza C.S. Brant

2014-01-01

Full Text Available OBJECTIVES: There is evidence that outdoor workers exposed to high levels of air pollution exhibit airway inflammation and increased airway symptoms. We hypothesized that these workers would experience increased airway symptoms and decreased nasal mucociliary clearance associated with their exposure to air pollution. METHODS: In total, 25 non-smoking commercial motorcyclists, aged 18-44 years, were included in this study. These drivers work 8-12 hours per day, 5 days per week, driving on urban streets. Nasal mucociliary clearance was measured by the saccharine transit test; airway acidification was measured by assessing the pH of exhaled breath condensate; and airway symptoms were measured by the Sino-nasal Outcome Test-20 questionnaire. To assess personal air pollution exposure, the subjects used a passive-diffusion nitrogen dioxide (NO2 concentration-monitoring system during the 14 days before each assessment. The associations between NO2 and the airway outcomes were analyzed using the Mann-Whitney test and the Chi-Square test. Clinicaltrials.gov: NCT01976039. RESULTS: Compared with clearance in healthy adult males, mucociliary clearance was decreased in 32% of the motorcyclists. Additionally, 64% of the motorcyclists had airway acidification and 92% experienced airway symptoms. The median personal NO2 exposure level was 75 mg/m3 for these subjects and a significant association was observed between NO2 and impaired mucociliary clearance (p = 0.036. CONCLUSION: Non-smoking commercial motorcyclists exhibit increased airway symptoms and airway acidification as well as decreased nasal mucociliary clearance, all of which are significantly associated with the amount of exposure to air pollution.

Eosinophils in the lung – modulating apoptosis and efferocytosis in airway inflammation

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Jennifer M Felton

2014-07-01

Full Text Available Due to the key role of the lung in efficient transfer of oxygen in exchange for carbon dioxide, a controlled inflammatory response is essential for restoration of tissue homeostasis following airway exposure to bacterial pathogens or environmental toxins. Unregulated or prolonged inflammatory responses in the lungs can lead to tissue damage, disrupting normal tissue architecture and consequently compromising efficient gaseous exchange. Failure to resolve inflammation underlies the development and/or progression of a number of inflammatory lung diseases including asthma. Eosinophils, granulocytic cells of the innate immune system, are primarily involved in defence against parasitic infections. However, the propagation of the allergic inflammatory response in chronic asthma is thought to involve excessive recruitment and impaired apoptosis of eosinophils together with defective phagocytic clearance of apoptotic cells (efferocytosis. In terms of therapeutic approaches for treatment of asthma, the widespread use of glucocorticoids is associated with a number of adverse health consequences after long-term use, while some patients suffer from steroid-resistant disease. A new approach for therapeutic intervention would be to promote the resolution of inflammation via modulation of eosinophil apoptosis and the phagocytic clearance of apoptotic cells. This review focuses on the mechanisms underpinning eosinophil-mediated lung damage, currently available treatments and therapeutic targets that might in future be harnessed to facilitate inflammation resolution by the manipulation of cell survival and clearance pathways.

How important is the myeloperoxidase microbicidal system of phagocytic cells?

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Thong, Y H

1982-03-01

The myeloperoxidase system is presented by most immunology textbooks as a major microbicidal system of phagocytic cells. This theory, however, has not bee subjected to vigorous testing in the clinical arena. Of 14 patients with primary myeloperoxidase deficiency, only 3 had infectious complication. All 3 patients have more plausible explanation than myeloperoxidase deficiency for their infectious complications. Two of these patients were healthy until middle age when they developed systemic candidiasis after the onset of diabetes mellitus. The third patient was an infant with a maturational defect in neutrophil chemotaxis whose infectious complications ceased after the normalization of the chemotactic defect. The results of these "experiments of nature" indicate that the meyloperoxidase system is not a major microbicidal mechanism of phagocytic cells.

Interactions of phagocytes with the Lyme disease spirochete: role of the Fc receptor

International Nuclear Information System (INIS)

Benach, J.L.; Fleit, H.B.; Habicht, G.S.; Coleman, J.L.; Bosler, E.M.; Lane, B.P.

1984-01-01

The phagocytic capacity of murine and human mononuclear and polymorphonuclear phagocytes (including peripheral blood monocytes and neutrophils), rabbit and murine peritoneal exudate cells, and the murine macrophage cell line P388D1 against the Lyme disease spirochete was studied. All of these cells were capable of phagocytosing the spirochete; phagocytosis was measured by the uptake of radiolabeled spirochetes, the appearance of immunofluorescent bodies in phagocytic cells, and electron microscopy. Both opsonized and nonopsonized organisms were phagocytosed. The uptake of opsonized organisms by neutrophils was blocked by a monoclonal antibody specific for the Fc receptor and by immune complexes; these findings suggested that most phagocytosis is mediated by the Fc receptor. Similarly, the uptake of opsonized organisms by human monocytes was inhibited by human monomeric IgG1 and by immune complexes. These results illustrate the role of immune phagocytosis of spirochetes in host defense against Lyme disease

Hydrazinonicotinamide prolongs quantum dot circulation and reduces reticuloendothelial system clearance by suppressing opsonization and phagocyte engulfment

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Jung, Kyung-Ho; Park, Jin Won; Paik, Jin-Young; Lee, Eun Jeong; Choe, Yearn Seong; Lee, Kyung-Han

2012-12-01

In this study, we investigated the effects of hydrazinonicotinamide (HYNIC)—a bifunctional crosslinker widely used to 99mTc radiolabel protein and nanoparticles for imaging studies—on quantum dot opsonization, macrophage engulfment and in vivo kinetics. In streptavidin-coated quantum dots (SA-QDots), conjugation with HYNIC increased the net negative charge without affecting the zeta potential. Confocal microscopy and fluorescence-activated cell sorting showed HYNIC attachment to suppress SA-QDot engulfment by macrophages. Furthermore, HYNIC conjugation suppressed surface opsonization by serum protein including IgG. When intravenously injected into mice, HYNIC conjugation significantly prolonged the circulation of SA-QDots and reduced their hepatosplenic uptake. Diminished reticuloendothelial system clearance of SA-QDots and aminoPEG-QDots by HYNIC conjugation was also demonstrated by in vivo and ex vivo optical imaging. The effects of HYNIC on the opsonization, phagocytosis and in vivo kinetics of quantum dots were reversed by removal of the hydrazine component from HYNIC. Thus, surface functionalization with HYNIC can improve the in vivo kinetics of quantum dots by reducing phagocytosis via suppression of surface opsonization.

[51Cr]EDTA plasma clearance and endogenous creatinine clearance in advanced renal insufficiency

International Nuclear Information System (INIS)

Svendsen, U.G.; Munck, O.; Czartoryski, A.; Stafanger, G.

1978-01-01

Comparison of [ 51 Cr]EDTA plasma clearance corrected for extrarenal elimination with 24 h endogenous creatinine clearance in patients with advanced renal failure showed that the corrected [ 51 Cr]EDTA clearance was lower than creatinine clearance, and thus might be a better approximation to the glomerular filtration rate in uraemic patients. The corrections cannot be used on [ 51 Cr]EDTA clearance values below the mean extrarenal clearance, averaging 3.7 ml/min. (Auth.)

The description of a method for accurately estimating creatinine clearance in acute kidney injury.

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Mellas, John

2016-05-01

Acute kidney injury (AKI) is a common and serious condition encountered in hospitalized patients. The severity of kidney injury is defined by the RIFLE, AKIN, and KDIGO criteria which attempt to establish the degree of renal impairment. The KDIGO guidelines state that the creatinine clearance should be measured whenever possible in AKI and that the serum creatinine concentration and creatinine clearance remain the best clinical indicators of renal function. Neither the RIFLE, AKIN, nor KDIGO criteria estimate actual creatinine clearance. Furthermore there are no accepted methods for accurately estimating creatinine clearance (K) in AKI. The present study describes a unique method for estimating K in AKI using urine creatinine excretion over an established time interval (E), an estimate of creatinine production over the same time interval (P), and the estimated static glomerular filtration rate (sGFR), at time zero, utilizing the CKD-EPI formula. Using these variables estimated creatinine clearance (Ke)=E/P * sGFR. The method was tested for validity using simulated patients where actual creatinine clearance (Ka) was compared to Ke in several patients, both male and female, and of various ages, body weights, and degrees of renal impairment. These measurements were made at several serum creatinine concentrations in an attempt to determine the accuracy of this method in the non-steady state. In addition E/P and Ke was calculated in hospitalized patients, with AKI, and seen in nephrology consultation by the author. In these patients the accuracy of the method was determined by looking at the following metrics; E/P>1, E/P1 and 0.907 (0.841, 0.973) for 0.95 ml/min accurately predicted the ability to terminate renal replacement therapy in AKI. Include the need to measure urine volume accurately. Furthermore the precision of the method requires accurate estimates of sGFR, while a reasonable measure of P is crucial to estimating Ke. The present study provides the

Selective Biological Responses of Phagocytes and Lungs to Purified Histones.

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Fattahi, Fatemeh; Grailer, Jamison J; Lu, Hope; Dick, Rachel S; Parlett, Michella; Zetoune, Firas S; Nuñez, Gabriel; Ward, Peter A

2017-01-01

Histones invoke strong proinflammatory responses in many different organs and cells. We assessed biological responses to purified or recombinant histones, using human and murine phagocytes and mouse lungs. H1 had the strongest ability in vitro to induce cell swelling independent of requirements for toll-like receptors (TLRs) 2 or 4. These responses were also associated with lactate dehydrogenase release. H3 and H2B were the strongest inducers of [Ca2+]i elevations in phagocytes. Cytokine and chemokine release from mouse and human phagocytes was predominately a function of H2A and H2B. Double TLR2 and TLR4 knockout (KO) mice had dramatically reduced cytokine release induced in macrophages exposed to individual histones. In contrast, macrophages from single TLR-KO mice showed few inhibitory effects on cytokine production. Using the NLRP3 inflammasome protocol, release of mature IL-1β was predominantly a feature of H1. Acute lung injury following the airway delivery of histones suggested that H1, H2A, and H2B were linked to alveolar leak of albumin and the buildup of polymorphonuclear neutrophils as well as the release of chemokines and cytokines into bronchoalveolar fluids. These results demonstrate distinct biological roles for individual histones in the context of inflammation biology and the requirement of both TLR2 and TLR4. © 2017 S. Karger AG, Basel.

Circulating osteocrin stimulates bone growth by limiting C-type natriuretic peptide clearance.

Science.gov (United States)

Kanai, Yugo; Yasoda, Akihiro; Mori, Keita P; Watanabe-Takano, Haruko; Nagai-Okatani, Chiaki; Yamashita, Yui; Hirota, Keisho; Ueda, Yohei; Yamauchi, Ichiro; Kondo, Eri; Yamanaka, Shigeki; Sakane, Yoriko; Nakao, Kazumasa; Fujii, Toshihito; Yokoi, Hideki; Minamino, Naoto; Mukoyama, Masashi; Mochizuki, Naoki; Inagaki, Nobuya

2017-11-01

Although peptides are safe and useful as therapeutics, they are often easily degraded or metabolized. Dampening the clearance system for peptide ligands is a promising strategy for increasing the efficacy of peptide therapies. Natriuretic peptide receptor B (NPR-B) and its naturally occurring ligand, C-type natriuretic peptide (CNP), are potent stimulators of endochondral bone growth, and activating the CNP/NPR-B system is expected to be a powerful strategy for treating impaired skeletal growth. CNP is cleared by natriuretic peptide clearance receptor (NPR-C); therefore, we investigated the effect of reducing the rate of CNP clearance on skeletal growth by limiting the interaction between CNP and NPR-C. Specifically, we generated transgenic mice with increased circulating levels of osteocrin (OSTN) protein, a natural NPR-C ligand without natriuretic activity, and observed a dose-dependent skeletal overgrowth phenotype in these animals. Skeletal overgrowth in OSTN-transgenic mice was diminished in either CNP- or NPR-C-depleted backgrounds, confirming that CNP and NPR-C are indispensable for the bone growth-stimulating effect of OSTN. Interestingly, double-transgenic mice of CNP and OSTN had even higher levels of circulating CNP and additional increases in bone length, as compared with mice with elevated CNP alone. Together, these results support OSTN administration as an adjuvant agent for CNP therapy and provide a potential therapeutic approach for diseases with impaired skeletal growth.

CCR1+/CCR5+ mononuclear phagocytes accumulate in the central nervous system of patients with multiple sclerosis

DEFF Research Database (Denmark)

Trebst, C; Sørensen, Torben Lykke; Kivisäkk, P

2001-01-01

Mononuclear phagocytes (monocytes, macrophages, and microglia) are considered central to multiple sclerosis (MS) pathogenesis. Molecular cues that mediate mononuclear phagocyte accumulation and activation in the central nervous system (CNS) of MS patients may include chemokines RANTES/CCL5...

Whole-blood phagocytic and bactericidal activities of atomic bomb survivors, Hiroshima and Nagasaki

International Nuclear Information System (INIS)

Sasagawa, Sumiko; Yoshimoto, Yasuhiko; Toyota, Emiko; Neriishi, Shotaro; Yamakido, Michio; Matsuo, Miyo; Hosoda, Yutaka; Finch, S.C.

1989-04-01

This in vitro study evaluated the phagocytic and bactericidal activities of leukocytes in aliquots of whole blood from Hiroshima and Nagasaki atomic bomb survivors for Staphylococcus aureus. The data were analyzed by multiple linear regression. Any significant effects of exposure to A-bomb radiation could not be detected for both phagocytic and bactericidal activities of whole blood from A-bomb survivors. In addition, there were no significant effects of age categories, sex or city, except in neutrophil counts. (J.P.N.)

Supraependymal cells of hypothalamic third ventricle: identification as resident phagocytes of the brain.

Science.gov (United States)

Bleier, R; Albrecht, R; Cruce, J A

1975-07-25

Cells lying on the ventricular surface of the hypothalamic ependyma of the tegu lizard exhibit the pseudopodial and flaplike processes characteristic of macrophages found elsewhere. Since they ingest latex beads, they may be considered a resident phagocytic system of the brain. The importance of ependyma and ventricular phagocytes as a first line of defense against viral invasion of the brain, as well as their role in the pathogenesis of certain virus-related diseases, is suggested by a number of experimental and clinical observations.

Role of the phagocytes on embryos: some morphological aspects.

Science.gov (United States)

Da Silva, José Roberto Machado Cunha

2002-06-15

Phagocytosis in embryos was studied by Elie Metchnikoff more than a century ago and is a pillar of the Phagocytic Theory. Throughout the last three decades phagocytosis in embryos has been studied from different perspectives, which this review describes and analyzes. The following branches were identified: 1) the search for the origin and first identification of well-known adult phagocytes in embryos, including their role after induced injuries; 2) the search for the occurrence of phagocytosis in embryos and its role during their physiological development; and 3) the search for phagocytosis in embryos, as a tool to study identity and self-recognition. It is possible to verify that different cell types are able to undertake phagocytosis, under a variety of different stimuli, and that the nature of what is phagocytosed also varies widely. Although the overwhelming majority of species described among metazoarians are invertebrates, most published articles in this field relate to mammals (particularly mice and humans) and birds (particularly chicks). In order to enrich this field of knowledge, research using a wider variety of vertebrate and invertebrate species should be undertaken. Furthermore, the present knowledge of phagocytosis in embryos needs a revised paradigm capable of embracing all the above-mentioned research trends under a single, more general, biological theory. In this sense, Metchnikoff's Phagocytic Theory, which is based on a broad biological paradigm and is thus capable of dealing with all research trends mentioned herein, should be revisited in order to contribute to this edification. Copyright 2002 Wiley-Liss, Inc.

The Phagocyte, Metchnikoff, and the Foundation of Immunology.

Science.gov (United States)

Teti, Giuseppe; Biondo, Carmelo; Beninati, Concetta

2016-04-01

Since the ability of some cells to engulf particulate material was observed before Metchnikoff, he did not "discover" phagocytosis, as is sometimes mentioned in textbooks. Rather, he assigned to particle internalization the role of defending the host against noxious stimuli, which represented a new function relative to the previously recognized task of intracellular digestion. With this proposal, Metchnikoff built the conceptual framework within which immunity could finally be seen as an active host function triggered by noxious stimuli. In this sense, Metchnikoff can be rightly regarded as the father of all immunological sciences and not only of innate immunity or myeloid cell biology. Moreover, the recognition properties of his phagocyte fit surprisingly well with recent discoveries and modern models of immune sensing. For example, rather than assigning to immune recognition exclusively the function of eliminating nonself components (as others did after him), Metchnikoff viewed phagocytes as homeostatic agents capable of monitoring the internal environment and promoting tissue remodeling, thereby continuously defining the identity of the organism. No doubt, Metchnikoff's life and creativity can provide, still today, a rich source of inspiration.

Heparin induced alterations in clearance and distribution of blood-borne microparticles following operative trauma.

Science.gov (United States)

Saba, T M; Antikatzides, T G

1979-04-01

The influence of systemic heparin administration on the vascular clearance and tissue distribution of blood-borne microparticles was evaluated in normal rats and rats after operation (laparotomy plus intestinal manipulation) utilizing an (131)I- colloid which is phagocytized by the reticuloendothelial system (RES). Intravenous heparin administration (100 USP/100g body weight) into normal animals three minutes prior to colloid injection (50 mg/lOOg) induced a significant increase in pulmonary localization of the microparticles as compared to nonheparinized control rats, while hepatic and splenic uptake were decreased. Surgical trauma decreased hepatic RE uptake and increased pulmonary localization of the microparticles when injected systemically at 60 minutes postsurgery. Heparin administration 60 minutes after surgery and three minutes prior to colloid injection, magnified the increased pulmonary localization response with an associated further depression of the RES. The ability of heparin to alter both RE clearance function and lung localization of microparticles was dose dependent and a function of the interval between heparin administration and systemic particulate infusion. Thus, low dose heparin administration was capable of stimulating RE activity while heparin in doses of excess of 50 USP units/lOOg body weight decreased RE function. These findings suggest that the functional state of the hepatic RE system can be greatly affected in a dose-dependent manner by systemic heparin administration which may influence distribution of blood-borne microparticles.

Pranic meditation affects phagocyte functions and hormonal levels of recent practitioners.

Science.gov (United States)

Fernandes, César A; Nóbrega, Yanna K M; Tosta, C Eduardo

2012-08-01

Despite the recognized importance of phagocytes in the maintenance and recovery of health, the influence of meditation on their functions is not properly established. This investigation aimed at evaluating the influence of pranic meditation on the functions of phagocytes, and on the levels of hormones that influence them. A pre-post design was adopted. The investigation was carried out at a university research laboratory. Twenty-nine (29) healthy individuals of both sexes, 24-67 years old (median 45), with no previous experience in meditation, received 3-hour-duration weekly training on pranic meditation during 10 weeks and agreed to engage in daily home practice for 20 minutes. Pranic meditation is a novel method of meditation, based on the Vedic tradition, which uses techniques of breathing and visualization for quieting the mind, and for capturing and intentionally directing prana ("vital energy") wherever necessary. For assessing phagocytosis, the production of hydrogen peroxide and nitric oxide by monocytes, and the concentrations of corticotrophin and cortisol, blood was collected at the beginning (week 1), at the middle (week 5), and by the end (week 10) of the practice period. At the same intervals, melatonin concentrations were evaluated in the saliva. Those who meditated for more than 980 minutes showed increased phagocytosis, their monocytes produced higher concentrations of hydrogen peroxide, and their plasma levels of corticotrophin were reduced. The production of nitric oxide by monocytes, and the levels of cortisol and melatonin were not modified by meditation. This is the first study to show that a short program of pranic meditation practice was able to upregulate the function and metabolism of phagocytes, in parallel with the reduction of the plasma levels of corticotrophin. The results of this study point to a possible causal effect between these events, and indicate that pranic meditation could be useful for stimulating the function and

Impairment of the glymphatic system after diabetes.

Science.gov (United States)

Jiang, Quan; Zhang, Li; Ding, Guangliang; Davoodi-Bojd, Esmaeil; Li, Qingjiang; Li, Lian; Sadry, Neema; Nedergaard, Maiken; Chopp, Michael; Zhang, Zhenggang

2017-04-01

The glymphatic system has recently been shown to clear brain extracellular solutes and abnormalities in glymphatic clearance system may contribute to both initiation and progression of neurological diseases. Despite that diabetes is known as a risk factor for vascular diseases, little is known how diabetes affects the glymphatic system. The current study is the first investigation of the effect of diabetes on the glymphatic system and the link between alteration of glymphatic clearance and cognitive impairment in Type-2 diabetes mellitus rats. MRI analysis revealed that clearance of cerebrospinal fluid contrast agent Gd-DTPA from the interstitial space was slowed by a factor of three in the hippocampus of Type-2 diabetes mellitus rats compared to the non-DM rats and confirmed by florescence imaging analysis. Cognitive deficits detected by behavioral tests were highly and inversely correlated to the retention of Gd-DTPA contrast and fluorescent tracer in the hippocampus of Type-2 diabetes mellitus rats. Type-2 diabetes mellitus suppresses clearance of interstitial fluid in the hippocampus and hypothalamus, suggesting that an impairment of the glymphatic system contributes to Type-2 diabetes mellitus-induced cognitive deficits. Whole brain MRI provides a sensitive, non-invasive tool to quantitatively evaluate cerebrospinal fluid and interstitial fluid exchange in Type-2 diabetes mellitus and possibly in other neurological disorders, with potential clinical application.

Divergence of macrophage phagocytic and antimicrobial programs in leprosy.

Science.gov (United States)

Montoya, Dennis; Cruz, Daniel; Teles, Rosane M B; Lee, Delphine J; Ochoa, Maria Teresa; Krutzik, Stephan R; Chun, Rene; Schenk, Mirjam; Zhang, Xiaoran; Ferguson, Benjamin G; Burdick, Anne E; Sarno, Euzenir N; Rea, Thomas H; Hewison, Martin; Adams, John S; Cheng, Genhong; Modlin, Robert L

2009-10-22

Effective innate immunity against many microbial pathogens requires macrophage programs that upregulate phagocytosis and direct antimicrobial pathways, two functions generally assumed to be coordinately regulated. We investigated the regulation of these key functions in human blood-derived macrophages. Interleukin-10 (IL-10) induced the phagocytic pathway, including the C-type lectin CD209 and scavenger receptors, resulting in phagocytosis of mycobacteria and oxidized low-density lipoprotein. IL-15 induced the vitamin D-dependent antimicrobial pathway and CD209, yet the cells were less phagocytic. The differential regulation of macrophage functional programs was confirmed by analysis of leprosy lesions: the macrophage phagocytosis pathway was prominent in the clinically progressive, multibacillary form of the disease, whereas the vitamin D-dependent antimicrobial pathway predominated in the self-limited form and in patients undergoing reversal reactions from the multibacillary to the self-limited form. These data indicate that macrophage programs for phagocytosis and antimicrobial responses are distinct and differentially regulated in innate immunity to bacterial infections.

Mucociliary clearance

DEFF Research Database (Denmark)

Munkholm, Mathias; Mortensen, Jann

2014-01-01

Mucociliary clearance has long been known to be a significant innate defence mechanism against inhaled microbes and irritants. Important knowledge has been gathered regarding the anatomy and physiology of this system, and in recent years, extensive studies of the pathophysiology related to lung...... pharmacological interventions on clearance rate, to study the importance of defective mucus clearance in different lung diseases or as a diagnostic tool in the work-up of patients with recurrent airway diseases. The aim of this review is to provide an overview of the anatomy, physiology, pathophysiology...

The effect of propylthiouracil on function of phagocytic peripheral blood cells in persons with thyroid hyperfunction

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Đukić Aleksandar

2006-01-01

Full Text Available Introduction. It is known that hyperthyroidism as well as thyrosuppressive therapy can influence the cells of immunological system. Objective. To examine the function of phagocyte cells in persons with hyperthyroidism and to examine if propylthiouracil (PTU influences this function. Method. The study included 15 patients with hyperthyroidism and 10 healthy persons. The parameters of phagocytic activity of mononuclear and polymorphonuclear leucocytes were tested by method of ingestion of particles of inactivated yeast labeled with neutral-red. Results. It was demonstrated that patients with hyperthyroidism, before the onset of therapy as well as 14 days after introduction of PTU, had decreased number of leucocytes (before PTU: 6.7±3.2Ч109/l, after PTU: 6.1±2.0Ч109/l and control: 8.0±1.6Ч109/l; p=0.039, PMN leucocytes (before PTU: 3.9±2,4 Ч109/l, after PTU: 3.5±1.6Ч109/l and control: 4.8±0.9Ч109/l; p=0.037 and number of phagocyte PMN cells (before PTU: 0.9±0.9Ч109/l, after PTU: 0.9±0.7Ч109/l and control: 1.3±0.6 Ч109/l; p<0,05, but they had increased index of phagocytosis (before PTU: 2.0±0.2, after PTU: 1.9±0.2 and control: 1.7±0.2; p=0.029, while capacity of phagocytosis remained unchanged (before PTU: 1.9±1.7Ч109/l, after PTU: 1.6±1.9Ч109/l and control: 2.4±1.4Ч109/l; p>0.05. The number of mononuclear leucocytes and parameters of phagocytic activity of mononuclear phagocytes in persons with hyperthyroidism did not change significantly in comparison with the control group. Conclusion. Patients with hyperthyroidism had decreased number of leucocytes, PMN leucocytes and number of phagocyte PMN cells, and increased index of phagocytosis, while capacity of phagocytosis remained unchanged. The number and parameters of phagocytic activity of mononuclear leucocytes did not change. PTU therapy had no effect on the examined parameters.

Modulation of rat blood phagocyte activity by serotonin

Czech Academy of Sciences Publication Activity Database

Okénková, Kateřina; Lojek, Antonín; Kubala, Lukáš; Číž, Milan

2007-01-01

Roč. 101, č. 14 (2007), s245-s246 E-ISSN 1213-7103. [Mezioborová česko-slovenská toxikologická konference /12./. Praha, 11.06.2007-13.06.2007] R&D Projects: GA ČR(CZ) GA524/04/0897 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : phagocytes * serotonin * reactive oxygen species Subject RIV: BO - Biophysics

In vivo evaluation of the antibacterial capacity of tissue phagocytes

International Nuclear Information System (INIS)

Guerra, H.

1975-01-01

The phagocytic activity of guinea pig liver to deal with bacterial infection was investigated on 14 C- or 32 P-labelled Brucella melitensis. Some in vitro work has been started, using immunoglobulins (IgG, IgM) with antibody activity against whole Brucella

Cathepsin B is up-regulated and mediates extracellular matrix degradation in trabecular meshwork cells following phagocytic challenge.

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Kristine Porter

Full Text Available Cells in the trabecular meshwork (TM, a tissue responsible for draining aqueous humor out of the eye, are known to be highly phagocytic. Phagocytic activity in TM cells is thought to play an important role in outflow pathway physiology. However, the molecular mechanisms triggered by phagocytosis in TM cells are unknown. Here we investigated the effects of chronic phagocytic stress on lysosomal function using different phagocytic ligands (E. coli, carboxylated beads, collagen I-coated beads, and pigment. Lysotracker red co-localization and electron micrographs showed the maturation of E. coli- and collagen I-coated beads-containing phagosomes into phagolysosomes. Maturation of phagosomes into phagolysosomes was not observed with carboxylated beads or pigment particles. In addition, phagocytosis of E. coli and collagen I-coated beads led to increased lysosomal mass, and the specific up-regulation and activity of cathepsin B (CTSB. Higher levels of membrane-bound and secreted CTSB were also detected. Moreover, in vivo zymography showed the intralysosomal degradation of ECM components associated with active CTSB, as well as an overall increased gelatinolytic activity in phagocytically challenged TM cells. This increased gelatinolytic activity with phagocytosis was partially blocked with an intracellular CTSB inhibitor. Altogether, these results suggest a potential role of phagocytosis in outflow pathway tissue homeostasis through the up-regulation and/or proteolytic activation of extracellular matrix remodeling genes.

Molecular pharmacology of antihistamines in inhibition of oxidative burst of professional phagocytes.

Science.gov (United States)

Nosáľ, Radomír; Jančinová, Viera; Drábiková, Katarína; Perečko, Tomáš

2015-04-01

Antihistamines of the H₁and H₃/H₄groups interfere with oxidative burst of human professional phagocytes in vitro. In the concentration of 10 μM, H₁antihistamines of the 1st and 2nd generation inhibited oxidative burst of human neutrophils in the rank order of potency: dithiaden > loratadine > brompheniramine > chlorpheniramine > pheniramine. Of the H₁antihistamines, the most effective was dithiaden in suppressing oxidative burst of whole human blood and dose-dependently the chemiluminescence of isolated neutrophils at extra- and intracellular level. Inhibition of free oxygen radical generation in isolated neutrophils by dithiaden resulted from the inhibition of protein kinase C activation. The potentiation of recombinant caspase-3 by dithiaden is supportive of the antiinflammatory effect of dithiaden and suggestive of increasing the apoptosis of professional phagocytes. Of the H₃/H₄antihistamines, the most effective was JNJ7777120 in decreasing chemiluminescence in whole blood and also at extra- and intracellular sites of isolated neutrophils. JNJ 10191584 and thioperamide were less effective and the latter significantly potentiated free oxygen radical generation intracellularly. The results demonstrated that, compared with the H₃/H₄antihistamines investigated, H₁antihistamines were much more potent in inhibiting free oxygen radical generation in human professional phagocytes. This finding should be taken into account therapeutically.

Lipofuscin-mediated photic stress inhibits phagocytic activity of ARPE-19 cells; effect of donors' age and antioxidants.

Science.gov (United States)

Olchawa, Magdalena M; Furso, Justyna A; Szewczyk, Grzegorz M; Sarna, Tadeusz J

2017-10-01

The risk of chronic oxidative stress in the retinal pigment epithelium (RPE) increases with age due to accumulation of the photoreactive age pigment lipofuscin (LFG). Here, we asked whether sublethal and weakly lethal photic stress, induced by irradiation of ARPE-19 cells containing phagocytised LFG, affected the cell specific phagocytic activity, which is critically important for proper functioning and survival of the retina, and if natural antioxidants could modify the observed outcomes. ARPE-19 cells preloaded with LFG isolated from human donors of different age or containing LFG enriched with zeaxanthin and α-tocopherol (LFG-A), were irradiated with blue light. Phagocytosis of fluorescein-5-isothiocyanate (FITC)-labelled photoreceptor outer segments was determined by flow cytometry. Photoreactivity of LFG and LFG-A was analysed by measuring photoconsumption of oxygen and photogeneration of singlet oxygen mediated by the granules. LFG-mediated photic stress in ARPE-19 cells induced significant inhibition of their specific phagocytosis. The inhibitory effect increased with age of LFG donors and was reduced by enrichment of the granules with antioxidants. Oxygen consumption and generation of singlet oxygen induced by the photoexcited LFG increased with donor's age and was partially quenched by antioxidants. Although the phototoxic potential of lipofuscin increased with age, natural antioxidants reduced photoreactivity of LFG and their efficiency to induce oxidative stress. This study has demonstrated, for the first time, that mild oxidative stress, mediated by the age pigment lipofuscin, impairs specific phagocytic activity of RPE, and that natural antioxidants can protect this important cellular function by reducing lipofuscin photoreactivity.

TREM2-transduced myeloid precursors mediate nervous tissue debris clearance and facilitate recovery in an animal model of multiple sclerosis.

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Kazuya Takahashi

2007-04-01

Full Text Available BACKGROUND: In multiple sclerosis, inflammation can successfully be prevented, while promoting repair is still a major challenge. Microglial cells, the resident phagocytes of the central nervous system (CNS, are hematopoietic-derived myeloid cells and express the triggering receptor expressed on myeloid cells 2 (TREM2, an innate immune receptor. Myeloid cells are an accessible source for ex vivo gene therapy. We investigated whether myeloid precursor cells genetically modified to express TREM2 affect the disease course of experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis. METHODS AND FINDINGS: EAE was induced in mice by immunization with a myelin autoantigen. Intravenous application of TREM2-transduced bone marrow-derived myeloid precursor cells at the EAE peak led to an amelioration of clinical symptoms, reduction in axonal damage, and prevention of further demyelination. TREM2-transduced myeloid cells applied intravenously migrated into the inflammatory spinal cord lesions of EAE-diseased mice, showed increased lysosomal and phagocytic activity, cleared degenerated myelin, and created an anti-inflammatory cytokine milieu within the CNS. CONCLUSIONS: Intravenously applied bone marrow-derived and TREM2-tranduced myeloid precursor cells limit tissue destruction and facilitate repair within the murine CNS by clearance of cellular debris during EAE. TREM2 is a new attractive target for promotion of repair and resolution of inflammation in multiple sclerosis and other neuroinflammatory diseases.

Innate Immunity to Leishmania Infection: Within Phagocytes

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Marcela Freitas Lopes

2014-01-01

Full Text Available Infection by Leishmania takes place in the context of inflammation and tissue repair. Besides tissue resident macrophages, inflammatory macrophages and neutrophils are recruited to the infection site and serve both as host cells and as effectors against infection. Recent studies suggest additional important roles for monocytes and dendritic cells. This paper addresses recent experimental findings regarding the regulation of Leishmania major infection by these major phagocyte populations. In addition, the role of IL-4 on dendritic cells and monocytes is discussed.

Effect of bile on growth, peritoneal absorption, and blood clearance of Escherichia coli in E coli peritonitis

International Nuclear Information System (INIS)

Andersson, R.; Schalen, C.; Tranberg, K.G.

1991-01-01

The effect of intraperitoneal bile on growth, peritoneal absorption, and clearance of Escherichia coli was determined in E coli peritonitis in the rat. In E coli peritonitis, intraperitoneal bacterial counts gradually decreased, whereas they increased (after 2 hours) with subsequent development of bacteremia in E coli plus bile peritonitis. After an intraperitoneal injection of labeled bacteria, blood radioactivity was only initially lower in E coli plus bile peritonitis compared with E coli peritonitis. Clearance from blood was lower in E coli plus bile peritonitis than in E coli peritonitis. Organ localization was similar in E coli peritonitis and E coli plus bile peritonitis with decreased splenic, increased pulmonary, and unchanged hepatic uptakes compared with controls. Impaired peritoneal absorption of bacteria, together with impaired local host defense, is likely to enhance the noxious effect of bile in E coli peritonitis

Influence of indicators for thiotriazolin phagocytic activity of leukocytes in the blood in the later period of development of stomach ulcers against pneumonia

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L. O. Furdychko

2017-07-01

Full Text Available Important for the pathogenesis of pneumonia and gastric ulcers should state phagocytic activity of leukocytes (PHAL in the blood. In fact the state of nonspecific resistance factors to some extent depends on the disease, the development of complications, prognosis and therapy. Materials and methods. The study was conducted on 49 male guinea pigs. The experimental pneumonia caused by the method Shlyapnykova V. N., Solodova T. L., gastric ulcer simulated method Komarov V. I. Nonspecific resistance of animals we evaluated, examining the phagocytic activity of leukocytes (PHAL, nitroblue tetrazolium test (NST- test. Phagocytic activity of leukocytes (PHAL in blood were studied in terms phagocytic index (PHI and the phagocytic number (PHN and determined by the method Menshikov V. V. NST - test method Vyksmana M. E., Mayanskoho A. H. The figures research results processed by statistical method Student. Results and discussion. For the experiment, we selected two models of disease: experimental pneumonia (EP and peptic ulcer (PU. State PHAL determined by the level of phagocytic number (PHN, phagocytic index (PHI, NST-test levels in the ЕP+ PU. Found that in the 10-th and 18-th day of development of pathological process both in the stomach and the lungs of guinea pigs, there was reduction of PHI respectively 15,8% (P

The phagocyte inhibitory receptor sirpα in the immune system

NARCIS (Netherlands)

Álvarez Zárate, J.

2014-01-01

Phagocytes play a central role in the host defense against pathogens, by virtue of amongst other things their ability to recognize and destroy them. These processes have to be tightly controlled to prevent unwanted inflammation that could harm the host. From previous studies it has become clear that

Bronchoscintigraphy and pulmonary clearance of 99mTc-albumin colloid in study of mucociliary clearance

International Nuclear Information System (INIS)

Mortensen, Jann

1998-01-01

A radioaerosol based method for measuring MC was introduced. It included an inhalation protocol that resulted in a predominant deposition of radioaerosol in the central bronchi and two simple procedures of evaluation: 1) a visual semi-quantitative bronchoscintigraphic analysis, and 2) a quantitative analysis of the retention of the radioactivity at different points after the inhalation. The results showed that bronchoscintigraphy was a simple technique that may be used to visualize a stimulation of mucociliary transport in the central airways of individuals that do not suffer from too much mucus hypersecretion. Comparison of the MC between individuals, however, should preferably be performed by the method of quantitative analysis of the radioactivity disappearance. A change of MC was found to be one of the first detectable effects on lung function of tobacco smoking. It could be effectively detected by measurement of radioaerosol clearance both by bronchoscintigraphy and simple quantification of the MC. The MC may be either acutely enhanced, reduced or not changed by smoking. Long-term smoking impairs MC. The enhancement of MC by β 2 -agonists was very limited in most patients with CF. In the hope of increasing mucus transport in patients with CF, these are treated with various chest physiotherapy techniques. The radioaerosol based method of measurement of MC could assess mucus clearance by chest physiotherapy and cough. (au)

Brain drains: new insights into brain clearance pathways from lymphatic biology.

Science.gov (United States)

Bower, Neil I; Hogan, Benjamin M

2018-05-01

The lymphatic vasculature act as the drainage system for most of our tissues and organs, clearing interstitial fluid and waste and returning them to the blood circulation. This is not the case for the central nervous system (CNS), which is devoid of parenchymal lymphatic vessels. Nevertheless, the brain is responsible for 25% of the body's metabolism and only compromises 2% of the body's mass. This high metabolic load requires an efficient system to remove waste products and maintain homeostasis. Well-described mechanisms of waste clearance include phagocytic immune cell functions as well as perivascular fluid flow; however, the need for active drainage of waste from the brain is becoming increasingly appreciated. Recent developments in lymphatic vascular biology challenge the proposition that the brain lacks lymphatic drainage or an equivalent. In this review, we describe the roles of the glymphatic system (a key drainage mechanism in the absence of lymphatics), the recently characterized meningeal lymphatic vessels, and explore an enigmatic cell population found in zebrafish called mural lymphatic endothelial cells. These systems may play important individual and collective roles in draining and clearing wastes from the brain.

Effects of lighting illuminance levels on stair negotiation performance in individuals with visual impairment.

Science.gov (United States)

Shaheen, Aliah F; Sourlas, Alexandros; Horton, Khim; McLean, Christopher; Ewins, David; Gould, David; Ghoussayni, Salim

2018-04-01

Stair-related falls of older people cause a substantial financial and social burden. Deterioration of the visual system amongst other factors put older people at a high risk of falling. Improved lighting is often recommended. The aim of this study was to investigate the effect of lighting illuminance on stair negotiation performance in older individuals with visual impairment. Eleven participants aged 60 or over with a vision of 6/18 or worse ascended and descended a staircase under: 50 lx, 100 lx, 200 lx, 300 lx and distributed 200 lx lighting. A motion capture system was used to measure movements of the lower limb. Clearance, clearance variability, temporal and spatial parameters and joint/segment kinematics were computed. There was no effect on clearance or clearance variability. Participants had lower speed, cadence, increased cycle time and stance time in the 50 lx compared to 300 lx and distributed 200 lx lighting in descent. The minimum hip angle in ascent was increased in the 200 lx lighting. Clearance was found to be moderately correlated with balance scores. Individuals with visual impairment adopt precautionary gait in dim lighting conditions. This does not always result in improvements in the parameters associated with risk of falling (e.g. clearance). Copyright © 2018 Elsevier Ltd. All rights reserved.

Development of the clearance level verification evaluation system. 2. Construction of the clearance data management system

International Nuclear Information System (INIS)

Kubota, Shintaro; Usui, Hideo; Kawagoshi, Hiroshi

2014-06-01

Clearance is defined as the removal of radioactive materials or radioactive objects within authorized practices from any further regulatory control by the regulatory body. In Japan, clearance level and a procedure for its verification has been introduced under the Laws and Regulations, and solid clearance wastes inspected by the national authority can be handled and recycled as normal wastes. The most prevalent type of wastes have generated from the dismantling of nuclear facilities, so the Japan Atomic Energy Agency (JAEA) has been developing the Clearance Level Verification Evaluation System (CLEVES) as a convenient tool. The Clearance Data Management System (CDMS), which is a part of CLEVES, has been developed to support measurement, evaluation, making and recording documents with clearance level verification. In addition, validation of the evaluation result of the CDMS was carried out by inputting the data of actual clearance activities in the JAEA. Clearance level verification is easily applied by using the CDMS for the clearance activities. (author)

Decreased insulin clearance in individuals with elevated 1-h post-load plasma glucose levels.

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Maria Adelaide Marini

Full Text Available Reduced insulin clearance has been shown to predict the development of type 2 diabetes. Recently, it has been suggested that plasma glucose concentrations ≥ 8.6 mmol/l (155 mg/dl at 1 h during an oral glucose tolerance test (OGTT can identify individuals at high risk for type 2 diabetes among those who have normal glucose tolerance (NGT 1 h-high. The aim of this study was to examine whether NGT 1 h-high have a decrease in insulin clearance, as compared with NGT individuals with 1-h post-load glucose <8.6 mmol/l (l (155 mg/dl, NGT 1 h-low. To this end, 438 non-diabetic White individuals were subjected to OGTT and euglycemic-hyperinsulinemic clamp to evaluate insulin clearance and insulin sensitivity. As compared with NGT 1 h-low individuals, NGT 1 h-high had significantly higher 1-h and 2-h post-load plasma glucose and 2-h insulin levels as well as higher fasting glucose and insulin levels. NGT 1 h-high exhibited also a significant decrease in both insulin sensitivity (P<0.0001 and insulin clearance (P = 0.006 after adjusting for age, gender, adiposity measures, and insulin sensitivity. The differences in insulin clearance remained significant after adjustment for fasting glucose (P = 0.02 in addition to gender, age, and BMI. In univariate analyses adjusted for gender and age, insulin clearance was inversely correlated with body weight, body mass index, waist, fat mass, 1-h and 2-h post-load glucose levels, fasting, 1-h and 2-h post-load insulin levels, and insulin-stimulated glucose disposal. In conclusion, our data show that NGT 1 h-high have a reduction in insulin clearance as compared with NGT 1 h-low individuals; this suggests that impaired insulin clearance may contribute to sustained fasting and post-meal hyperinsulinemia.

Disruption of Sphingolipid Biosynthesis Blocks Phagocytosis of Candida albicans.

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Fikadu G Tafesse

2015-10-01

Full Text Available The ability of phagocytes to clear pathogens is an essential attribute of the innate immune response. The role of signaling lipid molecules such as phosphoinositides is well established, but the role of membrane sphingolipids in phagocytosis is largely unknown. Using a genetic approach and small molecule inhibitors, we show that phagocytosis of Candida albicans requires an intact sphingolipid biosynthetic pathway. Blockade of serine-palmitoyltransferase (SPT and ceramide synthase-enzymes involved in sphingolipid biosynthesis- by myriocin and fumonisin B1, respectively, impaired phagocytosis by phagocytes. We used CRISPR/Cas9-mediated genome editing to generate Sptlc2-deficient DC2.4 dendritic cells, which lack serine palmitoyl transferase activity. Sptlc2-/- DC2.4 cells exhibited a stark defect in phagocytosis, were unable to bind fungal particles and failed to form a normal phagocytic cup to engulf C. albicans. Supplementing the growth media with GM1, the major ganglioside present at the cell surface, restored phagocytic activity of Sptlc2-/- DC2.4 cells. While overall membrane trafficking and endocytic pathways remained functional, Sptlc2-/- DC2.4 cells express reduced levels of the pattern recognition receptors Dectin-1 and TLR2 at the cell surface. Consistent with the in vitro data, compromised sphingolipid biosynthesis in mice sensitizes the animal to C. albicans infection. Sphingolipid biosynthesis is therefore critical for phagocytosis and in vivo clearance of C. albicans.

Uptake and intracellular activity of AM-1155 in phagocytic cells.

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Yamamoto, T; Kusajima, H; Hosaka, M; Fukuda, H; Oomori, Y; Shinoda, H

1996-01-01

The uptake and intracellular activity of AM-1155 in murine J774.1 macrophages and human polymorphonuclear leukocytes were investigated. AM-1155 penetrated phagocytic cells rapidly and reversibly, although the penetration process was not affected by metabolic inhibitors such as sodium fluoride, cyanide m-chlorophenylhydrazone, or ouabain or by nucleoside transport system inhibitors such as adenosine. The intracellular concentration-to-extracellular concentration ratio of AM-1155 in both cell types of phagocytes ranged from 5 to 7. These ratios were almost equal to those for sparfloxacin. The intracellular activity of AM-1155 in J774.1 macrophages, examined with Staphylococcus aureus 209P as a test bacterium, was dependent on the extracellular concentration. AM-1155 at a concentration of 1 microgram/ml reduced the number of viable cells of S. aureus ingested by more than 90%. The intracellular activity of AM-1155 was more potent than those of sparfloxacin, ofloxacin, ciprofloxacin, flomoxef, and erythromycin. These results suggest that the potent intracellular activity of AM-1155 might mainly be due to the high intracellular concentration and its potent in vitro activity. PMID:9124835

Cellular immune responses and phagocytic activity of fishes exposed to pollution of volcano mud.

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Risjani, Yenny; Yunianta; Couteau, Jerome; Minier, Christophe

2014-05-01

Since May 29, 2006, a mud volcano in the Brantas Delta of the Sidoarjo district has emitted mud that has inundated nearby villages. Pollution in this area has been implicated in detrimental effects on fish health. In fishes, leukocyte and phagocytic cells play a vital role in body defenses. We report for the first time the effect of "LUSI" volcano mud on the immune systems of fish in the Brantas Delta. The aim of this study was to find biomarkers to allow the evaluation of the effects of volcanic mud and anthropogenic pollution on fish health in the Brantas Delta. The study took places at the Brantas Delta, which was polluted by volcano mud, and at reference sites in Karangkates and Pasuruan. Leukocyte numbers were determined using a Neubauer hemocytometer and a light microscope. Differential leukocyte counts were determined using blood smears stained with May Grunwald-Giemsa, providing neutrophil, lymphocyte and monocyte counts. Macrophages were taken from fish kidney, and their phagocytic activity was measured. In vitro analyses revealed that leukocyte and differential leukocyte counts (DLC) were higher in Channa striata and Chanos chanos caught from the polluted area. Macrophage numbers were higher in Oreochromis mossambicus than in the other species, indicating that this species is more sensitive to pollution. In areas close to volcanic mud eruption, all specimens had lower phagocytic activity. Our results show that immune cells were changed and phagocytic activity was reduced in the polluted area indicating cytotoxicity and alteration of the innate immune system in fishes exposed to LUSI volcano mud and anthropogenic pollution. Copyright © 2014 Elsevier Ltd. All rights reserved.

Leptospira interrogans stably infects zebrafish embryos, altering phagocyte behavior and homing to specific tissues.

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J Muse Davis

2009-06-01

Full Text Available Leptospirosis is an extremely widespread zoonotic infection with outcomes ranging from subclinical infection to fatal Weil's syndrome. Despite the global impact of the disease, key aspects of its pathogenesis remain unclear. To examine in detail the earliest steps in the host response to leptospires, we used fluorescently labelled Leptospira interrogans serovar Copenhageni to infect 30 hour post fertilization zebrafish embryos by either the caudal vein or hindbrain ventricle. These embryos have functional innate immunity but have not yet developed an adaptive immune system. Furthermore, they are optically transparent, allowing direct visualization of host-pathogen interactions from the moment of infection. We observed rapid uptake of leptospires by phagocytes, followed by persistent, intracellular infection over the first 48 hours. Phagocytosis of leptospires occasionally resulted in formation of large cellular vesicles consistent with apoptotic bodies. By 24 hours, clusters of infected phagocytes were accumulating lateral to the dorsal artery, presumably in early hematopoietic tissue. Our observations suggest that phagocytosis may be a key defense mechanism in the early stages of leptospirosis, and that phagocytic cells play roles in immunopathogenesis and likely in the dissemination of leptospires to specific target tissues.

The Phagocytic Function of Macrophage-Enforcing Innate Immunity and Tissue Homeostasis

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Daisuke Hirayama

2017-12-01

Full Text Available Macrophages are effector cells of the innate immune system that phagocytose bacteria and secrete both pro-inflammatory and antimicrobial mediators. In addition, macrophages play an important role in eliminating diseased and damaged cells through their programmed cell death. Generally, macrophages ingest and degrade dead cells, debris, tumor cells, and foreign materials. They promote homeostasis by responding to internal and external changes within the body, not only as phagocytes, but also through trophic, regulatory, and repair functions. Recent studies demonstrated that macrophages differentiate from hematopoietic stem cell-derived monocytes and embryonic yolk sac macrophages. The latter mainly give rise to tissue macrophages. Macrophages exist in all vertebrate tissues and have dual functions in host protection and tissue injury, which are maintained at a fine balance. Tissue macrophages have heterogeneous phenotypes in different tissue environments. In this review, we focused on the phagocytic function of macrophage-enforcing innate immunity and tissue homeostasis for a better understanding of the role of tissue macrophages in several pathological conditions.

Enhanced alveolar monocytic phagocyte (macrophage) proliferation in tobacco and marijuana smokers

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Barbers, R.G.; Evans, M.J.; Gong, H. Jr.; Tashkin, D.P. (Univ. of California-Los Angeles School of Medicine (USA))

1991-05-01

We tested the hypothesis that enhanced cell division accounted for the augmented numbers of monocytic phagocytes with characteristics attributed to alveolar macrophages (AM) found in the lungs of habitual tobacco (T) and marijuana (M) smokers. The monocytic phagocytes, that is, alveolar macrophages, were obtained by bronchoalveolar lavage (BAL) from 12 nonsmoking subjects; 10 subjects who smoked T only (TS); 13 subjects who smoked M only (MS); and 6 smokers of both T and M (MTS). The replication of these cells was determined by measuring the incorporation of ({sup 3}H)thymidine into the DNA of dividing cells and visually counting 2,000 cells on autoradiographically prepared cytocentrifuge cell preparations. This study demonstrated that the number of ({sup 3}H)thymidine-labeled monocytic phagocytes with characteristics of alveolar macrophages from either TS or MS have a higher proliferative index compared to cells (macrophages) from nonsmokers, p less than 0.05 by one-way ANOVA. The total number of BAL macrophages that are in mitosis in TS (17.90 +/- 4.50 labeled AM x 10(3)/ml) or MTS (10.50 +/- 4.20 labeled AM x 10(3)/ml) are 18- and 10-fold greater, respectively, than the number obtained from nonsmokers (1.01 +/- 0.18 labeled AM x 10(3)/ml). Interestingly, the number of ({sup 3}H)thymidine-labeled macrophages from MS (2.90 +/- 0.66 labeled AM x 10(3)/ml) are also greater than the number obtained from nonsmokers, although this is not statistically significant. The stimulus augmenting alveolar macrophage replication is as yet unknown but may likely be found in the T or M smoke.

Enhanced alveolar monocytic phagocyte (macrophage) proliferation in tobacco and marijuana smokers

International Nuclear Information System (INIS)

Barbers, R.G.; Evans, M.J.; Gong, H. Jr.; Tashkin, D.P.

1991-01-01

We tested the hypothesis that enhanced cell division accounted for the augmented numbers of monocytic phagocytes with characteristics attributed to alveolar macrophages (AM) found in the lungs of habitual tobacco (T) and marijuana (M) smokers. The monocytic phagocytes, that is, alveolar macrophages, were obtained by bronchoalveolar lavage (BAL) from 12 nonsmoking subjects; 10 subjects who smoked T only (TS); 13 subjects who smoked M only (MS); and 6 smokers of both T and M (MTS). The replication of these cells was determined by measuring the incorporation of [ 3 H]thymidine into the DNA of dividing cells and visually counting 2,000 cells on autoradiographically prepared cytocentrifuge cell preparations. This study demonstrated that the number of [ 3 H]thymidine-labeled monocytic phagocytes with characteristics of alveolar macrophages from either TS or MS have a higher proliferative index compared to cells (macrophages) from nonsmokers, p less than 0.05 by one-way ANOVA. The total number of BAL macrophages that are in mitosis in TS (17.90 +/- 4.50 labeled AM x 10(3)/ml) or MTS (10.50 +/- 4.20 labeled AM x 10(3)/ml) are 18- and 10-fold greater, respectively, than the number obtained from nonsmokers (1.01 +/- 0.18 labeled AM x 10(3)/ml). Interestingly, the number of [ 3 H]thymidine-labeled macrophages from MS (2.90 +/- 0.66 labeled AM x 10(3)/ml) are also greater than the number obtained from nonsmokers, although this is not statistically significant. The stimulus augmenting alveolar macrophage replication is as yet unknown but may likely be found in the T or M smoke

Recent activities on clearance in IAEA and clearance automatic laser inspection system (CLALIS)

International Nuclear Information System (INIS)

Hattori, Takatoshi; Sasaki, Michiya

2005-01-01

Exemption levels for bulk amounts of materials have been described in RS-G-1.7 published as a safety guide in IAEA on August 2004. In Japan, the Nuclear Safety Commission adopted the RS-G-1.7 values as Japanese clearance levels after the careful review of dose assessment results. After completing revises of regulatory laws in relation to clearance level, solid wastes from decommissioning and operating nuclear power plants will be targets of clearance inspection. In CRIEPI, Clearance Automatic Laser Inspection System (CLALIS) has been developed, which can give high reliability and objectivity to the measurement data. The CLALIS is a new monitoring system coupling with 3D laser shape measurement, Monte-Carlo calculation and gamma measurement techniques, which can keep a high accuracy in the measurement data using an automatic correction technique for self-shielding effects of metal waste itself and is expected to apply as a practical use in actual clearance inspections. (author)

Phagocytic activities of hemocytes from the deep-sea symbiotic mussels Bathymodiolus japonicus, B. platifrons, and B. septemdierum.

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Tame, Akihiro; Yoshida, Takao; Ohishi, Kazue; Maruyama, Tadashi

2015-07-01

Deep-sea mytilid mussels harbor symbiotic bacteria in their gill epithelial cells that are horizontally or environmentally transmitted to the next generation of hosts. To understand the immune defense system in deep-sea symbiotic mussels, we examined the hemocyte populations of the symbiotic Bathymodiolus mussel species Bathymodiolus japonicus, Bathymodiolus platifrons, and Bathymodiolus septemdierum, and characterized three types of hemocytes: agranulocytes (AGs), basophilic granulocytes (BGs), and eosinophilic granulocytes (EGs). Of these, the EG cells were the largest (diameter, 8.4-10.0 μm) and had eosinophilic cytoplasm with numerous eosinophilic granules (diameter, 0.8-1.2 μm). Meanwhile, the BGs were of medium size (diameter, 6.7-8.0 μm) and contained small basophilic granules (diameter, 0.3-0.4 μm) in basophilic cytoplasm, and the AGs, the smallest of the hemocytes (diameter, 4.8-6.0 μm), had basophilic cytoplasm lacking granules. A lectin binding assay revealed that concanavalin A bound to all three hemocyte types, while wheat germ agglutinin bound exclusively to EGs and BGs. The total hemocyte population densities within the hemolymph of all three Bathymodiolus mussel species were similar (8.4-13.3 × 10(5) cells/mL), and the percentages of circulating AGs, BGs, and EGs in the hemolymph of these organisms were 44.7-48.5%, 14.3-17.6%, and 34.3-41.0%, respectively. To analyze the functional differences between these hemocytes, the phagocytic activity and post-phagocytic phagosome-lysosome fusion events were analyzed in each cell type using a fluorescent Alexa Fluor(®) 488-conjugated Escherichia coli bioparticle and a LysoTracker(®) lysosomal marker, respectively. While the AGs exhibited no phagocytic activity, both types of granulocytes were phagocytic. Of the three hemocyte types, the EGs exhibited the highest level of phagocytic activity as well as rapid phagosome-lysosome fusion, which occurred within 2 h of incubation. Meanwhile, the BGs showed

Bronchoscintigraphy and pulmonary clearance of {sup 99{sup m}}Tc-albumin colloid in study of mucociliary clearance

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Mortensen, Jann

1998-12-31

A radioaerosol based method for measuring MC was introduced. It included an inhalation protocol that resulted in a predominant deposition of radioaerosol in the central bronchi and two simple procedures of evaluation: 1) a visual semi-quantitative bronchoscintigraphic analysis, and 2) a quantitative analysis of the retention of the radioactivity at different points after the inhalation. The results showed that bronchoscintigraphy was a simple technique that may be used to visualize a stimulation of mucociliary transport in the central airways of individuals that do not suffer from too much mucus hypersecretion. Comparison of the MC between individuals, however, should preferably be performed by the method of quantitative analysis of the radioactivity disappearance. A change of MC was found to be one of the first detectable effects on lung function of tobacco smoking. It could be effectively detected by measurement of radioaerosol clearance both by bronchoscintigraphy and simple quantification of the MC. The MC may be either acutely enhanced, reduced or not changed by smoking. Long-term smoking impairs MC. The enhancement of MC by {beta}{sub 2}-agonists was very limited in most patients with CF. In the hope of increasing mucus transport in patients with CF, these are treated with various chest physiotherapy techniques. The radioaerosol based method of measurement of MC could assess mucus clearance by chest physiotherapy and cough. (au) 141 refs.

Generic clearance values

International Nuclear Information System (INIS)

Bossio, M.C.; Muniz, C.C.

2009-01-01

This paper analyzes the Generic Clearance Values established for natural and artificial radionuclides with the objective of evaluating their degree of conservatism in views of adopting them into the regulatory body. Generic clearance values for natural radionuclides have been chosen by experts judgments as the optimum boundary between, on one hand, the ubiquitous unmodified soil concentrations and, on the other hand, activity concentrations in ores, mineral sands, industrial residues and wastes. For artificial radionuclides the clearance levels have been derived from the scenarios postulated in the document 'Safety Reports Series Nr 44' of the IAEA considering quantitative exemption criteria. A set of 8 scenarios were postulated covering external, ingestion and inhalation exposure pathways. For each radionuclide, the generic clearance level was derived as the more restrictive value obtained from the scenarios, that is the lowest ratio between the applicable individual dose and the dose per unit activity concentration (Bq/g). The individual dose was calculated by a formula depending on each scenario and pathway, with different parameters, such as exposure time, dosimetric factors, dilution factor, density of the material, geometric factors, etc. It was concluded that the basis and parameters used for the derivation of the generic clearance levels are quite conservative and therefore its the adoption in Argentina has been recommended. It is expected that their implementation will contribute to optimize the regulatory management system. (author)

Generic Clearance Values

International Nuclear Information System (INIS)

Bossio, M.C.; Muniz, C.C.

2010-01-01

This paper analyzes the Generic Clearance Values established for natural and artificial radionuclides with the objective of evaluating their degree of conservatism in views of adopting them into the regulatory body. Generic clearance values for natural radionuclides have been chosen by experts judgments as the optimum boundary between, on the one hand, the ubiquitous unmodified soil concentrations and, on the other hand, activity concentrations in ores, mineral sands, industrial residues and wastes. For artificial radionuclides the clearance levels have been derived from the scenarios postulated in the document Safety Reports Series 44 of the IAEA considering quantitative exemption criteria. A set of 8 scenarios were postulated covering external, ingestion and inhalation exposure pathways. For each radionuclide, the generic clearance level was derived as the more restrictive value obtained from the scenarios, that is the lowest ratio between the applicable individual dose and the dose per unit activity concentration (Bq/g). The individual dose was calculated by a formula depending on each scenario and pathway, with different parameters, such as exposure time, dosimetric factors, dilution factor, density of the material, geometric factors, etc. It was concluded that the basis and parameters used for the derivation of the generic clearance levels are quite conservative and therefore its the adoption in Argentina has been recommended. It is expected that their implementation will contribute to optimize the regulatory management system. (authors) [es

Loss of Acetylcholine Signaling Reduces Cell Clearance Deficiencies in Caenorhabditis elegans.

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Sérgio M Pinto

Full Text Available The ability to eliminate undesired cells by apoptosis is a key mechanism to maintain organismal health and homeostasis. Failure to clear apoptotic cells efficiently can cause autoimmune diseases in mammals. Genetic studies in Caenorhabditis elegans have greatly helped to decipher the regulation of apoptotic cell clearance. In this study, we show that the loss of levamisole-sensitive acetylcholine receptor, but not of a typical neuronal acetylcholine receptor causes a reduction in the number of persistent cell corpses in worms suffering from an engulfment deficiency. This reduction is not caused by impaired or delayed cell death but rather by a partial restoration of the cell clearance capacity. Mutants in acetylcholine turn-over elicit a similar phenotype, implying that acetylcholine signaling is the process responsible for these observations. Surprisingly, tissue specific RNAi suggests that UNC-38, a major component of the levamisole-sensitive receptor, functions in the dying germ cell to influence engulfment efficiency. Animals with loss of acetylcholine receptor exhibit a higher fraction of cell corpses positive for the "eat-me" signal phosphatidylserine. Our results suggest that modulation by ion channels of ion flow across plasma membrane in dying cells can influence the dynamics of phosphatidylserine exposure and thus clearance efficiency.

The modulatory role of cytokines IL-4 and IL-17 in the functional activity of phagocytes in diabetic pregnant women.

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Fagundes, Danny L G; França, Eduardo L; Gonzatti, Michelangelo B; Rugde, Marilza V C; Calderon, Iracema M P; Honorio-França, Adenilda C

2018-01-01

The study investigated the role of cytokines IL-4 and IL-17 in the modulation of the functional activity of mononuclear phagocytes in diabetic pregnant women with hyperglycemia. Sixty pregnant women were assigned to the following groups: nondiabetic (ND), mild gestational hyperglycemia (MGH), gestational diabetes mellitus (GDM), or type 2 diabetes mellitus (DM2). The functional activity of phagocytes from maternal blood, cord blood, and colostrum was assessed by determining their superoxide release, phagocytosis, microbicidal activity, and intracellular Ca 2+ release. Irrespective of glycemic status, colostrum and blood cells treated with IL-4 and IL-17 increased superoxide release in the presence of enteropathogenic Escherichia coli (EPEC). The highest phagocytosis rate was observed in cells from the DM2 group treated with IL-4. In all the groups, phagocytes from colostrum, maternal blood, and cord blood exhibited higher microbicidal activity against EPEC when treated with cytokines. IL-17 increased intracellular Ca 2+ release by colostrum phagocytes in diabetic groups. The results indicate that the IL-4 and IL-17 modulate the functional activity of phagocytes in the maternal blood, cord blood, and colostrum of diabetic mother. The natural immunity resulting from the interaction between the cells and cytokines tested may be an alternative procedure to improve the prognosis of maternal and newborn infections. © 2017 APMIS. Published by John Wiley & Sons Ltd.

Kupffer cell complement receptor clearance function and host defense.

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Loegering, D J

1986-01-01

Kupffer cells are well known to be important for normal host defense function. The development of methods to evaluate the in vivo function of specific receptors on Kupffer cells has made it possible to assess the role of these receptors in host defense. The rationale for studying complement receptors is based on the proposed important role of these receptors in host defense and on the observation that the hereditary deficiency of a complement receptor is associated with recurrent severe bacterial infections. The studies reviewed here demonstrate that forms of injury that are associated with depressed host defense including thermal injury, hemorrhagic shock, trauma, and surgery also cause a decrease in complement receptor clearance function. This decrease in Kupffer cell receptor clearance function was shown not to be the result of depressed hepatic blood flow or depletion of complement components. Complement receptor function was also depressed following the phagocytosis of particulates that are known to depress Kupffer cell host defense function. Endotoxemia and bacteremia also were associated with a depression of complement receptor function. Complement receptor function was experimentally depressed in uninjured animals by the phagocytosis of IgG-coated erythrocytes. There was a close association between the depression of complement receptor clearance function and increased susceptibility to the lethal effects of endotoxin and bacterial infection. These studies support the hypotheses that complement receptors on Kupffer cells are important for normal host defense and that depression of the function of these receptors impairs host defense.

In vitro formation of osteoclasts from long-term cultures of bone marrow mononuclear phagocytes

International Nuclear Information System (INIS)

Burger, E.H.; Van der Meer, J.W.; van de Gevel, J.S.; Gribnau, J.C.; Thesingh, G.W.; van Furth, R.

1982-01-01

The origin of osteoclasts was studied in an in vitro model using organ cultures of periosteum-free embryonic mouse long-bone primordia, which were co-cultured with various cell populations. The bone rudiments were freed of their periosteum-perichondrium by collagenase treatment in a stage before cartilage erosion and osteoclast formation, and co-cultured for 7 d with either embryonic liver or mononuclear phagocytes from various sources. Light and electron microscopic examination of the cultures showed that mineralized matrix-resorbing osteoclasts developed only in bones co-cultured with embryonic liver or with cultured bone marrow mononuclear phagocytes but not when co-cultured with blood monocytes or resident or exudate peritoneal macrophages. Osteoclasts developed from the weakly adherent, but not from the strongly adherent cells of bone marrow cultures, whereas 1,000 rad irradiation destroyed the capacity of such cultures to form osteoclasts. In bone cultures to which no other cells were added, osteoclasts were virtually absent. Bone-resorbing activity of in vitro formed osteoclasts was demonstrated by 45 Ca release studies. These studies demonstrate that osteoclasts develop from cells present in cultures of proliferating mononuclear phagocytes and that, at least in our system, monocytes and macrophages are unable to form osteoclasts. The most likely candidates for osteoclast precursor cells seem to be monoblasts and promonocytes

Defective natural killer and phagocytic activities in chronic obstructive pulmonary disease are restored by glycophosphopeptical (inmunoferón).

Science.gov (United States)

Prieto, A; Reyes, E; Bernstein, E D; Martinez, B; Monserrat, J; Izquierdo, J L; Callol, L; de LUCAS, P; Alvarez-Sala, R; Alvarez-Sala, J L; Villarrubia, V G; Alvarez-Mon, M

2001-06-01

We have investigated both modifications in natural (innate) immunity caused by chronic obstructive pulmonary disease (COPD) and the effects of a glycophosphopeptical immunomodulator (Inmunoferón) treatment on COPD-associated immunoalterations. In a double-blinded clinical trial, 60 patients with COPD received glycophosphopeptical or placebo during 90 consecutive days at oral doses of 3 g/d. Fifty-six sex- and age-matched healthy control subjects were included as a reference group for immunologic parameters. Peripheral blood natural killer (PBNK) cell cytotoxic activity and phagocytic activity of peripheral monocytes/macrophages (Mo/Ma) and polymorphonuclear (PMN) cells were assessed at baseline and then again at the end of treatments. We found both PBNK activity and phagocytic activity to be significantly decreased in patients with COPD compared with levels in healthy volunteers. The treatment with glycophosphopeptical provoked significant stimulatory effects on PBNK cytotoxic activity. This stimulation was not mediated by an increase in CD3(-)CD56(+) NK cells. Further, glycophosphopeptical significantly increased the percentage of monocytes and PMNs that phagocytize Escherichia coli in vitro, as well as increased phagocytic indices. We conclude that peripheral blood cells of patients with COPD show clear defects in natural immunity that are partially rescued by glycophosphopeptical.

Induction of heat-shock proteins and phagocytic function of chicken macrophage following in vitro heat exposure

International Nuclear Information System (INIS)

Miller, L.; Qureshi, M.A.

1992-01-01

The protein profiles and phagocytic ability of Sephadex-elicited chicken peritoneal macrophages were examined following heat-shock exposure. Macrophage cultures were exposed to various temperatures, time exposures and recovery periods. Densitometric analysis of SDS-PAGE autoradiographs revealed that heat-induced macrophages synthesized three major (23, 70 and 90 kD) heat-shock proteins (HSPs). The optimal temperature and time for induction of these HSPs was 45-46 degrees C for 1 h, with a variable recovery period for each HSP. Macrophages exposed to 45 degrees C for 30 and 60 min were significantly depressed in phagocytosis of uncoated sheep erythrocytes (SE) under 45 degrees C incubation conditions. However, phagocytosis of antibody-coated SE was not affected when compared to 41 degrees C control cultures. Macrophages allowed to recover at 41 degrees C following heat-shock exhibited no alterations in their phagocytic ability for either antibody-coated or uncoated SE. This study suggests that heat shock induces three major HSPs in chicken peritoneal macrophages in addition to maintaining their Fc-mediated phagocytic function while significantly depressing their nonspecific phagocytosis

Far beyond Phagocytosis: Phagocyte-Derived Extracellular Traps Act Efficiently against Protozoan Parasites In Vitro and In Vivo

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Liliana M. R. Silva

2016-01-01

Full Text Available Professional mononuclear phagocytes such as polymorphonuclear neutrophils (PMN, monocytes, and macrophages are considered as the first line of defence against invasive pathogens. The formation of extracellular traps (ETs by activated mononuclear phagocytes is meanwhile well accepted as an effector mechanism of the early host innate immune response acting against microbial infections. Recent investigations showed evidence that ETosis is a widely spread effector mechanism in vertebrates and invertebrates being utilized to entrap and kill bacteria, fungi, viruses, and protozoan parasites. ETs are released in response to intact protozoan parasites or to parasite-specific antigens in a controlled cell death process. Released ETs consist of nuclear DNA as backbone adorned with histones, antimicrobial peptides, and phagocyte-specific granular enzymes thereby producing a sticky extracellular matrix capable of entrapping and killing pathogens. This review summarizes recent data on protozoa-induced ETosis. Special attention will be given to molecular mechanisms of protozoa-induced ETosis and on its consequences for the parasites successful reproduction and life cycle accomplishment.

Impact of mild renal impairment on early postoperative mortality after open cardiac surgery

International Nuclear Information System (INIS)

A Abdel Ghani; Muath Al Nasar

2010-01-01

Preoperative severe renal impairment is included in the risk scores to predict outcome after open cardiac surgery. The purpose of this study was to assess the impact of pr operative mild renal impairment on the early postoperative mortality after open heart surgery. Data of all cases of open cardiac surgery performed from January 2005 to June 2006 were collected. Cases with preoperative creatinine clearance below 60 mL/min were excluded from the study. Data were retrospectively analyzed to find the impact of renal impairment on short-term outcome. Of the 500 cases studied, 47 had preoperative creatinine clearance between 89-60 mL/min. The overall mortality in the study cases was 6.8%. The mortality was 28.7% in those who developed postoperative ARF, 33.3% in those who required dialysis and 40.8% in those with preoperative mild renal impairment. Binary logistic regression analysis showed that female gender (P = 0.01), preoperative mild renal impairment (P 0.007) as well as occurrence of multi organ failure (P < 0.001) were the only independent variables determining the early postoperative mortality after cardiac surgeries. Among them, preoperative mild renal impairment was the most significant and the best predictor for early postoperative mortality after cardiac surgery. Our study suggests that renal impairment remains a strong predictor of early mortality even after adjustment for several confounders (Author).

Airway Clearance Techniques (ACTs)

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Airway Clearance Techniques (ACTs)

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Airway Clearance Techniques (ACTs)

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Airway Clearance Techniques (ACTs)

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Full Text Available ... today. ANNUAL FUND Become a Corporate Supporter Cause Marketing Make a Charitable Gift Our Corporate Supporters Workplace ... Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. Most are easy to ...

Airway Clearance Techniques (ACTs)

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Study on clearance system

International Nuclear Information System (INIS)

Onishi, Yuko; Miura, Hiroshi; Kawasaki, Satoru

2011-01-01

The clearance system is a legal system to release 'the radioactive waste not requiring treatment as radioactive waste' from the regulatory control. JNES supports NISA on approval and confirmation of clearance measurement and judgment developed by the operator. The objective of this study is to establish technical base of the validation method of the clearance measurement for various objects. In reactor facilities, the bulk measurement technique or the statistical sampling measurement technique may be applied to large scale objects or concrete walls. In this study, the criteria of those techniques were examined. In uranium processing facilities, it is important to confirm surface state of the object in case of detecting alpha rays. The result of the examination about the influence of the surface rust in the uranium clearance measurement by the alpha ray measurement showed that the pollution was distributed in rust layer uniformly. This result will be reflected to the revision of the Ministerial Ordinance on Clearance in 2011FY. To develop a manual for unexpected incidents, the response procedure for an unexpected incident was prepared, including a response system. (author)

Population pharmacokinetics of pomalidomide in patients with relapsed or refractory multiple myeloma with various degrees of impaired renal function.

Science.gov (United States)

Li, Yan; Wang, Xiaomin; O'Mara, Edward; Dimopoulos, Meletios A; Sonneveld, Pieter; Weisel, Katja C; Matous, Jeffrey; Siegel, David S; Shah, Jatin J; Kueenburg, Elisabeth; Sternas, Lars; Cavanaugh, Chloe; Zaki, Mohamed; Palmisano, Maria; Zhou, Simon

2017-01-01

Pomalidomide is an immunomodulatory drug for treatment of relapsed or refractory multiple myeloma (rrMM) in patients who often have comorbid renal conditions. To assess the impact of renal impairment on pomalidomide exposure, a population pharmacokinetics (PPK) model of pomalidomide in rrMM patients with various degrees of impaired renal function was developed. Intensive and sparse pomalidomide concentration data collected from two clinical studies in rrMM patients with normal renal function, moderately impaired renal function, severely impaired renal function not requiring dialysis, and with severely impaired renal function requiring dialysis were pooled over the dose range of 2 to 4 mg, to assess specifically the influence of the impaired renal function as a categorical variable and a continuous variable on pomalidomide clearance and plasma exposure. In addition, pomalidomide concentration data collected on dialysis days from both the withdrawal (arterial) side and from the returning (venous) side of the dialyzer, from rrMM patients with severely impaired renal function requiring dialysis, were used to assess the extent to which dialysis contributes to the removal of pomalidomide from blood circulation. PPK analyses demonstrated that moderate to severe renal impairment not requiring dialysis has no influence on pomalidomide clearance or plasma exposure, as compared to those patients with normal renal function, while pomalidomide exposure increased approximately 35% in patients with severe renal impairment requiring dialysis on nondialysis days. In addition, dialysis increased total body pomalidomide clearance from 5 L/h to 12 L/h, indicating that dialysis will significantly remove pomalidomide from the blood circulation. Thus, pomalidomide should be administered post-dialysis on the days of dialysis.

Airway Clearance Techniques (ACTs)

Medline Plus

Full Text Available ... to loosen mucus from airway walls. See how different airway clearance techniques work to help you clear the thick, sticky mucus ... Offer their tips for fitting ACTs into daily life Airway Clearance Techniques | Webcast ... Facebook Twitter ...

Evaluation of serum iohexol clearance for use in predicting carboplatin clearance in cats.

Science.gov (United States)

Bailey, Dennis B; Rassnick, Kenneth M; Prey, Joshua D; Dykes, Nathan L

2009-09-01

To determine whether a glomerular filtration rate (GFR) assay based on serum iohexol clearance can be used to predict carboplatin clearance in cats. 10 cats with tumors. GFR was measured concurrently by use of plasma clearance of technetium Tc 99m-labeled diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) to yield GFR(99mTc-DTPA) and serum clearance of iohexol to yield GFR(Iohexol). A single dose of carboplatin was administered IV as a bolus. Dose was calculated by use of a target value for the area under the plasma platinum concentration-versus-time curve (AUC(Target)) and estimation of platinum clearance (CL(PT)) derived from GFR(99mTc-DTPA) as follows: dose = AUC(Target) x 2.6 x GFR(99mTc-DTPA) x body weight, where AUC(Target) is 2.75 min.mg.mL(-1). Plasma platinum concentrations were measured via atomic absorption spectrophotometry. Values for GFR(99mTc-DTPA) and GFR(Iohexol) were compared by use of least-squares regression and Bland-Altman analysis. Least-squares regression was used to determine whether CL(PT) could be predicted from GFR(99mTc-DTPA) or GFR(Iohexol) (or both). GFR(99mTc-DTPA) and GFR(Iohexol) were strongly correlated (r = 0.90), but GFR(Iohexol) values were significantly larger by a factor of approximately 1.4. Platinum clearance had a significant linear relationship to GFR(99mTc-DTPA) (CL(PT) = 2.5 x GFR(99mTc-DTPA)) and to GFR(Iohexol) (CL(PT) = [1.3 x GFR(Iohexol)] + 1.4). In cats, serum iohexol clearance was an accurate predictor of CL(PT) and can be used to calculate the carboplatin dose as follows: dose = AUC(Target) x ([1.3 x GFR(Iohexol)] + 1.4) x body weight.

Escherichia coli clearance after splenic autotransplants

International Nuclear Information System (INIS)

Marques, R.G.; Petroianu, A.; Oliveira, M.B.N.; Bernardo-Filho, M.; Portela, M.C.

2002-01-01

Background: Splenic autotransplantation seems to be the only alternative for preservation of splenic tissue, after total splenectomy. The present study was carried out to analyze Escherichia coli depuration by mononuclear phagocyte system organs after total splenectomy and splenic autotransplantation. Methods: We utilized an experimental model including young and adult Wistar rats, of both sexes, submitted to total splenectomy and splenic autotransplantation. The evaluation method was intravenous inoculation of a suspension of Escherichia coli labeled with technetium-99m. We analyzed bacteria uptake by mononuclear phagocyte system organs and bacteria remnant in the bloodstream. Results: There was no difference between young and adult animals in bacteria uptake by mononuclear phagocyte system organs. In the comparison of groups, it was found out that the mean percent uptake by spleen and liver of animals in the control group was higher than that observed for animals with splenic implants. However, bacteria uptake in the lung was higher in the splenic implant group than in the control group. Although spleen bacteria uptake in the control group animals has been higher than that of animals in the splenic implant group, the remnant bacteria in the bloodstream was similar. Animals submitted to isolated total splenectomy showed higher bacteria remnant in the bloodstream than animals of the control group or the group submitted to total splenectomy combined with splenic autotransplantation. Conclusion: Our results indicate that autogenous splenic implant is efficacious in bacteria depuration in rats, by means of their macrophages phagocytosis. In addition, it does not modify bacteria removal function of liver and lung

Airway Clearance Techniques (ACTs)

Medline Plus

Full Text Available ... and Their Families When There's More Than One Person With CF in the Same School Daily Life ... Awards and Grants Career Development Awards Research Awards Training Awards CF ... Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your ...

Airway Clearance Techniques (ACTs)

Medline Plus

Full Text Available ... Team Your cystic fibrosis care team includes a group of CF health care professionals who partner with ... Awards and Grants Career Development Awards Research Awards Training Awards CF ... Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your ...

Every day I'm rufflin': Calcium sensing and actin dynamics in the growth factor-independent membrane ruffling of professional phagocytes.

Science.gov (United States)

Schlam, Daniel; Canton, Johnathan

2017-04-03

Professional phagocytes continuously extend dynamic, actin-driven membrane protrusions. These protrusions, often referred to as membrane ruffles, serve a critical role in the essential phagocyte processes of macropinocytosis and phagocytosis. Small GTPases, such as RAC1/2, spatially and temporally regulate membrane ruffle formation. We have recently shown that extracellular calcium regulates the elaboration of membrane ruffles primarily through the synthesis of phosphatidic acid (PtdOH) at the plasma membrane. RAC1/2 guanine nucleotide exchange factors harbouring polybasic stretches are recruited by PtdOH to sites of ruffle formation. Here we discuss our findings and offer perspectives on how the regulation of dynamic actin structures at the plasma membrane by small GTPases is a critical component of phagocyte function.

Apoptosis as a post-phagocytic winnowing mechanism in a coral-dinoflagellate mutualism.

Science.gov (United States)

Dunn, Simon R; Weis, Virginia M

2009-01-01

This study was aimed at detecting apoptosis as a post-phagocytic mechanism of symbiont selection during the onset of symbiosis in larvae of the scleractinian coral Fungia scutaria. Larvae were infected with one of three Symbiodinium types: freshly isolated homologous ITS-type C1f from adult F. scutaria, heterologous C31 from adult Montipora capitata, known to be unable to successfully colonize F. scutaria larvae, and type B1 from the symbiotic sea anemone Aiptasia spp. Apoptosis was detected by the activation of caspases, enzymes specific to apoptosis. Caspase activity was measured in situ by cleavage of a specific fluorophore and detection with confocal microscopy. At 6 h post infection, there was a significant increase in caspase activation in gastrodermal cells in C31-infected larvae, compared with larvae infected with C1f or B1 types. Compared with control larvae infected with C31, which had decreased infection rates present by 24 h post infection, when C31-infected larvae were incubated with a broad-scale caspase inhibitor, the per cent of larvae infected with C31 did not significantly decrease over time. This indicates that the reduction in infection success observed in untreated C31-infected larvae can be rescued with inhibition of caspases and apoptosis. This suggests the presence of a post-phagocytic recognition mechanism. Larvae infected with freshly isolated B1 retained infection success over time compared with C31-infected larvae, suggesting that there is host discrimination between heterologous algae. Initiation of this post-phagocytic response may occur more readily with a highly specific heterologous symbiont type such as C31, compared with a generalist heterologous type such as clade B1.

Swing limb mechanics and minimum toe clearance in people with knee osteoarthritis.

Science.gov (United States)

Levinger, Pazit; Lai, Daniel T H; Menz, Hylton B; Morrow, Adam D; Feller, Julian A; Bartlett, John R; Bergman, Neil R; Begg, Rezaul

2012-02-01

Knee osteoarthritis (OA) has been shown to be a risk factor for falls. Reductions in foot clearance during the swing phase of walking can cause a trip and potentially lead to a fall. This study examined the swing phase mechanics of people with and without knee OA during walking. Minimum toe clearance (MTC) height, joint angles at the time of MTC and the influence of the angular changes of the hip, knee and ankle of the swing leg on foot clearance using sensitivity analysis were investigated in 50 knee OA participants and 28 age-matched asymptomatic controls. Although both groups had a similar MTC height (controls: 12.8±6.7 mm, knee OA: 13.4±7.0 mm), the knee OA group used a different strategy to achieve the same foot clearance, as evidenced by greater knee flexion (52.5±5.3° vs 49.4±4.8°, p=0.007), greater hip abduction (-3.6±3.3° vs -1.8±3.3°, p=0.03) and less ankle adduction (2.8±1.9° vs 4.2±2.1°, p=0.01). MTC height was comparable between the groups, however a different swing phase mechanism was used by the knee OA. Although adequate MTC is an important component of safe locomotion, it does not appear to be impaired in people with knee OA. Other factors, such as inadequate responses to postural perturbation, may be responsible for falls in this group. Copyright © 2011 Elsevier B.V. All rights reserved.

Clearance Kinetics and Clearance Routes of Molecules From the Suprachoroidal Space After Microneedle Injection.

Science.gov (United States)

Chiang, Bryce; Wang, Ke; Ethier, C Ross; Prausnitz, Mark R

2017-01-01

To determine clearance kinetics and routes of clearance of molecules from the suprachoroidal space (SCS) of live New Zealand White rabbits. Suprachoroidal space collapse rate and pressure changes after microneedle injection into SCS were determined. Fluorescent fundus images were acquired to determine clearance rates of molecules ranging in size from 332 Da to 2 MDa. Microneedle injections of fluorescein were performed, and samples were taken from various sites over time to determine amount of fluorescein exiting the eye. Clearance transport was modeled theoretically and compared with experimental data. After injection, pressures in SCS and vitreous humor spiked and returned to baseline within 20 minutes; there was no difference between these two pressures. Suprachoroidal space collapse occurred within 40 minutes. One hour after fluorescein injection, 46% of fluorescein was still present in the eye, 15% had transported across sclera, 6% had been cleared by choroidal vasculature, and 4% had exited via leakage pathways. Characteristic clearance time increased in proportion with molecular radius, but total clearance of 2 MDa FITC-dextran was significantly slower (21 days) than smaller molecules. These data generally agreed with predictions from a theoretical model of molecular transport. Guided by experimental data in the context of model predictions, molecular clearance from SCS occurred in three regimes: (1) on a time scale of approximately 10 minutes, fluid and molecules exited SCS by diffusion into sclera and choroid, and by pressure-driven reflux via transscleral leakage sites; (2) in approximately 1 hour, molecules cleared from choroid by blood flow; and (3) in 1 to 10 hours, molecules cleared from sclera by diffusion and convection.

Study on clearance system

Energy Technology Data Exchange (ETDEWEB)

NONE

2013-08-15

The clearance system is a legal system to release 'the radioactive waste not requiring treatment as radioactive waste' from the regulatory control. JNES supports Nuclear Regulatory Agency on approval and confirmation of clearance measurement and judgment developed by the operator. The objective of this study is to establish technical base of the validation method of the clearance measurement for various objects. In uranium processing facilities, simulation sources emitting alpha-rays is used in a validity confirmation examination of the measuring equipment. In this study, these sources were examined by measuring alpha and beta spectra to evaluate the applicability and problem of these sources. In addition, the measuring method detecting gamma-rays was examined. This method can be applied to complicated objects. As a part to develop a manual for unexpected incidents in clearance system, a quick method for measurement of Strontium 90 was examined. In addition, the measuring methods for the judgment of the influence of fallout and for NR (Non-Radioactive) confirmation were examined. (author)

Sensation of stasis is poorly correlated with impaired esophageal bolus transport

NARCIS (Netherlands)

Bogte, A.; Bredenoord, A. J.; Oors, J.; Siersema, P. D.; Smout, A. J. P. M.

2014-01-01

It is common belief that symptoms of patients with non-obstructive dysphagia are the result of impaired bolus clearance in the esophagus, usually caused by esophageal motility disorders. We therefore investigated the relationship between transit of swallowed boluses and the symptom dysphagia. Twenty

Kidney function measured by clearance. Methods and indications. An update; Zur Messung der Nierenfunktion durch Clearancebestimmungen. Methoden und Indikationen. Ein Update

Energy Technology Data Exchange (ETDEWEB)

Durand, E. [Universitaetskrankenhaus Bicetre, Paris (France); Mueller-Suur, R. [Karolinska Inst., Danderyds Krankenhaus und Aleris Fysiologlab, Stockholm (Sweden)

2010-09-15

Renal function impairment can be monitored by many tests. Measurement of plasma-creatinine level is the most used method, 24 h plasma-creatininclearance with urine collection is used by others and also other alternative but indirect methods exist. However, the use of radionuclide-clearances is by far the easiest performed method with the highest accuracy and precision and gives very low irradiation dose. In the following we will discuss the different radiopharmaceuticals in use, their plus and minus, the different clearance methods in use, their limitations and give some clinically important indications to perform clearance investigations according to consensus reports. Summarizing the use of plasma clearance of 51-Cr-EDTA after a single injection with one blood sample can be generally recommended, however with some modifications in special clinical situations, which are pointed out. Please note, that this paper is, for a significant part, an update of a previous paper published 2003 in ''Der Nuklearmediziner'' (orig.)

Immune Defenses of the Invasive Apple Snail Pomacea canaliculata (Caenogastropoda, Ampullariidae: Phagocytic Hemocytes in the Circulation and the Kidney.

Directory of Open Access Journals (Sweden)

Juan A Cueto

Full Text Available Hemocytes in the circulation and kidney islets, as well as their phagocytic responses to microorganisms and fluorescent beads, have been studied in Pomacea canaliculata, using flow cytometry, light microscopy (including confocal laser scanning microscopy and transmission electron microscopy (TEM. Three circulating hemocyte types (hyalinocytes, agranulocytes and granulocytes were distinguished by phase contrast microscopy of living cells and after light and electron microscopy of fixed material. Also, three different populations of circulating hemocytes were separated by flow cytometry, which corresponded to the three hemocyte types. Hyalinocytes showed a low nucleus/cytoplasm ratio, and no apparent granules in stained material, but showed granules of moderate electron density under TEM (L granules and at least some L granules appear acidic when labeled with LysoTracker Red. Both phagocytic and non-phagocytic hyalinocytes lose most (if not all L granules when exposed to microorganisms in vitro. The phagosomes formed differed whether hyalinocytes were exposed to yeasts or to Gram positive or Gram negative bacteria. Agranulocytes showed a large nucleus/cytoplasm ratio and few or no granules. Granulocytes showed a low nucleus/cytoplasm ratio and numerous eosinophilic granules after staining. These granules are electron dense and rod-shaped under TEM (R granules. Granulocytes may show merging of R granules into gigantic ones, particularly when exposed to microorganisms. Fluorescent bead exposure of sorted hemocytes showed phagocytic activity in hyalinocytes, agranulocytes and granulocytes, but the phagocytic index was significantly higher in hyalinocytes. Extensive hemocyte aggregates ('islets' occupy most renal hemocoelic spaces and hyalinocyte-like cells are the most frequent component in them. Presumptive glycogen deposits were observed in most hyalinocytes in renal islets (they also occur in the circulation but less frequently and may mean that

The identification of CD163 expressing phagocytic chondrocytes in joint cartilage and its novel scavenger role in cartilage degradation.

Directory of Open Access Journals (Sweden)

Kai Jiao

Full Text Available BACKGROUND: Cartilage degradation is a typical characteristic of arthritis. This study examined whether there was a subset of phagocytic chondrocytes that expressed the specific macrophage marker, CD163, and investigated their role in cartilage degradation. METHODS: Cartilage from the knee and temporomandibular joints of Sprague-Dawley rats was harvested. Cartilage degradation was experimentally-induced in rat temporomandibular joints, using published biomechanical dental methods. The expression levels of CD163 and inflammatory factors within cartilage, and the ability of CD163(+ chondrocytes to conduct phagocytosis were investigated. Cartilage from the knees of patients with osteoarthritis and normal cartilage from knee amputations was also investigated. RESULTS: In the experimentally-induced degrading cartilage from temporomandibular joints, phagocytes were capable of engulfing neighboring apoptotic and necrotic cells, and the levels of CD163, TNF-α and MMPs were all increased (P0.05. CD163(+ chondrocytes were found in the cartilage mid-zone of temporomandibular joints and knee from healthy, three-week old rats. Furthermore, an increased number of CD163(+ chondrocytes with enhanced phagocytic activity were present in Col-II(+ chondrocytes isolated from the degraded cartilage of temporomandibular joints in the eight-week experimental group compared with their age-matched controls. Increased number with enhanced phagocytic activity of CD163(+ chondrocytes were also found in isolated Col-II(+ chondrocytes stimulated with TNF-α (P<0.05. Mid-zone distribution of CD163(+ cells accompanied with increased expression of CD163 and TNF-α were further confirmed in the isolated Col-II(+ chondrocytes from the knee cartilage of human patients with osteoarthritis, in contrast to the controls (both P<0.05. CONCLUSIONS: An increased number of CD163(+ chondrocytes with enhanced phagocytic activity were discovered within degraded joint cartilage, indicating a

Leishmania mexicana amazonensis: heterogeneity in 5-nucleotidase and peroxidase activities of mononuclear phagocytes during in vivo and in vitro infection

OpenAIRE

Côrte-Real, Suzana; Grimaldi Junior, Gabriel; Meirelles, Maria de Nazareth Leal de

1988-01-01

The degree of maturation of cells of the Mononuclear Phagocyte System (MPS), during in vivo and in vitro infection by Leishmania mexicana amazonenesis, was evaluated in this study. The macrophages' differentiation was assayed by cytochemical characterization at the ultrastrctural level, using two well-established markers: 5'-nucleotidase enzyme activity, for revealing the mature cells, and the peroxidase activity present in the cell granules to demonstrate immature mononuclear phagocytes. onl...

The effect of carvedilol on the oxidative burst of rat phagocytes

Czech Academy of Sciences Publication Activity Database

Moravcová, Aneta; Lojek, Antonín; Číž, Milan; Pečivová, J.; Jančinová, V.; Nosál, R.

2007-01-01

Roč. 101, č. 14 (2007), s232-s233 E-ISSN 1213-7103. [Mezioborová česko-slovenská toxikologická konference /12./. Praha, 11.06.2007-13.06.2007] R&D Projects: GA ČR(CZ) GA524/07/1511 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : carvedilol * phagocytes * oxidative burst Subject RIV: BO - Biophysics

Inflammatory Monocytes Mediate Early and Organ-Specific Innate Defense During Systemic Candidiasis

Science.gov (United States)

Ngo, Lisa Y.; Kasahara, Shinji; Kumasaka, Debra K.; Knoblaugh, Sue E.; Jhingran, Anupam; Hohl, Tobias M.

2014-01-01

Candida albicans is a commensal fungus that can cause systemic disease in patients with breaches in mucosal integrity, indwelling catheters, and defects in phagocyte function. Although circulating human and murine monocytes bind C. albicans and promote inflammation, it remains unclear whether C-C chemokine receptor 2 (CCR2)– and Ly6C-expressing inflammatory monocytes exert a protective or a deleterious function during systemic infection. During murine systemic candidiasis, interruption of CCR2-dependent inflammatory monocyte trafficking into infected kidneys impaired fungal clearance and decreased murine survival. Depletion of CCR2-expressing cells led to uncontrolled fungal growth in the kidneys and brain and demonstrated an essential antifungal role for inflammatory monocytes and their tissue-resident derivatives in the first 48 hours postinfection. Adoptive transfer of purified inflammatory monocytes in depleted hosts reversed the defect in fungal clearance to a substantial extent, indicating a compartmentally and temporally restricted protective function that can be transferred to enhance systemic innate antifungal immunity. PMID:23922372

Hacker Within! Ehrlichia chaffeensis Effector Driven Phagocyte Reprogramming Strategy

Directory of Open Access Journals (Sweden)

Taslima Taher Lina

2016-05-01

Full Text Available Ehrlichia chaffeensis is a small, gram negative, obligately intracellular bacterium that preferentially infects mononuclear phagocytes. It is the etiologic agent of human monocytotropic ehrlichiosis (HME, an emerging life-threatening tick-borne zoonosis. Mechanisms by which E. chaffeensis establishes intracellular infection, and avoids host defenses are not well understood, but involve functionally relevant host-pathogen interactions associated with tandem and ankyrin repeat effector proteins. In this review, we discuss the recent advances in our understanding of the molecular and cellular mechanisms that underlie Ehrlichia host cellular reprogramming strategies that enable intracellular survival.

Molecular cloning of rock bream (Oplegnathus fasciatus) tumor necrosis factor-alpha and its effect on the respiratory burst activity of phagocytes.

Science.gov (United States)

Kim, Min Sun; Hwang, Yoon Jung; Yoon, Ki Joon; Zenke, Kosuke; Nam, Yoon Kwon; Kim, Sung Koo; Kim, Ki Hong

2009-11-01

Rock bream (Oplegnathus fasciatus) tumor necrosis factor-alpha (rbTNF-alpha) gene was cloned, recombinantly produced, and the effect of the recombinant rbTNF-alpha on the respiratory burst activity of rock bream phagocytes was analyzed. Structurally, genomic DNA of rbTNF-alpha was comprised with four exons and three introns, and deduced amino acid sequence of its cDNA possessed the TNF family signature, a transmembrane domain, a protease cleavage site, and two cysteine residues, which are the typical characteristics of TNF-alpha gene in mammals and fish. The chemiluminescent (CL) response of rock bream phagocytes was significantly enhanced by pre-incubation with recombinant rbTNF-alpha, when opsonized zymosan was used as a stimulant of the respiratory burst. However, CL enhancing effect of the recombinant rbTNF-alpha was very weak when the respiratory burst activity of phagocytes was triggered with phorbol-12-myristate-13-acetate (PMA) instead of zymosan. These results suggest that rock bream TNF-alpha might have an ability to prime the respiratory burst activity of phagocytes against receptor-mediated phagocytosis inducing stimulants, such as zymosan, but have little ability against stimulants not accompanying receptor-mediated phagocytosis.

Effect of intravenous plasma transfusion on granulocyte and monocyte oxidative and phagocytic activity in dairy calves with failure of passive immunity.

Science.gov (United States)

Yang, Victoria C; Rayburn, Maire C; Chigerwe, Munashe

2017-12-01

Plasma administration has been recommended in calves older than 48h with failure of passive immunity (FPI) to provide immunity consistent with adequate colostral ingestion. However, the protective serum immunoglobulin G (IgG) concentrations (≥1000mg/dL) of plasma derived IgG only lasts up to 12h. In addition to IgG, maternally derived colostral cells also confer immunity. The objective of the study was to determine the effect of intravenous plasma transfusion on granulocyte and monocyte oxidative and phagocytic activity in calves with FPI. Twenty-seven, one day-old, Jersey calves were assigned into 3 groups. The colostral (CL, N=9) group received 3L of colostrum once by oroesophageal tubing. Two other groups of calves received 1L of colostrum once by oroesophageal tubing and were assigned based on their health status (sick or non-sick) at 4days of age, as the sick-group (SG, N=7) or the non-sick (NG, N=11) groups. At 4days of age, the SG and NG groups were administered plasma intravenously at 30mL/kg. Granulocyte and monocyte oxidative and phagocytic activity was determined by flow cytometry. There was no significant difference in the granulocyte and monocyte oxidative or phagocytic activity among the 3 groups (P>0.05). Plasma administration had no significant effect on the oxidative or phagocytic activity of granulocytes or monocytes. In clinical practice, plasma administration for enhancing oxidative or phagocytic activity of granulocytes or monocytes, alone, might not be justified in calves with FPI. Copyright © 2017 Elsevier Ltd. All rights reserved.

The zipper mechanism in phagocytosis: energetic requirements and variability in phagocytic cup shape

Directory of Open Access Journals (Sweden)

Dart Anna E

2010-11-01

Full Text Available Abstract Background Phagocytosis is the fundamental cellular process by which eukaryotic cells bind and engulf particles by their cell membrane. Particle engulfment involves particle recognition by cell-surface receptors, signaling and remodeling of the actin cytoskeleton to guide the membrane around the particle in a zipper-like fashion. Despite the signaling complexity, phagocytosis also depends strongly on biophysical parameters, such as particle shape, and the need for actin-driven force generation remains poorly understood. Results Here, we propose a novel, three-dimensional and stochastic biophysical model of phagocytosis, and study the engulfment of particles of various sizes and shapes, including spiral and rod-shaped particles reminiscent of bacteria. Highly curved shapes are not taken up, in line with recent experimental results. Furthermore, we surprisingly find that even without actin-driven force generation, engulfment proceeds in a large regime of parameter values, albeit more slowly and with highly variable phagocytic cups. We experimentally confirm these predictions using fibroblasts, transfected with immunoreceptor FcγRIIa for engulfment of immunoglobulin G-opsonized particles. Specifically, we compare the wild-type receptor with a mutant receptor, unable to signal to the actin cytoskeleton. Based on the reconstruction of phagocytic cups from imaging data, we indeed show that cells are able to engulf small particles even without support from biological actin-driven processes. Conclusions This suggests that biochemical pathways render the evolutionary ancient process of phagocytic highly robust, allowing cells to engulf even very large particles. The particle-shape dependence of phagocytosis makes a systematic investigation of host-pathogen interactions and an efficient design of a vehicle for drug delivery possible.

Efferocytosis is impaired in Gaucher macrophages.

Science.gov (United States)

Aflaki, Elma; Borger, Daniel K; Grey, Richard J; Kirby, Martha; Anderson, Stacie; Lopez, Grisel; Sidransky, Ellen

2017-04-01

Gaucher disease, the inherited deficiency of lysosomal glucocerebrosidase, is characterized by the presence of glucosylceramide-laden macrophages resulting from impaired digestion of aged erythrocytes or apoptotic leukocytes. Studies of macrophages from patients with type 1 Gaucher disease with genotypes N370S/N370S, N370S/L444P or N370S/c.84dupG revealed that Gaucher macrophages have impaired efferocytosis resulting from reduced levels of p67 phox and Rab7. The decreased Rab7 expression leads to impaired fusion of phagosomes with lysosomes. Moreover, there is defective translocation of p67 phox to phagosomes, resulting in reduced intracellular production of reactive oxygen species. These factors contribute to defective deposition and clearance of apoptotic cells in phagolysosomes, which may have an impact on the inflammatory response and contribute to the organomegaly and inflammation seen in patients with Gaucher disease. Copyright© Ferrata Storti Foundation.

Single-Dose pharmacokinetics of sustained-release fampridine (Fampridine-SR) in healthy volunteers and adults with renal impairment.

Science.gov (United States)

Smith, William; Swan, Suzanne; Marbury, Thomas; Henney, Herbert

2010-02-01

Fampridine-SR is a sustained-release formulation of fampridine (4-aminopyridine), a potassium channel blocker demonstrated to improve walking ability in patients with multiple sclerosis. This study evaluated the pharmacokinetics of fampridine and its metabolites after administration of fampridine-SR 10 mg in healthy volunteers and in subjects with mild, moderate, or severe renal impairment (5 per group). Analysis of variance was used to calculate 90% confidence intervals (CIs) for the ratios (impaired/healthy) of least squares mean in maximum plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC). Clearance was primarily through urinary excretion. In renally impaired subjects, fampridine plasma concentrations were consistently higher than in healthy individuals: ratios for C(max) ranged from 166.5% to 199.9% for mild and severe renal impairment, respectively. AUC(0-infinity) ratios ranged from 175.3% to 398.7%, respectively, for mild and severe renal impairment. Mean terminal disposition half-life was 6.4 hours in healthy individuals, compared with 7.4, 8.1, and 14.3 hours in patients with mild, moderate, and severe renal impairment, respectively. Regression analysis confirmed the significant relationship between creatinine clearance and extent of exposure as quantified by AUC for fampridine and its metabolites, suggesting cautious use in patients with mild renal impairment and avoidance in cases of moderate or severe renal impairment.

Cysteamine re-establishes the clearance of Pseudomonas aeruginosa by macrophages bearing the cystic fibrosis-relevant F508del-CFTR mutation.

Science.gov (United States)

Ferrari, Eleonora; Monzani, Romina; Villella, Valeria R; Esposito, Speranza; Saluzzo, Francesca; Rossin, Federica; D'Eletto, Manuela; Tosco, Antonella; De Gregorio, Fabiola; Izzo, Valentina; Maiuri, Maria C; Kroemer, Guido; Raia, Valeria; Maiuri, Luigi

2017-01-12

Cystic fibrosis (CF), the most common lethal monogenic disease in Caucasians, is characterized by recurrent bacterial infections and colonization, mainly by Pseudomonas aeruginosa, resulting in unresolved airway inflammation. CF is caused by mutations in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which functions as a chloride channel in epithelial cells, macrophages, and other cell types. Impaired bacterial handling by macrophages is a feature of CF airways, although it is still debated how defective CFTR impairs bacterial killing. Recent evidence indicates that a defective autophagy in CF macrophages leads to alterations of bacterial clearance upon infection. Here we use bone marrow-derived macrophages from transgenic mice to provide the genetic proof that defective CFTR compromises both uptake and clearance of internalized Pseudomonas aeruginosa. We demonstrate that the proteostasis regulator cysteamine, which rescues the function of the most common F508del-CFTR mutant and hence reduces lung inflammation in CF patients, can also repair the defects of CF macrophages, thus restoring both bacterial internalization and clearance through a process that involves upregulation of the pro-autophagic protein Beclin 1 and re-establishment of the autophagic pathway. Altogether these results indicate that cysteamine restores the function of several distinct cell types, including that of macrophages, which might contribute to its beneficial effects on CF.

Clearance of materials from accelerator facilities

Directory of Open Access Journals (Sweden)

Rokni Sayed H.

2017-01-01

Full Text Available A new Technical Standard that supports the clearance of materials and equipment (personal property from U.S. Department of Energy (DOE accelerator facilities has been developed. The Standard focuses on personal property that has the potential to be radiologically impacted by accelerator operations. It addresses material clearance programs and protocols for off-site releases without restriction on use. Common metals with potential volumetric activation are of main interest with technical bases provided in Appendices of the Standard. The clearance protocols in the Standard include three elements: 1 clearance criteria, 2 process knowledge, and 3 measurement methods. This paper presents the technical aspects of the new Standard, discusses operational experience gained in clearance of materials and equipment from several accelerator facilities at SLAC and examples as to how this Standard can be applied to benefit the entirety of the DOE Accelerator Complex.

Omega-3 polyunsaturated fatty acids promote amyloid-β clearance from the brain through mediating the function of the glymphatic system.

Science.gov (United States)

Ren, Huixia; Luo, Chuanming; Feng, Yanqing; Yao, Xiaoli; Shi, Zhe; Liang, Fengyin; Kang, Jing X; Wan, Jian-Bo; Pei, Zhong; Su, Huanxing

2017-01-01

Impairment of amyloid-β (Aβ) clearance leads to Aβ accumulation in the brain during the development of Alzheimer's disease (AD). Strategies that can restore or improve the clearance function hold great promise in delaying or preventing the onset of AD. Here, we show that n-3 polyunsaturated fatty acids (PUFAs), by use of fat-1 transgenic mice and oral administration of fish oil, significantly promote interstitial Aβ clearance from the brain and resist Aβ injury. Such beneficial effects were abolished in Aqp4-knockout mice, suggesting that the AQP4-dependent glymphatic system is actively involved in the promoting the effects of n-3 PUFAs on the clearance of extracellular Aβ. Imaging on clarified brain tissues clearly displayed that n-3 PUFAs markedly inhibit the activation of astrocytes and protect the AQP4 polarization in the affected brain region after Aβ injection. The results of the present study prove a novel mechanism by which n-3 PUFAs exert protective roles in reducing Aβ accumulation via mediating the glymphatic system function.-Ren, H., Luo, C., Feng, Y., Yao, X., Shi, Z., Liang, F., Kang, J. X., Wan, J.-B., Pei, Z., Su, H. Omega-3 polyunsaturated fatty acids promote amyloid-β clearance from the brain through mediating the function of the glymphatic system. © FASEB.

Quantitation of microbicidal activity of mononuclear phagocytes: an in vitro technique.

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Rege N

1993-01-01

Full Text Available An in vitro assay technique was set up to determine the phagocytic and microbicidal activity of a monocyte-macrophage cell line using Candida species as test organisms. The norms were determined for the activity of peritoneal macrophages of rats (24.69 +/- 2.6% phagocytosis and 35.4 +/- 5.22% ICK and human (27.89 +/- 3.63% phagocytosis and 50.91 +/- 6.3% ICK. The assay technique was used to test the degree of activation of macrophages induced by metronidazole, Tinospora cordifolia and Asparaqus racemousus and to compare their effects with a standard immunomodulator muramyl-dipeptide. All the three test agents increased the phagocytic and killing capacity of macrophages in a dose dependent manner upto a certain dose, beyond which either these activities were found to have plateaued or decreased. The optimal doses for MDP, Metronidazole, Asparagus racemosus and Tinospora cordifolia were found to be 100 micrograms, 300 mg/kg, 200 mg/kg and 100 mg/kg respectively. Patients with cirrhosis were screened for defects in monocyte function. The depressed monocyte function (20.58 +/- 5% phago and 41.24 +/- 12.19% ICK; P < 0.05 was observed indicating a compromised host defense. The utility of this candidicidal assay in experimental and clinical studies is discussed.

Chemical composition and phagocyte immunomodulatory activity of Ferula iliensis essential oils.

Science.gov (United States)

Özek, Gulmira; Schepetkin, Igor A; Utegenova, Gulzhakhan A; Kirpotina, Liliya N; Andrei, Spencer R; Özek, Temel; Başer, Kemal Hüsnü Can; Abidkulova, Karime T; Kushnarenko, Svetlana V; Khlebnikov, Andrei I; Damron, Derek S; Quinn, Mark T

2017-06-01

Essential oil extracts from Ferula iliensis have been used traditionally in Kazakhstan for treatment of inflammation and other illnesses. Because little is known about the biologic activity of these essential oils that contributes to their therapeutic properties, we analyzed their chemical composition and evaluated their phagocyte immunomodulatory activity. The main components of the extracted essential oils were ( E )-propenyl sec -butyl disulfide (15.7-39.4%) and ( Z )-propenyl sec -butyl disulfide (23.4-45.0%). Ferula essential oils stimulated [Ca 2+ ] i mobilization in human neutrophils and activated ROS production in human neutrophils and murine bone marrow phagocytes. Activation of human neutrophil [Ca 2+ ] i flux by Ferula essential oils was dose-dependently inhibited by capsazepine, a TRPV1 channel antagonist, indicating that TRPV1 channels mediate this response. Furthermore, Ferula essential oils stimulated Ca 2+ influx in TRPV1 channel-transfected HEK293 cells and desensitized the capsaicin-induced response in these cells. Additional molecular modeling with known TRPV1 channel agonists suggested that the active component is likely to be ( Z )-propenyl sec -butyl disulfide. Our results provide a cellular and molecular basis to explain at least part of the beneficial therapeutic properties of FEOs. © Society for Leukocyte Biology.

Clearance and release from control - An international perspective

International Nuclear Information System (INIS)

Thierfeldt, S.

2005-01-01

This paper tries to give an overview of the clearance, or release from regulatory control, on an international scale, including some of those countries where clearance has become or is about to become vital for D and D. The emphasis lies on the impact of clearance, and in particular of differences between clearance levels of various countries, on D and D. Relevance of clearance for D and D of nuclear installations Clearance is an essential part of waste management (or more general, material management) in nuclear installations, and in particular during the decommissioning phase where waste streams continues to arise. Of course, the relevance of clearance in a particular country depends on a number of factors, like: availability of a final repository and its price; prevailing decommissioning strategy; number of nuclear installations reaching decommissioning phase. This small selection of reasons why clearance may be of varying importance for different countries may already suffice to illustrate why up to now clearance has been developed and implemented in quite different ways. If one thinks of additional reasons that may influence clearance, like politics, the public opinion, availability of funds etc., the situation becomes even more complex. It is, however safe to draw the conclusion that countries with a certain number of nuclear installations which have been or will soon be shut down or which are already in the decommissioning phase will need to implement provisions for clearance. This has indeed been the case with countries like the UK, Germany, the USA, Sweden, and a number of others. It is not essential for clearance levels to be exactly equal between various countries. They may differ as long as the difference is not too large, e.g. the values fall into the same order of magnitude. This is the reason why for example Germany has no problems with clearance levels which differ from the EU recommendation RP 122 partially adopted in a number of EU countries

LRP1 in brain vascular smooth muscle cells mediates local clearance of Alzheimer's amyloid-β.

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Kanekiyo, Takahisa; Liu, Chia-Chen; Shinohara, Mitsuru; Li, Jie; Bu, Guojun

2012-11-14

Impaired clearance of amyloid-β (Aβ) is a major pathogenic event for Alzheimer's disease (AD). Aβ depositions in brain parenchyma as senile plaques and along cerebrovasculature as cerebral amyloid angiopathy (CAA) are hallmarks of AD. A major pathway that mediates brain Aβ clearance is the cerebrovascular system where Aβ is eliminated through the blood-brain barrier (BBB) and/or degraded by cerebrovascular cells along the interstitial fluid drainage pathway. An Aβ clearance receptor, the low-density lipoprotein receptor-related protein 1 (LRP1), is abundantly expressed in cerebrovasculature, in particular in vascular smooth muscle cells. Previous studies have indicated a role of LRP1 in endothelial cells in transcytosing Aβ out of the brain across the BBB; however, whether this represents a significant pathway for brain Aβ clearance remains controversial. Here, we demonstrate that Aβ can be cleared locally in the cerebrovasculature by an LRP1-dependent endocytic pathway in smooth muscle cells. The uptake and degradation of both endogenous and exogenous Aβ were significantly reduced in LRP1-suppressed human brain vascular smooth muscle cells. Conditional deletion of Lrp1 in vascular smooth muscle cell in amyloid model APP/PS1 mice accelerated brain Aβ accumulation and exacerbated Aβ deposition as amyloid plaques and CAA without affecting Aβ production. Our results demonstrate that LRP1 is a major Aβ clearance receptor in cerebral vascular smooth muscle cell and a disturbance of this pathway contributes to Aβ accumulation. These studies establish critical functions of the cerebrovasculature system in Aβ metabolism and identify a new pathway involved in the pathogenesis of both AD and CAA.

Rational customs clearance technology choice

OpenAIRE

Shramenko, N.; Andriets, V.

2008-01-01

Issues concerning cargo delivery efficiencyincrease by choice of rational customs clearance technology have been considered. Three possible variants of customs clearance andmethods which allow to define the most rational version of cargo delivery in international road communication based on main efficiency criteria for definite distance have been presented.

Impaired fatty acid oxidation as a cause for lipotoxicity in cardiomyocytes

Energy Technology Data Exchange (ETDEWEB)

Haffar, T. [Université de Montreal (Canada); Montreal Heart Institute (Canada); Bérubé-Simard, F. [Montreal Heart Institute (Canada); Bousette, N., E-mail: nicolas.bousette@umontreal.ca [Université de Montreal (Canada); Montreal Heart Institute (Canada)

2015-12-04

A major cause for diabetic cardiomyopathy is excess lipid accumulation. To elucidate mechanisms of lipotoxicity mediated diabetic heart disease we need to further our understanding of how lipid metabolism is altered in the diabetic heart. Here we investigated the role of lipid clearance by oxidation as a regulator of lipid-mediated toxicity (lipotoxicity). We evaluated the effect of pre-treating rat neonatal cardiomyocytes (NCMs) with either oleate (mono-unsaturated fatty acid) or palmitate (saturated fatty acid) on fatty acid oxidation (FAO) by measuring {sup 14}C–CO{sub 2} production. We evaluated carnitine palmitoyltransferase (Cpt1b) expression by western blotting and mitochondrial membrane potential by quantitative and qualitative fluorescence analyses using the JC-1 dye. We inhibited the Cpt1b pharmacologically using etomoxir and genetically by knocking down its expression using LentiVector mediated transduction of siRNAs targeting the Cpt1b gene. We found that palmitate had a slower clearance rate from NCMs than oleate, and this was associated with a significant decrease in FAO. This impairment in FAO was not the result of either loss of Cpt1b protein or mitochondrial integrity. Enhancing FAO with either oleate or carnitine was associated with a significant attenuation of palmitate mediated lipotoxicity. In contrast impairing FAO in oleate treated NCMs caused lipotoxicity. Here we demonstrate that a major difference between non-toxic unsaturated fatty acids and toxic saturated fatty acids is there ability to stimulate or inhibit fatty acid oxidation, respectively. This has important implications for diabetic cardiomyopathy since diabetic hearts consistently exhibit elevated lipid accumulation. - Highlights: • Palmitate had a slower clearance rate from NCMs than oleate. • Palmitate caused a significant decrease in fatty acid oxidation in cardiomyocytes. • Impaired FAO was not due to loss of Cpt1b protein or mitochondrial integrity. • Enhancing FAO

Impaired fatty acid oxidation as a cause for lipotoxicity in cardiomyocytes

International Nuclear Information System (INIS)

Haffar, T.; Bérubé-Simard, F.; Bousette, N.

2015-01-01

A major cause for diabetic cardiomyopathy is excess lipid accumulation. To elucidate mechanisms of lipotoxicity mediated diabetic heart disease we need to further our understanding of how lipid metabolism is altered in the diabetic heart. Here we investigated the role of lipid clearance by oxidation as a regulator of lipid-mediated toxicity (lipotoxicity). We evaluated the effect of pre-treating rat neonatal cardiomyocytes (NCMs) with either oleate (mono-unsaturated fatty acid) or palmitate (saturated fatty acid) on fatty acid oxidation (FAO) by measuring "1"4C–CO_2 production. We evaluated carnitine palmitoyltransferase (Cpt1b) expression by western blotting and mitochondrial membrane potential by quantitative and qualitative fluorescence analyses using the JC-1 dye. We inhibited the Cpt1b pharmacologically using etomoxir and genetically by knocking down its expression using LentiVector mediated transduction of siRNAs targeting the Cpt1b gene. We found that palmitate had a slower clearance rate from NCMs than oleate, and this was associated with a significant decrease in FAO. This impairment in FAO was not the result of either loss of Cpt1b protein or mitochondrial integrity. Enhancing FAO with either oleate or carnitine was associated with a significant attenuation of palmitate mediated lipotoxicity. In contrast impairing FAO in oleate treated NCMs caused lipotoxicity. Here we demonstrate that a major difference between non-toxic unsaturated fatty acids and toxic saturated fatty acids is there ability to stimulate or inhibit fatty acid oxidation, respectively. This has important implications for diabetic cardiomyopathy since diabetic hearts consistently exhibit elevated lipid accumulation. - Highlights: • Palmitate had a slower clearance rate from NCMs than oleate. • Palmitate caused a significant decrease in fatty acid oxidation in cardiomyocytes. • Impaired FAO was not due to loss of Cpt1b protein or mitochondrial integrity. • Enhancing FAO attenuated

Lessons Learned from Phagocytic Function Studies in a Large Cohort of Patients with Recurrent Infections

NARCIS (Netherlands)

Wolach, Baruch; Gavrieli, Ronit; Roos, Dirk; Berger-Achituv, Sivan

2012-01-01

Background There is a paucity of data on the relationship between demographic characteristics, specific clinical manifestations, and neutrophil dysfunction, guiding physicians to decide which clinical signs and symptoms are a code for an underlying phagocytic disorder. Methods The data over a

7 CFR 1927.55 - Title clearance services.

Science.gov (United States)

2010-01-01

... REGULATIONS TITLE CLEARANCE AND LOAN CLOSING Real Estate Title Clearance and Loan Closing § 1927.55 Title clearance services. (a) Responsibilities of closing agents. Services to be provided to the agency and the borrower by a closing agent in connection with the transaction vary depending on whether a title insurance...

Relationship between silicon concentration and creatinine clearance

International Nuclear Information System (INIS)

Miura, Y.; Nakai, K.; Itoh, C.; Horikiri, J.; Sera, K.; Sato, M.

1998-01-01

Silicon levels in dialysis patients are markedly increasing. Using PIXE we determined the relationship between silicon concentration and creatinine clearance in 30 samples. Urine silicon concentration were significantly correlated to creatinine clearance (p<0.001). And also serum silicon concentration were significantly correlated to creatinine clearance (p<0.0001). (author)

Disrupted epithelial/macrophage crosstalk via Spinster homologue 2-mediated S1P signaling may drive defective macrophage phagocytic function in COPD.

Science.gov (United States)

Tran, Hai B; Jersmann, Hubertus; Truong, Tung Thanh; Hamon, Rhys; Roscioli, Eugene; Ween, Miranda; Pitman, Melissa R; Pitson, Stuart M; Hodge, Greg; Reynolds, Paul N; Hodge, Sandra

2017-01-01

We have previously established a link between impaired phagocytic capacity and deregulated S1P signaling in alveolar macrophages from COPD subjects. We hypothesize that this defect may include a disruption of epithelial-macrophage crosstalk via Spns2-mediated intercellular S1P signaling. Primary alveolar macrophages and bronchial epithelial cells from COPD subjects and controls, cell lines, and a mouse model of chronic cigarette smoke exposure were studied. Cells were exposed to 10% cigarette smoke extract, or vehicle control. Spns2 expression and subcellular localization was studied by immunofluorescence, confocal microscopy and RT-PCR. Phagocytosis was assessed by flow-cytometry. Levels of intra- and extracellular S1P were measured by S1P [3H]-labeling. Spns2 expression was significantly increased (pS1P in the airway and that there is a possible disruption of epithelial/macrophage cross talk via Spns2-mediated S1P signaling in COPD and in response to cigarette smoke exposure.

Compressor airfoil tip clearance optimization system

Science.gov (United States)

Little, David A.; Pu, Zhengxiang

2015-08-18

A compressor airfoil tip clearance optimization system for reducing a gap between a tip of a compressor airfoil and a radially adjacent component of a turbine engine is disclosed. The turbine engine may include ID and OD flowpath boundaries configured to minimize compressor airfoil tip clearances during turbine engine operation in cooperation with one or more clearance reduction systems that are configured to move the rotor assembly axially to reduce tip clearance. The configurations of the ID and OD flowpath boundaries enhance the effectiveness of the axial movement of the rotor assembly, which includes movement of the ID flowpath boundary. During operation of the turbine engine, the rotor assembly may be moved axially to increase the efficiency of the turbine engine.

Platelet production, clearance and distribution in patients with idiopathic thrombocytopenic purpura

International Nuclear Information System (INIS)

Isaka, Yoshinari; Kambayashi, Junichi; Kimura, Kazufumi

1990-01-01

We have studied 8 normal subjects, and 12 patients with idiopathic thrombocytopenic purpura whose platelet counts ranged from 9x10 9 /L to 40x10 9 /L. Autologous platelets labeled with 111 In-tropolone were used for evaluation of mean platelet survival, platelet turnover, platelet sequestration sites, and platelet production (turnover) to clearance (sum of platelet uptake in the liver and the spleen) ratio. Platelet survival correlated directly with platelet counts. There was no significant correlation between the platelet sequestration pattern and platelet count, survival, or turnover. Sum of platelet uptake in the liver and the spleen showed a significant inverse correlation with platelet survival. No significant correlation was found between platelet turnover and platelet count. There was a significant correlation between the platelet production and clearance index when all subjects were analyzed. The distribution of platelet turnover showed considerable individual variation; eight of twelve patients showed platelet turnover less than mean minus 2SD of the control value, but others showed normal range. We conclude that although platelet destruction mechanism in RES shows a primary role of thrombocytopenia, impaired rate of effective thrombopoiesis may also contribute to disease severity in ITP. (author)

Noninvasive determination of individual renal clearance

International Nuclear Information System (INIS)

Chanard, J.; Brunois, J.P.; Ruiz, J.C.; Assailly, J.

1980-01-01

A noninvasive method for measurement of individual renal clearance is presented, based on analysis of the early rise of the kidneys' time-activity curves after injection of an appropriate tracer ( 131 I-ortho-iodohippurate for tubular function or 111 In DTPA for glomerular clearance). The analysis is based on the assumption that an insignificant amount of tracer leaves the kidney during the first few moments following injection. Therefore, the kidney activity during this period is directly proportional to the integral of the blood (heart) activity. After blood background subtraction, the linear correlation between the early part of the renogram and the corresponding blood integral activity curve allows calculation of an angular coefficient. The ratio of these coefficients calculated for each kidney is proportional to the ratio of the individual clearances. The latter are calculated from the total clearance simultaneously measured using a simplified method without urine collection. In control subjects with normal renal function individual renal clearances were not significantly different. In uninephrectomized patients a precision of 5% in calculating individual clearance was estimated from data recorded at the level of the remaining kidney. In patients with functional asymmetry, results were compared with 197 HgCl 2 quantitative renal fixation. A linear correlation was found (r = 0.95). The method we propose seems valuable for clinical investigation and allows sequential measurements. (orig.)

Inhibitory Effects of Standardized Extracts of Phyllanthus amarus and Phyllanthus urinaria and Their Marker Compounds on Phagocytic Activity of Human Neutrophils

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Yuandani

2013-01-01

Full Text Available The standardized methanol extracts of Phyllanthus amarus and P. urinaria, collected from Malaysia and Indonesia, and their isolated chemical markers, phyllanthin and hypophyllanthin, were evaluated for their effects on the chemotaxis, phagocytosis and chemiluminescence of human phagocytes. All the plant extracts strongly inhibited the migration of polymorphonuclear leukocytes (PMNs with the Malaysian P. amarus showing the strongest inhibitory activity (IC50 value, 1.1 µg/mL. There was moderate inhibition by the extracts of the bacteria engulfment by the phagocytes with the Malaysian P. amarus exhibiting the highest inhibition (50.8% of phagocytizing cells. The Malaysian P. amarus and P. urinaria showed strong reactive oxygen species (ROS inhibitory activity, with both extracts exhibiting IC50 value of 0.7 µg/mL. Phyllanthin and hypophyllanthin exhibited relatively strong activity against PMNs chemotaxis, with IC50 values slightly lower than that of ibuprofen (1.4 µg/mL. Phyllanthin exhibited strong inhibitory activity on the oxidative burst with an IC50 value comparable to that of aspirin (1.9 µg/mL. Phyllanthin exhibited strong engulfment inhibitory activity with percentage of phagocytizing cells of 14.2 and 27.1% for neutrophils and monocytes, respectively. The strong inhibitory activity of the extracts was due to the presence of high amounts of phyllanthin and hypophyllanthin although other constituents may also contribute.

In vivo approaches reveal a key role for DCs in CD4+ T cell activation and parasite clearance during the acute phase of experimental blood-stage malaria.

Directory of Open Access Journals (Sweden)

Henrique Borges da Silva

2015-02-01

Full Text Available Dendritic cells (DCs are phagocytes that are highly specialized for antigen presentation. Heterogeneous populations of macrophages and DCs form a phagocyte network inside the red pulp (RP of the spleen, which is a major site for the control of blood-borne infections such as malaria. However, the dynamics of splenic DCs during Plasmodium infections are poorly understood, limiting our knowledge regarding their protective role in malaria. Here, we used in vivo experimental approaches that enabled us to deplete or visualize DCs in order to clarify these issues. To elucidate the roles of DCs and marginal zone macrophages in the protection against blood-stage malaria, we infected DTx (diphtheria toxin-treated C57BL/6.CD11c-DTR mice, as well as C57BL/6 mice treated with low doses of clodronate liposomes (ClLip, with Plasmodium chabaudi AS (Pc parasites. The first evidence suggesting that DCs could contribute directly to parasite clearance was an early effect of the DTx treatment, but not of the ClLip treatment, in parasitemia control. DCs were also required for CD4+ T cell responses during infection. The phagocytosis of infected red blood cells (iRBCs by splenic DCs was analyzed by confocal intravital microscopy, as well as by flow cytometry and immunofluorescence, at three distinct phases of Pc malaria: at the first encounter, at pre-crisis concomitant with parasitemia growth and at crisis when the parasitemia decline coincides with spleen closure. In vivo and ex vivo imaging of the spleen revealed that DCs actively phagocytize iRBCs and interact with CD4+ T cells both in T cell-rich areas and in the RP. Subcapsular RP DCs were highly efficient in the recognition and capture of iRBCs during pre-crisis, while complete DC maturation was only achieved during crisis. These findings indicate that, beyond their classical role in antigen presentation, DCs also contribute to the direct elimination of iRBCs during acute Plasmodium infection.

In vivo approaches reveal a key role for DCs in CD4+ T cell activation and parasite clearance during the acute phase of experimental blood-stage malaria.

Science.gov (United States)

Borges da Silva, Henrique; Fonseca, Raíssa; Cassado, Alexandra Dos Anjos; Machado de Salles, Érika; de Menezes, Maria Nogueira; Langhorne, Jean; Perez, Katia Regina; Cuccovia, Iolanda Midea; Ryffel, Bernhard; Barreto, Vasco M; Marinho, Cláudio Romero Farias; Boscardin, Silvia Beatriz; Álvarez, José Maria; D'Império-Lima, Maria Regina; Tadokoro, Carlos Eduardo

2015-02-01

Dendritic cells (DCs) are phagocytes that are highly specialized for antigen presentation. Heterogeneous populations of macrophages and DCs form a phagocyte network inside the red pulp (RP) of the spleen, which is a major site for the control of blood-borne infections such as malaria. However, the dynamics of splenic DCs during Plasmodium infections are poorly understood, limiting our knowledge regarding their protective role in malaria. Here, we used in vivo experimental approaches that enabled us to deplete or visualize DCs in order to clarify these issues. To elucidate the roles of DCs and marginal zone macrophages in the protection against blood-stage malaria, we infected DTx (diphtheria toxin)-treated C57BL/6.CD11c-DTR mice, as well as C57BL/6 mice treated with low doses of clodronate liposomes (ClLip), with Plasmodium chabaudi AS (Pc) parasites. The first evidence suggesting that DCs could contribute directly to parasite clearance was an early effect of the DTx treatment, but not of the ClLip treatment, in parasitemia control. DCs were also required for CD4+ T cell responses during infection. The phagocytosis of infected red blood cells (iRBCs) by splenic DCs was analyzed by confocal intravital microscopy, as well as by flow cytometry and immunofluorescence, at three distinct phases of Pc malaria: at the first encounter, at pre-crisis concomitant with parasitemia growth and at crisis when the parasitemia decline coincides with spleen closure. In vivo and ex vivo imaging of the spleen revealed that DCs actively phagocytize iRBCs and interact with CD4+ T cells both in T cell-rich areas and in the RP. Subcapsular RP DCs were highly efficient in the recognition and capture of iRBCs during pre-crisis, while complete DC maturation was only achieved during crisis. These findings indicate that, beyond their classical role in antigen presentation, DCs also contribute to the direct elimination of iRBCs during acute Plasmodium infection.

A model of clearance rate regulation in mussels

Science.gov (United States)

Fréchette, Marcel

2012-10-01

Clearance rate regulation has been modelled as an instantaneous response to food availability, independent of the internal state of the animals. This view is incompatible with latent effects during ontogeny and phenotypic flexibility in clearance rate. Internal-state regulation of clearance rate is required to account for these patterns. Here I develop a model of internal-state based regulation of clearance rate. External factors such as suspended sediments are included in the model. To assess the relative merits of instantaneous regulation and internal-state regulation, I modelled blue mussel clearance rate and growth using a DEB model. In the usual standard feeding module, feeding is governed by a Holling's Type II response to food concentration. In the internal-state feeding module, gill ciliary activity and thus clearance rate are driven by internal reserve level. Factors such as suspended sediments were not included in the simulations. The two feeding modules were compared on the basis of their ability to capture the impact of latent effects, of environmental heterogeneity in food abundance and of physiological flexibility on clearance rate and individual growth. The Holling feeding module was unable to capture the effect of any of these sources of variability. In contrast, the internal-state feeding module did so without any modification or ad hoc calibration. Latent effects, however, appeared transient. With simple annual variability in temperature and food concentration, the relationship between clearance rate and food availability predicted by the internal-state feeding module was quite similar to that observed in Norwegian fjords. I conclude that in contrast with the usual Holling feeding module, internal-state regulation of clearance rate is consistent with well-documented growth and clearance rate patterns.

New Insights into the Immunobiology of Mononuclear Phagocytic Cells and Their Relevance to the Pathogenesis of Cardiovascular Diseases

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Liliana Maria Sanmarco

2018-01-01

Full Text Available Macrophages are the primary immune cells that reside within the myocardium, suggesting that these mononuclear phagocytes are essential in the orchestration of cardiac immunity and homeostasis. Independent of the nature of the injury, the heart triggers leukocyte activation and recruitment. However, inflammation is harmful to this vital terminally differentiated organ with extremely poor regenerative capacity. As such, cardiac tissue has evolved particular strategies to increase the stress tolerance and minimize the impact of inflammation. In this sense, growing evidences show that mononuclear phagocytic cells are particularly dynamic during cardiac inflammation or infection and would actively participate in tissue repair and functional recovery. They respond to soluble mediators such as metabolites or cytokines, which play central roles in the timing of the intrinsic cardiac stress response. During myocardial infarction two distinct phases of monocyte influx have been identified. Upon infarction, the heart modulates its chemokine expression profile that sequentially and actively recruits inflammatory monocytes, first, and healing monocytes, later. In the same way, a sudden switch from inflammatory macrophages (with microbicidal effectors toward anti-inflammatory macrophages occurs within the myocardium very shortly after infection with Trypanosoma cruzi, the causal agent of Chagas cardiomyopathy. While in sterile injury, healing response is necessary to stop tissue damage; during an intracellular infection, the anti-inflammatory milieu in infected hearts would promote microbial persistence. The balance of mononuclear phagocytic cells seems to be also dynamic in atherosclerosis influencing plaque initiation and fate. This review summarizes the participation of mononuclear phagocyte system in cardiovascular diseases, keeping in mind that the immune system evolved to promote the reestablishment of tissue homeostasis following infection/injury, and

Macrophage function as studied by the clearance of 125I-labeled polyvinylpyrrolidone in iron-deficient and iron-replete mice

International Nuclear Information System (INIS)

Kuvibidila, S.; Wade, S.

1987-01-01

This study evaluated the effects of iron deficiency and iron repletion on in vivo macrophage function determined by the clearance of 125 I-labeled polyvinylpyrrolidone (PVP). Two experiments were done. There were four groups of C57BL/6 female mice in experiment 1: the iron-deficient (ID), pair-fed (PF), control (C) and the high iron (HI) groups. In experiment 2, there were three ID groups (severe to moderate anemia), three PF, one C and four ID groups that were fed adequate iron for 14 (R-14), 7 (R-7), 3 (R-3) days before or on the day of PVP injection (R-0). The overall rate of PVP clearance from blood was lower in ID than in C or PF groups. This clearance is expressed by a constant, K, calculated from natural log (ln) of the cpm and the time postadministration of PVP that blood was drawn. The theoretical individual macrophages function (alpha PVP), derived from K and the weights of body, spleen and liver, was also lower in ID than in C or PF groups. The impairment was most severe with the most severe iron deficiency. Repletion for 7 to 15 d before PVP administration resulted in a partial correction of the clearance. Moderate undernutrition in the PF group had no effect

Defective bacterial clearance is responsible for the enhanced lung pathology characteristic of Mannheimia haemolytica pneumonia in bighorn sheep.

Science.gov (United States)

Subramaniam, Renuka; Herndon, Caroline N; Shanthalingam, Sudarvili; Dassanayake, Rohana P; Bavananthasivam, Jegarubee; Potter, Kathleen A; Knowles, Donald P; Foreyt, William J; Srikumaran, Subramaniam

2011-12-15

The molecular and cellular basis for the enhanced lung pathology and mortality caused by Mannheimia haemolytica in bighorn sheep (BHS, Ovis canadenesis), in comparison to domestic sheep (DS, Ovis aries), is not clear. Polymorphonuclear leukocytes (PMNs) of BHS are four- to eight-fold more susceptible to M. haemolytica leukotoxin-induced cytolysis, which is likely to reduce the number of functional phagocytes in the lung. We hypothesized that enhanced lung pathology is due to defective clearance of M. haemolytica from the lungs of BHS. To test this hypothesis, M. haemolytica (1 × 10(7) colony forming units [cfu]) were inoculated intra-tracheally into three groups each of BHS and DS, which were euthanized and necropsied at 4, 12, and 18 h post-inoculation (hpi). Bacterial and leukocyte counts were performed on broncho-alveolar lavage fluid (BALF) collected at necropsy. BALF from BHS euthanized at 4 and 12 hpi contained a significantly higher number of M. haemolytica than that from DS. More importantly, DS did not have any bacteria in BALF at 18 hpi, while the BHS still had significant numbers. As expected, the BHS did exhibit more extensive lung lesions at 12 and 18 hpi when compared to DS. At 18 hpi, necrotic PMNs were observed in the lesional lung tissues of BHS, but not DS. Furthermore, BALF from BHS had significantly lower titers of antibodies to Lkt and surface antigens of M. haemolytica, than that of DS. These findings suggest that the enhanced pathology in BHS lungs is due to defective clearance of M. haemolytica from the lungs. Copyright © 2011 Elsevier B.V. All rights reserved.

Dynamics of the changes in the number and phagocytic activity of leucocytes from whole-body gamma-irradiated guinea pigs with respect to R and S forms of Pseudomonas pseudomallei

International Nuclear Information System (INIS)

Najdenski, Kh.M.; Velyanov, D.K.

1987-01-01

Guinea pigs of both sexes received whole-body gamma irradiation (0.5 Gy, 4 x 0.5 Gy and 2 Gy; 92.5 rad/min). Two bacterial strains were used: Ps. pseudomallei R 1 5 and S 7 . The measurments were carried out on days 1, 3, 7, 15 and 30 after treatment. The changes observed were directly dependent on the dose applied: for sublethally (2 Gy) irradiated animals - an abrupt decrease of leukocytes and strongly expressed leukopenia lasting throughout the whole investigation; for fractiionally irradiated (4 x 0.5 Gy) -the number of leukocytes P<0.001 and leukopenia being observed to day 7 after irradiation; for 0.5 Gy irradiated -the leucocytes number equal to that of the controls on day 15 and significantly higher on day 30; less strongly expressed leukopenia. The alterations in phagocytic activity in relation to R and S forms of Ps. pseudomallei were similar: leukocytes from 2 Gy irradiated guinea pigs showed on day 1 a markedly raised phagocytic activity and phagocytized the R and S forms to a similar degree, while at later intervals of the study the phagocytic activity decreased and they began to phagocytize the R forms more actively. Leukocytes from 0.5 Gy treated animals phagocytized the R forms more actively than the S forms throughout the whole investigation

Dietary Fat and Sugar Induce Obesity and Impair Glucose Tolerance in Prepubertal Pigs

OpenAIRE

van Eyk, Gregory Ryan

2012-01-01

Dietary Fat and Sugar Induce Obesity and Impair Glucose Tolerance in Prepubertal Pigs Abstract A pig model of childhood obesity was used to study the effects of dietary energy on body adiposity, and blood parameters associated with impaired glucose clearance. Prepubertal female pigs weaned at 21 d of age were fed control (CON), refined sugar (SUG), fat (FAT), and sugar-fat (SUGFAT) diets in a completely randomized arrangement for 16 wk. Calories from fat were 8.9% for CON, 5.6% for SU...

Coal fly ash impairs airway antimicrobial peptides and increases bacterial growth.

Science.gov (United States)

Borcherding, Jennifer A; Chen, Haihan; Caraballo, Juan C; Baltrusaitis, Jonas; Pezzulo, Alejandro A; Zabner, Joseph; Grassian, Vicki H; Comellas, Alejandro P

2013-01-01

Air pollution is a risk factor for respiratory infections, and one of its main components is particulate matter (PM), which is comprised of a number of particles that contain iron, such as coal fly ash (CFA). Since free iron concentrations are extremely low in airway surface liquid (ASL), we hypothesize that CFA impairs antimicrobial peptides (AMP) function and can be a source of iron to bacteria. We tested this hypothesis in vivo by instilling mice with Pseudomonas aeruginosa (PA01) and CFA and determine the percentage of bacterial clearance. In addition, we tested bacterial clearance in cell culture by exposing primary human airway epithelial cells to PA01 and CFA and determining the AMP activity and bacterial growth in vitro. We report that CFA is a bioavailable source of iron for bacteria. We show that CFA interferes with bacterial clearance in vivo and in primary human airway epithelial cultures. Also, we demonstrate that CFA inhibits AMP activity in vitro, which we propose as a mechanism of our cell culture and in vivo results. Furthermore, PA01 uses CFA as an iron source with a direct correlation between CFA iron dissolution and bacterial growth. CFA concentrations used are very relevant to human daily exposures, thus posing a potential public health risk for susceptible subjects. Although CFA provides a source of bioavailable iron for bacteria, not all CFA particles have the same biological effects, and their propensity for iron dissolution is an important factor. CFA impairs lung innate immune mechanisms of bacterial clearance, specifically AMP activity. We expect that identifying the PM mechanisms of respiratory infections will translate into public health policies aimed at controlling, not only concentration of PM exposure, but physicochemical characteristics that will potentially cause respiratory infections in susceptible individuals and populations.

Predicting Human Clearance of OATP substrates using Cynomolgus monkey: In vitro-in vivo scaling of hepatic uptake clearance.

Science.gov (United States)

de Bruyn, Tom; Ufuk, Ayse; Cantrill, Carina; Kosa, Rachel E; Bi, Yi-An; Niosi, Mark; Modi, Sweta; Rodrigues, A David; Tremaine, Larry M; Varma, Manthena Vs; Galetin, Aleksandra; Houston, J Brian

2018-05-02

This work explores the utility of the cynomolgus monkey as a preclinical model to predict hepatic uptake clearance mediated by organic anion transporting polypeptide (OATP) transporters. Nine OATP substrates (rosuvastatin, pravastatin, repaglinide, fexofenadine, cerivastatin, telmisartan, pitavastatin, bosentan and valsartan) were investigated in plated cynomolgus monkey and human hepatocytes. Total uptake clearance and passive diffusion were measured in vitro from initial rates in the absence and presence of the OATP inhibitor rifamycin SV, respectively. Total uptake clearance values in plated hepatocytes ranged over three orders of magnitude in both species with a similar rank order and good agreement in the relative contribution of active transport to total uptake between cynomolgus monkey and human. In vivo hepatic clearance for these nine drugs was determined in cynomolgus monkey after intravenous dosing. Hepatic clearances showed a similar range to human parameters and good predictions from respective hepatocyte parameters (with 2.7 and 3.8-fold bias on average, respectively). The use of cross species empirical scaling factors (based on either dataset average or individual drug scaling factor from cynomolgus monkey data) improved prediction (less bias, better concordance) of human hepatic clearance from human hepatocyte data alone. In vitro intracellular binding in hepatocytes also correlated well between species. It is concluded that the minimal species differences observed for the current dataset between cynomolgus monkey and human hepatocyte uptake, both in vitro and in vivo, support future use of this preclinical model to delineate drug hepatic uptake and enable prediction of human in vivo intrinsic hepatic clearance. The American Society for Pharmacology and Experimental Therapeutics.

Melatonin signaling affects the timing in the daily rhythm of phagocytic activity by the retinal pigment epithelium.

Science.gov (United States)

Laurent, Virgine; Sengupta, Anamika; Sánchez-Bretaño, Aída; Hicks, David; Tosini, Gianluca

2017-12-01

Earlier studies in Xenopus have indicated a role for melatonin in the regulation of retinal disk shedding, but the role of melatonin in the regulation of daily rhythm in mammalian disk shedding and phagocytosis is still unclear. We recently produced a series of transgenic mice lacking melatonin receptor type 1 (MT 1 ) or type 2 (MT 2 ) in a melatonin-proficient background and have shown that removal of MT 1 and MT 2 receptors induces significant effects on daily and circadian regulation of the electroretinogram as well as on the viability of photoreceptor cells during aging. In this study we investigated the daily rhythm of phagocytic activity by the retinal pigment epithelium in MT 1 and MT 2 knock-out mice. Our data indicate that in MT 1 and MT 2 knock-out mice the peak of phagocytosis is advanced by 3 h with respect to wild-type mice and occurred in dark rather than after the onset of light, albeit the mean phagocytic activity over the 24-h period did not change among the three genotypes. Nevertheless, this small change in the profile of daily phagocytic rhythms may produce a significant effect on retinal health since MT 1 and MT 2 knock-out mice showed a significant increase in lipofuscin accumulation in the retinal pigment epithelium. Copyright © 2017 Elsevier Ltd. All rights reserved.

48 CFR 801.602-76 - Business clearance review.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Business clearance review... GENERAL DEPARTMENT OF VETERANS AFFAIRS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities 801.602-76 Business clearance review. (a) A business clearance review is a...

Effect of the Gc-derived macrophage-activating factor precursor (preGcMAF) on phagocytic activation of mouse peritoneal macrophages.

Science.gov (United States)

Uto, Yoshihiro; Yamamoto, Syota; Takeuchi, Ryota; Nakagawa, Yoshinori; Hirota, Keiji; Terada, Hiroshi; Onizuka, Shinya; Nakata, Eiji; Hori, Hitoshi

2011-07-01

The 1f1f subtype of the Gc protein (Gc(1f1f) protein) was converted into Gc-derived macrophage-activating factor (GcMAF) by enzymatic processing in the presence of β-galactosidase of an activated B-cell and sialidase of a T-cell. We hypothesized that preGc(1f1f)MAF, the only Gc(1f1f) protein lacking galactose, can be converted to GcMAF in vivo because sialic acid is cleaved by residual sialidase. Hence, we investigated the effect of preGc(1f1f)MAF on the phagocytic activation of mouse peritoneal macrophages. We examined the sugar moiety of preGc(1f1f)MAF with a Western blot using peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA) lectin. We also found that preGc(1f1f)MAF significantly enhanced phagocytic activity in mouse peritoneal macrophages but only in the presence of the mouse peritoneal fluid; the level of phagocytic activity was the same as that observed for GcMAF. PreGc(1f1f)MAF can be used as an effective macrophage activator in vivo.

Effects of Mycotoxins on Mucosal Microbial Infection and Related Pathogenesis

Science.gov (United States)

Park, Seong-Hwan; Kim, Dongwook; Kim, Juil; Moon, Yuseok

2015-01-01

Mycotoxins are fungal secondary metabolites detected in many agricultural commodities and water-damaged indoor environments. Susceptibility to mucosal infectious diseases is closely associated with immune dysfunction caused by mycotoxin exposure in humans and other animals. Many mycotoxins suppress immune function by decreasing the proliferation of activated lymphocytes, impairing phagocytic function of macrophages, and suppressing cytokine production, but some induce hypersensitive responses in different dose regimes. The present review describes various mycotoxin responses to infectious pathogens that trigger mucosa-associated diseases in the gastrointestinal and respiratory tracts of humans and other animals. In particular, it focuses on the effects of mycotoxin exposure on invasion, pathogen clearance, the production of cytokines and immunoglobulins, and the prognostic implications of interactions between infectious pathogens and mycotoxin exposure. PMID:26529017

Intracellular glutathione status regulates mouse bone marrow monocyte-derived macrophage differentiation and phagocytic activity

International Nuclear Information System (INIS)

Kim, Jin-Man; Kim, Hyunsoo; Kwon, Soon Bok; Lee, Soo Young; Chung, Sung-Chang; Jeong, Dae-Won; Min, Byung-Moo

2004-01-01

Although a redox shift can regulate the development of cells, including proliferation, differentiation, and survival, the role of the glutathione (GSH) redox status in macrophage differentiation remains unclear. In order to elucidate the role of a redox shift, macrophage-like cells were differentiated from the bone marrow-derived monocytes that were treated with a macrophage colony stimulating factor (M-CSF or CSF-1) for 3 days. The macrophagic cells were characterized by a time-dependent increase in three major symptoms: the number of phagocytic cells, the number of adherent cells, and the mRNA expression of c-fms, a M-CSF receptor that is one of the macrophage-specific markers and mediates development signals. Upon M-CSF-driven macrophage differentiation, the GSH/GSSG ratio was significantly lower on day 1 than that observed on day 0 but was constant on days 1-3. To assess the effect of the GSH-depleted and -repleted status on the differentiation and phagocytosis of the macrophages, GSH depletion by BSO, a specific inhibitor of the de novo GSH synthesis, inhibited the formation of the adherent macrophagic cells by the down-regulation of c-fms, but did not affect the phagocytic activity of the macrophages. To the contrary, GSH repletion by the addition of NAC, which is a GSH precursor, or reduced GSH in media had no effect on macrophage differentiation, and led to a decrease in the phagocytic activity. Furthermore, we observed that there is checkpoint that is capable of releasing from the inhibition of the formation of the adherent macrophagic cells according to GSH depletion by BSO. Summarizing, these results indicate that the intracellular GSH status plays an important role in the differentiation and phagocytosis of macrophages

Estimation of 131I hippuran clearance during pregnancy

International Nuclear Information System (INIS)

Voigt, R.; Stoll, W.; Zenner, I.; Arndt, J.; Friedrich-Schiller-Univ., Jena

1979-01-01

Changes in 131 I hippuran clearance were estimated by a non-catheter method, as well as total clearance and clearance of each kidney, in 43 women at various stages of pregnancy and in 13 non-pregnant women who were not using hormonal contraceptives. The results are demonstrated in graph form. The methods used are described in detail. The procedure for determining clearance in separate kidneys is indicated. It was found that clearance values increased up to the 35th and 26th weeks of pregnancy. The difference between the sides that were found corresponds with the previously known difference in the function of the right and left kidneys and ureters. (orig.) [de

Establishing exemption and clearance criteria by the regulatory authority

International Nuclear Information System (INIS)

Salih, A.E.A.

2012-04-01

This Project work discusses the relationship between the concepts of exemption and clearance, and their practical use in the overall scheme of regulatory control of practices. It also discusses how exemptions and clearance is established and the scope of its applications for regulatory control. The concept of general clearance levels for any type of material and any possible pathway of disposal is also introduced in this work. Guidance of the Group of Experts establishing scenarios for general clearance, parameter values, and a nuclide-specific list of calculated clearance levels is also presented. Regulatory authorities are required to develop guidance on exemption and clearance levels to assist licensees and registrants to know which practices and sources within practices are exempted from regulatory control and those to be cleared from further controls. Exemption and clearance levels are tools for assisting the Regulatory Authority to optimize the use of resources. (author)

Microglial Phagocytosis and Its Regulation: A Therapeutic Target in Parkinson’s Disease?

Directory of Open Access Journals (Sweden)

Elzbieta Janda

2018-04-01

Full Text Available The role of phagocytosis in the neuroprotective function of microglia has been appreciated for a long time, but only more recently a dysregulation of this process has been recognized in Parkinson’s disease (PD. Indeed, microglia play several critical roles in central nervous system (CNS, such as clearance of dying neurons and pathogens as well as immunomodulation, and to fulfill these complex tasks they engage distinct phenotypes. Regulation of phenotypic plasticity and phagocytosis in microglia can be impaired by defects in molecular machinery regulating critical homeostatic mechanisms, including autophagy. Here, we briefly summarize current knowledge on molecular mechanisms of microglia phagocytosis, and the neuro-pathological role of microglia in PD. Then we focus more in detail on the possible functional role of microglial phagocytosis in the pathogenesis and progression of PD. Evidence in support of either a beneficial or deleterious role of phagocytosis in dopaminergic degeneration is reported. Altered expression of target-recognizing receptors and lysosomal receptor CD68, as well as the emerging determinant role of α-synuclein (α-SYN in phagocytic function is discussed. We finally discuss the rationale to consider phagocytic processes as a therapeutic target to prevent or slow down dopaminergic degeneration.

14 CFR 1260.63 - Customs clearance and visas.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Customs clearance and visas. 1260.63 Section 1260.63 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance and Visas (For...

Pharmacokinetics and safety of olodaterol administered with the Respimat Soft Mist inhaler in subjects with impaired hepatic or renal function

Directory of Open Access Journals (Sweden)

Kunz C

2016-03-01

Full Text Available Christina Kunz,1 Doreen Luedtke,1 Anna Unseld,2 Alan Hamilton,3 Atef Halabi,4 Martina Wein,5 Stephan Formella6 1Translational Medicine and Clinical Pharmacology, 2Global Biometrics and Clinical Applications, Boehringer Ingelheim Pharma GmbH and Co KG, Biberach, Germany; 3Boehringer Ingelheim, Burlington, ON, Canada; 4CRS Clinical Research Services Kiel GmbH, Kiel, 5Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharma GmbH and Co KG, Biberach, 6Medicine Coordination, Boehringer Ingelheim Pharma GmbH and Co KG, Ingelheim, Germany Purpose: In two trials, the influences of hepatic and renal impairment on the pharmacokinetics of olodaterol, a novel long-acting inhaled β2-agonist for treatment of COPD, were investigated.Subjects and methods: The first trial included eight subjects with mild hepatic function impairment (Child–Pugh A, eight subjects with moderate impairment (Child–Pugh B, and 16 matched healthy subjects with normal hepatic function. The second trial included eight subjects with severe renal impairment (creatinine clearance <30 mL·min-1 and 14 matched healthy subjects with normal renal function. Subjects received single doses of 20 or 30 µg olodaterol administered with the Respimat Soft Mist inhaler.Results: Olodaterol was well tolerated in all subjects. The geometric mean ratios and 90% confidence intervals of dose-normalized area under the plasma concentration-time curve from time zero to 4 hours (AUC0–4 for subjects with mild and moderate hepatic impairment compared to healthy subjects were 97% (75%–125% and 105% (79%–140%, respectively. Corresponding values for dose-normalized maximum concentration (Cmax were 112% (84%–151% (mild impairment and 99% (73%–135% (moderate impairment. The geometric mean ratio (90% confidence interval of AUC0–4 for subjects with severe renal impairment compared to healthy subjects was 135% (94%–195%, and for Cmax was 137% (84%–222%. There was no significant relationship

Cell-Type Specific Determinants of NRAMP1 Expression in Professional Phagocytes

Directory of Open Access Journals (Sweden)

Mathieu F. M. Cellier

2013-01-01

Full Text Available The Natural resistance-associated macrophage protein 1 (Nramp1 or Solute carrier 11 member 1, Slc11a1 transports divalent metals across the membrane of late endosomes and lysosomes in professional phagocytes. Nramp1 represents an ancient eukaryotic cell-autonomous defense whereas the gene duplication that yielded Nramp1 and Nramp2 predated the origin of Sarcopterygians (lobe-finned fishes and tetrapods. SLC11A1 genetic polymorphisms associated with human resistance to tuberculosis consist of potential regulatory variants. Herein, current knowledge of the regulation of SLC11A1 gene expression is reviewed and comprehensive analysis of ENCODE data available for hematopoietic cell-types suggests a hypothesis for the regulation of SLC11A1 expression during myeloid development and phagocyte functional polarization. SLC11A1 is part of a 34.6 kb CTCF-insulated locus scattered with predicted regulatory elements: a 3' enhancer, a large 5' enhancer domain and four elements spread around the transcription start site (TSS, including several C/EBP and PU.1 sites. SLC11A1 locus ends appear mobilized by ETS-related factors early during myelopoiesis; activation of both 5' and 3' enhancers in myelo-monocytic cells correlate with transcription factor binding at the TSS. Characterizing the corresponding cis/trans determinants functionally will establish the mechanisms involved and possibly reveal genetic variation that impacts susceptibility to infectious or immune diseases.

Methotrexate Associated Renal Impairment Is Related to Delayed Elimination of High-Dose Methotrexate

Directory of Open Access Journals (Sweden)

Shi-Long Yang

2015-01-01

Full Text Available Although Methotrexate (MTX is an effective drug for the treatment of acute lymphoblastic leukemia (ALL, the toxicity remains a significant problem. In this prospective study, fifty-four patients with ALL were enrolled. 3 g or 5 g MTX/m2 was administered over 24 hours. Serum MTX concentrations were determined in 24, 48, and 96 hours after MTX infusion. Serum creatinine concentrations and creatinine clearance rate (CCR were determined before and 24 and 48 hours after MTX infusion. A total of 173 courses of MTX infusion were administered. The serum creatinine concentrations did not change much after MTX infusion while the CCR was gradually decreased. MTX clearance status was independently related to CCR decrease, with the risk of 8.07 to develop renal impairment in patients with delayed MTX elimination. Serum creatinine concentration, serum creatinine ratio, CCR, and CCR ratio at 24 hours were all related to MTX elimination delay. Patients with serum creatinine level >35.0 μmol/L, creatinine ratio >1.129, or CCR <100.0 mL/min were more likely to undergo MTX elimination delay. In conclusion, MTX could induce transient renal impairment and compromised renal function will delay MTX clearance. The serum creatinine concentration and the ratio and CCR are useful tools for evaluating MTX elimination status.

Delayed clearance of cerebrospinal fluid tracer from entorhinal cortex in idiopathic normal pressure hydrocephalus: A glymphatic magnetic resonance imaging study.

Science.gov (United States)

Eide, Per K; Ringstad, Geir

2018-01-01

The glymphatic system plays a key role for clearance of waste solutes from the rodent brain. We recently found evidence of glymphatic circulation in the human brain when using magnetic resonance imaging (MRI) contrast agent as cerebrospinal fluid (CSF) tracer in conjunction with multiple MRI acquisitions (gMRI). The present study explored the hypothesis that reduced glymphatic clearance in entorhinal cortex (ERC) may be instrumental in idiopathic normal pressure hydrocephalus (iNPH) dementia. gMRI acquisitions were obtained over a 24-48 h time span in cognitively affected iNPH patients and non-cognitively affected patients with suspected CSF leaks. The CSF tracer enrichment was determined as changes in normalized MRI T1 signal units. The study included 30 patients with iNPH and 8 individuals with suspected CSF leaks (i.e. reference individuals). Compared to reference individuals, iNPH patients presented with higher medial temporal lobe atrophy score and Evan's index and inferior ERC thickness. We found delayed clearance of the intrathecal CSF tracer gadobutrol from CSF, the ERC and adjacent white matter, suggesting impaired glymphatic circulation. Reduced clearance and accumulation of toxic waste product such as amyloid-β may be a mechanism behind dementia in iNPH. Glymphatic MRI (gMRI) may become a tool for assessment of early dementia.

Efficient internalization of mesoporous silica particles of different sizes by primary human macrophages without impairment of macrophage clearance of apoptotic or antibody-opsonized target cells

International Nuclear Information System (INIS)

Witasp, Erika; Kupferschmidt, Natalia; Bengtsson, Linnea; Hultenby, Kjell; Smedman, Christian; Paulie, Staffan; Garcia-Bennett, Alfonso E.; Fadeel, Bengt

2009-01-01

Macrophage recognition and ingestion of apoptotic cell corpses, a process referred to as programmed cell clearance, is of considerable importance for the maintenance of tissue homeostasis and in the resolution of inflammation. Moreover, macrophages are the first line of defense against microorganisms and other foreign materials including particles. However, there is sparse information on the mode of uptake of engineered nanomaterials by primary macrophages. In this study, mesoporous silica particles with cubic pore geometries and covalently fluorescein-grafted particles were synthesized through a novel route, and their interactions with primary human monocyte-derived macrophages were assessed. Efficient and active internalization of mesoporous silica particles of different sizes was observed by transmission electron microscopic and flow cytometric analysis and studies using pharmacological inhibitors suggested that uptake occurred through a process of endocytosis. Moreover, uptake of silica particles was independent of serum factors. The silica particles with very high surface areas due to their porous structure did not impair cell viability or function of macrophages, including the ingestion of different classes of apoptotic or opsonized target cells. The current findings are relevant to the development of mesoporous materials for drug delivery and other biomedical applications.

The influence of body posture on lithium clearance

DEFF Research Database (Denmark)

Kamper, A L; Strandgaard, S; Holstein-Rathlou, N H

1988-01-01

To establish appropriate standard circumstances for lithium clearance measurements, a study was undertaken in 12 healthy volunteers. In each subject, the glomerular filtration rate (GFR), as estimated by [51Cr]EDTA plasma clearance, and the renal clearances of lithium, sodium and potassium were...... during moderate physical activity. Hence, when renal tubular function is studied with the lithium clearance method, standardization of posture and physical activity is important. In such studies physical activity such as walking should particularly be avoided....... measured four times at 1-week intervals: two in the supine and one in the sitting position, and one when the subject was walking around. Glomerular filtration rate was not influenced by posture changes. On the contrary, lithium clearance, which in the supine position was 30 +/- 9 ml/min (1 SD), tended...

The influence of body posture on lithium clearance

DEFF Research Database (Denmark)

Kamper, A L; Strandgaard, S; Holstein-Rathlou, N H

1988-01-01

To establish appropriate standard circumstances for lithium clearance measurements, a study was undertaken in 12 healthy volunteers. In each subject, the glomerular filtration rate (GFR), as estimated by [51Cr]EDTA plasma clearance, and the renal clearances of lithium, sodium and potassium were...... measured four times at 1-week intervals: two in the supine and one in the sitting position, and one when the subject was walking around. Glomerular filtration rate was not influenced by posture changes. On the contrary, lithium clearance, which in the supine position was 30 +/- 9 ml/min (1 SD), tended...... during moderate physical activity. Hence, when renal tubular function is studied with the lithium clearance method, standardization of posture and physical activity is important. In such studies physical activity such as walking should particularly be avoided....

Clearance Laboratory - Capability and measurement sensitivity

Energy Technology Data Exchange (ETDEWEB)

Hedemann Jensen, P.; Lauridsen, B.; Silva, J.; Soegaard-Hansen, J.; Warming, L.

2005-08-01

A new low-level Clearance Laboratory has been built at the Risoe-site. Building materials with a low content of naturally occurring radionuclides have been used. To minimize transport of radon gas from soil into the laboratory the foundation has been supplied with a membrane. The laboratory has been equipped with two high-efficiency germanium detectors. These detectors will be used for clearance measurements on the predicted amount of 15,000 - 18,000 tonnes of non-active or nearly non-active materials, which will originate from the decommissioning of all the nuclear facilities at the Risoe-site. They will be used also for clearance measurements on buildings and land. Objects and materials to be measured for clearance are placed on a rotation table that can carry up to one tonne and can rotate once a minute to simulate some averaging of inhomogeneously distributed activity. Sensitivity and background measurements reveal that measuring times of 20 - 50 minutes would normally be sufficient to detect radionuclide concentrations of only a small fraction of the nuclide-specific clearance levels with a sufficiently low uncertainty. Probability calculations of the measurement capacity of the Clearance Laboratory indicate that the mean value of the total measuring time for all materials that potentially can be cleared would be 13 years with a 95% probability of being less than 25 years. The mean value of the annual amount of materials that can be measured in the laboratory is 600 tonnes with a 95% probability of being less than 1,200 tonnes. If needed, there is room for additional measuring systems to increase the capacity of the laboratory. (au)

Clearance Laboratory - Capability and measurement sensitivity

International Nuclear Information System (INIS)

Hedemann Jensen, P.; Lauridsen, B.; Silva, J.; Soegaard-Hansen, J.; Warming, L.

2005-09-01

A new low-level Clearance Laboratory has been built at the Risoe-site. Building materials with a low content of naturally occurring radionuclides have been used. To minimize transport of radon gas from soil into the laboratory the foundation has been supplied with a membrane. The laboratory has been equipped with two high-efficiency germanium detectors. These detectors will be used for clearance measurements on the predicted amount of 15,000 - 18,000 tonnes of non-active or nearly non-active materials, which will originate from the decommissioning of all the nuclear facilities at the Risoe-site. They will be used also for clearance measurements on buildings and land. Objects and materials to be measured for clearance are placed on a rotation table that can carry up to one tonne and can rotate once a minute to simulate some averaging of inhomogeneously distributed activity. Sensitivity and background measurements reveal that measuring times of 20 - 50 minutes would normally be sufficient to detect radionuclide concentrations of only a small fraction of the nuclide-specific clearance levels with a sufficiently low uncertainty. Probability calculations of the measurement capacity of the Clearance Laboratory indicate that the mean value of the total measuring time for all materials that potentially can be cleared would be 13 years with a 95% probability of being less than 25 years. The mean value of the annual amount of materials that can be measured in the laboratory is 600 tonnes with a 95% probability of being less than 1,200 tonnes. If needed, there is room for additional measuring systems to increase the capacity of the laboratory. (au)

Population pharmacokinetics of telapristone (CDB-4124) and its active monodemethylated metabolite CDB-4453, with a mixture model for total clearance.

Science.gov (United States)

Morris, Denise; Podolski, Joseph; Kirsch, Alan; Wiehle, Ronald; Fleckenstein, Lawrence

2011-12-01

Telapristone is a selective progesterone antagonist that is being developed for the long-term treatment of symptoms associated with endometriosis and uterine fibroids. The population pharmacokinetics of telapristone (CDB-4124) and CDB-4453 was investigated using nonlinear mixed-effects modeling. Data from two clinical studies (n = 32) were included in the analysis. A two-compartment (parent) one compartment (metabolite) mixture model (with two populations for apparent clearance) with first-order absorption and elimination adequately described the pharmacokinetics of telapristone and CDB-4453. Telapristone was rapidly absorbed with an absorption rate constant (Ka) of 1.26 h(-1). Moderate renal impairment resulted in a 74% decrease in Ka. The population estimates for oral clearance (CL/F) for the two populations were 11.6 and 3.34 L/h, respectively, with 25% of the subjects being allocated to the high-clearance group. Apparent volume of distribution for the central compartment (V2/F) was 37.4 L, apparent inter-compartmental clearance (Q/F) was 21.9 L/h, and apparent peripheral volume of distribution for the parent (V4/F) was 120 L. The ratio of the fraction of telapristone converted to CDB-4453 to the distribution volume of CDB-4453 (Fmet(est)) was 0.20/L. Apparent volume of distribution of the metabolite compartment (V3/F) was fixed to 1 L and apparent clearance of the metabolite (CLM/F) was 2.43 L/h. A two-compartment parent-metabolite model adequately described the pharmacokinetics of telapristone and CDB-4453. The clearance of telapristone was separated into two populations and could be the result of metabolism via polymorphic CYP3A5.

Potentiation of the generation of reactive oxidants by human phagocytes during exposure to benoxaprofen and ultraviolet radiation in vitro

Energy Technology Data Exchange (ETDEWEB)

Anderson, R.; Eftychis, H.A.

1986-09-01

The effects of ultraviolet (UV) radiation on the spontaneous membrane-associated oxidative metabolism of human polymorphonuclear leukocytes (PMNL) and mononuclear leukocytes (MNL), co-incubated in the presence and absence of the non-steroidal, anti-inflammatory drug (NSAID) benoxaprofen at various concentrations, were investigated in vitro. Assays of superoxide generation and luminol-enhanced chemiluminescence (CL) were used to detect the production of reactive oxidants by PMNL and MNL. The pro-oxidative effects of benoxaprofen and UV radiation alone and in combination are dependent on intact phagocyte membrane-associated oxidative metabolism. It is postulated that the pro-oxidative interactions which occur between human phagocytes, benoxaprofen and ultraviolet radiation cause the dermatological side-effects of benoxaprofen.

The Influence of Hepatic and Renal Impairment on the Pharmacokinetics of a Treatment for Herpes Zoster, Amenamevir (ASP2151): Phase 1, Open-Label, Single-Dose, Parallel-Group Studies.

Science.gov (United States)

Kusawake, Tomohiro; Kowalski, Donna; Takada, Akitsugu; Kato, Kota; Katashima, Masataka; Keirns, James J; Lewand, Michaelene; Lasseter, Kenneth C; Marbury, Thomas C; Preston, Richard A

2017-12-01

Amenamevir (ASP2151) is a nonnucleoside human herpesvirus helicase-primase inhibitor that was approved in Japan for the treatment of herpes zoster (shingles) in 2017. This article reports the results of two clinical trials that investigated the effects of renal and hepatic impairment on the pharmacokinetics of amenamevir. These studies were phase 1, open-label, single-dose (oral 400 mg), parallel-group studies evaluating the pharmacokinetics, safety, and tolerability of amenamevir in healthy participants and participants with moderate hepatic impairment and mild, moderate, and severe renal impairment. In the hepatic impairment study, the pharmacokinetic profile of amenamevir in participants with moderate hepatic impairment was generally similar to that of participants with normal hepatic function. In the renal impairment study, the area under the amenamevir concentration versus time curve from the time of dosing up to the time of the last sample with extrapolation to infinity of the terminal phase was increased by 78.1% in participants with severe renal impairment. There was a positive relationship between creatinine clearance and oral and renal clearance for amenamevir in the renal impairment study. In both studies, amenamevir was safe and well tolerated. The findings of the hepatic impairment study indicate that no dosing adjustment is required in patients with moderate hepatic impairment. In the renal impairment study, systemic amenamevir exposure was increased by renal impairment. However, it is unlikely that renal impairment will have a significant effect on the safety of amenamevir given that in previous pharmacokinetic and safety studies in healthy individuals amenamevir was safe and well tolerated after a single dose (5-2400 mg, fasted condition) and repeated doses for 7 days (300 or 600 mg, fed condition), and the amount of amenamevir exposure in the renal impairment study was covered by those studies. These findings suggest that amenamevir does not

Lithium clearance in chronic nephropathy

DEFF Research Database (Denmark)

Kamper, A L; Holstein-Rathlou, N H; Leyssac, P P

1989-01-01

1. Lithium clearance measurements were made in 72 patients with chronic nephropathy of different aetiology and moderate to severely reduced renal function. 2. Lithium clearance was strictly correlated with glomerular filtration rate, and there was no suggestion of distal tubular reabsorption...... of lithium or influence of osmotic diuresis. 3. Fractional reabsorption of lithium was reduced in most patients with glomerular filtration rates below 25 ml/min. 4. Calculated fractional distal reabsorption of sodium was reduced in most patients with glomerular filtration rates below 50 ml/min. 5. Lithium...... that lithium clearance may be a measure of the delivery of sodium and water from the renal proximal tubule. With this assumption it was found that adjustment of the sodium excretion in chronic nephropathy initially takes place in the distal parts of the nephron (loop of Henle, distal tubule and collecting duct...

Experience and lessons learnt from clearance in Germany

International Nuclear Information System (INIS)

Thierfeldt, Stefan

2002-01-01

Clearance is an important corner-stone of waste management in nuclear installations in Germany. It has been practised successfully for around two decades. The importance of clearance can also be judged from the fact that it has been included detailedly in the new German Radiation Protection Ordinance. Currently, there are 19 NPPs and a number of fuel cycle installations in operation in Germany. The main waste quantities, however, arise from the dismantling of NPPs and fuel cycle installations which are currently in decommissioning. As most of the decommissioning projects are targeted for early dismantling instead of safe enclosure, there is already considerable experience with the application of clearance procedures and verification of clearance levels. The German waste management strategy is governed by two options: Clearance of the material (after decontamination and release measurement). After clearance, the material is no longer regarded as radioactive in a legal sense. Final disposal of the material as radioactive waste in a deep geological repository (no near-surface disposal facilities exist or are planned in Germany). A deep geological repository is planned to be operable around 2030. Stefan Thierfeldt described German clearance requirements and lessons learned from their application to decommissioning of power reactors. The great majority of the waste was in fact recycled, although the costs were dominated by the small fraction that had to be disposed of as radioactive waste. Among the lessons learned from the German experience were some revealing insights into the public perception of both clearance and of recycling of material from decommissioning of a nuclear installation

19 CFR 122.26 - Entry and clearance.

Science.gov (United States)

2010-04-01

... AIR COMMERCE REGULATIONS Private Aircraft § 122.26 Entry and clearance. Private aircraft, as defined... information as set forth in § 122.22(c), and grants electronic clearance via electronic mail or telephone...

Comparison of renal clearance of 99mTc-DTPA and inulin, 131I-hippurate and PAH as well as of the creatinine clearance in Wistar rats

International Nuclear Information System (INIS)

Hagemann, J.; Li Min Su; Strangfeld, D.; Schuerer, M.; Siewert, H.; Pietsch, R.; Kruse, I.; Priem, F.

1988-01-01

Order of magnitude and standard deviation of 99m Tc-DTPA and 131 I-hippurate slope clearance were analyzed successively in 56 male Wistar rats. The clearance of 99m Tc-DTPA was 17.4 ± 3.43 μl · s -1 (100 g b-w) -1 , of 131 I-hippurate 34.3 ± 7.21 μl · s -1 (100 g b-w) -1 . In 17 rats inulin and PAH clearances were analyzed by steady state method with permanent infusion and 3 to 4 urine collection periods 3 days later. The endogeneous creatinine clearance was determined within the same periods. The 99m Tc-DTPA slope clearance corresponded to the inulin clearance, as well as the hippurate clearance to the PAH clearance. The high filtration fraction calculated from nuclear medicine and chemical clearance methods and the low PAH extraction (42%) let suggest that PAH and hippurate are eliminated only incompletely from plasma in rat kidney and are unsuitable for determination of renal blood supply in rats. The creatinine clearance with 4.7 ± 1.38 μl · s -1 (100 g b-w) -1 was far beneath the clearance of inulin and 99m Tc-DTPA, supposing that creatinine is reabsorbed tubularly in part and the creatinine clearance can not be used for valuation of the GFR in rats. However, for this the 99m Tc-DTPA clearance in Wistar rats seems to be well suited. (author)

Enhancement in ex vivo phagocytic capacity of peritoneal leukocytes in mice by oral delivery of various lactic-acid-producing bacteria.

Science.gov (United States)

Lee, Yeonhee; Lee, Taik-Soo

2005-01-01

Lactic-acid-producing bacteria (LABs) are known to have immunomodulating activity. In the current study, various LABs were tested for their immunity-enhancing activity, especially the phagocytic activity of leukocytes. Viable but not heat-killed cells of Weissella kimchii strain PL9001, Lactobacillus fermentum strain PL9005, and L. plantarum strain PL9011 significantly increased the ex vivo phagocytic capacity of mouse peritoneal leukocytes to ingest fluorescein isothiocyanate (FITC)-labeled Escherichia coli in a strain-dependent manner. Results of this and previous studies suggest these LABs as candidates for new probiotics. This is the first report of the enhancement of peritoneal leukocyte activity of these species.

Secretin enhances [14C]erythritol clearance in unanesthetized dogs

International Nuclear Information System (INIS)

Lewis, M.H.; Baker, A.L.; Dhorajiwala, J.; Moossa, A.R.

1982-01-01

To determine the effect of secretin infusion on clearance of inert markers into bile, unanesthetized dogs fitted with Thomas cannulas received continuous infusions of [ 14 C]erythritol and [ 3 H]inulin throughout study. Taurocholic acid administered sequentially at 9.0, 20.0, and 40.0 mumol/min enhanced [ 14 C]erythritol clearance, and GIH secretin (3 units/min) administered along with TCA (40.0 mumol/min) increased [ 14 C]erythritol clearance from 4.9 +/- 1.2 ml/10 min to 6.8 +/- 1.3 ml/10 min (P less than 0.001), but simultaneously measured [ 3 H]inulin clearance was unaltered. Secretin alone also increased [ 14 C]erythritol clearance but did not alter [ 3 H]inulin clearance. The increase in [ 14 C]erythritol clearance per unit increase in bile flow was less during secretin infusion than TCA. Thus, secretin increases [ 14 C]erythritol transport through restricted channels, probably distal to the canaliculi. [ 14 C]Erythritol may not be an accurate marker for canalicular bile flow in dogs during secretin infusion

Comparison of renal clearance of 99mTc-DTPA and inulin 131I-hippurate and PAH as well as creatinine clearance in Wistar-rats

International Nuclear Information System (INIS)

Hagemann, J.; Li Min Su; Strangfeld, D.; Schuerer, M.; Siewert, H.; Pietsch, R.; Kruse, I.; Priem, F.

1988-01-01

Averages and standard deviations of 99m Tc-DTPA and 131 I-hippurate slope clearance were consecutively determined for 56 male Wistar rats, with a body-weight of 271 ± 69 g in a single investigation. Clearance of 99m Tc-DTPA was 17.4 ± 3.4, that of 131 I-hippurate was 34.3 ± 7.2 μl · s -1 per 100 g body weight. For 17 rats inulin and PAH clearances were determined after 3 days with the steady-state method with continuous infusion and 3-4 periods of urine collection. During the same periods endogeneous creatinine clearance was determined. 99m Tc-DTPA slope clearance correlated well with inulin clearance, also the hippurate with the PAH clearance. The high values of the filtration fraction, calculated from radioisotope and chemical methods, and the low PAH extraction of 42% lead to the conclusion, that PAH and hippurate are incompletely eliminated by the rat kidney from plasma and therefore are inadequate for determining renal blood flow in rats. Creatinine clearance was 4.7 ± 1.38 μl · s -1 per 100 g body weight, much lower than that of inulin and 99m Tc-DTPA. Therefore is assumed, that tubular reabsorption of creatinine occurs and creatinine clearance cannot serve for the evaluation of GFR in rats. For this, however, the clearance of 99m Tc-DTPA seems well applicable in Wistar rats. (author)

Depletion of dendritic cells enhances innate anti-bacterial host defense through modulation of phagocyte homeostasis.

Directory of Open Access Journals (Sweden)

Stella E Autenrieth

2012-02-01

Full Text Available Dendritic cells (DCs as professional antigen-presenting cells play an important role in the initiation and modulation of the adaptive immune response. However, their role in the innate immune response against bacterial infections is not completely defined. Here we have analyzed the role of DCs and their impact on the innate anti-bacterial host defense in an experimental infection model of Yersinia enterocolitica (Ye. We used CD11c-diphtheria toxin (DT mice to deplete DCs prior to severe infection with Ye. DC depletion significantly increased animal survival after Ye infection. The bacterial load in the spleen of DC-depleted mice was significantly lower than that of control mice throughout the infection. DC depletion was accompanied by an increase in the serum levels of CXCL1, G-CSF, IL-1α, and CCL2 and an increase in the numbers of splenic phagocytes. Functionally, splenocytes from DC-depleted mice exhibited an increased bacterial killing capacity compared to splenocytes from control mice. Cellular studies further showed that this was due to an increased production of reactive oxygen species (ROS by neutrophils. Adoptive transfer of neutrophils from DC-depleted mice into control mice prior to Ye infection reduced the bacterial load to the level of Ye-infected DC-depleted mice, suggesting that the increased number of phagocytes with additional ROS production account for the decreased bacterial load. Furthermore, after incubation with serum from DC-depleted mice splenocytes from control mice increased their bacterial killing capacity, most likely due to enhanced ROS production by neutrophils, indicating that serum factors from DC-depleted mice account for this effect. In summary, we could show that DC depletion triggers phagocyte accumulation in the spleen and enhances their anti-bacterial killing capacity upon bacterial infection.

Disposition of [G-(3)H]paclitaxel and cremophor EL in a patient with severely impaired renal function

NARCIS (Netherlands)

A.J. Gelderblom (Hans); J. Verweij (Jaap); E. Brouwer (Eric); M. Pillay; P. de Bruijn (Peter); K. Nooter (Kees); G. Stoter (Gerrit); A. Sparreboom (Alex)

1999-01-01

textabstractIn the present work, we studied the pharmacokinetics and metabolic disposition of [G-(3)H]paclitaxel in a female patient with recurrent ovarian cancer and severe renal impairment (creatinine clearance: approximately 20 ml/min) due to chronic hypertension and

Metabolic clearance rate and urinary clearance of purified beta-core

International Nuclear Information System (INIS)

Wehmann, R.E.; Blithe, D.L.; Flack, M.R.; Nisula, B.C.

1989-01-01

We injected a highly purified preparation of the beta-core molecule, a fragment of hCG beta excreted in pregnancy urine, into five men and three women to determine its kinetic parameters, MCR, and urinary clearance. The beta-core molecule was distributed in an initial volume [1950 +/- 156 (mean +/- SEM) mL/m2 body surface area] approximately equal to the estimated plasma volume. Its disappearance was multiexponential on a semilogarithmic plot, with a rapid phase t1/2 of 3.5 +/- 0.7 min and a slow phase t1/2 of 22.4 +/- 4.2 min. The transit time (the mean time spent by a molecule of beta-core in transit) was 20.6 +/- 2.1 min. The MCR was 192.0 +/- 8.0 mL/min.m2 body surface area. About 5% of the injected dose of beta-core was excreted into the urine in the first 30 min after injection, and low levels of excretion persisted for up to 7 days. The urinary clearance rate of beta-core was 13.7 +/- 1.4 mL/min.m2, accounting for about 8% of the elimination of beta-core from the plasma. The beta-core immunoreactivity in serum and urine was characterized by gel filtration and three independent RIA systems to show that its properties were indistinguishable from those of the injected beta-core. Serum levels of beta-core in pregnant women were less than 0.2 ng/mL, while the amounts excreted in their urine were as much as 5 mg/day. Based on these clearance parameters of beta-core in normal subjects, less than 0.2% of the beta-core excreted in pregnancy urine is derived by urinary clearance of plasma beta-core. Therefore, more than 99% of the beta-core excreted in pregnancy urine is derived from beta-core in a compartment separate from plasma. In particular, these data indicate that there is relatively little placental secretion of beta-core into plasma and that placental secretion does not account for the vast majority of beta-core in pregnancy urine

Find-me and eat-me signals in apoptotic cell clearance: progress and conundrums

Science.gov (United States)

2010-01-01

Everyday we turnover billions of cells. The quick, efficient, and immunologically silent disposal of the dying cells requires a coordinated orchestration of multiple steps, through which phagocytes selectively recognize and engulf apoptotic cells. Recent studies have suggested an important role for soluble mediators released by apoptotic cells that attract phagocytes (“find-me” signals). New information has also emerged on multiple receptors that can recognize phosphatidylserine, the key “eat-me” signal exposed on the surface of apoptotic cells. This perspective discusses recent exciting progress, gaps in our understanding, and the conflicting issues that arise from the newly acquired knowledge. PMID:20805564

Induced dural lymphangiogenesis facilities soluble amyloid-beta clearance from brain in a transgenic mouse model of Alzheimer's disease

Directory of Open Access Journals (Sweden)

Ya-Ru Wen

2018-01-01

Full Text Available Impaired amyloid-β clearance from the brain is a core pathological event in Alzheimer's disease. The therapeutic effect of current pharmacotherapies is unsatisfactory, and some treatments cause severe side effects. The meningeal lymphatic vessels might be a new route for amyloid-β clearance. This study investigated whether promoting dural lymphangiogenesis facilitated the clearance of amyloid-β from the brain. First, human lymphatic endothelial cells were treated with 100 ng/mL recombinant human vascular endothelial growth factor-C (rhVEGF-C protein. Light microscopy verified that rhVEGF-C, a specific ligand for vascular endothelial growth factor receptor-3 (VEGFR-3, significantly promoted tube formation of human lymphatic endothelial cells in vitro. In an in vivo study, 200 μg/mL rhVEGF-C was injected into the cisterna magna of APP/PS1 transgenic mice, once every 2 days, four times in total. Immunofluorescence staining demonstrated high levels of dural lymphangiogenesis in Alzheimer's disease mice. One week after rhVEGF-C administration, enzyme-linked immunosorbent assay results showed that levels of soluble amyloid-β were decreased in cerebrospinal fluid and brain. The Morris water maze test demonstrated that spatial cognition was restored. These results indicate that the upregulation of dural lymphangiogenesis facilities amyloid-β clearance from the brain of APP/PS1 mice, suggesting the potential of the VEGF-C/VEGFR-3 signaling pathway as a therapeutic target for Alzheimer's disease.

Interleukin-10 Modulation of Virus Clearance and Disease in Mice with Alphaviral Encephalomyelitis.

Science.gov (United States)

Martin, Nina M; Griffin, Diane E

2018-03-15

Alphaviruses are an important cause of mosquito-borne outbreaks of arthritis, rash, and encephalomyelitis. Previous studies in mice with a virulent strain (neuroadapted SINV [NSV]) of the alphavirus Sindbis virus (SINV) identified a role for Th17 cells and regulation by interleukin-10 (IL-10) in the pathogenesis of fatal encephalomyelitis (K. A. Kulcsar, V. K. Baxter, I. P. Greene, and D. E. Griffin, Proc Natl Acad Sci U S A 111:16053-16058, 2014, https://doi.org/10.1073/pnas.1418966111). To determine the role of virus virulence in generation of immune responses, we analyzed the modulatory effects of IL-10 on disease severity, virus clearance, and the CD4 + T cell response to infection with a recombinant strain of SINV of intermediate virulence (TE12). The absence of IL-10 during TE12 infection led to longer morbidity, more weight loss, higher mortality, and slower viral clearance than in wild-type mice. More severe disease and impaired virus clearance in IL-10 -/- mice were associated with more Th1 cells, fewer Th2 cells, innate lymphoid type 2 cells, regulatory cells, and B cells, and delayed production of antiviral antibody in the central nervous system (CNS) without an effect on Th17 cells. Therefore, IL-10 deficiency led to more severe disease in TE12-infected mice by increasing Th1 cells and by hampering development of the local B cell responses necessary for rapid production of antiviral antibody and virus clearance from the CNS. In addition, the shift from Th17 to Th1 responses with decreased virus virulence indicates that the effects of IL-10 deficiency on immunopathologic responses in the CNS during alphavirus infection are influenced by virus strain. IMPORTANCE Alphaviruses cause mosquito-borne outbreaks of encephalomyelitis, but determinants of outcome are incompletely understood. We analyzed the effects of the anti-inflammatory cytokine IL-10 on disease severity and virus clearance after infection with an alphavirus strain of intermediate virulence

Allometric scaling for predicting human clearance of bisphenol A

International Nuclear Information System (INIS)

Collet, Séverine H.; Picard-Hagen, Nicole; Lacroix, Marlène Z.; Puel, Sylvie; Viguié, Catherine; Bousquet-Melou, Alain; Toutain, Pierre-Louis; Gayrard, Véronique

2015-01-01

The investigation of interspecies differences in bisphenol A (BPA) pharmacokinetics (PK) may be useful for translating findings from animal studies to humans, identifying major processes involved in BPA clearance mechanisms, and predicting BPA PK parameters in man. For the first time, a large range of species in terms of body weight, from 0.02 kg (mice) to 495 kg (horses) was used to predict BPA clearance in man by an allometric approach. BPA PK was evaluated after intravenous administration of BPA in horses, sheep, pigs, dogs, rats and mice. A non-compartmental analysis was used to estimate plasma clearance and steady state volume of distribution and predict BPA PK parameters in humans from allometric scaling. In all the species investigated, BPA plasma clearance was high and of the same order of magnitude as their respective hepatic blood flow. By an allometric scaling, the human clearance was estimated to be 1.79 L/min (equivalent to 25.6 mL/kg.min) with a 95% prediction interval of 0.36 to 8.83 L/min. Our results support the hypothesis that there are highly efficient and hepatic mechanisms of BPA clearance in man. - Highlights: • Allometric scaling was used to predict BPA pharmacokinetic parameters in humans. • In all species, BPA plasma clearance approached hepatic blood flow. • Human BPA clearance was estimated to be 1.79 L/min

Allometric scaling for predicting human clearance of bisphenol A

Energy Technology Data Exchange (ETDEWEB)

Collet, Séverine H., E-mail: s.collet@envt.fr; Picard-Hagen, Nicole, E-mail: n.hagen-picard@envt.fr; Lacroix, Marlène Z., E-mail: m.lacroix@envt.fr; Puel, Sylvie, E-mail: s.puel@envt.fr; Viguié, Catherine, E-mail: c.viguie@envt.fr; Bousquet-Melou, Alain, E-mail: a.bousquet-Melou@envt.fr; Toutain, Pierre-Louis, E-mail: pltoutain@wanadoo.fr; Gayrard, Véronique, E-mail: v.gayrard@envt.fr

2015-05-01

The investigation of interspecies differences in bisphenol A (BPA) pharmacokinetics (PK) may be useful for translating findings from animal studies to humans, identifying major processes involved in BPA clearance mechanisms, and predicting BPA PK parameters in man. For the first time, a large range of species in terms of body weight, from 0.02 kg (mice) to 495 kg (horses) was used to predict BPA clearance in man by an allometric approach. BPA PK was evaluated after intravenous administration of BPA in horses, sheep, pigs, dogs, rats and mice. A non-compartmental analysis was used to estimate plasma clearance and steady state volume of distribution and predict BPA PK parameters in humans from allometric scaling. In all the species investigated, BPA plasma clearance was high and of the same order of magnitude as their respective hepatic blood flow. By an allometric scaling, the human clearance was estimated to be 1.79 L/min (equivalent to 25.6 mL/kg.min) with a 95% prediction interval of 0.36 to 8.83 L/min. Our results support the hypothesis that there are highly efficient and hepatic mechanisms of BPA clearance in man. - Highlights: • Allometric scaling was used to predict BPA pharmacokinetic parameters in humans. • In all species, BPA plasma clearance approached hepatic blood flow. • Human BPA clearance was estimated to be 1.79 L/min.

MR velocity mapping measurement of renal artery blood flow in patients with impaired kidney function

DEFF Research Database (Denmark)

Cortsen, M; Petersen, L.J.; Stahlberg, F

1996-01-01

Renal blood flow (RBF) was measured in 9 patients with chronic impaired kidney function using MR velocity mapping and compared to PAH clearance and 99mTc-DTPA scintigraphy. An image plane suitable for flow measurement perpendicular to the renal arteries was chosen from 2-dimensional MR angiography....... MR velocity mapping was performed in both renal arteries using an ECG-triggered gradient echo pulse sequence previously validated in normal volunteers. Effective renal plasma flow was calculated from the clearance rate of PAH during constant infusion and the split of renal function was evaluated...... by 99mTc-DTPA scintigraphy. A reduction of RBF was found, and there was a significant correlation between PAH clearance multiplied by 1/(1-hematocrit) and RBF determined by MR velocity mapping. Furthermore, a significant correlation between the distribution of renal function and the percent distribution...

48 CFR 2452.237-75 - Clearance of contractor personnel.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Clearance of contractor... Clauses 2452.237-75 Clearance of contractor personnel. As prescribed in 2437.110(e), insert the following clause in solicitations and contracts. Clearance of Contractor Personnel (OCT 1999) (a) General. This...

Comparative evaluation of iohexol and inulin clearance for glomerular filtration rate determinations

International Nuclear Information System (INIS)

Lindblad, H.G.; Berg, U.B.

1994-01-01

The authors have evaluated iohexol as a filtration marker in 150 children. The clearance of iohexol was compared with that of inulin or with a formula clearance. The single-sample clearance of iohexol showed a good correlation with the clearance of inulin. The clearance of iohexol correlated well with the formula clearance. The optimal blood sampling time for iohexol clearance determinations appears to be between 120 and 180 min after injection, at least in patient with relatively normal filtration rates. It is concluded that iohexol clearance is an accurate method of determining the glomerular filtration rate in clinical practice. 25 refs., 5 figs

Security Clearance Tracking System

Data.gov (United States)

National Archives and Records Administration — SCTS supports the adjudication process of private background investigations and clearances for potential employees, contractors, interns and student workers.

THE COMPARATIVE ANALYSIS OF RENAL FUNCTION IN LIVER DISEASES USING COCKCROFT-GAULT FORMULAE AND CREATININE CLEARANCE

Directory of Open Access Journals (Sweden)

Karem Ravi Teja

2018-01-01

Full Text Available BACKGROUND Kidney dysfunction in liver disease can be due to different aetiologies and can have diverse manifestations. Most of the abnormalities of kidney function in cirrhosis are of functional origin namely, sodium retention, impaired free water excretion and renal vasoconstriction with decrease in renal perfusion and glomerular filtration rate. Renal dysfunction in chronic liver disease usually follows a progressive course- the final phase being Hepatorenal Syndrome (HRS. MATERIALS AND METHODS This study included patients with chronic liver disease being treated as inpatients in the Department of General Medicine, Konaseema Institute of Medical Sciences, Amalapuram. Evidence for chronic liver disease being defined by a compatible clinical profile (signs of liver cell failure or reduced liver span along with biochemical (altered liver function tests, reversal of albuminglobulin ratio or sonographic evidence (altered echotexture of liver or tissue diagnosis (positive liver biopsy for cirrhosis. RESULTS Eighteen percent, i.e. 5 out of the 28 patients with creatinine clearance more than 60 mL/minute by Cockcroft-Gault formula were found to have creatinine clearance values less than 40 mL/minute when done by timed urine collection P value calculated was found to be less than 0.0001, which is statistically significant. CONCLUSION In chronic liver disease, serum creatinine alone is not a reliable marker to assess renal dysfunction. Calculating creatinine clearance by using Cockcroft-Gault formula overestimates renal function in cirrhotics. Creatinine clearance measured by timed urine collections should be done routinely to assess renal reserve in advanced liver disease. Alcoholism appears to have adverse effect on renal function when compared with other aetiologies of cirrhosis.

Centrifugal compressor tip clearance and impeller flow

Energy Technology Data Exchange (ETDEWEB)

Jaatinen-Varri, Ahti; Tiainen, Jonna; Turunen-Saaresti, Teemu; Gronman, Aki; Ameli, Alireza; Backman, Jari [Laboratory of Fluid Dynamics, LUT School of Energy Systems, Lappeenranta University of Technology, Lappeenranta (Finland); Engeda, Abraham [Turbomachinery Laboratory, Dept. of Mechanical Engineering, Michigan State University, East Lansing (United States)

2016-11-15

Compressors consume a considerable portion of the electricity used in the industrial sector. Hence, improvements in compressor efficiency lead to energy savings and reduce environmental impacts. The efficiency of an unshrouded centrifugal compressor suffers from leakage flow over the blade tips. The effect of tip leakage flow on the passage flow differs between the full and splitter blade passages. In this study, the differences in the flow fields between the full and splitter blade passages were studied numerically in detail. An industrial high-speed compressor with a design pressure ratio of 1.78 was modelled. Numerical studies were conducted with six different tip clearances and three different diffuser widths. The results show that increasing tip clearance considerably increases the reversed flow into the impeller with an unpinched diffuser. The reversed flow then partly mixes into the flow in the same blade passage it entered the impeller and the rest migrates over the blade, mixing with the tip clearance flow. Furthermore, as the reversed and clearance flow mix into the wake, the wake is weakened. As pinch reduces both the reversed flow and clearance flow, the passage wakes are stronger with pinches. However, the pinch is beneficial as the losses at the impeller outlet decrease.

Centrifugal compressor tip clearance and impeller flow

International Nuclear Information System (INIS)

Jaatinen-Varri, Ahti; Tiainen, Jonna; Turunen-Saaresti, Teemu; Gronman, Aki; Ameli, Alireza; Backman, Jari; Engeda, Abraham

2016-01-01

Compressors consume a considerable portion of the electricity used in the industrial sector. Hence, improvements in compressor efficiency lead to energy savings and reduce environmental impacts. The efficiency of an unshrouded centrifugal compressor suffers from leakage flow over the blade tips. The effect of tip leakage flow on the passage flow differs between the full and splitter blade passages. In this study, the differences in the flow fields between the full and splitter blade passages were studied numerically in detail. An industrial high-speed compressor with a design pressure ratio of 1.78 was modelled. Numerical studies were conducted with six different tip clearances and three different diffuser widths. The results show that increasing tip clearance considerably increases the reversed flow into the impeller with an unpinched diffuser. The reversed flow then partly mixes into the flow in the same blade passage it entered the impeller and the rest migrates over the blade, mixing with the tip clearance flow. Furthermore, as the reversed and clearance flow mix into the wake, the wake is weakened. As pinch reduces both the reversed flow and clearance flow, the passage wakes are stronger with pinches. However, the pinch is beneficial as the losses at the impeller outlet decrease

Diminished creatinine clearance in anorexia nervosa: reversal with weight gain.

OpenAIRE

Boag, F; Weerakoon, J; Ginsburg, J; Havard, C W; Dandona, P

1985-01-01

To assess whether patients with anorexia nervosa have abnormalities in creatinine clearance, we measured plasma creatinine concentration, urinary creatinine excretion, and creatinine clearance in 10 patients with anorexia nervosa before and during treatment. Urinary creatinine excretion and creatinine clearance were diminished in all patients. Nine patients had significant decreases in their plasma creatinine and creatinine clearance was increased even when corrected for body weight and body ...

Cerebrospinal Fluid Clearance in Alzheimer Disease Measured with Dynamic PET.

Science.gov (United States)

de Leon, Mony J; Li, Yi; Okamura, Nobuyuki; Tsui, Wai H; Saint-Louis, Les A; Glodzik, Lidia; Osorio, Ricardo S; Fortea, Juan; Butler, Tracy; Pirraglia, Elizabeth; Fossati, Silvia; Kim, Hee-Jin; Carare, Roxana O; Nedergaard, Maiken; Benveniste, Helene; Rusinek, Henry

2017-09-01

Evidence supporting the hypothesis that reduced cerebrospinal fluid (CSF) clearance is involved in the pathophysiology of Alzheimer disease (AD) comes primarily from rodent models. However, unlike rodents, in which predominant extracranial CSF egress is via olfactory nerves traversing the cribriform plate, human CSF clearance pathways are not well characterized. Dynamic PET with 18 F-THK5117, a tracer for tau pathology, was used to estimate the ventricular CSF time-activity as a biomarker for CSF clearance. We tested 3 hypotheses: extracranial CSF is detected at the superior turbinates; CSF clearance is reduced in AD; and CSF clearance is inversely associated with amyloid deposition. Methods: Fifteen subjects, 8 with AD and 7 normal control volunteers, were examined with 18 F-THK5117. Ten subjects additionally underwent 11 C-Pittsburgh compound B ( 11 C-PiB) PET scanning, and 8 were 11 C-PiB-positive. Ventricular time-activity curves of 18 F-THK5117 were used to identify highly correlated time-activity curves from extracranial voxels. Results: For all subjects, the greatest density of CSF-positive extracranial voxels was in the nasal turbinates. Tracer concentration analyses validated the superior nasal turbinate CSF signal intensity. AD patients showed ventricular tracer clearance reduced by 23% and 66% fewer superior turbinate CSF egress sites. Ventricular CSF clearance was inversely associated with amyloid deposition. Conclusion: The human nasal turbinate is part of the CSF clearance system. Lateral ventricle and superior nasal turbinate CSF clearance abnormalities are found in AD. Ventricular CSF clearance reductions are associated with increased brain amyloid depositions. These data suggest that PET-measured CSF clearance is a biomarker of potential interest in AD and other neurodegenerative diseases. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Analysis of conservativity analysis for clearance levels. Final report

International Nuclear Information System (INIS)

Deckert, A.; Thierfeldt, S.

1997-07-01

When deriving clearance levels for material from nuclear installations it is necessary to proceed with a certain degree of conservativity. This can, however, differ between various sets of clearance levels leading to inconsistencies between clearance pathways. The aim of the work therefore is to compare levels of conservativity for the following two sets of clearance levels: clearance levels for disposal as conventional waste and for metallic materials for recycling/reuse. A method was developed to quantify the degree of conservativity and make it comparable. The actual and future situation for disposal of (conventional) wastes in Germany was analysed. In addition, the masses, nuclide vectors, geographical distribution etc. for slightly radioactive material being cleared for conventional disposal was analysed and modelled and the resulting dose distributions were calculated. The values for the clearance levels were taken from the 1995 recommendation by the German Commission on Radiation Protection (SSK). By using realistic scenarios, the exposure was calculated for the personnel on the landfills and for persons of the general public being exposed via groundwater pathways. It could be shown that the trivial dose range will not be exceeded even if the masses of cleared material per landfill site exceed 100 Mg/a. Because of the types and distribution of nuclear installations in Germany and because of the nuclide vectors it is therefore not necessary to limit the masses per landfill sites. Clearance levels that are determined by the exposure pathways external exposure to and the inhalation of dust by the landfill personnel show a similar level of conservativity as those for metal scrap. This means that the clearance levels for gamma emitting nuclides are not overly restrictive. Although radiologically justified, raising the clearance levels would not lead to an increase of the material quantities because other nuclides of the respective nuclide vectors are limiting. In

Disrupted epithelial/macrophage crosstalk via Spinster homologue 2-mediated S1P signaling may drive defective macrophage phagocytic function in COPD.

Directory of Open Access Journals (Sweden)

Hai B Tran

Full Text Available We have previously established a link between impaired phagocytic capacity and deregulated S1P signaling in alveolar macrophages from COPD subjects. We hypothesize that this defect may include a disruption of epithelial-macrophage crosstalk via Spns2-mediated intercellular S1P signaling.Primary alveolar macrophages and bronchial epithelial cells from COPD subjects and controls, cell lines, and a mouse model of chronic cigarette smoke exposure were studied. Cells were exposed to 10% cigarette smoke extract, or vehicle control. Spns2 expression and subcellular localization was studied by immunofluorescence, confocal microscopy and RT-PCR. Phagocytosis was assessed by flow-cytometry. Levels of intra- and extracellular S1P were measured by S1P [3H]-labeling.Spns2 expression was significantly increased (p<0.05 in alveolar macrophages from current-smokers/COPD patients (n = 5 compared to healthy nonsmokers (n = 8 and non-smoker lung transplant patients (n = 4. Consistent with this finding, cigarette smoke induced a significant increase in Spns2 expression in both human alveolar and THP-1 macrophages. In contrast, a remarkable Spns2 down-regulation was noted in response to cigarette smoke in 16HBE14o- cell line (p<0.001 in 3 experiments, primary nasal epithelial cells (p<0.01 in 2 experiments, and in smoke-exposed mice (p<0.001, n = 6 animals per group. Spns2 was localized to cilia in primary bronchial epithelial cells. In both macrophage and epithelial cell types, Spns2 was also found localized to cytoplasm and the nucleus, in line with a predicted bipartile Nuclear Localization Signal at the position aa282 of the human Spns2 sequence. In smoke-exposed mice, alveolar macrophage phagocytic function positively correlated with Spns2 protein expression in bronchial epithelial cells.Our data suggest that the epithelium may be the major source for extracellular S1P in the airway and that there is a possible disruption of epithelial/macrophage cross talk via

Numerical investigation of hub clearance flow in a Kaplan turbine

Science.gov (United States)

Wu, H.; Feng, J. J.; Wu, G. K.; Luo, X. Q.

2012-11-01

In this paper, the flow field considering the hub clearance flow in a Kaplan turbine has been investigated through using the commercial CFD code ANSYS CFX based on high-quality structured grids generated by ANSYS ICEM CFD. The turbulence is simulated by k-ω based shear stress transport (SST) turbulence model together with automatic near wall treatments. Four kinds of simulations have been conducted for the runner geometry without hub clearance, with only the hub front clearance, with only the rear hub clearance, and with both front and rear clearance. The analysis of the obtained results is focused on the flow structure of the hub clearance flow, the effect on the turbine performance including hydraulic efficiency and cavitation performance, which can improve the understanding on the flow field in a Kaplan turbine.

Numerical investigation of hub clearance flow in a Kaplan turbine

International Nuclear Information System (INIS)

Wu, H; Feng, J J; Wu, G K; Luo, X Q

2012-01-01

In this paper, the flow field considering the hub clearance flow in a Kaplan turbine has been investigated through using the commercial CFD code ANSYS CFX based on high-quality structured grids generated by ANSYS ICEM CFD. The turbulence is simulated by k-ω based shear stress transport (SST) turbulence model together with automatic near wall treatments. Four kinds of simulations have been conducted for the runner geometry without hub clearance, with only the hub front clearance, with only the rear hub clearance, and with both front and rear clearance. The analysis of the obtained results is focused on the flow structure of the hub clearance flow, the effect on the turbine performance including hydraulic efficiency and cavitation performance, which can improve the understanding on the flow field in a Kaplan turbine.

Determination of renal clearance of 131I-hippuran

International Nuclear Information System (INIS)

Ridzon, S.

1982-01-01

The author presents his own method for the determination of total renal clearance of 131 I-hippuran under conditions of its diminishing plasma concentration following single intravenous administration. Total renal clearance is determined as the ratio of the amount of activity excreted into the urine over a certain time interval and of the area limited by the curve of activity decrease in plasma and by the time axis in the corresponding interval. The results are demonstrated in five investigated healthy subjects, and very good agreement of the calculated values of total renal clearance for different time intervals in the same subject is pointed out. When isotope nephrography is simultaneously performed, the method allows to determine also the values of isolated renal clearance for each kidney separately. (author)

Airway Clearance Techniques (ACTs)

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Full Text Available ... Research Consortia CF Biomarker Consortium CFTR 3-D Structure Consortium CFTR Folding Consortium Epithelial Stem Cell Consortium Mucociliary Clearance Consortium SUCCESS WITH THERAPIES RESEARCH ...

DMPD: CR3 (CD11b, CD18): a phagocyte and NK cell membrane receptor with multipleligand specificities and functions. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available ) (.html) (.csml) Show CR3 (CD11b, CD18): a phagocyte and NK cell membrane receptor with multipleligand specificities and function...d NK cell membrane receptor with multipleligand specificities and functions. Authors Ross GD, Vetvicka V. Pu...igand specificities and functions. Ross GD, Vetvicka V. Clin Exp Immunol. 1993 May;92(2):181-4. (.png) (.svg...8485905 CR3 (CD11b, CD18): a phagocyte and NK cell membrane receptor with multiplel

Inherited Disorders of Bilirubin Clearance

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Memon, Naureen; Weinberger, Barry I; Hegyi, Thomas; Aleksunes, Lauren M

2016-01-01

Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective 1) unconjugated bilirubin uptake and intrahepatic storage, 2) conjugation of glucuronic acid to bilirubin (e.g. Gilbert syndrome, Crigler-Najjar syndrome, Lucey-Driscoll syndrome, breast milk jaundice), 3) bilirubin excretion into bile (Dubin-Johnson syndrome), or 4) conjugated bilirubin re-uptake (Rotor syndrome). In this review, the molecular mechanisms and clinical manifestations of these conditions are described, as well as current approaches to diagnosis and therapy. PMID:26595536

Approaches towards establishing of clearance levels in Japan

International Nuclear Information System (INIS)

Sumitani, N.; Watanabe, I.; Okoshi, M.

1998-01-01

It is important to establish necessary regulatory systems for decommissioning waste management, especially to establish clearance levels from regulatory control. To establish the regulatory systems, the Nuclear Safety Commission (NSC) has been discussing the unconditional clearance levels for materials from nuclear reactors since May 1997. The NSC tries to derive unconditional clearance levels for the materials such as concrete and ferrous metal, arising from nuclear reactor decommissioning. In the derivation, both disposal and recycle/reuse of the materials are considered. Typical scenarios and parameter values for dose estimation are selected considering the Japanese natural and social conditions. Preliminary clearance levels were derived from 10 μSv/yr of individual dose criterion and deterministic analysis. For most radionuclides, the preliminary results are the same order of magnitude recommended in IAEA-TECDOC-855. Some radionuclides such as β emitters, however, are different order of magnitude from those recommended in IAEA-TECDOC-855. It is necessary that international organizations lead the discussions on the clearance levels to conclude final consensus. (author)

Green technology; only Forest Clearance is needed

Indian Academy of Sciences (India)

First page Back Continue Last page Graphics. How was Forest Clearance granted before the procedures for constitution of ESZ was completed? How was Forest Clearance granted before the procedures for constitution of ESZ was completed? How was land in Murmurwadi still under litigation made available? How was ...

Nuclear regulation. NRC's security clearance program can be strengthened

International Nuclear Information System (INIS)

Fultz, Keith O.; Kruslicky, Mary Ann; Bagnulo, John E.

1988-12-01

Because of the national security implications of its programs, the Nuclear Regulatory Commission (NRC) investigates the background of its employees and consultants as well as others to ensure that they are reliable and trustworthy. If the investigation indicates that an employee will not endanger national security, NRC grants a security clearance that allows access to classified information, material, and facilities. NRC also requires periodic checks for some clearance holders to ensure their continued clearance eligibility. The Chairman, Subcommittee on Environment, Energy, and Natural Resources, House Committee on Government Operations, asked GAO to review NRC's personnel security clearance program and assess the procedures that NRC uses to ensure that those who operate nuclear power plants do not pose a threat to the public. The Atomic Energy Act of 1954 requires NRC to conduct background investigations of its employees and consultants as well as others who have access to classified information, material, or facilities. To do this, NRC established a personnel security clearance program. Under NRC policies, a security clearance is granted after the Office of Personnel Management (OPM) or the Federal Bureau of Investigation checks the background of those applying for an NRC clearance. NRC also periodically reassesses the integrity of those holding the highest level clearance. NRC employees, consultants, contractors, and licensees as well as other federal employees hold approximately 10,600 NRC clearances. NRC does not grant clearances to commercial nuclear utility employees unless they require access to classified information or special nuclear material. However, the utilities have voluntarily established screening programs to ensure that their employees do not pose a threat to nuclear plants. NRC faces a dilemma when it hires new employees. Although its policy calls for new hires to be cleared before they start work, the security clearance process takes so long

Airway Clearance Techniques (ACTs)

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Full Text Available ... Cell Consortium Mucociliary Clearance Consortium SUCCESS WITH THERAPIES RESEARCH CONSORTIUM Therapeutics Development Network TDN Coordinating Center Study Services Working With the TDN Tools and Resources ...

Airway Clearance Techniques (ACTs)

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Full Text Available ... 3-D Structure Consortium CFTR Folding Consortium Epithelial Stem Cell Consortium Mucociliary Clearance Consortium SUCCESS WITH THERAPIES RESEARCH CONSORTIUM Therapeutics Development Network TDN Coordinating Center ...

Lysosomal impairment in Parkinson's disease.

Science.gov (United States)

Dehay, Benjamin; Martinez-Vicente, Marta; Caldwell, Guy A; Caldwell, Kim A; Yue, Zhenyue; Cookson, Mark R; Klein, Christine; Vila, Miquel; Bezard, Erwan

2013-06-01

Impairment of autophagy-lysosomal pathways (ALPs) is increasingly regarded as a major pathogenic event in neurodegenerative diseases, including Parkinson's disease (PD). ALP alterations are observed in sporadic PD brains and in toxic and genetic rodent models of PD-related neurodegeneration. In addition, PD-linked mutations and post-translational modifications of α-synuclein impair its own lysosomal-mediated degradation, thereby contributing to its accumulation and aggregation. Furthermore, other PD-related genes, such as leucine-rich repeat kinase-2 (LRRK2), parkin, and phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1), have been mechanistically linked to alterations in ALPs. Conversely, mutations in lysosomal-related genes, such as glucocerebrosidase (GBA) and lysosomal type 5 P-type ATPase (ATP13A2), have been linked to PD. New data offer mechanistic molecular evidence for such a connection, unraveling a causal link between lysosomal impairment, α-synuclein accumulation, and neurotoxicity. First, PD-related GBA deficiency/mutations initiate a positive feedback loop in which reduced lysosomal function leads to α-synuclein accumulation, which, in turn, further decreases lysosomal GBA activity by impairing the trafficking of GBA from the endoplasmic reticulum-Golgi to lysosomes, leading to neurodegeneration. Second, PD-related mutations/deficiency in the ATP13A2 gene lead to a general lysosomal impairment characterized by lysosomal membrane instability, impaired lysosomal acidification, decreased processing of lysosomal enzymes, reduced degradation of lysosomal substrates, and diminished clearance of autophagosomes, collectively contributing to α-synuclein accumulation and cell death. According to these new findings, primary lysosomal defects could potentially account for Lewy body formation and neurodegeneration in PD, laying the groundwork for the prospective development of new neuroprotective/disease-modifying therapeutic strategies

Extracellular requirements for the endocytosis of carcinogenic crystalline nickel sulfide particles by facultative phagocytes

International Nuclear Information System (INIS)

Heck, J.D.; Costa, M.

1982-01-01

Various culture medium components were examined for their effect upon the phagocytosis of carcinogenic crystalline and non-carcinogenic amorphous NiS by cultured fibroblastic cells using both a visual and radioactive assay for phagocytosis. Crystalline 63 NiS was phagocytosed by cells in a simple salts/glucose maintenance medium to an extent similar to that observed in complex culture medium fortified with 10% fetal bovine serum (FBS), suggesting that serum proteins and other components in complex culture medium exert little influence upon the uptake of these heavy metal particles. Phagocytosis of crystalline NiS was shown to be highly dependent upon Ca 2+ since omission of Ca 2+ from the salts/glucose medium substantially reduced phagocytosis, while readdition of Ca 2+ stimulated uptake in a concentration-dependent manner. The uptake of the NiS particles was inhibited by trifluoperazine, a calmodulin antagonist, implicating intracellular Ca 2+ in this phagocytosis process. Since the opposite surface charge of crystalline and amorphous NiS has been related to their different phagocytic uptake by cells whose primary function is not phagocytosis (facultative phagocytes), these results show that the culture medium components do not modify the surface charge of these particles in a way that significantly influences their uptake. (Auth.)

A study for promoting measures of social acceptance on clearance system

International Nuclear Information System (INIS)

Okoshi, Minoru; Torii, Hiroyuki; Fujii, Yasuhiko

2007-01-01

Clearance is one of the useful concepts to manage large amounts of slightly contaminated solid radioactive materials generated from the decommissioning of nuclear facilities. Cleared materials are expected to be disposed of as conventional wastes or recycled to produce consumer goods. In Japan, the legal frame-work for clearance was established in 2005 by amending the Law to regulate nuclear materials, reactors and so on. However, it is not so clear whether the general public understands clearance well. In this paper, major concerns about clearance from the general public are analyzed based on the public comments for reports on clearance prepared by the Nuclear Safety Commission and the Nuclear Institute Safety Agency. The major anxieties for clearance expressed by the general public are the safety of clearance, unknown factors of radiation effects, possibilities of excess radiation exposure due to inadequate measurements of radioactivities and fairness in decision making. In order to deal with those anxieties, some countermeasures including the confidence in nuclear operators and regulatory authorities and controllability of clearance by the general public are discussed to promote the social acceptance of clearance by the general public. (author)

Dictyostelium discoideum as a novel host system to study the interaction between phagocytes and yeasts

Directory of Open Access Journals (Sweden)

Barbara Koller

2016-10-01

Full Text Available The social amoeba Dictyostelium discoideum is a well-established model organism to study the interaction between bacteria and phagocytes. In contrast, research using D. discoideum as a host model for fungi is rare. We describe a comprehensive study, which uses D. discoideum as a host model system to investigate the interaction with apathogenic (Saccharomyces cerevisiae and pathogenic (Candida sp. yeast. We show that Dictyostelium can be co-cultivated with yeasts on solid media, offering a convenient test to study the interaction between fungi and phagocytes. We demonstrate that a number of D. discoideum mutants increase (atg1-, kil1-, kil2- or decrease (atg6- the ability of the amoebae to predate yeast cells. On the yeast side, growth characteristics, reduced phagocytosis rate, as well as known virulence factors of C. albicans (EFG1, CPH1, HGC1, ICL1 contribute to the resistance of yeast cells against predation by the amoebae. Investigating haploid C. albicans strains, we suggest using the amoebae plate test for screening purposes after random mutagenesis. Finally, we discuss the potential of our adapted amoebae plate test to use D. discoideum for risk assessment of yeast strains.

Salmeterol improves fluid clearance from alveolar-capillary membrane in COPD patients: a pilot study.

Science.gov (United States)

Di Marco, Fabiano; Guazzi, Marco; Sferrazza Papa, Giuseppe Francesco; Vicenzi, Marco; Santus, Pierachille; Busatto, Paolo; Piffer, Federico; Blasi, Francesco; Centanni, Stefano

2012-02-01

The cardiovascular component associated with chronic obstructive pulmonary disease (COPD) plays a major role in disease prognosis, accounting for 25% of the deaths. Experimental and initial clinical data suggest that beta-adrenergic agonists accelerate fluid clearance from the alveolar airspace, with potentially positive effects on cardiogenic and noncardiogenic pulmonary oedema. This pilot study investigated the acute effects of the long-acting beta-2 agonist, salmeterol, on alveolar fluid clearance after rapid saline intravenous infusion by evaluating diffusive and mechanical lung properties. Ten COPD and 10 healthy subjects were treated with salmeterol or placebo 4 h before the patient's mechanical and diffusive lung properties were measured during four non consecutive days, just before and after a rapid saline infusion, or during a similar period without an infusion. In both COPD and healthy subjects, rapid saline infusion with placebo or salmeterol premedication lead to a significant decrease in diffusion capacity for carbon monoxide (DLCO) and forced expiratory volume in 1 s (FEV1). Nonetheless, salmeterol pretreatment lead to a significantly reduced gas exchange impairment caused by saline infusion (-64% of DLCO reduction compared with placebo), whereas it did not affect changes in FEV1. In the control setting with no infusion, we found no significant change in either DLCO or mechanical properties of the lung. Salmeterol appears to provide a protective effect, not related to bronchodilation, against an acute alveolar fluid clearance challenge secondary to lung fluid overload in COPD patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

Airway Clearance Techniques (ACTs)

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Full Text Available ... 3-D Structure Consortium CFTR Folding Consortium Epithelial Stem Cell Consortium Mucociliary Clearance Consortium SUCCESS WITH THERAPIES RESEARCH CONSORTIUM Therapeutics Development Network TDN Coordinating Center Study ...

Total skin clearance results in improvements in health-related quality of life and reduced symptom severity among patients with moderate to severe psoriasis.

Science.gov (United States)

Viswanathan, Hema N; Chau, Dina; Milmont, Cassandra E; Yang, Wenjjing; Erondu, Ngozi; Revicki, Dennis A; Klekotka, Paul

2015-06-01

Newer therapies provide high levels of skin clearance in patients with moderate to severe psoriasis. However, insufficient evidence exists on the impact of total skin clearance from the patient's perspective. To examine effects of total skin clearance on health-related quality of life (HRQoL) and psoriasis symptom severity in subjects with moderate to severe psoriasis. Pooled data from a phase 2 dose-ranging trial in psoriasis using brodalumab (antibody to interleukin-17 receptor A) were used to compare subjects with static physician global assessment (sPGA) 1 versus sPGA 0 and subjects with Psoriasis Area and Severity Index (PASI) 75 to Quality Index (DLQI = 0) and no psoriasis symptoms (Psoriasis Symptom Inventory = 0). Of subjects with sPGA 0 (clear) and 1 (almost clear), 61.4% and 45.7% had a DLQI = 0 (p = 0.15), and 65.5% and 32.6% had a Psoriasis Symptom Inventory = 0 (p = 0.001), respectively. Significantly more subjects with sPGA 1 continued to report itching, redness, scaling, and flaking compared to subjects with sPGA 0. Similar results were observed based on PASI score. A higher proportion of subjects with total skin clearance reported no impairment in HRQoL and no psoriasis symptoms than those who were almost clear.

Mechanisms of the adjuvant effect of hemoglobin in experimental peritonitis. VII. Hemoglobin does not inhibit clearance of Escherichia coli from the peritoneal cavity

International Nuclear Information System (INIS)

Dunn, D.L.; Barke, R.A.; Lee, J.T. Jr.; Condie, R.M.; Humphrey, E.W.; Simmons, R.L.

1983-01-01

Hemoglobin has been shown to be a potent adjuvant in experimental Escherichia coli peritonitis, although a satisfactory mechanistic rationale is still obscure. Hemoglobin has been thought to impair intraperitoneal neutrophil function, delay clearance of bacteria from the peritoneal cavity by the normal absorptive mechanisms, or directly enhance bacterial growth. Using highly purified stroma-free hemoglobin (SFHgb), we have largely discounted any direct effect of hemoglobin on peritoneal white blood cell function. In the present study, we confirmed that uncontrolled proliferation of bacteria takes place in the presence of hemoglobin in the peritoneal cavity. Nonviable 5-iododeoxyuridine 125 I-labelled bacteria were then used to directly study peritoneal clearance kinetics, eliminating the problem of bacterial growth. SFHgb had no influence on the removal of intraperitoneal bacteria. The rate of bloodstream appearance of radiolabel was similar with or without intraperitoneal SFHgb. Thus, SFHgb does not prevent clearance of bacteria from the peritoneal cavity by interfering with normal host clearance mechanisms. SFHgb may act as a bacterial growth adjuvant, either by serving as a bacterial nutrient or by suitably modifying the environment so that extensive bacterial proliferation can occur. The latter hypothesis appears to be an area in which investigation concerning the adjuvant effect of hemoglobin may prove most fruitful

Intraarticular volume and clearance in human synovial effusions

International Nuclear Information System (INIS)

Wallis, W.J.; Simkin, P.A.; Nelp, W.B.; Foster, D.M.

1985-01-01

Intraarticular volumes were measured by radiolabeled albumin (RISA) distribution in chronic knee effusions from 11 rheumatoid arthritis patients and 9 osteoarthritis patients. Volumes of synovial fluid obtained at joint aspiration were substantially less than those found by RISA dilution. Up to 24 hours was needed for full distribution of RISA throughout the intraarticular compartment. Measured 123I and RISA radioactivity over the knee described monoexponential rate constants, lambda (minute-1). The clearance of 123I and RISA from synovial effusions was derived by the formulation volume (ml) X lambda (minute-1) = clearance (ml/minute). RISA clearance in rheumatoid effusions was significantly greater than that found in osteoarthritis effusions. Intraarticular volume and isotope clearance were easily quantified and provide measures for further evaluating the microvascular physiology of synovial effusions

Effect of needle puncture and electro-acupuncture on mucociliary clearance in anesthetized quails

Directory of Open Access Journals (Sweden)

Wang Tianshan

2006-02-01

Full Text Available Abstract Background Acupuncture therapy for obstructive respiratory diseases has been effectively used in clinical practice and the acupuncture points or acupoints of Zhongfu and Tiantu are commonly-used acupoints to treat patients with the diseases. Since the impaired mucociliary clearance is among the most important features of airway inflammation in most obstructive respiratory diseases, the effect of needle puncture and electro-acupuncture at the specific acupoints on tracheal mucociliary clearance was investigated in anesthetized quails. Methods Mucociliary transport velocity on tracheal mucosa was measured through observing the optimal pathway, and fucose and protein contents in tracheal lavages were determined with biochemical methods. In the therapeutic group, needle puncture or electro-acupuncture stimulation to the acupoints was applied without or with constant current output in 2 mA and at frequency of 100 Hz for 60 minutes. In the sham group, electro-acupuncture stimulation to Liangmen was applied. Results Our present experiments demonstrated that the electro-acupuncture stimulation to Zhongfu and Tiantu significantly increased tracheal mucociliary transport velocity and decreased the content of protein in the tracheal lavage, compared with the control group. Moreover, either needle puncture or electro-acupuncture stimulation to Zhongfu and Tiantu significantly reverted the human neutrophil elastase-induced decrease in tracheal mucociliary transport velocity and human neutrophil elastase -induced increase in the contents of fucose and protein in the tracheal lavage, compared with the control group. Conclusion These results suggest that either needle puncture or electro-acupuncture stimulation to the effective acupoints significantly improves both airway mucociliary clearance and the airway surface liquid and that the improvements maybe ascribed to both the special function of the points and the substantial stimulation of electricity.

Test Rig for Evaluating Active Turbine Blade Tip Clearance Control Concepts

Science.gov (United States)

Lattime, Scott B.; Steinetz, Bruce M.; Robbie, Malcolm G.

2003-01-01

Improved blade tip sealing in the high pressure compressor and high pressure turbine can provide dramatic improvements in specific fuel consumption, time-on-wing, compressor stall margin and engine efficiency as well as increased payload and mission range capabilities of both military and commercial gas turbine engines. The preliminary design of a mechanically actuated active clearance control (ACC) system for turbine blade tip clearance management is presented along with the design of a bench top test rig in which the system is to be evaluated. The ACC system utilizes mechanically actuated seal carrier segments and clearance measurement feedback to provide fast and precise active clearance control throughout engine operation. The purpose of this active clearance control system is to improve upon current case cooling methods. These systems have relatively slow response and do not use clearance measurement, thereby forcing cold build clearances to set the minimum clearances at extreme operating conditions (e.g., takeoff, re-burst) and not allowing cruise clearances to be minimized due to the possibility of throttle transients (e.g., step change in altitude). The active turbine blade tip clearance control system design presented herein will be evaluated to ensure that proper response and positional accuracy is achievable under simulated high-pressure turbine conditions. The test rig will simulate proper seal carrier pressure and temperature loading as well as the magnitudes and rates of blade tip clearance changes of an actual gas turbine engine. The results of these evaluations will be presented in future works.

Population pharmacokinetics of pomalidomide in patients with relapsed or refractory multiple myeloma with various degrees of impaired renal function

Directory of Open Access Journals (Sweden)

Li Y

2017-11-01

Full Text Available Yan Li,1 Xiaomin Wang,2 Edward O’Mara,1 Meletios A Dimopoulos,3 Pieter Sonneveld,4 Katja C Weisel,5 Jeffrey Matous,6 David S Siegel,7 Jatin J Shah,8 Elisabeth Kueenburg,9 Lars Sternas,9 Chloe Cavanaugh,9 Mohamed Zaki,9 Maria Palmisano,1 Simon Zhou1 1Translational Development and Clinical Pharmacology, Celgene Corporation, Summit, NJ, USA; 2Non-Clinical Development and Drug Metabolism and Pharmacokinetics, Celgene Corporation, Summit, NJ, USA; 3Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece; 4Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands; 5Department of Hematology, University Hospital Tübingen, Tübingen, Germany; 6Department of Hematology/Oncology, Colorado Blood Cancer Institute, Denver, CO, USA; 7Myeloma Division, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA; 8Department of Lymphoma/Myeloma, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX, USA; 9Global Clinical R&D, Celgene Corporation, Summit, NJ, USA Abstract: Pomalidomide is an immunomodulatory drug for treatment of relapsed or refractory multiple myeloma (rrMM in patients who often have comorbid renal conditions. To assess the impact of renal impairment on pomalidomide exposure, a population pharmacokinetics (PPK model of pomalidomide in rrMM patients with various degrees of impaired renal function was developed. Intensive and sparse pomalidomide concentration data collected from two clinical studies in rrMM patients with normal renal function, moderately impaired renal function, severely impaired renal function not requiring dialysis, and with severely impaired renal function requiring dialysis were pooled over the dose range of 2 to 4 mg, to assess specifically the influence of the impaired renal function as a categorical variable and a continuous variable on pomalidomide clearance and plasma exposure. In addition, pomalidomide

The tear turnover and tear clearance tests - a review.

Science.gov (United States)

Garaszczuk, Izabela K; Montes Mico, Robert; Iskander, D Robert; Expósito, Alejandro Cerviño

2018-03-01

The aim is to provide a summary of methods available for the assessment of tear turnover and tear clearance rates. The review defines tear clearance and tear turnover and describes their implication for ocular surface health. Additionally, it describes main types of techniques for measuring tear turnover, including fluorescein tear clearance tests, techniques utilizing electromagnetic spectrum and tracer molecule and novel experimental techniques utilizing optical coherence tomography and fluorescein profilometry. Areas covered: Internet databases (PubMed, Science Direct, Google Scholar) and most frequently cited references were used as a principal resource of information on tear turnover rate and tear clearance rate, presenting methodologies and equipment, as well as their definition and implications for the anterior eye surface health and function. Keywords used for data-search were as follows: tear turnover, tear clearance, fluorescein clearance, scintigraphy, fluorophotometry, tear flow, drainage, tear meniscus dynamics, Krehbiel flow and lacrimal functional unit. Expert commentary: After decades, the topic of tear turnover assessment has been reintroduced. Recently, new techniques have been developed to propose less invasive, less time consuming and simpler methodologies for the assessment of tear dynamics that have the potential to be utilized in clinical practice.

Airway Clearance Techniques (ACTs)

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Full Text Available ... Community in Health Care Reform Milestones in Health Care Reform How Tax Reform Could Impact People With CF The ... Home Life With CF Treatments and Therapies Airway Clearance ...

Current Concepts of Hyperinflammation in Chronic Granulomatous Disease

NARCIS (Netherlands)

Rieber, Nikolaus; Hector, Andreas; Kuijpers, Taco; Roos, Dirk; Hartl, Dominik

2012-01-01

Chronic granulomatous disease (CGD) is the most common inherited disorder of phagocytic functions, caused by genetic defects in the leukocyte nicotinamide dinucleotide phosphate (NADPH) oxidase. Consequently, CGD phagocytes are impaired in destroying phagocytosed microorganisms, rendering the

Integrins and small GTPases as modulators of phagocytosis.

Science.gov (United States)

Sayedyahossein, Samar; Dagnino, Lina

2013-01-01

Phagocytosis is the mechanism whereby cells engulf large particles. This process has long been recognized as a critical component of the innate immune response, which constitutes the organism's defense against microorganisms. In addition, phagocytic internalization of apoptotic cells or cell fragments plays important roles in tissue homeostasis and remodeling. Phagocytosis requires target interactions with receptors on the plasma membrane of the phagocytic cell. Integrins have been identified as important mediators of particle clearance, in addition to their well-established roles in cell adhesion, migration and mechanotransduction. Indeed, these ubiquitously expressed proteins impart phagocytic capacity to epithelial, endothelial and mesenchymal cell types. The importance of integrins in particle internalization is emphasized by the ability of microbial and viral pathogens to exploit their signaling pathways to invade host cells, and by the wide variety of disorders that arise from abnormalities in integrin-dependent phagocytic uptake. Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of clearance on cartilage tribology in hip hemi-arthroplasty.

Science.gov (United States)

Lizhang, Jia; Taylor, Simon D; Jin, Zhongmin; Fisher, John; Williams, Sophie

2013-12-01

Hemi-arthroplasty of the hip (an artificial femoral head articulating against the natural acetabulum) is used to treat fractured necks of femur; however, there is evidence that articulation causes erosion of the cartilage, resulting in pain for the patient. Parameters that may influence this cartilage erosion include head material and roughness, clearance between the head and acetabulum and activity levels of the patient. This study has assessed the effect of clearance of hemi-arthroplasty articulations on the contact stress, friction and cartilage deformation in an in vitro tribological simulation of the hemi-arthroplasty joint that applied dynamic loads and motion. It has been demonstrated that peak contact stress increased from 5.6 to 10.6 MPa as radial clearance increased from small (1.8 mm). In all samples, friction factor increased with time and was significantly less with extra-large clearances compared to small (<0.6 mm), medium (0.6-1.2 mm) and large (1.2-1.8 mm) clearances. The cartilage deformation observed was significantly greater in acetabulum samples paired to give small or extra-large clearances compared to those with medium or large clearances.

CD70-deficiency impairs effector CD8 T cell generation and viral clearance but is dispensable for the recall response to LCMV

Science.gov (United States)

Munitic, Ivana; Kuka, Mirela; Allam, Atef; Scoville, Jonathan P.; Ashwell, Jonathan D.

2012-01-01

CD27 interactions with its ligand, CD70, are thought to be necessary for optimal primary and memory adaptive immune responses to a variety of pathogens. Thus far all studies addressing the function of the CD27-CD70 axis have been performed either in mice lacking CD27, overexpressing CD70, or in which these receptors were blocked or mimicked by antibodies or recombinant soluble CD70. Because these methods have in some cases led to divergent results, we generated CD70-deficient mice to directly assess its role in vivo. We find that lack of CD70-mediated stimulation during primary responses to LCMV lowered the magnitude of CD8 antigen-specific T cell response, resulting in impaired viral clearance, without affecting CD4 T cell responses. Unexpectedly, CD70-CD27 costimulation was not needed for memory CD8 T cell generation or the ability to mount a recall response to LCMV. Adoptive transfers of wild type (WT) memory T cells into CD70−/− or WT hosts also showed no need for CD70-mediated stimulation during the course of the recall response. Moreover, CD70-expression by CD8 T cells could not rescue endogenous CD70−/− cells from defective expansion, arguing against a role for CD70-mediated T:T help in this model. Therefore, CD70 appears to be an important factor in the initiation of a robust and effective primary response but dispensable for CD8 T cell memory responses. PMID:23269247

Modified Augmented Renal Clearance Score Predicts Rapid Piperacillin and Tazobactam Clearance in Critically Ill Surgery and Trauma Patients

Science.gov (United States)

2014-04-24

collision; VAP , ventilator-associated pneumonia. TABLE 2. PK Parameter Estimates for Free Piperacillin and Tazobactam in Patients Stratified by ARC Score...SOFA score are typically generated during routine care of the most severely ill patients . Positive screening test results (high ARC scores) can be...Modified Augmented Renal Clearance score predicts rapid piperacillin and tazobactam clearance in critically ill surgery and trauma patients Kevin S

Oxidative stress can alter the antigenicity of immunodominant peptides

DEFF Research Database (Denmark)

Weiskopf, Daniela; Schwanninger, Angelika; Weinberger, Birgit

2010-01-01

APCs operate frequently under oxidative stress induced by aging, tissue damage, pathogens, or inflammatory responses. Phagocytic cells produce peroxides and free-radical species that facilitate pathogen clearance and can in the case of APCs, also lead to oxidative modifications of antigenic prote...

Airway Clearance Techniques (ACTs)

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Full Text Available ... in CF Clinical Care Guidelines Cystic Fibrosis-Related Diabetes Clinical Care Guidelines Liver Disease Clinical Care Guidelines Respiratory Care Guidelines CF Airway Clearance Therapies Clinical Care Guidelines Chronic Medications to Maintain Lung ...

2015 Annual Report on Security Clearance Determinations

Science.gov (United States)

2016-06-28

only have delegated investigative authority over their civilian employee population and therefore, can only report the overall timeliness for that...completed or pending security clearance determinations for government employees and contractors during the preceding fiscal year that have taken longer...Clearance Determinations to Congress. The IAA directs this report to include the number of United States Government (USG) employees who held a

Cystic fibrosis: a mucosal immunodeficiency syndrome

Science.gov (United States)

Cohen, Taylor Sitarik; Prince, Alice

2013-01-01

Cystic fibrosis transmembrane conductance regulator (CFTR) functions as a channel that regulates the transport of ions and the movement of water across the epithelial barrier. Mutations in CFTR, which form the basis for the clinical manifestations of cystic fibrosis, affect the epithelial innate immune function in the lung, resulting in exaggerated and ineffective airway inflammation that fails to eradicate pulmonary pathogens. Compounding the effects of excessive neutrophil recruitment, the mutant CFTR channel does not transport antioxidants to counteract neutrophil-associated oxidative stress. Whereas mutant CFTR expression in leukocytes outside of the lung does not markedly impair their function, the expected regulation of inflammation in the airways is clearly deficient in cystic fibrosis. The resulting bacterial infections, which are caused by organisms that have substantial genetic and metabolic flexibility, can resist multiple classes of antibiotics and evade phagocytic clearance. The development of animal models that approximate the human pulmonary phenotypes—airway inflammation and spontaneous infection—may provide the much-needed tools to establish how CFTR regulates mucosal immunity and to test directly the effect of pharmacologic potentiation and correction of mutant CFTR function on bacterial clearance. PMID:22481418

Dynamic modelling and experimental study of cantilever beam with clearance

International Nuclear Information System (INIS)

Li, B; Jin, W; Han, L; He, Z

2012-01-01

Clearances occur in almost all mechanical systems, typically such as the clearance between slide plate of gun barrel and guide. Therefore, to study the clearances of mechanisms can be very important to increase the working performance and lifetime of mechanisms. In this paper, rigid dynamic modelling of cantilever with clearance was done according to the subject investigated. In the rigid dynamic modelling, clearance is equivalent to the spring-dashpot model, the impact of beam and boundary face was also taken into consideration. In ADAMS software, the dynamic simulation was carried out according to the model above. The software simulated the movement of cantilever with clearance under external excitation. Research found: When the clearance is larger, the force of impact will become larger. In order to study how the stiffness of the cantilever's supporting part influences natural frequency of the system, A Euler beam which is restricted by a draught spring and a torsion spring at its end was raised. Through numerical calculation, the relationship between natural frequency and stiffness was found. When the value of the stiffness is close to the limit value, the corresponding boundary condition is illustrated. An ADAMS experiment was carried out to check the theory and the simulation.

Dynamic modelling and experimental study of cantilever beam with clearance

Science.gov (United States)

Li, B.; Jin, W.; Han, L.; He, Z.

2012-05-01

Clearances occur in almost all mechanical systems, typically such as the clearance between slide plate of gun barrel and guide. Therefore, to study the clearances of mechanisms can be very important to increase the working performance and lifetime of mechanisms. In this paper, rigid dynamic modelling of cantilever with clearance was done according to the subject investigated. In the rigid dynamic modelling, clearance is equivalent to the spring-dashpot model, the impact of beam and boundary face was also taken into consideration. In ADAMS software, the dynamic simulation was carried out according to the model above. The software simulated the movement of cantilever with clearance under external excitation. Research found: When the clearance is larger, the force of impact will become larger. In order to study how the stiffness of the cantilever's supporting part influences natural frequency of the system, A Euler beam which is restricted by a draught spring and a torsion spring at its end was raised. Through numerical calculation, the relationship between natural frequency and stiffness was found. When the value of the stiffness is close to the limit value, the corresponding boundary condition is illustrated. An ADAMS experiment was carried out to check the theory and the simulation.

Airway Clearance Techniques (ACTs)

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Full Text Available ... many challenges, including medical, social, and financial. By learning more about how you can manage your disease every day, you can ultimately help find a ... Cycle of Breathing Technique Airway Clearance Techniques Autogenic ...

Refrigeration system with clearance seals

International Nuclear Information System (INIS)

Holland, N. J.

1985-01-01

In a refrigeration system such as a split Stirling system, fluid seals associated with the reciprocating displacer are virtually dragless clearance seals. Movement of the displacer relative to the pressure variations in the working volume of gas is retarded by a discrete braking element. Because it is not necessary that the brake providing any sealing action, the brake can be designed for greater durability and less dependence on ambient and operating temperatures. Similarly, the clearance seal can be formed of elements having low thermal expansion such that the seal is not temperature dependent. In the primary embodiments the braking element is a split friction brake

Chaos vibration of pinion and rack steering trapezoidal mechanism containing two clearances

Science.gov (United States)

Wei, Daogao; Wang, Yu; Jiang, Tong; Zheng, Sifa; Zhao, Wenjing; Pan, Zhijie

2017-08-01

The multi-clearances of breaking type steering trapezoidal mechanism joints influences vehicle steering stability. Hence, to ascertain the influence of clearance value on steering stability, this paper takes the steering mechanism of a certain vehicle type as a prototype that can be simplified into a planar six-bar linkage, then establishes the system dynamic differential equations after considering the two clearances of tie rods and the steering knuckle arms. The influence of the clearance parameters on the movement stability of the steering mechanism is studied using a numerical computation method. Results show that when the two clearances are equal, the planar movement of the tie rods changes from period-doubling to chaos as the clearances increase. When the two clearances are 0.25 mm and 1.5 mm respectively, the planar movements of the two side tie rods come into chaos, causing the steering stability to deteriorate. Moreover, with the increase of clearances, turning moment fluctuates more intensively and the peak value increases.

Onset of apoprotein E secretion during differentiation of mouse bone marrow-derived mononuclear phagocytes

International Nuclear Information System (INIS)

Werb, Z.; Chin, J.R.

1983-01-01

A number of macrophage functions were sequentially expressed when the bone marrow precursors of mononuclear phagocytes differentiated in culture in the presence of a specific growth factor, colony-stimulating factor-1. The authors defined the expression of apoprotein E (ApoE), a major secreted protein of resident peritoneal macrophages, during maturation of adherent bone marrow-derived mononuclear phagocytes into macrophages. By 5 d the bone marrow macrophages were active secretory cells, but few cells contained intracellular immunoreactive ApoE, and little, if any, ApoE was secreted. ApoE secretion was initiated at 9 d, and this correlated with an increase in the percentage of macrophages containing intracellular ApoE. The onset of ApoE secretion was selective, and little change occurred in the other major secreted proteins detected by [ 35 S]methionine incorporation. In parallel, the high rate of plasminogen activator secretion, which peaked at 7 d, decreased markedly. ApoE secretion was not associated with altered expression of the macrophage surface antigen, la, or with secretion of fibronectin. Virtually all cells in independent colonies of bone marrow-derived macrophages eventually expressed ApoE. The proliferating monocyte/macrophage-like cell lines P388D1, J774.2, WHEI-3, RAW 264.1, and MGI.D + secreted little or no ApoE. These data establish that ApoE secretion is developmentally regulated

Airway Clearance Techniques (ACTs)

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Full Text Available ... decisions about your health care. CF Genetics: The Basics CF Mutations Video Series Find Out More About ... of Breathing Technique Airway Clearance Techniques Autogenic Drainage Basics of Lung Care Chest Physical Therapy Coughing and ...

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Full Text Available ... Clinician Career Development Awards Clinician Training Awards Mutation Analysis Program Network News Network News: March 2018 Network ... for airway clearance. Facebook Twitter Email More Related Content Medications Autogenic Drainage Positive Expiratory Pressure High-Frequency ...

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Full Text Available ... today. ANNUAL FUND Become a Corporate Supporter Cause Marketing Make a Charitable Gift Our Corporate Supporters Workplace ... for airway clearance. Facebook Twitter Email More Related Content Medications Autogenic Drainage Positive Expiratory Pressure High-Frequency ...

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Full Text Available ... specialized CF care and a range of treatment options. Airway Clearance Active Cycle of Breathing Technique Airway ... on their own. Share Facebook Twitter Email More options Print Share Facebook Twitter Email Print Permalink All ...

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Full Text Available ... Clinician Career Development Awards Clinician Training Awards Mutation Analysis Program Network News Network News: June 2018 Network ... for airway clearance. Facebook Twitter Email More Related Content Medications Autogenic Drainage Positive Expiratory Pressure High-Frequency ...

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Full Text Available ... a Family Parenting as an Adult With CF Treatments and Therapies People with cystic fibrosis are living ... to specialized CF care and a range of treatment options. Airway Clearance Active Cycle of Breathing Technique ...

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Full Text Available ... Physical Therapy Coughing and Huffing High-Frequency Chest Wall Oscillation Positive Expiratory Pressure Clinical Trials Clinical Trials ... clapping) or vibration to loosen mucus from airway walls. See how different airway clearance techniques work to ...

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Full Text Available ... in part to specialized CF care and a range of treatment options. Airway Clearance Active Cycle of ... a cure for CF and supports a broad range of research initiatives to tackle the disease from ...

Airway Clearance Techniques (ACTs)

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Full Text Available ... ACTs involve coughing or huffing . Many of them use percussion (clapping) or vibration to loosen mucus from airway walls. See how different airway clearance techniques work to help you clear the thick, sticky mucus ...

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Full Text Available ... Clinical Care Guidelines Liver Disease Clinical Care Guidelines Respiratory Care Guidelines CF Airway Clearance Therapies Clinical Care ... attack bacteria. Choose What's Best for You Your respiratory therapist or another member of your CF care ...

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Full Text Available ... Cycle of Breathing Technique Airway Clearance Techniques Autogenic Drainage Basics of Lung Care Chest Physical Therapy Coughing ... Facebook Twitter Email More Related Content Medications Autogenic Drainage Positive Expiratory Pressure High-Frequency Chest Wall Oscillation ( ...

Impaired transport of thyroid hormones into livers of obese (ob/ob) mice

International Nuclear Information System (INIS)

Hillgartner, F.B.; Romsos, D.R.

1988-01-01

Obese (ob/ob) mice exhibit impaired hepatic thyroid hormone action that is mediated, at least in part, by a reduced nuclear 3,5,3'-triiodothyronine (T 3 ) receptor occupancy. The possibility that lowered occupancy in obese mice may be caused by decreased transport of T 3 across the hepatic plasma membrane was examined by measuring the unidirectional influx of [ 125 I]T 3 into livers of 8- to 10-wk-old obese and lean mice using a tissue-sampling portal vein-injection technique. Influx of [ 125 I]thyroxine (T 4 ), a substrate for T 4 5'-deiodinase, was also measured. Unidirectional clearance of T 3 and T 4 was 64 and 80% lower, respectively, in obese mice than in lean mice. Hepatic T 3 and T 4 uptake was nonsaturable in both lean and obese mice, suggesting that transport occurs by lipid-mediated free diffusion. Clearance of another lipid-soluble hormone, hydrocortisone, was also lower in obese mice than in lean mice. Decreased membrane permeability to the above hormones in obese mice may result from reported changes in membrane lipid composition. In conclusion, decreased hepatic thyroid hormone uptake may contribute to impaired thyroid hormone action and T 3 production in livers of obese mice

Measurement with nasal scintigraphy of nasal mucociliary clearance in normal man

International Nuclear Information System (INIS)

Murai, Sumiko

1989-01-01

Nasal mucociliary function was evaluated by nasal scintigraphy in normal subjects. A microdrop of HSA or saline labelled with 99m Tc was dripped into the middle part of each middle meatus in the nasal cavity and its clearance was observed by scinticamera. The accumulated concentration of RI was determined every 30 seconds for 10 minutes. The changes of accumulated concentration were studied, and a curve of decreasing RI-counts was obtained, with the 'clearance rate' defined as 100% for the count at the initial 30 seconds and 'half time' as the time when radioactivity was reduced to one half the initial count. Nasal resistance was measured by rhinomanometry with the oscillation method. In nonsmokers, 10μl of saline was cleared (78.0±10.4%) significantly faster than 10μl of HSA (59.9±24.6%), and there was no significant difference in the clearance between 10μl and 5μl of HSA (55.9±27.7%). In smakers, the mucociliary clearance of 10μl of HSA and saline was significantly lower than in nonsmokers. The clearance of 10μl of HSA reflects a pathological state much better than that of 5μl. In nonsmokers, there is a significant negative correlation between nasal resistance and clearance rate, suggesting that the more patent the nose, the faster the mucociliary clearance. When both nostrils were closed, the clearance rate was significantly depressed. When one nostril was closed, there was no significant effect on clearance. Nasal resistance was decreased by exercise with a bicycle ergometer. Nasal mucociliary clearance was slightly decreased after exercise but not significantly so. (J.P.N.)

78 FR 77027 - Overhead Clearance (Air-Draft) Accidents

Science.gov (United States)

2013-12-20

... No. USCG-2013-0466] Overhead Clearance (Air-Draft) Accidents AGENCY: Coast Guard, DHS. ACTION... clearance (air-draft) accidents. In its petition, which calls for vessel masters to be provided with... accidents that it says were avoidable and that resulted in damage to or destruction of waterway...

Elimination of self-reactive T cells in the thymus: a timeline for negative selection.

Directory of Open Access Journals (Sweden)

Ivan Lilyanov Dzhagalov

Full Text Available The elimination of autoreactive T cells occurs via thymocyte apoptosis and removal by thymic phagocytes, but the sequence of events in vivo, and the relationship between thymocyte death and phagocytic clearance, are unknown. Here we address these questions by following a synchronized cohort of thymocytes undergoing negative selection within a three-dimensional thymic tissue environment, from the initial encounter with a negative selecting ligand to thymocyte death and clearance. Encounter with cognate peptide-MHC complexes results in rapid calcium flux and migratory arrest in auto-reactive thymocytes over a broad range of peptide concentrations, followed by a lag period in which gene expression changes occurred, but there was little sign of thymocyte death. Caspase 3 activation and thymocyte loss were first detectable at 2 and 3 hours, respectively, and entry of individual thymocytes into the death program occurred asynchronously over the next 10 hours. Two-photon time-lapse imaging revealed that thymocyte death and phagocytosis occurred simultaneously, often with thymocytes engulfed prior to changes in chromatin and membrane permeability. Our data provide a timeline for negative selection and reveal close coupling between cell death and clearance in the thymus.

The role of clearance in Germany - release of materials, buildings and sites

International Nuclear Information System (INIS)

Thierfeldt, S.

2005-01-01

Clearance in Germany is far advanced. A complex regulatory framework exists in the Radiation Protection Ordinance (RPO/Strahlenschutzverordnung, StrlSchV) since 2001 which has replaced previous recommendations on clearance issued by the German Radiation Protection Commission (Strahlenschutzkommission, SSK). A number of options exist both for unconditional clearance (e.g. of all kinds of materials with no restrictions on the destination or future use) and for clearance for a specific purpose (e.g. recycling of metal scrap). For each clearance option there is a set of nuclide specific clearance levels which have been derived on the basis of the 10 Sv/a individual dose criterion using complex radiological models which are tailored to the respective material cycles (metal scrap, buildings, building rubble, waste for disposal, sites). The clearance levels have been thoroughly reviewed by the SSK. An extensive comparison to sets of clearance levels used in other countries or issued as guidance by international bodies revealed that the correspondence between values is between good and acceptable taking into account country-specific approaches and special assumptions which would not necessarily pertain to German situations. Clearance is a major factor in the material management, especially of nuclear installations undergoing decommissioning. The variety of clearance options leaves the operator of a nuclear installation sufficient flexibility for optimisation of the material management. Clearance is of particular importance in a country like Germany where the estimated costs for a future repository are very high and the interim storage facilities for radioactive material are limited and costly. While the licensee is responsible for his material management, the issuance of a clearance permit is done by the regulatory body upon application. The regulators may choose to use the clearance levels and regulations as stipulated by the RPO, or to impose site-specific regulations on

Whole body and regional clearances of noradrenaline and adrenaline in man

DEFF Research Database (Denmark)

Christensen, N J; Galbo, H; Gjerris, A

1984-01-01

the clearance values based on arterial and venous sampling averaged 1.4 and 2.5 l/min, respectively (p less than 0.02). The difference in clearance values was due to peripheral uptake of NA averaging 45%. The plasma appearance rate on NA averaged 2.4 nmol/min before surgery and it increased to 9.5 nmol...... we found no correlation between clearance values based on venous and arterial sampling. In other experiments we measured the influence of physical exercise in young healthy subjects on the clearance rate of plasma adrenaline (A). The clearance of A, which at rest averaged 1.9 l/min tended to increase...

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Full Text Available ... Make a Charitable Gift Our Corporate Supporters Workplace Engagement DONATE YOUR PROPERTY eCards for a Cure About ... airway walls. See how different airway clearance techniques work to help you clear the thick, sticky mucus ...

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Full Text Available ... people with cystic fibrosis so that they make smart decisions about CF-related research, treatment, and access ... Facebook Twitter YouTube Instagram Email DONATE Breadcrumb Navigation Home Life With CF Treatments and Therapies Airway Clearance ...

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Full Text Available ... 3-D Structure Consortium CFTR Folding Consortium Epithelial Stem Cell Consortium Mucociliary Clearance Consortium SUCCESS WITH THERAPIES RESEARCH ... ACTs involve coughing or huffing . Many of them use percussion (clapping) or vibration to loosen mucus from ...

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Online monitoring of dynamic tip clearance of turbine blades in high temperature environments

Science.gov (United States)

Han, Yu; Zhong, Chong; Zhu, Xiaoliang; Zhe, Jiang

2018-04-01

Minimized tip clearance reduces the gas leakage over turbine blade tips and improves the thrust and efficiency of turbomachinery. An accurate tip clearance sensor, measuring the dynamic clearances between blade tips and the turbine case, is a critical component for tip clearance control. This paper presents a robust inductive tip clearance sensor capable of monitoring dynamic tip clearances of turbine machines in high-temperature environments and at high rotational speeds. The sensor can also self-sense the temperature at a blade tip in situ such that temperature effect on tip clearance measurement can be estimated and compensated. To evaluate the sensor’s performance, the sensor was tested for measuring the tip clearances of turbine blades under various working temperatures ranging from 700 K to 1300 K and at turbine rotational speeds ranging from 3000 to 10 000 rpm. The blade tip clearance was varied from 50 to 2000 µm. The experiment results proved that the sensor can accurately measure the blade tip clearances with a temporal resolution of 10 µm. The capability of accurately measuring the tip clearances at high temperatures (~1300 K) and high turbine rotation speeds (~30 000 rpm), along with its compact size, makes it promising for online monitoring and active control of blade tip clearances of high-temperature turbomachinery.

Creatinine clearance during cimetidine administration for measurement of glomerular filtration rate

NARCIS (Netherlands)

van Acker, B. A.; Koomen, G. C.; Koopman, M. G.; de Waart, D. R.; Arisz, L.

1992-01-01

Creatinine clearance inaccurately estimates true glomerular filtration rate (GFR) because of tubular secretion of creatinine. We studied the ability of oral cimetidine, a blocker of tubular creatinine secretion, to improve the accuracy of measuring creatinine clearance. Clearances of inulin and

Chronic Granulomatous Disease: The European Experience

NARCIS (Netherlands)

van den Berg, J. Merlijn; van Koppen, Elsbeth; Ahlin, Anders; Belohradsky, Bernd H.; Bernatowska, Ewa; Corbeel, Lucien; Español, Teresa; Fischer, Alain; Kurenko-Deptuch, Magdalena; Mouy, Richard; Petropoulou, Theoni; Roesler, Joachim; Seger, Reinhard; Stasia, Marie-José; Valerius, Niels H.; Weening, Ron S.; Wolach, Baruch; Roos, Dirk; Kuijpers, Taco W.

2009-01-01

CGD is an immunodeficiency caused by deletions or mutations in genes that encode subunits of the leukocyte NADPH oxidase complex. Normally, assembly of the NADPH oxidase complex in phagosomes of certain phagocytic cells leads to a "respiratory burst'', essential for the clearance of phagocytosed

Chronic granulomatous disease: the European experience

NARCIS (Netherlands)

van den Berg, J.M.; van Koppen, E.; Åhlin, A.; Belohradsky, B.H.; Bernatowska, E.; Corbeel, L.; Español, T.; Fischer, A.; Kurenko-Deptuch, M.; Mouy, R.; Petropoulou, T.; Roesler, J.; Seger, R.; Stasia, M.J.; Valerius, N.H.; Weening, R.S.; Wolach, B.; Roos, D.; Kuijpers, T.W.

2009-01-01

CGD is an immunodeficiency caused by deletions or mutations in genes that encode subunits of the leukocyte NADPH oxidase complex. Normally, assembly of the NADPH oxidase complex in phagosomes of certain phagocytic cells leads to a "respiratory burst'', essential for the clearance of phagocytosed

Depressed reticuloendothelial clearance of platelets in rats after trauma.

Science.gov (United States)

Kaplan, J E; Moon, D G; Minnear, F L; Saba, T M

1984-02-01

Platelet microembolization may contribute to microcirculatory and organ damage following trauma and shock. It is hypothesized that posttraumatic reticuloendothelial depression predisposes to such microembolization by failure to clear altered platelets from the circulation. The present study evaluated the short-term (1 h) clearance and organ localization of radiolabeled homologous damaged platelets in normal rats and in rats following sublethal Noble-Collip drum trauma. Platelets were collected in citrated platelet-rich plasma from normal rats and labeled with 51Cr in citrated saline. Platelets were altered by repeated centrifugation in protein-free medium. These platelets differed functionally and morphologically from normal platelets. Disappearance of iv injected damaged platelets conformed to a two-compartment exponential clearance. Velocity of clearance in the rapid compartment correlated with hepatic platelet localization, whereas velocity of clearance in the second compartment correlated with splenic platelet localization. Clearance rate of the rapid compartment was depressed at 1 h after trauma and elevated at 24 h. These changes were associated with a decrease in hepatic platelet localization at 1 h and an increase above normal at 24 h. Splenic platelet localization was decreased by 3 h following trauma. Pulmonary platelet localization was increased at all times following trauma. It is concluded that the posttrauma state is associated with a defect in the reticuloendothelial system clearance of altered platelets, which may augment embolization of platelets in the lung.

Intercalibration of mussel Mytilus edulis clearance rate measurements

NARCIS (Netherlands)

Kjerulf Petersen, J.; Bougrier, S.; Smaal, A.C.; Garen, P.; Robert, S.; Larsen, J.E.N.; Brummelhuis, E.B.M.

2004-01-01

Clearance rate (CR) was measured in blue mussels Mytilus edulis L. from Aiguillon Bay and the Oosterschelde using 3 different methods: the flow-through method, the bio-deposition method and the indirect or clearance method. CR differed significantly as a function of the method used and of the origin

Airway Clearance Techniques (ACTs)

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DOD PERSONNEL CLEARANCES: Additional OMB Actions Are Needed to Improve the Security Clearance Process

National Research Council Canada - National Science Library

2006-01-01

Our independent analysis of timeliness data showed that industry personnel contracted to work for the federal government waited more than one year on average to receive top secret clearances, longer...

Expanding the tools for identifying mononuclear phagocyte subsets in swine: Reagents to porcine CD11c and XCR1

Czech Academy of Sciences Publication Activity Database

Deloizy, Ch.; Bouguyon, E.; Fossum, E.; Šebo, Peter; Osička, Radim; Bole, A.; Pierres, M.; Biacchesi, S.; Dalod, M.; Bogen, B.; Bertho, N.; Schwartz-Cornil, I.

2016-01-01

Roč. 65, December 2016 (2016), s. 31-40 ISSN 0145-305X R&D Projects: GA ČR GA15-09157S Institutional support: RVO:61388971 Keywords : Mononuclear phagocytes * Dendritic cells * Pig model Subject RIV: EE - Microbiology, Virology Impact factor: 3.218, year: 2016

Effects of heart rate on myocardial thallium-201 uptake and clearance

International Nuclear Information System (INIS)

Nordrehaug, J.E.; Danielsen, R.; Vik-Mo, H.

1989-01-01

The effects of heart rate on the myocardial uptake and clearance of 201 Tl were studied prospectively in seven healthy men, mean age 43 +/- 7 (s.d.) yr. Initial and delayed (3 hr) thallium images were obtained in three views after three bicycle exercise tests: to maximal, 80% and 60% of predicted maximal heart rate. The mean of three views initial myocardial 201 Tl uptake was higher at maximal than at both 80% and 60% of predicted maximal heart rate, being 81% (p less than 0.01) and 60% (p less than 0.01) of maximal activity, respectively. The myocardial activity in the delayed images was identical. There was a linear relationship between heart rate and the initial myocardial activity, r = 0.86 (p less than 0.001). The mean (range) 201 Tl clearance was 58% (51-65), 47% (34-56), and 34% (22-49) (all differences p less than 0.01), respectively. Concordance among the three individual views in estimating clearance was best for the highest exercise level. There was a linear relationship between heart rate and clearance, r = 0.80 (p less than 0.001). Clearance was altered by only 1.67 x 10%/heart bpm (0.024 hr/heart beat). Clearance in the liver, spleen and lungs increased at submaximal exercise levels. Thus, a linear relationship between heart rate and clearance is the result of changes in the initial exercise myocardial 201 Tl activity. Submaximal exercise may reduce reproducibility of clearance estimation, and the change of myocardial clearance with heart rate seems less than previously suggested

Factors affecting lower calyceal stone clearance after Extracorporeal ...

African Journals Online (AJOL)

shanker

have been identified [1,3]. These include stone characteristics, the type of lithotripter used, LPC anatomy and body habitus. For iso- lated LPC stones, the pelvicalyceal angle, infundibulum length and width are considered important determinants for stone clearance. The impact of body habitus on stone clearance has so far ...

Delayed clearance of triglyceride‐rich lipoproteins in young, healthy obese subjects†

Science.gov (United States)

Goll, R.; Lekahl, S.; Moen, O. S.; Florholmen, J.

2015-01-01

Summary Obesity is associated with the metabolic syndrome. The aims were, first, to study the postprandial triglyceride clearance in young, healthy obese subjects and, second, to investigate if fasting triglycerides can predict delayed postprandial triglyceride clearance. Eighteen apparently healthy, obese subjects with no clinical signs of metabolic disturbances participated. Controls were age‐ and sex‐matched, healthy, normal weight subjects. Subclinical markers of metabolic disturbances were assessed by measuring postprandial triglycerides in serum and in chylomicrons by oral fat tolerance test. Postprandial triglyceride clearance for 8 h was assessed indirectly as removal of the lipid from serum during the oral fat tolerance test. Insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA‐IR). Twelve (66%) of the apparently healthy obese individuals had insulin resistance measured by HOMA‐IR. There was a delayed clearance of serum triglycerides and chylomicron triglycerides at 6 h when compared with the control group, while, at 8 h, the differences were only detected for the chylomicron triglyceride clearance. Triglyceride response was significantly greater in the obese subjects. Fasting triglycerides in upper normal level predicted a delayed postprandial triglyceride clearance and insulin resistance. In young, apparently healthy obese subjects early metabolic disturbances including insulin resistance and delayed postprandial triglyceride clearance can be detected. Fasting serum triglyceride in upper normal level predicted delayed postprandial triglyceride clearance and insulin resistance. PMID:26469529

Delayed clearance of triglyceride-rich lipoproteins in young, healthy obese subjects.

Science.gov (United States)

Larsen, M A; Goll, R; Lekahl, S; Moen, O S; Florholmen, J

2015-12-01

Obesity is associated with the metabolic syndrome. The aims were, first, to study the postprandial triglyceride clearance in young, healthy obese subjects and, second, to investigate if fasting triglycerides can predict delayed postprandial triglyceride clearance. Eighteen apparently healthy, obese subjects with no clinical signs of metabolic disturbances participated. Controls were age- and sex-matched, healthy, normal weight subjects. Subclinical markers of metabolic disturbances were assessed by measuring postprandial triglycerides in serum and in chylomicrons by oral fat tolerance test. Postprandial triglyceride clearance for 8 h was assessed indirectly as removal of the lipid from serum during the oral fat tolerance test. Insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA-IR). Twelve (66%) of the apparently healthy obese individuals had insulin resistance measured by HOMA-IR. There was a delayed clearance of serum triglycerides and chylomicron triglycerides at 6 h when compared with the control group, while, at 8 h, the differences were only detected for the chylomicron triglyceride clearance. Triglyceride response was significantly greater in the obese subjects. Fasting triglycerides in upper normal level predicted a delayed postprandial triglyceride clearance and insulin resistance. In young, apparently healthy obese subjects early metabolic disturbances including insulin resistance and delayed postprandial triglyceride clearance can be detected. Fasting serum triglyceride in upper normal level predicted delayed postprandial triglyceride clearance and insulin resistance. © 2015 World Obesity.

Dynamic characteristics analysis of deployable space structures considering joint clearance

Science.gov (United States)

Li, Tuanjie; Guo, Jian; Cao, Yuyan

2011-04-01

The clearance in joints influences the dynamic stability and the performance of deployable space structures (DSS). A virtual experimental modal analysis (VEMA) method is proposed to deal with the effects of joint clearance and link flexibility on the dynamic characteristics of the DSS in this paper. The focus is on the finite element modeling of the clearance joint, VEMA and the modal parameters identification of the DSS. The finite element models (FEM) of the clearance joint and the deployable structure are established in ANSYS. The transient dynamic analysis is conducted to provide the time history data of excitation and response for the VEMA. The fast Fourier transform (FFT) technique is used to transform the data from time domain to frequency domain. The frequency response function is calculated to identify the modal parameters of the deployable structure. Experimental verification is provided to indicate the VEMA method is both a cost and time efficient approach to obtain the dynamic characteristics of the DSS. Finally, we analyze the effects of clearance size and gravity on the dynamic characteristics of the DSS. The analysis results indicate that the joint clearance and gravity strongly influence the dynamic characteristics of the DSS.

Pharmacokinetics and Safety of a Single Oral Dose of Mirogabalin in Japanese Subjects With Varying Degrees of Renal Impairment.

Science.gov (United States)

Kato, Manabu; Tajima, Naoyuki; Shimizu, Takako; Sugihara, Masahiro; Furihata, Kenichi; Harada, Kazuhiro; Ishizuka, Hitoshi

2018-01-01

Mirogabalin (DS-5565) is a novel preferentially selective α 2 δ-1 ligand being developed for the treatment of diabetic peripheral neuropathic pain and postherpetic neuralgia. The current multicenter open-label study determined the effect of varying degrees of renal impairment on the pharmacokinetics and safety of a single dose of mirogabalin 5 mg in Japanese subjects. A total of 30 subjects (6 subjects per renal function category [normal, mild, moderate, or severe impairment; and end-stage renal disease (ESRD)]) were enrolled and completed the study. The AUC last increased with severity of renal impairment; the geometric least-squares mean ratios of AUC last compared with subjects with normal renal function were 1.3, 1.9, 3.6, and 5.3 for patients with mild, moderate, and severe impairment and ESRD, respectively. In accordance with this AUC last increase, apparent total body clearance (CL/F), renal clearance (CLr), and the cumulative percentage of mirogabalin dose excreted into urine all decreased with severity of renal impairment. There were no deaths and no severe treatment-related adverse events (TEAEs), serious TEAEs, or TEAEs resulting in study discontinuation. Mirogabalin was well tolerated in Japanese subjects with normal renal function and those with mild to severe renal impairment. It was also tolerated in subjects with ESRD but with a higher incidence of TEAEs. The most frequently reported TEAEs were dizziness (ESRD, n = 3), somnolence (ESRD, n = 2), and vomiting (ESRD, n = 2). Based on these data, a mirogabalin dose adjustment will be considered in Japanese subjects with moderate to severe renal impairment and those with ESRD. © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

32 CFR 644.522 - Clearance of military scrap.

Science.gov (United States)

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Clearance of military scrap. 644.522 Section 644... Excess Land and Improvements § 644.522 Clearance of military scrap. Military scrap can contain or be... destruction, by using command, of all military scrap and scrap metal from lands suitable for cultivation or...

Applicability of Clearance Automatic Laser Inspection System to Clearance Measurement of Concrete Segments

International Nuclear Information System (INIS)

Sasaki, M.; Ogino, H.; Hattori, T.

2009-01-01

In the decommissioning of a nuclear power plant, large amounts of metal scrap and concrete segments require disposal when dismantling the nuclear reactor and surrounding facilities. When their activity level is negligible or sufficiently small, they can be regarded as general industrial waste. To distinguish between radioactive and nonradioactive materials, the clearance level for each radionuclide has been determined in units of activity concentration. These clearance levels are indicated in the International Atomic Energy Agency (IAEA) Safety Standards Series No. RS-G-1.7. The Japanese regulatory authority decided in 2005 to adopt the values given in RS-G-1.7 as clearance levels in legislation. Recently, a Clearance Automatic Laser Inspection System (CLALIS) has been developed utilizing gamma-ray measurement, automatic laser shape measurement and Monte Carlo calculation. CLALIS comprises four laser scanners and eight large plastic scintillation detectors surrounded by a 5-cm-thick lead shield. Using three-dimensional (3D) laser scanning, a measurement target, which is placed on the measuring tray, is represented as a dot image. The dot image is converted into voxels after noise removal, and is written in MCNP (A General Monte Carlo N-Particle Transport Code System) input files. When the gamma-ray measurement is carried out, the MCNP calculations are also carried out to obtain the calibration factor and background (BG) correction factors. For the clearance measurement of concrete segments, the effect of gamma-rays from natural radionuclides in the measurement target, such as K-40 and the radioactive decay products of Th-232 and U-238, should be taken into account to ensure adequate waste management. Since NE102A plastic scintillation detectors are used for gamma-ray measurement in CLALIS, it is impossible to distinguish between the count rates of natural radionuclides and contaminants on the basis of gamma-ray energy information. To overcome this problem, the

Airway Clearance Techniques (ACTs)

Medline Plus

Full Text Available ... Offer their tips for fitting ACTs into daily life Airway Clearance Techniques | Webcast To learn more about how you can help your infant or child manage their lung health, watch parents of children with CF and a respiratory therapist ...

Photochemical Targeting Of Phagocytic Trabecular Meshwork Cells Using Chlorin E6 Coupled Microspheres

Science.gov (United States)

Latina, M. A.; Kobsa, P. H.; Rakestraw, S. L.; Crean, E. A.; Hasan, T.; Yarmush, M. L.

1989-03-01

We have investigated a novel and efficient delivery system utilizing photosensitizer-coupled-latex microspheres to photochemically target and kill phagocytic trabecular meshwork (TM) cells. TM cells are the most actively phagocytic cells within the anterior chamber of the eye and are located within an optically accessible discrete band. This delivery system, along with the property of cell photocytosis, will achieve double selectivity by combining preferential localization of the photosensitizer to the target cells with spatial localization of illumination on the target cells. All experiments were performed with preconfluent bovine TM cells, 3rd to 4th passage, plated in 15 mm wells. Chlorin e6 monoethylene diamine monoamide was conjugated to the surface of 1.0 Am MX Duke Scientific fluorescent latex microspheres. Spectroscopic analysis revealed an average of 1.3 x 10 -17 moles of chlorin e6 per microsphere. TM cells were incubated for 18 hours with 5 x 10 7 microspheres/ml in MEM with 10% FCS, washed with MEM, and irradiated through fresh media using an argon-pumped dye laser emitting .2 W at 660 nm. A dose-survival study indicated that energy doses of 10 J/cm2 or greater resulted in greater than 95% cell death as determined by ethidium bromide exclusion. Cell death could be demonstrated as early as 4 hours post-irradiation. TM cells incubated with a solution of chlorin e6 at a concentration equal to that conjugated to the microspheres showed no cell death. Unirradiated controls also showed no cell death.

[EFFICIENCY OF COMBINATION OF ROFLUMILAST AND QUERCETIN FOR CORRECTION OXYGEN- INDEPENDENT MECHANISMS AND PHAGOCYTIC ACTIVITY OF MACROPHAGE CELLS OF PATIENTS WITH ACUTE EXACERBATION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE WHEN COMBINED WITH CORONARY HEART DISEASE].

Science.gov (United States)

Gerych, P; Yatsyshyn, R

2015-01-01

Studied oxygen independent reaction and phagocytic activity of macrophage cells of patients with chronic obstructive pulmonary disease (COPD) II-III stage when combined with coronary heart disease (CHD). The increasing oxygen independent reactions monocytes and neutrophils and a decrease of the parameters that characterize the functional state of phagocytic cells, indicating a decrease in the functional capacity of macrophage phagocytic system (MPS) in patients with acute exacerbation of COPD, which runs as its own or in combination with stable coronary heart disease angina I-II. FC. Severity immunodeficiency state in terms of cellular component of nonspecific immunity in patients with acute exacerbation of COPD II-III stage in conjunction with the accompanying CHD increases with the progression of heart failure. Inclusion of basic therapy of COPD exacerbation and standard treatment of coronary artery disease and drug combinations Roflumilastand quercetin causes normalization of phagocytic indices MFS, indicating improved immune status and improves myocardial perfusion in terms of daily ECG monitoring.

Clearance level and industrial waste management

International Nuclear Information System (INIS)

Asano, Toichi

1999-01-01

Defining the clearance level enables the radioactive waste with lower radioactivity than a certain level to be the general industrial waste and therefore consideration for public acceptance is essential. For this, it is necessary to understand laws concerning not only atomic power and radioactivity but also disposal and cleaning of general waste. It is also necessary that the waste below the clearance level should be as much as possible handled in the modern common concept of recycling of resources. In 1996, the weight of industrial waste was about 400 million tons, of which 40% was disposed by burning and dehydration, 39% was re-used and 21% was subjected to the final disposal like reclamation. Reduction, re-use and recycling of the generated waste are required for making the society with recycling of resources. Scrap concrete materials below the clearance level of 0.6 million tons are estimated to be generated by dismantling the light water reactor of 1 million kW output and profitable technology for recycling the scrap is under investigation. (K.H.)

Factors Associated with Spontaneous Clearance of Hepatitis C Virus in Chinese Population

Directory of Open Access Journals (Sweden)

Fei Kong

2014-01-01

Full Text Available Hepatitis C virus (HCV infections spontaneously clear in approximately 15–45% of infected individuals. Factors which influence spontaneous HCV clearance remain to be identified. The purpose of the present study was to identify variables associated with spontaneous HCV clearance in a referred population of Chinese patients. The prevalence of host, viral, and environmental factors known to influence the outcome of HCV infections was compared in 92 HCV spontaneous clearance subjects and 318 HCV persistent infection subjects. Univariate and multivariate analyses were performed to identify those factors associated with spontaneous HCV clearance. In univariate analysis, female gender, a history of icteric hepatitis, serologic evidence of concurrent HBV infection, and rs12979860 CC genotype were positively associated with spontaneous HCV clearance, while alcohol consumption was negatively associated with clearance. In multivariate analysis, female gender, a history of icteric hepatitis, concurrent HBV infection, and rs12979860 CC genotype remained independent variables associated with spontaneous HCV clearance. Spontaneous HCV clearance is more likely to occur in females, subjects with a history of icteric hepatitis, HBV coinfections, and those with the rs12979860 CC genotype.

High Prolactin Excretion in Patients with Diabetes Mellitus and Impaired Renal Function.

Science.gov (United States)

Triebel, Jakob; Moreno-Vega, Aura Ileana; Vázquez-Membrillo, Miguel; Nava, Gabriel; García-Franco, Renata; López-Star, Ellery; Baldivieso-Hurtado, Olivia; Ochoa, Daniel; Macotela, Yazmín; Bertsch, Thomas; Martinez de la Escalera, Gonzalo; Clapp, Carmen

2015-01-01

The metabolic clearance of prolactin (PRL) is partially executed by the kidney. Here, we investigate the urine excretion of PRL in patients with Diabetes Mellitus and renal impairment. Serum and urine samples were collected from male, mestizo patients in central Mexico employing a cross-sectional study design. Ninety-eight individuals had either no diabetes and normal renal function (control), diabetes and normal renal function, or diabetes with impaired renal function. PRL was determined by a chemiluminescent immunometric assay; protein, albumin, and creatinine were evaluated using quantitative colorimetric assays. The results were analyzed using ANOVA-testing. Patients with Diabetes Mellitus and renal impairment had significantly higher urine PRL levels than patients with Diabetes Mellitus and normal renal function and control patients. Higher urine PRL levels were associated with lower glomerular filtration rates, higher serum creatinine, and higher urinary albumin-to-creatinine ratios (UACR). Urine PRL levels correlated positively with UACR. Serum PRL levels were similar among groups. Patients with Diabetes Mellitus and impaired renal function demonstrate a high urinary PRL excretion. Urinary PRL excretion in the context of proteinuria could contribute to PRL dysregulation in renal impairment.

Airway Clearance Techniques (ACTs)

Medline Plus

Full Text Available ... how you can help your infant or child manage their lung health, watch parents of children with CF and a respiratory therapist talk about the different techniques they use for airway clearance. Facebook Twitter Email More Related Content Medications Autogenic Drainage ...

49 CFR 236.22 - Semaphore signal arm; clearance to other objects.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Semaphore signal arm; clearance to other objects... Rules and Instructions: All Systems Roadway Signals and Cab Signals § 236.22 Semaphore signal arm; clearance to other objects. At least one-half inch clearance shall be provided between semaphore signal arm...

Whole body and regional clearances of noradrenaline and adrenaline in man

DEFF Research Database (Denmark)

Christensen, N J; Galbo, H; Gjerris, Anne Cathrine Roslev

1984-01-01

we found no correlation between clearance values based on venous and arterial sampling. In other experiments we measured the influence of physical exercise in young healthy subjects on the clearance rate of plasma adrenaline (A). The clearance of A, which at rest averaged 1.9 l/min tended to increase...

Using Terrestrial Laser Scanners to Calculate and Map Vertical Bridge Clearance

Science.gov (United States)

Zhang, C.; Arditi, D.; Chen, Z.

2013-08-01

The vertical clearance of a bridge over a highway is important in preventing oversized vehicles from hitting the bridge. The vertical clearance of a bridge is traditionally measured by using surveying equipment such as leveling rods and total stations. Typically, measurements are taken at multiple locations in order to determine the minimum vertical clearance under the bridge. This process is time and labor consuming. Also, these measurements may not be accurate because of the traffic, the uneven surface, and the reading error caused by the surveyor. Additionally, when one is faced with a multitude of reports especially in large projects with multiple ramps and bridges, it is not easy and it often takes a long time to find the bridge under study. This research provides a highly accurate measurement of the vertical bridge clearance by using terrestrial laser scanners. The clearance can be measured in the office by processing the collected point cloud data. The minimum vertical clearance is easily identified and the measurement is visualized and geo-referenced. An approach to reduce data noise caused by traffic is also introduced in this study. In addition, to help reduce the confusion of finding the bridge under study and to facilitate access to the clearance data, the clearance measurements are geo-referenced to an online mapping system. This system allows access to the final deliverable very easily through a single web portal. Finally, Illinois Department of Transportation's Circle Interchange is used to demonstrate this new method.

Elimination of soluble 123I-labeled aggregates of IgG in patients with systemic lupus erythematosus. Effect of serum IgG and numbers of erythrocyte complement receptor type 1

International Nuclear Information System (INIS)

Halma, C.; Breedveld, F.C.; Daha, M.R.; Blok, D.; Evers-Schouten, J.H.; Hermans, J.; Pauwels, E.K.; van Es, L.A.

1991-01-01

Using soluble 123 I-labeled aggregates of human IgG ( 123 I-AHIgG) as a probe, we examined the function of the mononuclear phagocyte system in 22 patients with systemic lupus erythematosus (SLE) and 12 healthy controls. In SLE patients, a decreased number of erythrocyte complement receptor type 1 was associated with less binding of 123 I-AHIgG to erythrocytes and a faster initial rate of elimination of 123 I-AHIgG (mean +/- SEM half-maximal clearance time 5.23 +/- 0.2 minutes, versus 6.58 +/- 0.2 minutes in the controls), with possible spillover of the material outside the mononuclear phagocyte system of the liver and spleen. However, multiple regression analysis showed that serum concentrations of IgG were the most important factor predicting the rate of 123 I-AHIgG elimination. IgG concentration may thus reflect immune complex clearance, which in turn, would influence the inflammatory reaction, in SLE

Constitutive androstane receptor activation promotes bilirubin clearance in a murine model of alcoholic liver disease.

Science.gov (United States)

Wang, Xiuyan; Zheng, Liyu; Wu, Jinming; Tang, Binbin; Zhang, Mengqin; Zhu, Debin; Lin, Xianfan

2017-06-01

Increased plasma levels of bilirubin have been reported in rat models and patients with alcoholic liver disease (ALD). The constitutive androstane receptor (CAR) is a known xenobiotic receptor, which induces the detoxification and transport of bilirubin. In the present study, the bilirubin transport regulatory mechanisms, and the role of CAR activation in hepatic and extrahepatic bilirubin clearance were investigated in a murine model of ALD. The mice were fed a Lieber-DeCarli ethanol diet or an isocaloric control diet for 4 weeks, followed by the administration of CAR agonists, 1,4-bis-[2‑(3,5-dichlorpyridyloxy)]benzene (TCPOBOP) and phenobarbital (PB), and their vehicles to examine the effect of the pharmacological activation of CAR on serum levels of bilirubin and on the bilirubin clearance pathway in ALD by serological survey, western blotting and reverse transcription‑quantitative polymerase chain reaction. The results showed that chronic ethanol ingestion impaired the nuclear translocation of CAR, which was accompanied by elevated serum levels of bilirubin, suppression of the expression of hepatic and renal organic anion transporting polypeptide (OATP) 1A1 and hepatic multidrug resistance‑associated protein 2 (MRP2), and induction of the expression of UDP-glucuronosyltransferase (UGT) 1A1. The activation of CAR by TCPOBOP and PB resulted in downregulation of the serum levels of bilirubin followed by selective upregulation of the expression levels of OATP1A1, OATP1A4, UGT1A1 and MRP2 in ALD. These results revealed the bilirubin transport regulatory mechanisms and highlighted the importance of CAR in modulating the bilirubin clearance pathway in the ALD mouse model.

Complement Receptor 3-Mediated Inhibition of Inflammasome Priming by Ras GTPase-Activating Protein During Francisella tularensis Phagocytosis by Human Mononuclear Phagocytes

Directory of Open Access Journals (Sweden)

Ky V. Hoang

2018-03-01

Full Text Available Francisella tularensis is a remarkably infectious facultative intracellular bacterium of macrophages that causes tularemia. Early evasion of host immune responses contributes to the success of F. tularensis as a pathogen. F. tularensis entry into human monocytes and macrophages is mediated by the major phagocytic receptor, complement receptor 3 (CR3, CD11b/CD18. We recently determined that despite a significant increase in macrophage uptake following C3 opsonization of the virulent Type A F. tularensis spp. tularensis Schu S4, this phagocytic pathway results in limited pro-inflammatory cytokine production. Notably, MAP kinase/ERK activation is suppressed immediately during C3-opsonized Schu S4-CR3 phagocytosis. A mathematical model of CR3-TLR2 crosstalk predicted early involvement of Ras GTPase-activating protein (RasGAP in immune suppression by CR3. Here, we link CR3-mediated uptake of opsonized Schu S4 by human monocytes and macrophages with inhibition of early signal 1 inflammasome activation, evidenced by limited caspase-1 cleavage and IL-18 release. This inhibition is due to increased RasGAP activity, leading to a reduction in the Ras-ERK signaling cascade upstream of the early inflammasome activation event. Thus, our data uncover a novel signaling pathway mediated by CR3 following engagement of opsonized virulent F. tularensis to limit inflammasome activation in human phagocytic cells, thereby contributing to evasion of the host innate immune system.

Effects of lethal and non-lethal malaria on the mononuclear phagocyte system

Directory of Open Access Journals (Sweden)

Carlos Eduardo Tosta

1983-03-01

Full Text Available The effects ofone non-lethal species ofmalarialparasite, Plasmodium yoelii, and one lethal species, P. berghei, on the mononuclear phagocyte system (MPS of BALB/c mice were studied. P. yoelii caused a greater and more sustained expansion and activation of the MPS, and the two major populations of spleen phagocytic cells-red pulp and marginal zone macrophages - exhibited a greater increase in numbers in this infection. During the course of P. berghei mataria, the spleen was progressively occupied by haematopoietic tissue and, at the terminal stage of infection, an extensive depletion of lymphocytes and macrophages was apparent. The possibility was suggested that the outcome of mataria may be inftuenced by the particular way the parasite interacts with the MPS.Estudou-se o efeito da infecção causada por espécie letal (Plasmodium berghei e não- letal (P. yoelii de plasmódio sobre o sistema de fagócitos mononucleares de camundongo BALB/c. O P. yoelii causou maior e mais prolongada expansão e ativação do sistema de macrófagos. As duas mais importantes populações de fagócitos esplênicos - macrófagos de polpa vermelha e da zona marginal - exibiam maior aumento do número de células nesta infecção. Durante a evolução da malária por P. berghei, o baço foi progressivamente ocupado por tecido hematopoiético e, na fase terminal da infecção, observou-se significativa depleção dos linfócitos e macrófagos esplênicos. Os dados apresentados indicam que a evolução da malária depende do tipo de interação entre o plasmódio e o sistema de fagócitos mononucleares.

CT-guided radiolabelled aerosol studies for assessing pulmonary impairment in children with bronchiectasis

International Nuclear Information System (INIS)

Pifferi, M.; Baldini, M.; Caramella, D.; Bartolozzi, C.; Di Mauro, M.; Cangiotti, A.M.

2000-01-01

Objective. To determine whether CT-guided mucociliary clearance studies allow differentiation between bronchiectasis associated with primary ciliary dyskinesia (PCD) and those unrelated to congenital or genetically transmitted defects. Materials and methods. Fifteen children aged 4-18 years with a CT diagnosis of bronchiectasis were included in the study. Six had PCD, while in nine cases no congenital disorder was demonstrated. Results. CT showed bronchiectasis in 26 (29 %) of 90 lung regions. Radiolabelled aerosol studies were conducted globally for each lung and on the regions affected by bronchiectasis. Global half-time of activity (t 1/2 ) values of patients with PCD were significantly higher (P 1/2 values. Patients with bronchiectasis unrelated to congenital disorders showed significantly higher regional t 1/2 values in the affected regions with respect to the corresponding global pulmonary t 1/2 (P < 0.06). Conclusions. The combination of morphological CT information with functional data concerning the clearance of radiolabelled aerosol adds to our understanding of pulmonary impairment in children with bronchiectasis. In particular, regional studies allow the recognition of different mucociliary clearance patterns in bronchiectasis associated with PCD and those unrelated to congenital or genetically transmitted defects. (orig.)

Respiratory clearance of aerosolized radioactive solutes of varying molecular weight

International Nuclear Information System (INIS)

Huchon, G.J.; Montgomery, A.B.; Lipavsky, A.; Hoeffel, J.M.; Murray, J.F.

1987-01-01

To determine the influence of varying molecular weight (mol wt) on respiratory clearance of aerosolized solutes, we studied eight radiopharmaceuticals, each administered to four dogs: sodium /sup 99m/Tc pertechnetate (TcO4), /sup 99m/Tc glucoheptonate ([/sup 99m/Tc]GH), 51Cr-ethylenedinitrotetraacetate ([51Cr]EDTA), /sup 99m/Tc diethylenetriaminepentaacetate ([99mTc] DTPA), 111 In diethylenetriaminepentaacetate ([ 111 In]DTPA), 67 Ga desferoxaminemesylate ([ 67 Ga]DFOM), /sup 99m/Tc dextran ([/sup 99m/Tc]DX) and 111 In transferrin ([ 111 In]TF). After aerosolization (0.8 m MMD, 2.4 GSD), clearance was determined for 30 min and then corrected by intravenous injection for nonairspace radioactivity. In-TF clearance (0.11 +/- 0.10%/min) was lower than TcO4 (6.32 +/- 0.62%/min), [/sup 99m/Tc]GH (1.50 +/- 0.37%/min), [ 51 Cr]EDTA (2.38 +/- 1.02%/min), [/sup 99m/Tc]DTPA (3.51 +/- 0.40%/min), [ 111 In]DTPA (2.35 +/- 0.42%/min), [ 67 Ga] DFOM (1.99 +/- 0.49%/min) and [/sup 99m/Tc]DX (1.81 +/- 0.75%/min) clearances (p less than 0.001). TcO4 clearance was higher than others (p less than 0.001). Technetium binding to DX was unsatisfactory; aerosolization caused unbinding from DTPA. We conclude that respiratory clearance of large mol wt solutes within 30 min is negligible and, that clearance of molecules between 347-5099 daltons differs greatly, suggesting that binding and/or intrapulmonary retention affect transfer

Comparison of German and international clearance regulations - chances and limits for harmonization

International Nuclear Information System (INIS)

Thierfeldt, S.; Schartmann, F.

2005-01-01

The regulations on clearance in the German nuclear regulatory framework (especially sect. 29 and Annexes III and IV of the Radiation Protection Ordinance) are comprehensive and well founded. Germany has developed some of its clearance levels in advance of recommendations issued by the EC. Therefore, there are differences between the German and international clearance regulations. That has been investigated by a working group on clearance of the German Commission on Radiological Protection (SSK) which has performed an analysis of differences and their reasons for clearance levels in Germany and other countries (UK, The Netherlands, Sweden, USA and others). Differences can mainly be explained by country specific approaches in scenarios. Differences especially for the most relevant nuclides are not significant from a radiological point of view. The level of radiological protection (trivial dose range, a few 10 μSv/a) is guaranteed in all countries. The international discussion on the international harmonisation of clearance levels (mainly within the scope of the OECD/NEA and IAEA) can be enlightened on the basis of these results. This discussion concentrates on the question how far a harmonisation of clearance level values is actually necessary and possible. The IAEA Safety Guide RS-G-1.7 'Application of the concepts of exclusion, exemption and clearance' is of particular importance, because it proposes a set of values which might in the long-term take the role of international unconditional clearance levels. International harmonisation is only relevant for unconditional clearance of those materials, which are traded in large quantities among countries, in particular metal scrap. Harmonisation of the values to the same order of magnitude is sufficient. (orig.)

Discrepancy between circadian rhythms of inulin and creatinine clearance

NARCIS (Netherlands)

van Acker, B. A.; Koomen, G. C.; Koopman, M. G.; Krediet, R. T.; Arisz, L.

1992-01-01

To elucidate the disparity between circadian rhythmicity of inulin and creatinine clearance, we simultaneously measured inulin and creatinine clearances every 3 hours during 1 day in 14 normal subjects and in 8 patients with nephrotic syndrome. All patients and normal subjects had a circadian rhythm

Lung clearance of 99m Tc- DTPA in systemic lupus erythematous

International Nuclear Information System (INIS)

Dalcin, P.T.R; Barreto, S.S.M.; Xavier, R.M.; Brenol, J.C.T.; Cunha, R.D.; Marroni, B.J.

2002-01-01

The early demonstration of lung involvement in systemic lupus erythematosus (SLE) patients is a difficult but important task. In the present study we attempted to identify abnormalities in pulmonary clearance of 99 mTc-DTPA in SLE, correlating their clearance data with clinical findings and disease activity. Forty-six consecutive SLE patients with and without active disease (LACC score) and 30 normal volunteers were studied. All subjects were submitted to pulmonary scintigraphy with 99 mTc-DTPA to evaluate the pulmonary clearance, and to a chest X-ray, and SLE patients were submitted to tests of disease activity, spirometry, arterial blood gases and tests to assess acute-phase proteins. Pulmonary clearance was faster in SLE patients with active disease when compared to normal controls [half-life of 67.04 min (51.52-82.55 min) in active SLE versus 85.87 min (78.85-92.87 min) in controls, P<0.05] and there was a higher frequency of abnormal clearance rates in patients with active disease (11 of 26 patients, 42.3%) when compared with SLE patients without disease activity (2 of 20 patients, 10%) (P = 0.04). A significant correlation was observed between the clearance rates and cough (P<0.05), but not between the clearance rates and dyspnoea symptoms or radiological findings, duration of SLE disease, antinuclear antibody titers and patterns, C-reactive protein or anti-double stranded DNA antibodies. We conclude that the pulmonary clearance of 99 m Tc-DTPA is increased in SLE patients with active disease. (author)

Effect of five medicinal plants used in Indian system of medicines on ...

African Journals Online (AJOL)

Effect of five medicinal plants used in Indian system of medicines on immune function in Wistar rats. ... The activity was investigated by phagocytic carbon clearance, antibody titre and delayed type hypersensitivity test. The control group received 0.1% carboxyl methyl cellulose and other groups received the different doses ...

Airway Clearance Techniques (ACTs)

Medline Plus

Full Text Available ... cystic fibrosis. CF CARE CENTER finder We provide funding for and accredit more than 120 care centers ... Community in Health Care Reform Milestones in Health Care Reform How Tax Reform Could Impact People With CF The ... Home Life With CF Treatments and Therapies Airway Clearance ...

48 CFR 32.502-2 - Contract finance office clearance.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... finance office clearance. The contracting officer shall obtain the approval of the contract finance office...

48 CFR 832.502-2 - Contract finance office clearance.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... finance office clearance. Contracting officers must obtain approval from the DSPE before taking the...

Secretion clearance strategies in Australian and New Zealand Intensive Care Units.

Science.gov (United States)

Ntoumenopoulos, George; Hammond, Naomi; Watts, Nicola R; Thompson, Kelly; Hanlon, Gabrielle; Paratz, Jennifer D; Thomas, Peter

2017-06-26

To describe the processes of care for secretion clearance in adult, intubated and mechanically ventilated patients in Australian and New Zealand Intensive Care Units (ICUs). A prospective, cross-sectional study was conducted through the Australian and New Zealand Intensive Care Society Clinical Trials Group (ANZICS CTG) Point Prevalence Program. Forty-seven ICUs collected data from 230 patients intubated and ventilated on the study day. Secretion clearance techniques beyond standard suctioning were used in 84/230 (37%) of patients during the study period. Chest wall vibration 34/84 (40%), manual lung hyperinflation 24/84 (29%), chest wall percussion 20/84 (24%), postural drainage/patient positioning 17/84 (20%) and other techniques including mobilisation 15/84 (18%), were the most common secretion clearance techniques employed. On average (SD), patients received airway suctioning 8.8 (5.0) times during the 24-h study period. Mucus plugging events were infrequent (2.7%). The additional secretion clearance techniques were provided by physiotherapy staff in 24/47 (51%) ICUs and by both nursing and physiotherapy staff in the remaining 23/47 (49%) ICUs. One-third of intubated and ventilated patients received additional secretion clearance techniques. Mucus plugging events were infrequent with these additional secretion clearance approaches. Prospective studies must examine additional secretion clearance practices, prevalence of mucus plugging episodes and impact on patient outcomes. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Influence of peak exercise heart rate on normal thallium-201 myocardial clearance

International Nuclear Information System (INIS)

Kaul, S.; Chesler, D.A.; Pohost, G.M.; Strauss, H.W.; Okada, R.D.; Boucher, C.A.

1986-01-01

Measurement of myocardial clearance rates between initial and delayed images is a major justification for adding computer quantification to the interpretation of exercise 201 TI images. To clarify the range of normal thallium clearance and its relationship to the level of exercise achieved, exercise thallium images in 89 normal subjects were analyzed: 45 asymptomatic subjects with less than 1% probability of coronary artery disease (CAD) (Group I), and 44 patients with chest pain found to have no significant CAD on angiography (Group II). Mean initial regional thallium uptake was similar in the two groups, but myocardial thallium clearance (mean +/- 1 s.d.) was slower in Group II, expressed as a longer half-life in the myocardium (8.2 +/- 7.6 hr compared with 3.4 +/- 0.7 hr p less than 0.001). Analysis of variance using ten clinical and exercise variables as covariates showed that the slower clearance in Group II was related to a lower peak exercise heart rate (HR) (154 +/- 27 compared with 183 +/- 11, respectively, p less than 0.001). By linear regression analysis, a decrease in peak HR of 1 beat/min was associated with a slower thallium clearance (longer half-life) of 0.05 hr. Using this formula, the clearance value in each patient was then corrected for peak exercise heart rate by decreasing measured clearance by 0.05 hr multiplied by the amount peak exercise heart rate which was below 183 (the mean value in Group I). There were no differences in the corrected clearance between the two groups. We conclude that thallium myocardial clearance after exercise is related in part to factors other than the presence of CAD, being slower when peak exercise HR is lower. Therefore, thallium clearance rates alone uncorrected for peak exercise heart rate should be used with caution when diagnosing CAD

A Study to Determine Clearance Levels of Radioactive Wastes in Kenya

Energy Technology Data Exchange (ETDEWEB)

Mukakaa, Zaphania O. [KAIST, Daejeon (Korea, Republic of); Kim, Sung Il [KINS, Daejeon (Korea, Republic of)

2015-10-15

Due to lack of a radioactive waste disposal facility in Kenya, radioactive wastes are stored in a bonded warehouse until such a time when their activity is low and they meet the criterion for clearance. The International Atomic Energy Agency (IAEA) has established activity concentrations of radionuclides to act as a universal guideline or standard for clearance in member countries. Radioactive wastes whose activity would yield a trivial risk to the people and environment, i.e. with an annual dose below 10 µSv are usually cleared from regulatory control with no further regulatory control mechanisms being taken. The Radiation Protection Board currently depends on the IAEA's generic clearance level activity concentrations for purposes of clearing the radiation wastes within its inventory. This study aims to determine activity concentrations of radionuclides in the Kenyan inventory that correspond to the clearance level dose of 10 µSv/a as set by the IAEA. The RESidual RADioactivity (RESRAD) computer code, an important tool developed in 1989 to aid in evaluation of sites with radioactive contamination, will aid in modeling these clearance level values using a pathways analysis method and available site-specific data from Kenya. Afterwards, the obtained clearance level values will be compared with the IAEA's generic clearance level values of the corresponding radionuclides. The results modeled using the RESRAD code are conservative. For most of the radionuclides in the Kenyan inventory, the values do correspond with the IAEA standard generic clearance level values, albeit with minor differences. For most of the radionuclides, the difference is within the acceptable uncertainty limit. For these low probability events the effective dose resulting from them should not exceed 1 mSv per year. Thus, consideration was given to doses to the skin and an equivalent dose to the skin of 50 mSv per year was duly used in estimating the clearance level activities. The

Factors contributing to delay in parasite clearance in uncomplicated falciparum malaria in children

Directory of Open Access Journals (Sweden)

Sijuade Abayomi

2010-02-01

Full Text Available Abstract Background Drug resistance in Plasmodium falciparum is common in many endemic and other settings but there is no clear recommendation on when to change therapy when there is delay in parasite clearance after initiation of therapy in African children. Methods The factors contributing to delay in parasite clearance, defined as a clearance time > 2 d, in falciparum malaria were characterized in 2,752 prospectively studied children treated with anti-malarial drugs between 1996 and 2008. Results 1,237 of 2,752 children (45% had delay in parasite clearance. Overall 211 children (17% with delay in clearance subsequently failed therapy and they constituted 72% of those who had drug failure, i.e., 211 of 291 children. The following were independent risk factors for delay in parasite clearance at enrolment: age less than or equal to 2 years (Adjusted odds ratio [AOR] = 2.13, 95% confidence interval [CI]1.44-3.15, P 50,000/ul (AOR = 2.21, 95% CI = 1.77-2.75, P 20000/μl a day after treatment began, were independent risk factors for delay in clearance. Non-artemisinin monotherapies were associated with delay in clearance and treatment failures, and in those treated with chloroquine or amodiaquine, with pfmdr 1/pfcrt mutants. Delay in clearance significantly increased gametocyte carriage (P Conclusion Delay in parasite clearance is multifactorial, is related to drug resistance and treatment failure in uncomplicated malaria and has implications for malaria control efforts in sub-Saharan Africa.

Effect of glucose-insulin-potassium infusion on thallium myocardial clearance

International Nuclear Information System (INIS)

Wilson, R.A.; Okada, R.D.; Strauss, H.W.; Pohost, G.M.

1983-01-01

Factors influencing the rate of 201 Tl clearance from the myocardium have not been clearly defined. This study determined the effect of an intravenous infusion of glucose-insulin-potassium (GIK) on the net 201 Tl clearance rates from myocardium with and without initial 201 Tl loading. Anesthetized open-chest dogs underwent 5 min of left anterior descending coronary artery occlusion and intravenous 201 Tl was injected and the occlusion released 5 min later. Thirty minutes after 201 Tl injection, 30 ml of either GIK (nine dogs) or saline (five dogs) was infused intravenously. The clearance rates of 201 Tl from the anterior wall (without initial 201 Tl loading) and from the posterior wall (with initial 201 Tl loading) were monitored with miniaturized cadmium telluride detectors placed on the myocardium. Calculation of net myocardial clearance rates was performed by linear regression analysis from serial 1 min counts. Compared with saline infusion, GIK increased the net clearance of 201 Tl from both myocardial regions with and without initial loading. The most marked change induced by GIK infusion was in the myocardial region without initial 201 Tl loading; a net increase in 201 Tl activity (72 +/- 42 cpm/30 min) was converted into a net loss (-594 +/- 228 cpm/30 min). There was no significant change in 201 Tl clearance after the saline infusion. Heart rate, aortic and left atrial pressure, sonomicrometer-measured transmural myocardial wall thickness, microsphere-determined myocardial blood flow, and blood glucose and potassium concentrations did not change significantly during GIK or saline infusions. Thus, GIK infusion appears to increase net 201 Tl clearance from myocardial zones with and without initial 201 Tl loading

Comparison of measurements of plasma clearance of Mebrofenine and of indocyanine green

International Nuclear Information System (INIS)

Maurel, G.; Coutris, G.; Vaubourdolle, M.; Attal, P.; Patureau, R.; Tabsoba, Th.; Mensch, B.; Askienazy, Pr.S.

1997-01-01

The importance of clearance measurements in evaluating renal or hepatic function needs not further demonstration. The isotopic methods were proved in renal exploration but their utilization in exploration of hepato-biliary function needs to be evaluated. In this work we have compared the measurement of plasma clearance by Mebrofenine, a radiopharmaceutical of specifically hepatic elimination, with the reference method, the clearance of indocyanine green. On the basis of scintigraphic data from 23 patients who benefited by a hepato-biliary exploration by Mebrofenine- 99m Tc for pre-surgery account and surveillance, we have determined the plasma clearance of this radiopharmaceutical. The method makes use of the curve of normalized cardiac activity by a blood sampling, taken 60 minutes after injection. The measurement of the clearance of indocyanine green was effected within a delay inferior to 1 month from the moment of biliary scintigraphy. The average clearance of Mebrofenine- 99m Tc is of 553 ml/min for 1.73 m 2 of corporal surface (typical interval is 374 ml/min), the value of indocyanine green is of 450 ml/min (typical interval is 229 ml/min). The two measurements of clearance are correlated (p = 0.05). In conclusion, the measurement of clearance by Mebrofenine- 99m appears to be adapted to the evaluation of hepato-biliary function

48 CFR 1432.502-2 - Contract finance office clearance.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... finance office clearance. The CO shall obtain approval of the bureau finance office prior to taking...

Determining vancomycin clearance in an overweight and obese population.

Science.gov (United States)

Leong, Julie V B; Boro, Maureen S; Winter, Michaele

2011-04-01

Two methods of calculating vancomycin clearance were compared to determine the best body weight measure to use when dosing vancomycin for overweight and obese patients. Hospitalized veterans weighing more than 120% of their ideal body weight (IBW) with serum vancomycin concentrations (SVCs) drawn between January 1, 2003, and June 30, 2005, were eligible for study inclusion. Exclusion criteria included weight of more than 300% the IBW, unstable renal function, dialysis, uncertain vancomycin dosing or sampling times, and distribution-phase sampling. Data from January 1 through December 31, 2003 (phase 1) determined the best-fit weight for vancomycin clearance for the Leonard and Boro method. The bias and precision of the modified Leonard and Boro method using the best-fit weight for vancomycin clearance were then compared with those of the Rushing and Ambrose method for predicting SVCs from January 1, 2004, through June 30, 2005 (phase 2). Forty-eight patients were included in phase 1, with 67 SVCs for analysis. During phase 1, adjusted body weight (ABW), using the Leonard and Boro method, was superior in predicting vancomycin clearance and the resultant SVCs. A total of 96 patients were included in phase 2 of the study, with 160 SVCs for analysis. The modified Leonard and Boro method was significantly more precise than the Rushing and Ambrose method in predicting vancomycin clearance. Use of ABW proved to be superior compared with total body weight when estimating vancomycin clearance in overweight and obese patients. While there was no difference in bias between methods, the modified Leonard and Boro method was significantly more precise than the Rushing and Ambrose method in predicting SVCs when dosing vancomycin for obese patients.

Tip clearance effect on through-flow and performance of a centrifugal compressor

International Nuclear Information System (INIS)

Eum, Hark Jin; Kang, Young Seok; Kang, Shin Hyoung

2004-01-01

Numerical simulations have been performed to investigate tip clearance effect on through-flow and performance of a centrifugal compressor which has the same configuration of impeller with six different tip clearances. Secondary flow and loss distribution have been surveyed to understand the flow mechanism due to the tip clearance. Tip leakage flow strongly interacts with mainstream flow and considerably changes the secondary flow and the loss distribution inside the impeller passage. A method has been described to quantitatively estimate the tip clearance effect on the performance drop and the efficiency drop. The tip clearance has caused specific work reduction and additional entropy generation. The former, which is called inviscid loss, is independent of any internal loss and the latter, which is called viscous loss, is dependent on every loss in the flow passage. Two components equally affected the performance drop as the tip clearances were small, while the efficiency drop was influenced by the viscous component alone. The additional entropy generation was modeled with all the kinetic energy of the tip leakage flow. Therefore, the present paper can provide how to quantitatively estimate the tip clearance effect on the performance and efficiency

Tear clearance implications for ocular surface health.

Science.gov (United States)

de Paiva, Cintia Sade; Pflugfelder, Stephen C

2004-03-01

Tear clearance/turnover provides a global assessment of the function of the lacrimal functional unit and of tear exchange on the ocular surface. It is an indirect measure of dry eye induced inflammation on the ocular surface. It shows better correlation with the severity of ocular irritation symptoms and corneal epithelial disease in dry eye than the Schirmer 1 test. Delayed tear clearance may prove to be the best measure for identifying patients with tear film disorders who may respond to anti-inflammatory therapy.

Clearance of Tc-99m DTPA in hemodialysis and peritoneal dialysis: concise communication

International Nuclear Information System (INIS)

Wainer, E.; Boner, G.; Lubin, E.; Rosenfeld, J.B.

1981-01-01

The clearance of Tc-99m DTPA was studied in 14 patients undergoing hemodialysis (HD) or peritoneal dialysis (PD). Mean Tc-99m DTPA clearance during HD was 37.8% +/- 10.1 of creatinine clearance. Mean Tc-99m DTPA clearance in PD was 65.1% +/- 10.3 of creatinine clearance. Tc-99m DTPA, with a larger molecular weight than that of creatinine, is cleared relatively better during PD than during HD. Thus Tc-99m DTPA may be used in the assessment of the effectiveness of different dialytic treatments for substances of similar molecular weight. In addition, our study shows that clearance of DTPA both in HD and PD is sufficiently high to allow the removal of this chelating agent in patients with renal failure

Effect of isolated hepatic ischemia on organic anion clearance and oxidative metabolism.

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Minard, G; Bynoe, R; Wood, G C; Fabian, T C; Croce, M; Kudsk, K A

1992-04-01

Hepatic failure is frequently seen following severe hemorrhagic shock, sepsis, and trauma. Clearance of various drugs has been used to evaluate hepatocellular dysfunction, including indocyanine green (ICG), an organic anionic dye that is transported similarly to bilirubin, and antipyrine (AP), a marker of oxidative phosphorylation. Previous investigators have noted a decrease in ICG excretion following systemic hemorrhage. The effect of isolated hepatic ischemia on the clearances of ICG and AP was studied in 16 pigs after 90 minutes of vascular occlusion to the liver. Antipyrine clearance decreased almost 50% from baseline values at 24 and 72 hours after the ischemia procedure, indicating a significant depression in the cytochrome P-450 system. On the other hand, ICG clearance did not change significantly. In conclusion, ICG clearance is not depressed after isolated hepatic ischemia in pigs. Changes in organic anion clearance after systemic hemorrhage may be because of release of toxic products from ischemic peripheral tissue.

Clearance of 99mTc-DTPA and experimentally increased alveolar surfactant content

International Nuclear Information System (INIS)

Bos, J.A.H.; Wollmer, P.; Bakker, W.; Hannappel, E.; Lachmann, B.

1992-01-01

The authors measured clearance of 99m Tc-labeled diethylenetriamine pentaacetic acid ( 99m Tc-DTPA) in rabbits with experimentally increased alveolar surfactant content. In one group of animals, surfactant production was increased by treatment with ambroxol, and another group of animals was treated with tracheal instillation of natural surfactant. A group of untreated control animals and animals treated with instillation of saline were also studied. Clearance was measured during standard conditions of mechanical ventilation and during ventilation with large tidal volumes. In ambroxol- and surfactant-treated groups, clearance rate was reduced compared with untreated control animals. In contrast, clearance rate increased after saline instillation. The differences were observed at both modes of ventilation. The findings indicate that the pulmonary surfactant system is a rate-limiting factor for the clearance of 99m Tc-DTPA and that the volume dependence of clearance is not explained by stretching of the alveolar wall only. 28 refs., 2 figs., 1 tab

Intermittent fasting promotes bacterial clearance and intestinal IgA production in Salmonella typhimurium-infected mice.

Science.gov (United States)

Godínez-Victoria, M; Campos-Rodriguez, R; Rivera-Aguilar, V; Lara-Padilla, E; Pacheco-Yepez, J; Jarillo-Luna, R A; Drago-Serrano, M E

2014-05-01

The impact of intermittent fasting versus ad libitum feeding during Salmonella typhimurium infection was evaluated in terms of duodenum IgA levels, bacterial clearance and intestinal and extra-intestinal infection susceptibility. Mice that were intermittently fasted for 12 weeks or fed ad libitum were infected with S. typhimurium and assessed at 7 and 14 days post-infection. Next, we evaluated bacterial load in the faeces, Peyer's patches, spleen and liver by plate counting, as well as total and specific intestinal IgA and plasmatic corticosterone levels (by immunoenzymatic assay) and lamina propria IgA levels in plasma cells (by cytofluorometry). Polymeric immunoglobulin receptor, α- and J-chains, Pax-5 factor, pro-inflammatory cytokine (tumour necrosis factor-α and interferon-γ) and anti-inflammatory cytokine (transforming growth factor-β) mRNA levels were assessed in mucosal and liver samples (by real-time PCR). Compared with the infected ad libitum mice, the intermittently fasted infected animals had (1) lower intestinal and systemic bacterial loads; (2) higher SIgA and IgA plasma cell levels; (3) higher mRNA expression of most intestinal parameters; and (4) increased or decreased corticosterone levels on day 7 and 14 post-infection, respectively. No contribution of liver IgA was observed at the intestinal level. Apparently, the changes following metabolic stress induced by intermittent fasting during food deprivation days increased the resistance to S. typhimurium infection by triggering intestinal IgA production and presumably, pathogen elimination by phagocytic inflammatory cells. © 2014 John Wiley & Sons Ltd.

The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal

Directory of Open Access Journals (Sweden)

Hafner Martin

2004-08-01

Full Text Available Abstract Background Phagocytosis of apoptotic cells is fundamental to animal development, immune function and cellular homeostasis. The phosphatidylserine receptor (Ptdsr on phagocytes has been implicated in the recognition and engulfment of apoptotic cells and in anti-inflammatory signaling. To determine the biological function of the phosphatidylserine receptor in vivo, we inactivated the Ptdsr gene in the mouse. Results Ablation of Ptdsr function in mice causes perinatal lethality, growth retardation and a delay in terminal differentiation of the kidney, intestine, liver and lungs during embryogenesis. Moreover, eye development can be severely disturbed, ranging from defects in retinal differentiation to complete unilateral or bilateral absence of eyes. Ptdsr -/- mice with anophthalmia develop novel lesions, with induction of ectopic retinal-pigmented epithelium in nasal cavities. A comprehensive investigation of apoptotic cell clearance in vivo and in vitro demonstrated that engulfment of apoptotic cells was normal in Ptdsr knockout mice, but Ptdsr-deficient macrophages were impaired in pro- and anti-inflammatory cytokine signaling after stimulation with apoptotic cells or with lipopolysaccharide. Conclusion Ptdsr is essential for the development and differentiation of multiple organs during embryogenesis but not for apoptotic cell removal. Ptdsr may thus have a novel, unexpected developmental function as an important differentiation-promoting gene. Moreover, Ptdsr is not required for apoptotic cell clearance by macrophages but seems to be necessary for the regulation of macrophage cytokine responses. These results clearly contradict the current view that the phosphatidylserine receptor primarily functions in apoptotic cell clearance.

Mechanisms of Host-Pathogen Protein Complex Formation and Bacterial Immune Evasion of Streptococcus suis Protein Fhb.

Science.gov (United States)

Li, Xueqin; Liu, Peng; Gan, Shuzhen; Zhang, Chunmao; Zheng, Yuling; Jiang, Yongqiang; Yuan, Yuan

2016-08-12

Streptococcus suis serotype 2 (S. suis 2)-induced sepsis and meningitis are often accompanied by bacteremia. The evasion of polymorphonuclear leukocyte-mediated phagocytic clearance is central to the establishment of bacteremia caused by S. suis 2 and is facilitated by the ability of factor H (FH)-binding protein (Fhb) to bind FH on the bacterial surface, thereby impeding alternative pathway complement activation and phagocytic clearance. Here, C3b/C3d was found to bind to Fhb, along with FH, forming a large immune complex. The formation of this immune complex was mediated by domain II of Fhb via electrostatic and hydrophobic interactions, which, to our knowledge, is a new type of interaction. Interestingly, Fhb was found to be associated with the cell envelope and also present in the culture supernatant, where secreted Fhb inhibited complement activation via interactions with domain II, thereby enhancing antiphagocytic clearance by polymorphonuclear leukocytes. Thus, Fhb is a multifunctional bacterial protein, which binds host complement component C3 as well as FH and interferes with innate immune recognition in a secret protein manner. S. suis 2 therefore appears to have developed a new strategy to combat host innate immunity and enhance survival in host blood. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Mechanisms of Host-Pathogen Protein Complex Formation and Bacterial Immune Evasion of Streptococcus suis Protein Fhb*

Science.gov (United States)

Li, Xueqin; Liu, Peng; Gan, Shuzhen; Zhang, Chunmao; Zheng, Yuling; Jiang, Yongqiang; Yuan, Yuan

2016-01-01

Streptococcus suis serotype 2 (S. suis 2)-induced sepsis and meningitis are often accompanied by bacteremia. The evasion of polymorphonuclear leukocyte-mediated phagocytic clearance is central to the establishment of bacteremia caused by S. suis 2 and is facilitated by the ability of factor H (FH)-binding protein (Fhb) to bind FH on the bacterial surface, thereby impeding alternative pathway complement activation and phagocytic clearance. Here, C3b/C3d was found to bind to Fhb, along with FH, forming a large immune complex. The formation of this immune complex was mediated by domain II of Fhb via electrostatic and hydrophobic interactions, which, to our knowledge, is a new type of interaction. Interestingly, Fhb was found to be associated with the cell envelope and also present in the culture supernatant, where secreted Fhb inhibited complement activation via interactions with domain II, thereby enhancing antiphagocytic clearance by polymorphonuclear leukocytes. Thus, Fhb is a multifunctional bacterial protein, which binds host complement component C3 as well as FH and interferes with innate immune recognition in a secret protein manner. S. suis 2 therefore appears to have developed a new strategy to combat host innate immunity and enhance survival in host blood. PMID:27342778

Domiciliary humidification improves lung mucociliary clearance in patients with bronchiectasis.

Science.gov (United States)

Hasani, A; Chapman, T H; McCool, D; Smith, R E; Dilworth, J P; Agnew, J E

2008-01-01

Inspired air humidification has been reported to show some benefit in bronchiectatic patients. We have investigated the possibility that one effect might be to enhance mucociliary clearance. Such enhancement might, if it occurs, help to lessen the risks of recurrent infective episodes. Using a radioaerosol technique, we measured lung mucociliary clearance before and after 7 days of domiciliary humidification. Patients inhaled high flow saturated air at 37 degrees C via a patient-operated humidification nasal inhalation system for 3 h per day. We assessed tracheobronchial mucociliary clearance from the retention of (99m)Tc-labelled polystyrene tracer particles monitored for 6 h, with a follow-up 24-h reading. Ten out of 14 initially recruited patients (age 37-75 years; seven females) completed the study (two withdrew after their initial screening and two prior to the initial clearance test). Seven patients studied were non-smokers; three were ex-smokers (1-9 pack-years). Initial tracer radioaerosol distribution was closely similar between pre- and post-treatment. Following humidification, lung mucociliary clearance significantly improved, the area under the tracheobronchial retention curve decreased from 319 +/- 50 to 271 +/- 46%h (p humidification treatment improved lung mucociliary clearance in our bronchiectatic patients. Given this finding plus increasing laboratory and clinical interest in humidification mechanisms and effects, we believe further clinical trials of humidification therapy are desirable, coupled with analysis of humidification effects on mucus properties and transport.

The influence of partial renal function impairment on thyroid hormones level in acute renal failure-ARF patients

International Nuclear Information System (INIS)

Ilic, S.; Vlajkovic, M.; Rajic, M.; Bogicevic, M.

2002-01-01

The aim of this study was to assess the relationship of thyroid hormone levels with glomerular and tubular renal function in ARF. In thirty one patients with different underlying diseases, glomerular filtration (GFR) was estimated by measuring 99mTc-DTPA clearance and tubular function by 131I-OIH clearance. The thyroid status was evaluated by radioimmunoassays of T4, FT4, T3, FT3, rT3 and TSH, while the cortisol level was used to indicate the stress role. All the measurements were performed within 7 days as well after 1,3,6 and 12 months from the ARF onset. The results obtained were compared with those of 30 healthy subjects. At the ARF beginning, the impairment of renal function was manifested by the fall of 99mTc-DTPA clearance to 21∫7ml/min and 131I-OIH clearance to 172±34ml/min, while end values were 77±19ml/min and 395±70ml/min, respectively. The hormone analysis within 7 days, showed T3 decrease to 1.21±0.16nmol/l and the increase rT3 to 38±7ng/1ooml, as well as cortisol to 350±71ng/ml, but at the end of the study these hormone levels were normalized. Other hormone levels didn't differ significantly from control values. Regression analysis established significant correlation of 99mTc-DTPA clearance with T3 (r=0.693, p 100, OIH>500), partial recovery (DTPA 51-100, OIH 250-500) and without any recovery (DTPA<50,OIH<250), showed hormone disturbances proportional to the degree of renal function damage. The most severe disorders were found in the third group, where both total and free T4 and T3 were lowered, while rT3 and cortisol elevated at 7th day from ARF onset. After 12 months all these values associated with that of TSH were observed as declined.This study suggests thyroid hormone levels to be dependent on the renal function in ARF. Greater impairment of glomerular related to tubular function appears to be more responsible for thyroid dysfunction, due to uremic toxins retention as well as stress induced by the extreme function failure

48 CFR 245.7101-4 - DD Form 1640, Request for Plant Clearance.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false DD Form 1640, Request for Plant Clearance. 245.7101-4 Section 245.7101-4 Federal Acquisition Regulations System DEFENSE... Forms 245.7101-4 DD Form 1640, Request for Plant Clearance. Use to request plant clearance assistance or...

Renal clearance of 99mTc-methylene-diphosphonate in human beings

International Nuclear Information System (INIS)

Vattimo, A.

1987-01-01

The renal clearance of 99m Tc-MDP was measured in 13 patients who had bone scans and compared with the renal clearance of 51 Cr-EDTA. No difference was found between the renal clearance of the two tracers, showing a close correlation (r = 0.98). These data suggest that the 99m Tc-MDP is excreted by the kidneys by glomerular filtration without tubular secretion. (orig.) [de

Exercise increases the lung clearance of inhaled Tc-99m DTPA

International Nuclear Information System (INIS)

Meignan, M.; Rosso, J.; Cinotti, L.; Galle, P.

1985-01-01

It has been suggested that blood flow have little effect on the lung clearance of Tc-99m DTPA which depends on the alveolar distension. However an increase of pulmonary blood flow, induces a recruitment of new vascular areas which can enhance this clearance. To assess this hypothesis the pulmonary apical and basal clearances of a sumicronic aerosol of Tc-99m DTPA were studied at rest and at exercise in seven non smoking volunteers in upright posture. As a matter of fact exercising upright is known to increase primarily the apical blood flow. After inhalation the subjects were seated on a bicycle their back against a gamma camera which was linked to a computer. The lung radioactivity was registered successively during a resting and an exercising period. At rest there was a gradient of clearance from the apex to the base of the lung, the apical clearance being significantly higher. At exercise (50 Watts, 60 c. min /sup -1/, 7 min.) this regional gradient was enhanced by a large and significant increase of the apical clearances (0.0340 min /sup -1/ +-0.0063 SD versus 0.00183 min /sup -1/ +- 0.074 SD at rest, n = 7, p < 0.01). By contrast the changes of the basal clearances were slight and unsignificant (0.0146 min /sup -1/ +- 0.0062 SD versus 0.0140 min /sup -1/ +- 0.0082 SD). Since exercise induces little distension of the apical alveoli but drastically enhances the apical blood flow, the observed increase of the apical lung clearance could be primarily attributed to the recruitment of new capillaries induced by exercise in the apices. This led to an increase of the surface area permeability product

Oxygen Tension Beneath Scleral Lenses of Different Clearances.

Science.gov (United States)

Giasson, Claude J; Morency, Jeanne; Melillo, Marc; Michaud, Langis

2017-04-01

To evaluate the relative partial pressure in oxygen (pO2) at the corneal surface under Boston XO2 scleral lenses (SL) fitted with targeted clearances of 200 and 400 μm (SL200 and SL400). During this prospective study, the right eyes of eight normal subjects were fitted with SL200 and SL400. Clearance, validated after 5 minutes of wear with an optical coherence tomograph, was used with lens thicknesses to calculate transmissibility and estimate pO2. Corneal pO2s were measured with an oxygen electrode after 5 minutes of (1) corneal exposure to calibrating gases with various pO2 or of (2) SL wear. Decays in pO2 were modeled to an exponential. Linear regression between exponent k of these decays and calibrating gas pO2s allowed for the calculation of corneal pO2 under SL. Differences between pO2s beneath SL200 and SL400 were tested with a mixed ANOVA. The estimated transmissibility based on thicknesses and clearances (239.7 ± 34.7; 434.5 ± 33.2 μm) predicted a corneal pO2 of 8.52 ± 0.51 and 6.37 ± 0.28% for SL200 and SL400. These values were close to measured pO2: 9.07 ± 0.86 and 6.19 ± 0.87% (mean ± SEM) (P time, an 18-mm scleral lens fitted with a 400-μm clearance reduces the oxygen tension available to the cornea by 30% compared to a similar lens fitted with a 200-μm clearance after 5 minutes of wear.

Acute exposure to acid fog. Effects on mucociliary clearance

International Nuclear Information System (INIS)

Laube, B.L.; Bowes, S.M. III; Links, J.M.; Thomas, K.K.; Frank, R.

1993-01-01

Submicrometric sulfuric acid (H2SO4) aerosol can affect mucociliary clearance without eliciting irritative symptoms or changes in pulmonary function. The effect of larger fog droplets containing H2SO4 on mucociliary clearance is unknown. We quantified mucociliary clearance from the trachea (n = 4) and small airways (n = 7) of young healthy male adults after an acute exposure to H2SO4 fog (MMAD = 10.3 microns; pH = 2.0; liquid water content = 481 +/- 65 mg/m3; osmolarity = 30 mOsm). Acid fog (AF) or saline fog (SF) (10.9 microns; 492 +/- 116 mg/m3; 30 mOsm) was administered for 40 min of unencumbered breathing (no mouth-piece) at rest and for 20 min of exercise sufficient to produce oronasal breathing. Fog exposures were followed by a methacholine (MCh) challenge (a measure of airway reactivity) or inhalation of technetium-99M radioaerosol (MMAD = 3.4 microns) on 2 study days each. Changes in symptoms and forced ventilatory function were also assessed. Clearance was quantified from computer-assisted analyses of gamma camera images of the lower respiratory tract in terms of %removal/min of the radiolabel from the trachea 25 min after inhalation and from the outer zone of the right lung after 1.9 to 3 h. Symptoms, forced ventilatory function, and MCh response were unaffected by either fog. Tracheal clearance was more rapid in four of four subjects after AF (0.83 +/- 1.58% removal/min) compared with that after SF (-0.54 +/- 0.85% removal/min). Outer zone clearance was more rapid in six of seven subjects after AF (0.22 +/- 0.15% removal/min) compared with that after SF (0.01 +/- 0.09% removal/min)

20 CFR 655.150 - Interstate clearance of job order.

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2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated worksites...

Dimerization of glycoprotein Ibα is not sufficient to induce platelet clearance.

Science.gov (United States)

Liang, X; Syed, A K; Russell, S R; Ware, J; Li, R

2016-02-01

ESSENTIALS: Many anti-glycoprotein (GP)Ibα antibodies induce platelet clearance in a dimer-dependent manner. Characterization of monoclonal antibodies that bind the mechanosensitive domain (MSD) of GPIbα. An anti-MSD antibody binds two copies of GPIbα in platelets but does not induce platelet clearance. The prevailing clustering model of GPIbα signaling is incorrect or needs revision. The mechanism of platelet clearance is not clear. Many antibodies binding the membrane-distal ligand-binding domain of glycoprotein (GP)Ibα induce rapid clearance of platelets and acute thrombocytopenia, which requires the bifurcated antibody structure. It was thought that binding of these antibodies induced lateral dimerization or clustering of GPIbα in the plasma membrane, which leads to downstream signaling and platelet clearance. However, many antibodies targeting GPIbβ and GPIX, which are associated with GPIbα in the GPIb-IX complex, do not induce platelet clearance, which is in contradiction to the clustering model. To test whether dimerization or clustering of GPIbα is sufficient to transmit the signal that leads to platelet clearance. We have recently raised several mAbs targeting the mechanosensitive domain (MSD) of GPIbα. Binding of these anti-MSD antibodies was characterized with biochemical methods. Their ability to stimulate platelets and induce platelet clearance in mice was assessed. Infusion of anti-MSD antibodies does not cause thrombocytopenia in mice. These antibodies show no detectable effects on platelet activation and aggregation in vitro. Further biochemical investigation showed that the anti-MSD antibody 3D1 binds two copies of GPIbα on the platelet surface. Therefore, lateral dimerization of GPIbα induced by antibody binding is not sufficient to initiate GPIb-IX signaling and induce platelet clearance. Our results suggest that a factor other than or in addition to clustering of GPIbα is required to induce platelet clearance. © 2015 International

HPT Clearance Control: Intelligent Engine Systems-Phase 1

Science.gov (United States)

2005-01-01

The following work has been completed to satisfy the Phase I Deliverables for the "HPT Clearance Control" project under NASA GRC's "Intelligent Engine Systems" program: (1) Need for the development of an advanced HPT ACC system has been very clearly laid out, (2) Several existing and potential clearance control systems have been reviewed, (3) A scorecard has been developed to document the system, performance (fuel burn, range, payload, etc.), thermal, and mechanical characteristics of the existing clearance control systems, (4) Engine size and flight cycle selection for the advanced HPT ACC system has been reviewed with "large engine"/"long range mission" combination showing the most benefit, (5) A scoring criteria has been developed to tie together performance parameters for an objective, data driven comparison of competing systems, and (6) The existing HPT ACC systems have been scored based on this scoring system.

32 CFR 154.16 - Security clearance.

Science.gov (United States)

2010-07-01

... part. The Director, Washington Headquarters Services (WHS) will initiate the required investigation... clearance, as appropriate. The Assistant Secretary of Defense (Legislative Affairs) will be notified by WHS...

Estimation of normal chromium-51 ethylene diamine tetra-acetic acid clearance in children

International Nuclear Information System (INIS)

Piepsz, A.; Pintelon, H.; Ham, H.R.

1994-01-01

In order to estimate the normal range of chromium-51 ethylene diamine tetra-acetic acid (EDTA) clearance in children, we selected a series of 256 patients with past or present urinary tract infection who showed, at the time of the clearance determination, normal technetium-99m dimercaptosuccinic acid (DMSA) scintigraphy and normal left to right DMSA relative uptake. The clearance was calculated by means of either the simplified second exponential method or the 120-min single blood sample; Chantler's correction was used in order to correct for having neglected the first exponential. There was a progressive increase in clearance from the first weeks of life (mean value around 1 month: 55 ml/min/1.73 m 2 ), with a plateau at around 18 months. Between 2 and 17 years of age, the clearance values remained constant, with a mean value of 114 ml/min/1.73 m 2 (SD: 24 ml/min); this is similar to the level described for inulin clearance. No significant differences were observed between boys and girls, or between clearance values calculated with one or with two blood samples. Taking into account the hour of intravenous injection of the tracer, we did not observe any influence of the lunchtime meal on the distribution of the 51 Cr-EDTA clearance values. (orig.)

Analysis of foot clearance in firefighters during ascent and descent of stairs.

Science.gov (United States)

Kesler, Richard M; Horn, Gavin P; Rosengren, Karl S; Hsiao-Wecksler, Elizabeth T

2016-01-01

Slips, trips, and falls are a leading cause of injury to firefighters with many injuries occurring while traversing stairs, possibly exaggerated by acute fatigue from firefighting activities and/or asymmetric load carriage. This study examined the effects that fatigue, induced by simulated firefighting activities, and hose load carriage have on foot clearance while traversing stairs. Landing and passing foot clearances for each stair during ascent and descent of a short staircase were investigated. Clearances decreased significantly (p < 0.05) post-exercise for nine of 12 ascent parameters and increased for two of eight descent parameters. Load carriage resulted in significantly decreased (p < 0.05) clearance over three ascent parameters, and one increase during descent. Decreased clearances during ascent caused by fatigue or load carriage may result in an increased trip risk. Increased clearances during descent may suggest use of a compensation strategy to ensure stair clearance or an increased risk of over-stepping during descent. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Activation and clearance of vanadium alloys and beryllium multipliers in fusion reactors

International Nuclear Information System (INIS)

Bartenev, S.; Romanovskij, V.; Ciampichetti, A.; Zucchetti, M.; Forrest, R.; Kolbasov, B.; Romanov, P.

2006-01-01

Design of fusion reactors includes the development of low-activation materials. V-Cr-Ti alloys are among the candidate structural materials for the first wall and blanket, with the scarce and costly V as the main component. It is worth considering its regeneration and refabrication as well as to avoid its disposal as radioactive waste. However, to do so, it is necessary to bring its radioactivity down to sufficiently low levels. We have two possible goals: · Recycling (within the nuclear industry) for first wall and front blanket components. In that case, contact dose rate must be sufficiently low. · Clearance (release from nuclear regulatory control) for back blanket and backplate components. In that case, the clearance index must be below unity. In fact, for components less exposed to neutron activation, clearance may be reachable, after a conceivable period of decay. Maximum radionuclide concentrations in the alloys allowing their clearance were determined, using new IAEA Clearance Limits. For this purpose, also for less neutron-exposed structures, such as the back part of the blanket and the backplate, clearance is possible only if certain activation products are separated. As for recycling within the nuclear industry of first wall components, also for clearance it turns out that the development of isotope chemical separation techniques is interesting and necessary for our purposes. A suitable method for achieving the required substantial radioactivity reduction of activated V-Cr-Ti alloys is radiochemical extraction reprocessing, Such a technology, permitting to remove metallic activation products from spent materials, was developed and tested experimentally in Russia. Concerning clearance of less activated components, based on the estimated element distribution factors in the extraction and re-extraction processes, and computations, it was shown that the alloy components may be purified from the activation products, using this technology, down to an

Airway Clearance Techniques (ACTs)

Medline Plus

Full Text Available ... NACFC Carolyn and C Richard Mattingly Leadership in Mental Health Care Award Mary M. Kontos Award NACFC Reflections ... help your infant or child manage their lung health, watch parents of children with CF and a respiratory therapist talk about the different techniques they use for airway clearance. ... Instagram Email Find a Clinical Trial Help us blaze ...

7 CFR 1927.53 - Costs of title clearance and closing of transactions.

Science.gov (United States)

2010-01-01

... 7 Agriculture 12 2010-01-01 2010-01-01 false Costs of title clearance and closing of transactions... and Loan Closing § 1927.53 Costs of title clearance and closing of transactions. The borrower or the... payment of all costs of title clearance and closing of the transaction and will arrange for payment before...

Experimental Investigation of Factors Influencing Operating Rotor Tip Clearance in Multistage Compressors

Directory of Open Access Journals (Sweden)

Reid A. Berdanier

2015-01-01

Full Text Available An analysis of compressor rotor tip clearance measurements using capacitance probe instrumentation is discussed for a three-stage axial compressor. Thermal variations and centrifugal effects related to rotational speed changes affect clearance heights relative to the assembled configuration. These two primary contributions to measured changes are discussed both independently and in combination. Emphasis is given to tip clearance changes due to changing loading condition and at several compressor operating speeds. Measurements show a tip clearance change approaching 0.1 mm (0.2% rotor span when comparing a near-choke operating condition to a near-stall operating condition for the third stage. Additional consideration is given to environmental contributions such as ambient temperature, for which changes in tip clearance height on the order of 0.05 mm (0.1% rotor span were noted for temperature variations of 15°C. Experimental compressor operating clearances are presented for several temperatures, operating speeds, and loading conditions, and comparisons are drawn between these measured variations and predicted changes under the same conditions.

USING TERRESTRIAL LASER SCANNERS TO CALCULATE AND MAP VERTICAL BRIDGE CLEARANCE

OpenAIRE

C. Zhang; D. Arditi; Z. Chen

2013-01-01

The vertical clearance of a bridge over a highway is important in preventing oversized vehicles from hitting the bridge. The vertical clearance of a bridge is traditionally measured by using surveying equipment such as leveling rods and total stations. Typically, measurements are taken at multiple locations in order to determine the minimum vertical clearance under the bridge. This process is time and labor consuming. Also, these measurements may not be accurate because of the traffi...

Brain-wide pathway for waste clearance captured by contrast-enhanced MRI

OpenAIRE

Iliff, Jeffrey J.; Lee, Hedok; Yu, Mei; Feng, Tian; Logan, Jean; Nedergaard, Maiken; Benveniste, Helene

2013-01-01

The glymphatic system is a recently defined brain-wide paravascular pathway for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange that facilitates efficient clearance of solutes and waste from the brain. CSF enters the brain along para-arterial channels to exchange with ISF, which is in turn cleared from the brain along para-venous pathways. Because soluble amyloid β clearance depends on glymphatic pathway function, we proposed that failure of this clearance system contributes t...

Analysis of renal impairment in MM-003, a phase III study of pomalidomide + low - dose dexamethasone versus high - dose dexamethasone in refractory or relapsed and refractory multiple myeloma

Science.gov (United States)

Weisel, Katja C.; Dimopoulos, Meletios A.; Moreau, Philippe; Lacy, Martha Q.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Banos, Anne; Oriol, Albert; Alegre, Adrian; Chen, Christine; Cavo, Michele; Garderet, Laurent; Ivanova, Valentina; Martinez-Lopez, Joaquin; Knop, Stefan; Yu, Xin; Hong, Kevin; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H.; Miguel, Jesus San

2016-01-01

Pomalidomide + low-dose dexamethasone is effective and well tolerated for refractory or relapsed and refractory multiple myeloma after bortezomib and lenalidomide failure. The phase III trial MM-003 compared pomalidomide + low-dose dexamethasone with high-dose dexamethasone. This subanalysis grouped patients by baseline creatinine clearance ≥ 30 − < 60 mL/min (n=93, pomalidomide + low-dose dexamethasone; n=56, high-dose dexamethasone) or ≥ 60 mL/min (n=205, pomalidomide + low-dose dexamethasone; n=93, high-dose dexamethasone). Median progression-free survival was similar for both subgroups and favored pomalidomide + low-dose dexamethasone versus high-dose dexamethasone: 4.0 versus 1.9 months in the group with baseline creatinine clearance ≥ 30 − < 60 mL/min (P<0.001) and 4.0 versus 2.0 months in the group with baseline creatinine clearance ≥ 60 mL/min (P<0.001). Median overall survival for pomalidomide + low-dose dexamethasone versus high-dose dexamethasone was 10.4 versus 4.9 months (P=0.030) and 15.5 versus 9.2 months (P=0.133), respectively. Improved renal function, defined as an increase in creatinine clearance from < 60 to ≥ 60 mL/min, was similar in pomalidomide + low-dose dexamethasone and high-dose dexamethasone patients (42% and 47%, respectively). Improvement in progression-free and overall survival in these patients was comparable with that in patients without renal impairment. There was no increase in discontinuations of therapy, dose modifications, and adverse events in patients with moderate renal impairment. Pomalidomide at a starting dose of 4 mg + low-dose dexamethasone is well tolerated in patients with refractory or relapsed and refractory multiple myeloma, and of comparable efficacy if moderate renal impairment is present. This trial was registered with clinicaltrials.gov identifier 01311687 and EudraCT identifier 2010-019820-30. PMID:27081177

Gamma-variate plasma clearance versus urinary plasma clearance of 51Cr-EDTA in patients with cirrhosis with and without fluid retention

DEFF Research Database (Denmark)

Fuglsang, Stefan; Henriksen, Ulrik L; Hansen, Hanne Boskov

2017-01-01

In patients with fluid retention, the plasma clearance of (51) Cr-EDTA (Clexp obtained by multiexponential fit) may overestimate the glomerular filtration rate (GFR). The present study was undertaken to compare a gamma-variate plasma clearance (Clgv) with the urinary plasma clearance of (51) Cr......-EDTA (Clu ) in patients with cirrhosis with and without fluid retention. A total of 81 patients with cirrhosis (22 without fluid retention, 59 with ascites) received a quantitative intravenous injection of (51) Cr-EDTA followed by plasma and quantitative urinary samples for 5 h. Clgv was determined from...... the injected dose relative to the plasma concentration-time area, obtained by a gamma-variate iterative fit. Clexp and Clu were determined by standard technique. In patients without fluid retention, Clgv , Clexp and Clu were closely similar. The difference between Clgv and Clu (Clgv - Clu = ΔCl) was mean -0...

Measurement of single kidney contrast media clearance by multiphasic spiral computed tomography: preliminary results

International Nuclear Information System (INIS)

Hackstein, N.; Puille, M.F.; Bak, Benjamin H.; Scharwat, Oliver; Rau, W.S.

2001-01-01

Objective. We present preliminary results of a new method (hereinafter called 'CT-clearance') to measure single kidney contrast media clearance by performing multiphasic helical CT of the kidneys. CT-clearance was calculated according to an extension of the Patlak-Plot. In contrast to prior investigators, who repeatedly measured a single slice, this method makes it possible to calculate single kidney clearance from at least three spiral CTs, utilizing the whole kidney volume. Methods. Spiral CT of the kidneys was performed unenhanced and about 30 and 100 s after administration of about 120 ml iopromide. Sum-density of the whole kidneys and aortic density was calculated from this data. Using this data, renal clearance of contrast media was calculated by CT-clearance in 29 patients. As reference, Serum-clearance was calculated in 24 patients by application of a modified one-exponential slope model. Information on the relative kidney function was gained by renal scintigraphy with Tc99m-MAG-3 or Tc99m-DMSA in 29 patients. Results. Linear regression analysis revealed a correlation coefficient of CT-clearance with Serum-clearance of r=0.78 with Cl (CT) [ml/min]=22.2+1.03 * Cl (serum), n=24. Linear regression of the relative kidney function (rkf) of the right kidney calculated by CT-clearance compared to scintigraphy results provided a correlation coefficient r=0.89 with rkf(CT)[%]=18.6+0.58 * rkf(scintigraphy), n=29. Conclusion. The obtained results of contrast media clearance measured by CT-clearance are in the physiological range of the parameter. Future studies should be performed to improve the methodology with the aim of higher accuracy. More specifically, better determination of the aortic density curve might improve the accuracy

Lung clearance of {sup 99m} Tc- DTPA in systemic lupus erythematous

Energy Technology Data Exchange (ETDEWEB)

Dalcin, P.T.R; Barreto, S.S.M.; Xavier, R.M.; Brenol, J.C.T. [Rio Grande do Sul Univ., Porto Alegre, RS (Brazil). Hospital de Clinicas. Dept. de Medicina Interna; Cunha, R.D.; Marroni, B.J. [Rio Grande do Sul Univ., Porto Alegre, RS (Brazil). Hospital de Clinicas. Servico de Medicina Nuclear]. E-mail: rxavier@hcpa.ufrgs.br

2002-06-01

The early demonstration of lung involvement in systemic lupus erythematosus (SLE) patients is a difficult but important task. In the present study we attempted to identify abnormalities in pulmonary clearance of 99 mTc-DTPA in SLE, correlating their clearance data with clinical findings and disease activity. Forty-six consecutive SLE patients with and without active disease (LACC score) and 30 normal volunteers were studied. All subjects were submitted to pulmonary scintigraphy with 99 mTc-DTPA to evaluate the pulmonary clearance, and to a chest X-ray, and SLE patients were submitted to tests of disease activity, spirometry, arterial blood gases and tests to assess acute-phase proteins. Pulmonary clearance was faster in SLE patients with active disease when compared to normal controls [half-life of 67.04 min (51.52-82.55 min) in active SLE versus 85.87 min (78.85-92.87 min) in controls, P<0.05] and there was a higher frequency of abnormal clearance rates in patients with active disease (11 of 26 patients, 42.3%) when compared with SLE patients without disease activity (2 of 20 patients, 10%) (P = 0.04). A significant correlation was observed between the clearance rates and cough (P<0.05), but not between the clearance rates and dyspnoea symptoms or radiological findings, duration of SLE disease, antinuclear antibody titers and patterns, C-reactive protein or anti-double stranded DNA antibodies. We conclude that the pulmonary clearance of 99 m Tc-DTPA is increased in SLE patients with active disease. (author)

A pharmacologic study on the mechanism of action of Kakkon-to: body temperature elevation and phagocytic activation of macrophages in dogs.

Science.gov (United States)

Muraoka, Kenichi; Yoshida, Satoshi; Hasegawa, Kazumasa; Nakanishi, Nobuo; Fukuzawa, Isao; Tomita, Akio; Cyong, Jong Chol

2004-10-01

The phagocytic activity of macrophages as a novel approach to scientific elucidation of the effects of Chinese medicines was studied through administration of a kampo preparation, by measuring the rise in body temperature, which is thought to stimulate innate defensive functions of organisms and enhance the immune systems. Using dogs as experimental models, a rise in body temperature following administration of Kakkon-to was observed, and the average number and average rate of phagocytosis of macrophages in blood using latex micro-particles was investigated. The body temperature of the treated animals significantly increased 30 minutes after administration (ptemperatures before and after administration showed significant increases over controls from 1 to 11 hours, ptemperature but also enhances the phagocytic activity of macrophages, an in vivo defense mechanism, suggesting that Kakkon-to contributes to the suppression of multiplication of common cold viruses and influenza viruses, which consequently results in improvement of various symptoms during infection with common cold viruses.

Comparison of arterial intimal clearances of LDL from diabetic and nondiabetic cholesterol-fed rabbits. Differences in intimal clearance explained by size differences

International Nuclear Information System (INIS)

Nordestgaard, B.G.; Zilversmit, D.B.

1989-01-01

Arterial intimal clearances of low density lipoproteins (LDL) from diabetic cholesterol-fed rabbits (D-LDL) and LDL from nondiabetic cholesterol-fed rabbits (N-LDL) were compared. In six experiments, D-LDL and N-LDL were isolated from a diabetic and a nondiabetic rabbit, were iodinated with 125I and 131I, respectively, were mixed, and were reinjected into the same two rabbits as well as into a normal rabbit. Fractional catabolic rates for D-LDL and N-LDL in normal rabbits were 0.065 and 0.074 h-1 (p less than 0.05), respectively. For five of the six pairs of LDL, the D-LDL was smaller than N-LDL as determined by gel filtration. The arterial permeability to N-LDL, when normalized for differences in arterial cholesterol content, did not appear to differ between diabetic and nondiabetic rabbits. The relative arterial intimal clearance (D-LDL/N-LDL) in arteries from diabetic and nondiabetic rabbits was inversely related to the relative molecular weight (D-LDL/N-LDL). For example, when the molecular weight of D-LDL was as low as 60% of that of N-LDL (i.e., the diameter of D-LDL was reduced 16%), the intimal clearance of D-LDL was 40% larger than that of N-LDL. When, on the other hand, molecular weights and diameters of the two LDL were similar, the intimal clearance was also quite similar. These results suggest that arterial intimal clearance of LDL from diabetic and nondiabetic cholesterol-fed rabbits is comparable unless the two types of LDL have a different size

Clearance of slightly radioactive material from radiological control in Germany

International Nuclear Information System (INIS)

Thierfeldt, S.

1995-01-01

Clearance from radiological control of slightly radioactive material arising from operation or decommissioning of nuclear installations has been practiced in Germany for nearly two decades. Meanwhile, for the clearance of metal generally approved and applicable recommendations for clearance levels have been issued. For other materials like building waste, case-by-case decisions are made by the state licensing authorities. Efforts to implement consistent sets of clearance levels for all kinds of material are under way. As several decommissioning projects will soon generate large amounts of materials from dismantling, a solution needs to be reached soon. The legal framework in Germany governing the use of atomic energy consists of the Atomic Energy Act and several ordinances. Rules and guidelines including the recommendations of the German Commission for Radiation Protection (SSK) exist on a lower level and are not legally binding. Several generic studies for the derivation of clearance levels for metals and building debris with alpha, beta, and gamma contamination have been performed on behalf of the Federal Ministry for Environment, Nature Conservation and Nuclear Safety, which oriented themselves on an individual dose of 10 microSv/a in agreement with IAEA recommendations. Stochastic models have been used for establishing the connection between specific activity of the material to be released and the resulting individual doses, with significant advantages over deterministic scenarios. In the future, for new SSK recommendations or an ordinance on clearance, the increase of masses from demolition of installations, higher recycling rates in the conventional sector and harmonization with international regulations and standards have to be taken into account

Efficacy, safety and pharmacokinetics of sugammadex 4 mg kg-1 for reversal of deep neuromuscular blockade in patients with severe renal impairment

NARCIS (Netherlands)

Panhuizen, I. F.; Gold, S. J. A.; Buerkle, C.; Snoeck, M. M. J.; Harper, N. J. N.; Kaspers, M. J. G. H.; van den Heuvel, M. W.; Hollmann, M. W.

2015-01-01

This study evaluated efficacy and safety of sugammadex 4 mg kg(-1) for deep neuromuscular blockade (NMB) reversal in patients with severe renal impairment (creatinine clearance [CLCR] <30 ml min(-1)) vs those with normal renal function (CLCR ≥80 ml min(-1)). Sugammadex 4 mg kg(-1) was administered

Impaired brain glymphatic flow in a rodent model of chronic liver disease and minimal hepatic encephalopathy

OpenAIRE

Lythgoe, Mark; Hosford, Patrick; Arias, Natalia; Gallego-Duran, Rocio; Hadjihambi, Anna; Jalan, Rajiv; Gourine, Alexander; Habtesion, Abeba; Davies, Nathan; Harrison, Ian

2017-01-01

Neuronal function is exquisitely sensitive to alterations in extracellular environment. In patients with hepatic encephalopathy (HE), accumulation of metabolic waste products and noxious substances in the interstitial fluid of the brain may contribute to neuronal dysfunction and cognitive impairment. In a rat model of chronic liver disease, we used an emerging dynamic contrast-enhanced MRI technique to assess the efficacy of the glymphatic system, which facilitates clearance of solutes from t...

Caffeic acid and quercetin exert caspases-independent apoptotic effects on Leishmania major promastigotes, and reactivate the death of infected phagocytes derived from BALB/c mice

Directory of Open Access Journals (Sweden)

Radia Belkhelfa-Slimani

2017-04-01

Conclusions: The leishmanicidal effect of caffeic acid and quercetin on promastigotes and amastigotes, as well as reactivation of infected phagocytes apoptosis, suggested a potential therapeutic role against cutaneous leishmaniasis.

Clearance of building structures for conventional non-nuclear reuse

International Nuclear Information System (INIS)

Buss, K.; Boehringer, S.

1998-01-01

At the example of a fuel assembly plant the strategy of control measurements on building surfaces, which shall be conventionally reused after their clearance, is regarded. Based on the given clearance levels the used measuring methods, especially with regard of possibly covered or intruded uranium contamination, are shown. The possibility of using the in-situ-γ-spectroscopy is discussed. (orig.) [de

CO2 clearance by membrane lungs.

Science.gov (United States)

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

2018-05-01

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

Assessment of inflammatory bowel disease activity by technetium 99m phagocyte scanning

International Nuclear Information System (INIS)

Pullman, W.E.; Sullivan, P.J.; Barratt, P.J.; Lising, J.; Booth, J.A.; Doe, W.F.

1988-01-01

Autologous technetium 99m-labeled phagocyte scanning has been used to assess disease activity in inflammatory bowel disease in 51 consecutive patients. Strong correlations were found between the 24-h fecal excretion of isotope and the histologic score of mucosal biopsy specimens (rS = 0.84, p less than 0.001, where rS is Spearman's rank correlation coefficient), and between the 24-h fecal excretion of isotope and a clinical inflammatory bowel disease activity index based on the Crohn's disease activity index (rS = 0.87, p less than 0.001). To develop a clinically useful and objective measure of inflammatory bowel disease activity that did not require a 24-h stool collection, the intensity of bowel uptake on scanning was graded visually from 0 to 4, a ratio of count rates for the region of interest to the iliac crest reference region was calculated, and the rapidity of labeled phagocyte uptake into inflamed bowel was measured as the peak uptake time. Visual grading of disease activity on the scans was validated by comparing it with the ratio of count rates from inflamed bowel regions of interest and those from the iliac crest reference region. The ratio of count rates showed a significant correlation with the clinical disease activity index (r = 0.75, p less than 0.001). The visual scan grade also correlated well with the clinical activity index (r = 0.87, p less than 0.001). Count rates from hourly scans were also used to calculate the time of peak uptake of counts for a given region of interest. There was a strong negative correlation between this peak uptake time and the fecal excretion of isotope (rS = -0.81, p less than 0.001), a clinical activity index (r = -0.60, p less than 0.001), and the histologic score of the mucosal biopsy specimens (r = -0.84, p less than 0.001)

Dynamic analysis of cross shaft type universal joint with clearance

International Nuclear Information System (INIS)

Lu, Jian Wei; Wang, Gong Cheng; Chen, Hao; Vakakis, Alexander F.; Bergman, Lawrence A.

2013-01-01

Cross shaft type universal joint is widely used in ground vehicles to transfer torque between two intersecting axes, and its transmission feature can make a great contribution to NVH performance of the vehicle. We looked at the assembling clearance at cross shaft neck, and presented a dynamic model of cross shaft type universal joint with clearance at cross shaft neck. Two-state model is applied to describe the contact force between the cross shaft and driving joint fork based on Hertz theorem, and lumped mass method is applied to build up the dynamic model of the universal joint. Based on this model, numerical analysis is carried out to discuss the transmission feature of the universal joint with clearance at cross shaft neck, and the influence of clearance on the dynamic behavior of the system is evaluated with numerical results based on time history, power spectrum, and phase portrait. The method and conclusions presented are helpful to improvement of the transmission feature of cross shaft type universal joint.

Cellular defense of the avian respiratory system: effects of Pasteurella multocida on respiratory burst activity of avian respiratory tract phagocytes.

Science.gov (United States)

Ochs, D L; Toth, T E; Pyle, R H; Siegel, P B

1988-12-01

The respiratory tract of healthy chickens contain few free-residing phagocytic cells. Intratracheal inoculation with Pasteurella multocida stimulated a significant (P less than 0.05) migration of cells to the lungs and air sacs of White Rock chickens within 2 hours after inoculation. We found the maximal number of avian respiratory tract phagocytes (22.9 +/- 14.0 x 10(6] at 8 hours after inoculation. Flow cytometric analysis of these cells revealed 2 populations on the basis of cell-size and cellular granularity. One of these was similar in size and granularity to those of blood heterophils. Only this population was capable of generating oxidative metabolites in response to phorbol myristate acetate. The ability of the heterophils to produce hydrogen peroxide, measured as the oxidation of intracellularly loaded 2',7'-dichlorofluorescein, decreased with time after inoculation. These results suggest that the migration of heterophils, which are capable of high levels of oxidative metabolism, to the lungs and air sacs may be an important defense mechanism of poultry against bacterial infections of the respiratory tract.

Uncertainty analysis of 99mTc-HEPIDA liver clearance determination

International Nuclear Information System (INIS)

Surma, M. J.

2005-01-01

The aim of the study was to obtain information on the accuracy and precision of 99mT c-HEPIDA hepatic (Cl H p) and plasma (Cl P l) clearances and selection of an appropriate estimator of the measurement uncertainty of a single determination of these quantities. In a simulation (Monte Carlo) experiment, it was assumed that the recorded results of plasma and hepatic clearances, as obtained from 185 patients, provided authentic information about 99mT c-HEPIDA behaviour in the body over a wide range of the clearances studied. The time-course 99mT c-HEPIDA concentration in blood plasma has been described by means of biexponential function with parameter values derived for each patient. For each patient, using these data and urinary excretion data, there had been 5000 simulations performed; in each of the latter, the directly measured numbers have been substituted by simulated ones, obtained by means of varying the real ones, using random generated values. These reflected errors of plasma and radioactive standard pipetting (from 1 to 5%) and stochasticity of counting radioactive decay (1%). The time of blood sampling and urine voiding was also varied, assuming realistic uncertainty. The varied values were then used for computation of the simulated clearances. From the 5000 calculated clearances for each patient, mean-values were calculated, as well as mean standard errors, standard deviations and mean uncertainty of measurements using a widely accepted rule of partial error propagation, and, in addition, a modified rule of the latter. Accuracy of clearance (Cl P l, Cl H p, Cl U r) determination was assessed on the basis of comparison of mean values from simulations with those from directly recorded values. Precision was identified with standard deviation of each of the 5000 simulations. The uncertainty thus obtained was compared with results of calculated traditional and modified uncertainty. There was good agreement between standard deviation of the simulations with

Online feedback-controlled renal constant infusion clearances in rats.

Science.gov (United States)

Schock-Kusch, Daniel; Shulhevich, Yury; Xie, Qing; Hesser, Juergen; Stsepankou, Dzmitry; Neudecker, Sabine; Friedemann, Jochen; Koenig, Stefan; Heinrich, Ralf; Hoecklin, Friederike; Pill, Johannes; Gretz, Norbert

2012-08-01

Constant infusion clearance techniques using exogenous renal markers are considered the gold standard for assessing the glomerular filtration rate. Here we describe a constant infusion clearance method in rats allowing the real-time monitoring of steady-state conditions using an automated closed-loop approach based on the transcutaneous measurement of the renal marker FITC-sinistrin. In order to optimize parameters to reach steady-state conditions as fast as possible, a Matlab-based simulation tool was established. Based on this, a real-time feedback-regulated approach for constant infusion clearance monitoring was developed. This was validated by determining hourly FITC-sinistrin plasma concentrations and the glomerular filtration rate in healthy and unilaterally nephrectomized rats. The transcutaneously assessed FITC-sinistrin fluorescence signal was found to reflect the plasma concentration. Our method allows the precise determination of the onset of steady-state marker concentration. Moreover, the steady state can be monitored and controlled in real time for several hours. This procedure is simple to perform since no urine samples and only one blood sample are required. Thus, we developed a real-time feedback-based system for optimal regulation and monitoring of a constant infusion clearance technique.

Elevated cystatin C: is it a reflection for kidney or liver impairment in hepatic children?

Science.gov (United States)

El-Sayed, Behairy; El-Araby, Hanaa; Adawy, Nermin; Hassona, Mona; El-Nady, Naglaa; Zakaria, Haidy; Khedr, Mohammed

2017-09-01

To assess if elevated serum cystatin C (Cyst-C) is an indicator for renal or hepatic dysfunction in presence of liver fibrosis. Data of 50 children with chronic liver diseases (CLDs), out of which 25 were without renal impairment, and 25 with renal impairment were analyzed. Twenty healthy children served as a healthy control group. Routine investigations, creatinine clearance, hepatitis viral markers, abdominal ultrasonography, and liver biopsy were performed for patients with CLDs. Measurement of serum Cyst-C concentration by particle induced immunonephelometry were completed for both patients and control group. Results showed that serum Cyst-C is not correlated with the degree of hepatic impairment ( p > 0.05). Cyst-C levels were significantly higher in patients with renal impairment (3.66 ± 0.85) than those without (0.71 ± 0.12), and healthy control group (0.63 ± 0.85). Cystatin-C showed significant elevation in patients with severe fibrosis with renal impairment (3.66 ± 0.85) than those without (0.76 ± 0.04) ( p without renal impairment. Cyst-C > 2.34 mg/l predicting GFR 2.73 mg/l predicting GFR impairment in children with CLDs. Further studies are needed to estimate the accuracy of serum Cyst-C for early detection of renal impairment and close monitoring of the hepatic children.

The atherogenic bacterium Porphyromonas gingivalis evades circulating phagocytes by adhering to erythrocytes

DEFF Research Database (Denmark)

Belstrøm, Daniel; Holmstrup, Palle; Damgaard, Christian

2011-01-01

A relationship between periodontitis and coronary heart disease has been investigated intensively. A pathogenic role for the oral bacterium Porphyromonas gingivalis has been suggested for both diseases. We examined whether complement activation by P. gingivalis strain ATCC 33277 allows...... the bacterium to adhere to human red blood cells (RBCs) and thereby evade attack by circulating phagocytes. On incubation with normal human serum, the P. gingivalis strain efficiently fixed complement component 3 (C3). Incubation of bacteria with washed whole blood cells suspended in autologous serum resulted...... in a dose- and time-dependent adherence to RBCs. The adherence required functionally intact complement receptor 1 (CR1; also called CD35) on the RBCs and significantly inhibited the uptake of P. gingivalis by neutrophils and B cells within 1 min of incubation (by 64% and 51%, respectively...

Exclusion, exemption, clearance European Union approach

International Nuclear Information System (INIS)

Janssens, A.

1997-01-01

The presentation overviews the following issues: Euratom Basic Safety Standards; administrative requirements; radiation protection of the population. Scope of the Standards: natural radiation sources; exclusion. Exemption; Clearance; Import of radioactive scrap metal

A simple method for the verification of clearance levels for non-radioactive solid waste

International Nuclear Information System (INIS)

Holland, B.

1997-01-01

ANSTO's radiopharmaceutical production laboratories generate 25 m 3 of solid waste per month. Most of this waste is not radioactive. Up until recently the non-radioactive waste was cleared from the controlled area and stored for 10 halflives prior to disposal as normal solid refuse. To eliminate the storage and ''double handling'' of the large quantities of non-radioactive waste a simple clearance method was devised to allow direct disposal. This paper describes how clearance levels were determined. Here the term ''clearance level'' is used as a general term for the release of material regardless of whether it was previously subject to regulatory control. This contrasts with the IAEA definition of a clearance level and highlights a potential problem with the implementation of exemption levels to keep material out of regulatory control and the use of clearance levels to allow removal of materials from regulatory control. Several common hand held contamination monitors were tested to determine their limits of detection and ability to meet these clearance levels. The clearance method includes waste segregation and size limitation features to ensure the waste is monitored in a consistent manner, compatible with the limits of detection. The clearance levels achieved were subsequently found to be compatible with some of the unconditional clearance levels in IAEA-TECDOC-855 and the measurement method also meets the required features of that document. The ANSTO non-radioactive waste clearance system has been in operation for more than 12 months and has proved simple and effective to operate. Approximately 12m 3 of the solid waste is now been treated directly as normal solid refuse. This paper describes the ANSTO clearance system, the contamination monitor tests and details practical problems associated with the direct monitoring of solid waste, including averaging of the activity in the package. The paper also briefly highlights the potential problem with the use of

Nuclear security. DOE actions to improve the personnel clearance program

International Nuclear Information System (INIS)

Fultz, Keith O.; Bannerman, Carl J.; Daniel, Beverly A.

1988-11-01

The status of the Department of Energy's (DOE) implementation of recommendations in our two reports on DOE's personnel security clearance program was determined. The recommendations were aimed at improving the timeliness, accuracy, and efficiency of personnel security clearance decisions. Specifically, the objective was to determine and report on steps DOE is taking to implement these recommendations. In summary, it was found that DOE has either initiated action or is studying ways to address all the recommendations, but none of the recommendations have been completely implemented. The effectiveness of the DOE actions will depend, in part, on the adequacy of its internal control system for overseeing and evaluating program operations. DOE's personnel security clearance program is intended to provide reasonable assurance that personnel with access to classified information and materials are trustworthy. The Department requests that the Office of Personnel Management or the Federal Bureau of Investigation collect personal data on each person who requires such access to do his or her job. Based on these background investigations, DOE officials authorize individuals whose personal histories indicate that they are trustworthy to have access to classified information, secured facilities, and controlled materials as needed to perform their jobs. DOE has five types of these authorizations or personnel security clearances and must update information on personnel holding each type at 5-year intervals to confirm their continuing reliability. The five types are based on the types of security interests to which the person needs access, e.g., persons needing nuclear weapons-related data must have a Q clearance, and persons with a top secret clearance can have access to national security data classified as top secret

Clearance potential of ITER vacuum vessel activated materials

International Nuclear Information System (INIS)

Cepraga, D.G.; Cambi, G.; Frisoni, M.

2002-01-01

To demonstrate fusion's environmental attractiveness over the entire life cycle, a waste analysis is mandatory. The clearance is recommended by IAEA for releasing activated solid materials from regulatory control and for waste management policy. The paper focuses on the approach used to support waste analyses for ITER Generic Site Safety Report. The Material Unconditional Clearance Index of all the materials/zones on the equatorial mid-plane of ITER machine have been evaluated, based on IAEA-TECDOC-855. The Bonami-Nitawl-XSDNRPM sequence of the Scale-4.4a code system (using Vitenea-J library) has been firstly used for radiation transport analyses. Then the Anita-2000 code package is used for the activation calculation. The paper presents also, as an example, an application of the clearance indexes estimation for the ITER vacuum vessel materials. The results of the Anita-2000 have been compared with those obtained using the Fispact-99 activation code. (author)

Metabolic clearance of insulin from the cerebrospinal fluid in the anesthetized rat

International Nuclear Information System (INIS)

Manin, M.; Broer, Y.; Balage, M.; Rostene, W.; Grizard, J.

1990-01-01

Infusion of 125I-(Tyr A14)-insulin at tracer doses into the cerebrospinal fluid (CSF) resulted in a slow rate of increase in the CSF-labeled insulin during the first 2 hours with a plateau thereafter. Labeled insulin was cleared from the CSF at a higher rate than 3H-inulin, a marker of CSF bulk flow. The labeled insulin was mainly distributed in all the ventricular and periventricular brain regions. Small amounts of degraded insulin appeared in the CSF. Coinfusion with an excess of unlabeled insulin impaired the clearance and degradation of labeled insulin. It also inhibited the labeling in medial hypothalamus, olfactory bulbs and brain stem. In contrast, coinfusion of ribonuclease B (used to test the specificity of uptake) was without any effect. It was concluded that there is an active insulin intake from CSF into brain specific compartments that is presumably essential for the effects of insulin on brain function

Contrast media and glomerular filtration: dose dependence of clearance for three agents

International Nuclear Information System (INIS)

Baeck, S.E.K.; Krutzen, E.; Nilsson-Ehle, P.

1988-01-01

Determination of plasma clearance of contrast agents has been advocated as a means to assess glomerular filtration rate. To evaluate the feasibility of different agents for this purpose, we have compared, in healthy volunteers, the dose dependence of plasma clearance for three contrast media (iohexol, a nonionic agent, and iothalamate and metrizoate, which are ionic substances), with special emphasis on the lower dose range (2-20 mL corresponding to 0.9-12.9 g, depending on dose and agent). Iohexol and iothalamate were cleared at constant rates, irrespective of given dose, whereas metrizoate clearance increased significantly at lower doses. In general, the clearances or iothalamate and metrizoate were, respectively, moderately and markedly higher than that of iohexol. The clearance of different doses of metrizoate (2 mL versus a radiographic dose of 40 mL or more) was also compared with the clearance of [ 51 Cr]EDTA in two groups of patients with reduced renal function. When compared with [ 51 Cr]EDTA in patients with renal dysfunction, metrizoate was cleared significantly faster after a 2-mL dose, whereas clearances were identical when the metrizoate dose was 40 mL or more. These findings indicate that tubular secretion plays an active role in the elimination of metrizoate. The pharmacokinetic properties of iohexol, in combination with its low toxicity, make it a suitable agent for determination of glomerular filtration rate in clinical practice

Clearance from the anterior chamber of RBCs from human diabetics

International Nuclear Information System (INIS)

Williams, G.A.; Hatchell, D.L.; Collier, B.D.; Knobel, J.

1984-01-01

Erythrocytes from diabetic patients manifest decreased deformability and increased adherence. These abnormal membrane properties may diminish the ability of erythrocytes (RBCs) from diabetics to undergo deformation in passage through the trabecular meshwork. Using sodium chromate Cr 51-labeled RBCs from type I diabetic patients with proliferative retinopathy and normal control subjects, we studied RBC clearance from the rabbit anterior chamber. The mean time for 50% clearance (T50) of RBCs from diabetics (76 hours) was significantly longer than that for RBCs from normal subjects (19.5 hours). In this model, RBCs from diabetics have a slower clearance from the anterior chamber than do RBCs from normal subjects

Experimental Study of Unshrouded Impeller Pump Stage Sensitivity to Tip Clearance

Science.gov (United States)

Williams, Robert W.; Zoladz, Thomas; Storey, Anne K.; Skelley, Stephen E.

2002-01-01

This viewgraph presentation provides information on an experiment. Its objective is to experimentally determine unshrouded impeller performance sensitivity to tip clearance. The experiment included: Determining impeller efficiency at scaled operating conditions in water at MSFC's Pump Test Equipment (PTE) Facility; Testing unshrouded impeller at three different tip clearances; Testing each tip clearance configuration at on- and off-design conditions, and collecting unsteady- and steady-state data in each configuration; Determining impeller efficiency directly using drive line torquemeter and pump inlet and exit total pressure measurements.

Exaggerated natriuresis and lithium clearance in spontaneously hypertensive rats

DEFF Research Database (Denmark)

Holstein-Rathlou, N H; Kanters, J K; Leyssac, P P

1988-01-01

Since hypertension is associated with changes in the handling of various cations (including sodium and lithium) across the cell membrane, the present study investigated the validity of the lithium clearance method in hypertension by comparing two measures of proximal reabsorption. Thus, fractional...... lithium excretion and transit time (TT)-occlusion time (OT; e-TT/T) were determined successively in the same spontaneously hypertensive rat (SHR, Okamoto strain). The rats were examined both before and after an acute saline load. The results show that the lithium clearance method can be used...... for the determination of proximal reabsorption in SHR. Utilizing the lithium clearance method, the changes in renal sodium handling underlying the exaggerated natriuresis were investigated in unanaesthetized catheterized rats. It was found that the exaggerated natriuresis was associated with an increased output from...

Kinematics Simulation Analysis of Packaging Robot with Joint Clearance

Science.gov (United States)

Zhang, Y. W.; Meng, W. J.; Wang, L. Q.; Cui, G. H.

2018-03-01

Considering the influence of joint clearance on the motion error, repeated positioning accuracy and overall position of the machine, this paper presents simulation analysis of a packaging robot — 2 degrees of freedom(DOF) planar parallel robot based on the characteristics of high precision and fast speed of packaging equipment. The motion constraint equation of the mechanism is established, and the analysis and simulation of the motion error are carried out in the case of turning the revolute clearance. The simulation results show that the size of the joint clearance will affect the movement accuracy and packaging efficiency of the packaging robot. The analysis provides a reference point of view for the packaging equipment design and selection criteria and has a great significance on the packaging industry automation.

Numerical study on tip clearance effect on performance of a centrifugal compressor

International Nuclear Information System (INIS)

Eum, Hark Jin; Kang, Shin Kyoung

2003-01-01

Effect of tip leakage flow on through flow and performance of a centrifugal compressor impeller was numerically studied using CFX-TASCflow. Seven different tip clearances were used to consider the influence of tip clearance on performance. Secondary flow and loss factor were evaluated to understand the loss mechanism inside the impeller due to tip leakage flow. The calculated results were circumferentially averaged along the passage and at the impeller exit for quantitative discussion. Tip clearance effect on performance could be decomposed into inviscid and viscous components using one dimensional equation. The inviscid component is related with the specific work reduction and the viscous component is related with the additional entropy generation. Two components affected performance equally, while efficiency drop was mainly influenced by viscous loss. Performance and efficiency drop due to tip clearance were proportional to the ratio of tip clearance to exit blade height. A simple model suggested in the present study predict performance and efficiency drop quite successfully

Plasma Creatinine Clearance in the Dog

Science.gov (United States)

Frazier, Loy W.

1977-01-01

Lists materials and methods for an experiment that demonstrates the concept of glomerular filtration rate (GFR) using anesthesized dogs. In the dog, GFR is equivalent to the renal plasma clearance of exogenous creatinine. (CS)

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

Directory of Open Access Journals (Sweden)

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.

Renal clearance of /sup 99m/Tc-methylene-diphosphonate in human beings

Energy Technology Data Exchange (ETDEWEB)

Vattimo, A.

1987-12-01

The renal clearance of /sup 99m/Tc-MDP was measured in 13 patients who had bone scans and compared with the renal clearance of /sup 51/Cr-EDTA. No difference was found between the renal clearance of the two tracers, showing a close correlation (r = 0.98). These data suggest that the /sup 99m/Tc-MDP is excreted by the kidneys by glomerular filtration without tubular secretion.

Frequency and factors effecting non clearance of lower pole renal stones

International Nuclear Information System (INIS)

Ullah, A.; Zubair, M.; Khan, N.; Malik, A.

2015-01-01

Renal stone disease is a major health hazard in Pakistan and extra-corporeal shockwave lithotripsy is one of comprehensive method used to treat these stones. The aim of this study is to determine the frequency of factors affecting the non-clearance of stone fragments of lower pole renal stone after extra corporeal shockwave lithotripsy. The study was done with the objective to determine the frequency the spatial anatomical factors which can influence the non-clearance of lower pole stone fragments after ESWL. Methods: One and nineteen (119) patients with lower pole renal stone less than 10 mm were subjected to maximum 3 sessions of extracorporeal shock wave lithotripsy. KUB radiographs, ultrasonography and intravenous urography were used as investigative tools for lower pole renal calyceal anatomy. X ray KUB and ultrasound were done after a week for clearance. Data was analysed with the help of SPSS version 10.0 and presented in the forms of tables and graphs. Results: There were 77 (64.71%) males and 42 (35.29%) females. Infundibulo-pelvic angle (IPA)>40 degree was present in 93 (78.15%), Infundibular length (IL) <22 mm in 107 (89.92%) and Infundibular width (IW) >4 mm was present in 100 (84.03%) patients. The frequency of stone non clearance was noted in 31 (26.05%). Infundibulo-pelvic angle (IPA)>40 degree (p=0.000), Infundibular length (IL)<22 mm (p=0.001) and Infundibular width (IW)>4 mm (p=0.046) were significant variables affecting stone clearance. Conclusion: The frequency of non-clearance of lower calyx of kidney stone is 26.05%. The clearance of fragments of the lower calyx kidney stones is affected by three spatial anatomical factors, i.e., Infundibulopelvic angle, Infundibular width and infundibular length. (author)

Intermittent Hypoxia Affects the Spontaneous Differentiation In Vitro of Human Neutrophils into Long-Lived Giant Phagocytes

Directory of Open Access Journals (Sweden)

Larissa Dyugovskaya

2016-01-01

Full Text Available Previously we identified, for the first time, a new small-size subset of neutrophil-derived giant phagocytes (Gϕ which spontaneously develop in vitro without additional growth factors or cytokines. Gϕ are CD66b+/CD63+/MPO+/LC3B+ and are characterized by extended lifespan, large phagolysosomes, active phagocytosis, and reactive oxygen species (ROS production, and autophagy largely controls their formation. Hypoxia, and particularly hypoxia/reoxygenation, is a prominent feature of many pathological processes. Herein we investigated Gϕ formation by applying various hypoxic conditions. Chronic intermittent hypoxia (IH (29 cycles/day for 5 days completely abolished Gϕ formation, while acute IH had dose-dependent effects. Exposure to 24 h (56 IH cycles decreased their size, yield, phagocytic ability, autophagy, mitophagy, and gp91-phox/p22-phox expression, whereas under 24 h sustained hypoxia (SH the size and expression of LC3B and gp91-phox/p22-phox resembled Gϕ formed in normoxia. Diphenyl iodide (DPI, a NADPH oxidase inhibitor, as well as the PI3K/Akt and autophagy inhibitor LY294002 abolished Gϕ formation at all oxygen conditions. However, the potent antioxidant, N-acetylcysteine (NAC abrogated the effects of IH by inducing large CD66b+/LC3B+ Gϕ and increased both NADPH oxidase expression and phagocytosis. These findings suggest that NADPH oxidase, autophagy, and the PI3K/Akt pathway are involved in Gϕ development.

Delayed clearance of serum HBsAg in compensated cirrhosis B

DEFF Research Database (Denmark)

Fattovich, G; Giustina, G; Sanchez-Tapias, J

1998-01-01

The aim of this study was to evaluate the incidence, prognostic factors and clinical significance of delayed clearance of serum HBsAg in compensated cirrhosis B.......The aim of this study was to evaluate the incidence, prognostic factors and clinical significance of delayed clearance of serum HBsAg in compensated cirrhosis B....

Tissues Use Resident Dendritic Cells and Macrophages to Maintain Homeostasis and to Regain Homeostasis upon Tissue Injury: The Immunoregulatory Role of Changing Tissue Environments

Science.gov (United States)

Lech, Maciej; Gröbmayr, Regina; Weidenbusch, Marc; Anders, Hans-Joachim

2012-01-01

Most tissues harbor resident mononuclear phagocytes, that is, dendritic cells and macrophages. A classification that sufficiently covers their phenotypic heterogeneity and plasticity during homeostasis and disease does not yet exist because cell culture-based phenotypes often do not match those found in vivo. The plasticity of mononuclear phagocytes becomes obvious during dynamic or complex disease processes. Different data interpretation also originates from different conceptual perspectives. An immune-centric view assumes that a particular priming of phagocytes then causes a particular type of pathology in target tissues, conceptually similar to antigen-specific T-cell priming. A tissue-centric view assumes that changing tissue microenvironments shape the phenotypes of their resident and infiltrating mononuclear phagocytes to fulfill the tissue's need to maintain or regain homeostasis. Here we discuss the latter concept, for example, why different organs host different types of mononuclear phagocytes during homeostasis. We further discuss how injuries alter tissue environments and how this primes mononuclear phagocytes to enforce this particular environment, for example, to support host defense and pathogen clearance, to support the resolution of inflammation, to support epithelial and mesenchymal healing, and to support the resolution of fibrosis to the smallest possible scar. Thus, organ- and disease phase-specific microenvironments determine macrophage and dendritic cell heterogeneity in a temporal and spatial manner, which assures their support to maintain and regain homeostasis in whatever condition. Mononuclear phagocytes contributions to tissue pathologies relate to their central roles in orchestrating all stages of host defense and wound healing, which often become maladaptive processes, especially in sterile and/or diffuse tissue injuries. PMID:23251037

Turbulent Heat Transfer of a Finned Plate in a Duct as Tip Clearance Changes

Energy Technology Data Exchange (ETDEWEB)

Park, Hae-Kyun; Chung, Bum-Jin [Kyung Hee University, Yongin (Korea, Republic of)

2015-05-15

Fins are employed to enhance the cooling performance of a system. There are a number of studies relevant to geometry of fins. Meanwhile, the studies relevant to tip clearance, have not performed enough, which is the distance between the tips of the fins and the wall. We investigated the optimal tip clearance, which maximizes the heat transfers by experimental and numerical analyses with wider range of Re{sub Dh} than the previous studies. Turbulent heat transfers of a finned plate were measured. For an extended range of tip clearance and Re{sub Dh} than other studies. A joint experimental and numerical analyses was performed to measure heat transfers. Mass transfer experiments using electroplating system was used and FLUENT 6.3.26 was used for the calculation. For the narrow tip clearances below 5 mm, were investigated by numerical method only. The bypass flow to the tip clearance region contributes to heat transfer area at the tip clearance region and does not contributes that of the fin region. Thus, the optimal tip clearance was founded and it exists vicinity of 0.2 mm.

Impaired free water excretion in child C cirrhosis and ascites: relations to distal tubular function and the vasopressin system

DEFF Research Database (Denmark)

Krag, Aleksander; Møller, Søren; Pedersen, Erling B

2010-01-01

were studied during a 400 ml/h oral water load. Results: Child C patients had a lower baseline glomerular filtration rate (32 vs 63 ml/min, Pwater clearance () did not differ (-0......: In Child C cirrhosis, ascites and mild hyponatraemia, there is an impaired ability to excrete solute-free water. The patients are characterised by a low glomerular filtration rate, a low distal tubular flow and an inability to increase free water clearance during water loading. This may be related......Abstract Background: Water retention in advanced cirrhosis and ascites may involve disturbances in renal distal tubular function and in the vasopressin system. Methods: Twelve patients with Child B cirrhosis and ascites were compared with 11 patients with Child C cirrhosis and ascites. The subjects...

Novel sensors to enable closed-loop active clearance control in gas turbine engines

Science.gov (United States)

Geisheimer, Jonathan; Holst, Tom

2014-06-01

Active clearance control within the turbine section of gas turbine engines presents and opportunity within aerospace and industrial applications to improve operating efficiencies and the life of downstream components. Open loop clearance control is currently employed during the development of all new large core aerospace engines; however, the ability to measure the gap between the blades and the case and close down the clearance further presents as opportunity to gain even greater efficiencies. The turbine area is one of the harshest environments for long term placement of a sensor in addition to the extreme accuracy requirements required to enable closed loop clearance control. This paper gives an overview of the challenges of clearance measurements within the turbine as well as discusses the latest developments of a microwave sensor designed for this application.

Does sleep disturbance affect the amyloid clearance mechanisms in Alzheimer's disease?

Science.gov (United States)

Yulug, Burak; Hanoglu, Lutfu; Kilic, Ertugrul

2017-10-01

Sleep is an important factor that plays a key role in Alzheimer's disease pathogenesis. However, it is still unclear whether poor-quality sleep may overlap with sleep disturbances in the underlying dysfunctional mechanisms of amyloid beta (Aβ) clearance metabolism. Here, we aimed to evaluate the current evidence on the role of sleep deprivation in Aβ clearance metabolism. To that end, we discuss possible mechanisms underlying the bidirectional interaction between the sleep deprivation and Aβ clearance pathways. © 2017 The Authors. Psychiatry and Clinical Neurosciences © 2017 Japanese Society of Psychiatry and Neurology.

76 FR 59379 - Proposed Information Collection; Comment Request; Generic Clearance for Research in Development...

Science.gov (United States)

2011-09-26

...-XXXX. Type of Review: Generic Clearance Request. Title: Generic Clearance for Research in Development... information collected through qualitative evaluation methods will inform the disclosure form's design and... Proposed Information Collection; Comment Request; Generic Clearance for Research in Development of...

A comparison of analytic procedures for measurement of fractional dextran clearances

NARCIS (Netherlands)

Hemmelder, MH; de Jong, PE; de Zeeuw, D

Fractional dextran clearances have been extensively used to study glomerular size selectivity. We report on an analysis of different laboratory procedures involved in measuring fractional dextran clearances. The deproteinization of plasma samples by 20% trichloroacetic acid (TCA) revealed a protein

Spontaneous Clearance of Hepatitis C after Liver and Renal Transplantation

Directory of Open Access Journals (Sweden)

CH Dale

2009-01-01

Full Text Available Spontaneous clearance of hepatitis C virus (HCV is rare in immunocompromised patients, such as those who have undergone organ transplantation. It has been recognized that patients receiving liver transplantation for HCV-related disease have decreased graft and patient survival compared with those transplanted for other etiologies. There is a growing trend toward treating HCV recurrence aggressively after liver transplantation. For other organ transplant recipients with concurrent HCV, treatment is not often an option, given the high rates of graft rejection and loss secondary to interferon and its immunomodulatory effects. Although spontaneous clearance of HCV has been reported in recipients of solitary liver and renal transplants, a common factor arising in these cases has been previous exposure to interferon. To date, no reports of spontaneous clearance of HCV RNA have been reported in a multiorgan transplant recipient. A case of spontaneous clearance of HCV RNA in an immunocompromised patient, within five months of simultaneous liver and kidney retransplantation is described. Importantly, this patient had no previous exposure to interferon.

Derivation methods for clearance levels applied to reactors

International Nuclear Information System (INIS)

Okoshi, Minoru; Seki, Takeo

2001-01-01

In order to support the discussion by the Nuclear Safety Commission, JAERI derived the unconditional clearance levels for concrete and metal arising from the operation and dismantling of nuclear reactors. The clearance levels of 20 radionuclides were derived from 10 μSv/y of individual doses by deterministic approach. In this approach, calculation models were established to assess individual doses resulting from 73 exposure pathways related to disposal and recycle/reuse, and realistic parameter values were selected considering Japanese natural and social conditions. The appropriateness of selected parameter values was confirmed by stochastic analyses. (author)

The influence of body posture on lithium clearance

DEFF Research Database (Denmark)

Kamper, A L; Strandgaard, S; Holstein-Rathlou, N H

1988-01-01

measured four times at 1-week intervals: two in the supine and one in the sitting position, and one when the subject was walking around. Glomerular filtration rate was not influenced by posture changes. On the contrary, lithium clearance, which in the supine position was 30 +/- 9 ml/min (1 SD), tended...... during moderate physical activity. Hence, when renal tubular function is studied with the lithium clearance method, standardization of posture and physical activity is important. In such studies physical activity such as walking should particularly be avoided....

Wavelet-based multiscale analysis of minimum toe clearance variability in the young and elderly during walking.

Science.gov (United States)

Khandoker, Ahsan H; Karmakar, Chandan K; Begg, Rezaul K; Palaniswami, Marimuthu

2007-01-01

As humans age or are influenced by pathology of the neuromuscular system, gait patterns are known to adjust, accommodating for reduced function in the balance control system. The aim of this study was to investigate the effectiveness of a wavelet based multiscale analysis of a gait variable [minimum toe clearance (MTC)] in deriving indexes for understanding age-related declines in gait performance and screening of balance impairments in the elderly. MTC during walking on a treadmill for 30 healthy young, 27 healthy elderly and 10 falls risk elderly subjects with a history of tripping falls were analyzed. The MTC signal from each subject was decomposed to eight detailed signals at different wavelet scales by using the discrete wavelet transform. The variances of detailed signals at scales 8 to 1 were calculated. The multiscale exponent (beta) was then estimated from the slope of the variance progression at successive scales. The variance at scale 5 was significantly (ppathological conditions. Early detection of gait pattern changes due to ageing and balance impairments using wavelet-based multiscale analysis might provide the opportunity to initiate preemptive measures to be undertaken to avoid injurious falls.

Clearance of labelled creatinine

International Nuclear Information System (INIS)

Eberstadt, P.; Liverant, J.

1982-01-01

Creatinine, extensively used in clinical work to evaluate glomerular filtration rate (G.F.R.) has caused controversy. Using simultaneously on dogs a gamma emitting agent measuring G.F.R., creatinine clearance proved to be higher. Aided by quantitative determinations and compartmental analysis fortunately the respective dilution spaces can be calculated. In the majority of these animals creatinine spaces are larger but in some equal to the ones of inulin

The role of CD1d-restricted NKT cells in the clearance of Pseudomonas aeruginosa from the lung is dependent on the host genetic background.

Science.gov (United States)

Benoit, Patrick; Sigounas, Vaia Yioula; Thompson, Jenna L; van Rooijen, Nico; Poynter, Matthew E; Wargo, Matthew J; Boyson, Jonathan E

2015-06-01

Pseudomonas aeruginosa is an important human opportunistic pathogen, accounting for a significant fraction of hospital-acquired lung infections. CD1d-restricted NKT cells comprise an unusual innate-like T cell subset that plays important roles in both bacterial and viral infections. Previous reports have differed in their conclusions regarding the role of NKT cells in clearance of P. aeruginosa from the lung. Since there is significant strain-dependent variation in NKT cell number and function among different inbred strains of mice, we investigated whether the role of NKT cells was dependent on the host genetic background. We found that NKT cells did indeed play a critical role in the clearance of P. aeruginosa from the lungs of BALB/c mice but that they played no discernible role in clearance from the lungs of C57BL/6 mice. We found that the strain-dependent role of NKT cells was associated with significant strain-dependent differences in cytokine production by lung NKT cells and that impaired clearance of P. aeruginosa in BALB/c CD1d(-/-) mice was associated with an increase in neutrophil influx to the lung and increased levels of proinflammatory cytokines and chemokines after infection. Finally, we found that the role of alveolar macrophages was also dependent on the genetic background. These data provide further support for a model in which the unusually high level of variability in NKT cell number and function among different genetic backgrounds may be an important contributor to infectious-disease susceptibility and pathology. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Relationship of end-expiratory pressure, lung volume, and /sup 99m/Tc-DTPA clearance

International Nuclear Information System (INIS)

Cooper, J.A.; van der Zee, H.; Line, B.R.; Malik, A.B.

1987-01-01

We investigated the dose-response effect of positive end-expiratory pressure (PEEP) and increased lung volume on the pulmonary clearance rate of aerosolized technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA). Clearance of lung radioactivity was expressed as percent decrease per minute. Base-line clearance was measured while anesthetized sheep (n = 20) were ventilated with 0 cmH 2 O end-expiratory pressure. Clearance was remeasured during ventilation at 2.5, 5, 10, 15, or 20 cmH 2 O PEEP. Further studies showed stepwise increases in functional residual capacity (FRC) (P less than 0.05) measured at 0, 2.5, 5, 10, 15, and 20 cmH 2 O PEEP. At 2.5 cmH 2 O PEEP, the clearance rate was not different from that at base line (P less than 0.05), although FRC was increased from base line. Clearance rate increased progressively with increasing PEEP at 5, 10, and 15 cmH 2 O (P less than 0.05). Between 15 and 20 cmH 2 O PEEP, clearance rate was again unchanged, despite an increase in FRC. The pulmonary clearance of aerosolized /sup 99m/Tc-DTPA shows a sigmoidal response to increasing FRC and PEEP, having both threshold and maximal effects. This relationship is most consistent with the hypothesis that alveolar epithelial permeability is increased by lung inflation

A specific primed immune response in Drosophila is dependent on phagocytes.

Directory of Open Access Journals (Sweden)

Linh N Pham

2007-03-01

Full Text Available Drosophila melanogaster, like other invertebrates, relies solely on its innate immune response to fight invading microbes; by definition, innate immunity lacks adaptive characteristics. However, we show here that priming Drosophila with a sublethal dose of Streptococcus pneumoniae protects against an otherwise-lethal second challenge of S. pneumoniae. This protective effect exhibits coarse specificity for S. pneumoniae and persists for the life of the fly. Although not all microbial challenges induced this specific primed response, we find that a similar specific protection can be elicited by Beauveria bassiana, a natural fly pathogen. To characterize this primed response, we focused on S. pneumoniae-induced protection. The mechanism underlying this protective effect requires phagocytes and the Toll pathway. However, activation of the Toll pathway is not sufficient for priming-induced protection. This work contradicts the paradigm that insect immune responses cannot adapt and will promote the search for similar responses overlooked in organisms with an adaptive immune response.

Foot clearance and variability in mono- and multifocal intraocular lens users during stair navigation.

Science.gov (United States)

Renz, Erik; Hackney, Madeleine; Hall, Courtney

2016-01-01

Intraocular lenses (IOLs) provide distance and near refraction and are becoming the standard for cataract surgery. Multifocal glasses increase variability of toe clearance in older adults navigating stairs and increase fall risk; however, little is known about the biomechanics of stair navigation in individuals with multifocal IOLs. This study compared clearance while ascending and descending stairs in individuals with monofocal versus multifocal IOLs. Eight participants with multifocal IOLs (4 men, 4 women; mean age = 66.5 yr, standard deviation [SD] = 6.26) and fifteen male participants with monofocal IOLs (mean age = 69.9 yr, SD = 6.9) underwent vision and mobility testing. Motion analysis recorded kinematic and custom software-calculated clearances in three-dimensional space. No significant differences were found between groups on minimum clearance or variability. Clearance differed for ascending versus descending stairs: the first step onto the stair had the greatest toe clearance during ascent, whereas the final step to the floor had the greatest heel clearance during descent. This preliminary study indicates that multifocal IOLs have similar biomechanic characteristics to monofocal IOLs. Given that step characteristics are related to fall risk, we can tentatively speculate that multifocal IOLs may carry no additional fall risk.

Low serum hyaluronic acid levels associated with spontaneous HBsAg clearance

NARCIS (Netherlands)

Harkisoen, S.; Arends, J. E.; van den Hoek, A.; van Erpecum, K. J.; Boland, G. J.; Hoepelman, A. I. M.

2015-01-01

Purpose The pathophysiological underlying mechanism of spontaneous HBsAg clearance in hepatitis B virus (HBV) infected patients is largely unknown. However, serum hyaluronic acid (sHA) plays a role in liver fibrosis progression and reversely could serve as a potential biomarker for HBsAg clearance.

Hypocapnic but not metabolic alkalosis impairs alveolar fluid reabsorption.

Science.gov (United States)

Myrianthefs, Pavlos M; Briva, Arturo; Lecuona, Emilia; Dumasius, Vidas; Rutschman, David H; Ridge, Karen M; Baltopoulos, George J; Sznajder, Jacob Iasha

2005-06-01

Acid-base disturbances, such as metabolic or respiratory alkalosis, are relatively common in critically ill patients. We examined the effects of alkalosis (hypocapnic or metabolic alkalosis) on alveolar fluid reabsorption in the isolated and continuously perfused rat lung model. We found that alveolar fluid reabsorption after 1 hour was impaired by low levels of CO2 partial pressure (PCO2; 10 and 20 mm Hg) independent of pH levels (7.7 or 7.4). In addition, PCO2 higher than 30 mm Hg or metabolic alkalosis did not have an effect on this process. The hypocapnia-mediated decrease of alveolar fluid reabsorption was associated with decreased Na,K-ATPase activity and protein abundance at the basolateral membranes of distal airspaces. The effect of low PCO2 on alveolar fluid reabsorption was reversible because clearance normalized after correcting the PCO2 back to normal levels. These data suggest that hypocapnic but not metabolic alkalosis impairs alveolar fluid reabsorption. Conceivably, correction of hypocapnic alkalosis in critically ill patients may contribute to the normalization of lung ability to clear edema.

A pre- and postoperative study of split isotope clearance in childhood

International Nuclear Information System (INIS)

Faerber, D.; Czempiel, H.; Muehle, P.; Schick, F.; Wenzl, H.; Technische Univ. Muenchen; Technische Univ. Muenchen

1979-01-01

In 1978 43 patients have been operated in the Department of Pediatric Surgery, Krankenhaus Muenchen-Schwabing, because of recurrent urinary-tract infections with ureterovesical reflux or obstructive urinary-tract diseases. In all patients a split whole body clearance-study with a method modified after the method of Muehle with 131 J-Hippuran was carried out pre- or postoperatively, respectively. In 78,5% of these cases the clearance-results were corresponding to the results of X-ray examination; 6 of the remaining patients had a worse clearance result and 3 had a better result than the X-ray findings would have suggested. (orig.) [de

Scan Manifestation and Trace-Dose Radiogold Clearance Rates in Obstructive Jaundice

International Nuclear Information System (INIS)

Kim, Dong Jip; Bahk, Yong Whee; Shinn, Kyung Sub

1969-01-01

The present study has been undertaken to analyze scan manifestation in obstructive jaundice. Scan changes were correlated with the duration of jaundice. In addition, clearance rates of trace dose of colloidal radiogold were assessed in each case. The materials were consisted of 19 cases with surgically and/or histopathologically verified obstructive jaundice from various causes including common duct stone, empyema of the gall bladder and carcinoma of the pancreas head etc. Blood clearance rates of colloidal 198 Au were determined after the injection of 8 uCi by simple geometrical drawing of recorded strip charts. Scan was performed following additional injection of the sam radiogold. In 16 out of 19 cases, the scan rather typical 'arborifrom' mottlings around the porta hepatis. The intensity and appearance of such mottlings on the scan was related with the duration of jaundice and level of serum bilirubin and alkaline phosphatase. The blood clearance rates remained to be within normal range in 74 percent of the patients. In the remaining 26 percent, clearance rate ranged between 4.1 and 6 minutes. It is concluded that the association of 'arboriform' mottlings and normal or mildly delayed clearance rates in the patients with jaundice is characteristic of obstructive change in the biliary system.

Scan Manifestation and Trace-Dose Radiogold Clearance Rates in Obstructive Jaundice

Energy Technology Data Exchange (ETDEWEB)

Kim, Dong Jip; Bahk, Yong Whee; Shinn, Kyung Sub [Catholic University College of Medicine, Seoul (Korea, Republic of)

1969-09-15

The present study has been undertaken to analyze scan manifestation in obstructive jaundice. Scan changes were correlated with the duration of jaundice. In addition, clearance rates of trace dose of colloidal radiogold were assessed in each case. The materials were consisted of 19 cases with surgically and/or histopathologically verified obstructive jaundice from various causes including common duct stone, empyema of the gall bladder and carcinoma of the pancreas head etc. Blood clearance rates of colloidal {sup 198}Au were determined after the injection of 8 uCi by simple geometrical drawing of recorded strip charts. Scan was performed following additional injection of the sam radiogold. In 16 out of 19 cases, the scan rather typical 'arborifrom' mottlings around the porta hepatis. The intensity and appearance of such mottlings on the scan was related with the duration of jaundice and level of serum bilirubin and alkaline phosphatase. The blood clearance rates remained to be within normal range in 74 percent of the patients. In the remaining 26 percent, clearance rate ranged between 4.1 and 6 minutes. It is concluded that the association of 'arboriform' mottlings and normal or mildly delayed clearance rates in the patients with jaundice is characteristic of obstructive change in the biliary system.

Interaction between the macrophage system and IgA immune complexes in IgA nephropathy.

Science.gov (United States)

Roccatello, D; Coppo, R; Basolo, B; Martina, G; Rollino, C; Cordonnier, D; Busquet, G; Picciotto, G; Sena, L M; Piccoli, G

1983-01-01

In nine patients with IgA nephropathy, the function of the mononuclear phagocyte system was assessed by measuring in vivo clearance of anti-D coated red blood cells (RBC) and in vitro phagocytosis of sensitised RBC by monocytes. A strict correlation was found between in vivo macrophage function and in vitro monocyte phagocytosis. Statistical correlations were also found between in vivo clearance values and IgAIC and C3d values. A defective macrophage and monocyte function affects patients with major signs of clinical activity, highest IgAIC values, signs of complement activation and the most unfavourable clinical course.

Gait Training with Real-Time Augmented Toe-Ground Clearance Information Decreases Tripping Risk in Older Adults and a Person with Chronic Stroke

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Rezaul K Begg

2014-05-01

Full Text Available Falls risk increases with ageing but is substantially higher in people with stroke. Tripping-related balance loss is the primary cause of falls, and Minimum Toe Clearance (MTC during walking is closely linked to tripping risk. The aim of this study was to determine whether real-time augmented information of toe-ground clearance at MTC can increase toe clearance, and reduce tripping risk. Nine healthy older adults (76±9 years and one 71 year old female stroke patient participated. Vertical toe displacement was displayed in real-time such that participants could adjust their toe clearance during treadmill walking. Participants undertook a session of unconstrained walking (no-feedback baseline and, in a subsequent Feedback condition, were asked to modify their swing phase trajectory to match a target increased MTC. Tripping probability (PT pre- and post-training was calculated by modelling MTC distributions. Older adults showed significantly higher mean MTC for the post-training retention session (27.7 ±3.79mm compared to the normal walking trial (14.1± 8.3 mm. The PT on a 1cm obstacle for the older adults reduced from 1 in 578 strides to 1 in 105,988 strides. With gait training the stroke patient increased MTC and reduced variability (baseline 16±12 mm, post-training 24±8 mm which reduced obstacle contact probability from 1 in 3 strides in baseline to 1 in 161 strides post-training. The findings confirm that concurrent visual feedback of a lower limb kinematic gait parameter is effective in changing foot trajectory control and reducing tripping probability in older adults. There is potential for further investigation of augmented feedback training across a range of gait-impaired populations, such as stroke.

20 CFR 653.501 - Requirements for accepting and processing clearance orders.

Science.gov (United States)

2010-04-01

... the job order. (i) No agricultural or food processing order shall be included in job bank listings... clearance any job order seeking workers to perform agricultural or food processing work before reviewing it... order seeking workers to perform agricultural or food processing work into intrastate clearance unless...

10 CFR 95.21 - Withdrawal of requests for facility security clearance.

Science.gov (United States)

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Withdrawal of requests for facility security clearance. 95.21 Section 95.21 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION AND RESTRICTED DATA Physical Security § 95.21 Withdrawal of...

Clearance of insoluble dust from the lower respiratory tract

Energy Technology Data Exchange (ETDEWEB)

Morrow, P E; Gibb, F R; Johnson, L

1964-01-01

Clearance of tagged heavy metal aerosols (Fe, Hg, Mn, Ba, and U) in female beagles by in vivo counting was assessed. Fecal excretion paralleled lower respiratory tract clearance of Fe. No Fe was found in blood, indicating its biological insolubility. Ultrafiltration tests (an indication of biological solubility) ranked the heavy metals as: Hg, Mn, Fe, and U in order of decreasing solubility. The solubility ratios were remarkably similar to the ratios of inverse biological half-times.

Cortactin is involved in the entry of Coxiella burnetii into non-phagocytic cells.

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Eliana M Rosales

Full Text Available BACKGROUND: Cortactin is a key regulator of the actin cytoskeleton and is involved in pathogen-host cell interactions. Numerous pathogens exploit the phagocytic process and actin cytoskeleton to infect host cells. Coxiella burnetii, the etiologic agent of Q fever, is internalized by host cells through a molecular mechanism that is poorly understood. METHODOLOGY/PRINCIPAL FINDING: Here we analyzed the role of different cortactin motifs in the internalization of C. burnetii by non-phagocytic cells. C. burnetii internalization into HeLa cells was significantly reduced when the cells expressed GFP-cortactin W525K, which carries a mutation in the SH3 domain that renders the protein unable to bind targets such as N-WASP. However, internalization was unaffected when the cells expressed the W22A mutant, which has a mutation in the N-terminal acidic region that destroys the protein's ability to bind and activate Arp2/3. We also determined whether the phosphorylation status of cortactin is important for internalization. Expression of GFP-cortactin 3F, which lacks phosphorylatable tyrosines, significantly increased internalization of C. burnetii, while expression of GFP-cortactin 3D, a phosphotyrosine mimic, did not affect it. In contrast, expression of GFP-cortactin 2A, which lacks phosphorylatable serines, inhibited C. burnetii internalization, while expression of GFP-cortactin SD, a phosphoserine mimic, did not affect it. Interestingly, inhibitors of Src kinase and the MEK-ERK kinase pathway blocked internalization. In fact, both kinases reached maximal activity at 15 min of C. burnetii infection, after which activity decreased to basal levels. Despite the decrease in kinase activity, cortactin phosphorylation at Tyr421 reached a peak at 1 h of infection. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the SH3 domain of cortactin is implicated in C. burnetii entry into HeLa cells. Furthermore, cortactin phosphorylation at serine and dephosphorylation

Dependence of 'CT clearance' on dosage and time

International Nuclear Information System (INIS)

Kaltenborn, H.A.; Klose, K.J.; Dexheimer, C.; Steinijans, V.

1989-01-01

The contrast medium dose used in CT renal function analysis corresponds to about 1 ml/kg body weight at a measurement interval of 5 or 10 minutes. In the present study the dependence of 'CT clearance' on dosage and time was examined in 12 healthy subjects. The amount of clearance was directly proportional to the employed contrast medium dose and to the length of the measurement interval. On account of the superior signal-to-noise ratio, the higher dose (1 ml/kg body weight) will continue to be prefered in future. The measurement interval can be limited to 10 minutes. (orig.) [de

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

ROLE OF MONOCYTE PHAGOCYTIC SYSTEM IN FORMATION OF ANTIVIRAL RESISTANCE IN MICE AFTER PRELIMINARY INJECTION OF CRYOPRESERVED CORD BLOOD

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Kozhina OYu

2013-03-01

Full Text Available Now the task of preventive maintenance and search of biologically active substances, capable to make active the nonspecific immune response, remains an actual during flu epidemic. It has been previously established, that cryopreserved leucoconcentrate of human cord blood (cLHCB can act as modulator of activity of immunity. In the given work there was estimated influence of preventive injection of cLHCB and its components on functional activity of monocyte phagocytic system cells (MPSC in mice in the conditions of the induced influenzal infection. Preliminary introduction of cLHCB and its components 6 months prior to infection by flu virus makes 2 times increase of functional activity of macrophages, preventing inhibition of a nonspecific link of immunity. Thus, cLHCB inhibit of secondary immune deficiency development. The found increase in phagocytic activity of peritoneal cavity cells and 3 times increasesing of CD11b-marker expression after preventive injection of cLHCB testifies to rise of adherence and protective potential of MPSC that is one of possible mechanisms of formation of resistance to a flu virus. It is shown, that intranasal cLHCB injection before development of viral infection it can be o recommended as the method of preventive maintenance of flu.

Lactate clearance cut off for early mortality prediction in adult sepsis and septic shock patients

Science.gov (United States)

Sinto, R.; Widodo, D.; Pohan, H. T.

2018-03-01

Previous lactate clearance cut off for early mortality prediction in sepsis and septic shock patient was determined by consensus from small sample size-study. We investigated the best lactate clearance cut off and its ability to predict early mortality in sepsis and septic shock patients. This cohort study was conducted in Intensive Care Unit of CiptoMangunkusumo Hospital in 2013. Patients’ lactate clearance and eight other resuscitationendpoints were recorded, and theoutcome was observed during the first 120 hours. The clearance cut off was determined using receiver operating characteristic (ROC) analysis, and its ability was investigated with Cox’s proportional hazard regression analysis using other resuscitation endpoints as confounders. Total of 268 subjects was included, of whom 70 (26.11%) subjects died within the first 120 hours. The area under ROC of lactate clearance to predict early mortality was 0.78 (95% % confidence interval [CI] 0.71-0.84) with best cut off was <7.5% (sensitivity and specificity 88.99% and 81.4% respectively). Compared with group achieving lactate clearance target, group not achieving lactate clearance target had to increase early mortality risk (adjusted hazard ratio 13.42; 95%CI 7.19-25.07). In conclusion, the best lactate clearance cut off as anearly mortality predictor in sepsis and septic shock patients is 7.5%.

Deposition and lung clearence of insoluble particles following acute inhalation of trichloroethylene; Andamento della deposizione e della clearance respiratoria nel ratto di aerosol insolubile in seguito ad inalazione acuta di tricloroetilene

Energy Technology Data Exchange (ETDEWEB)

Calamosca, M.; Pettinato, G.

1993-12-31

The effects of acute inhalation of trichloroethylene (TCE), emitted by automobiles as a combustion by-product, on the rat respiratory tract were investigated. In a previous work on mice, the observed damage proved to be limited to Clara cells (CC) and dose-dependent. Injury was correlated with the metabolic properties of CC, where TCE is converted to toxic intermediate metabolites. Since rat CC are located in the distal bronchial tree, a damage at this level is supposed to affect also the mechanical clearance of insoluble particles. Sprague-Dawley, female rats were exposed for 30 min, to a concentration of 3500 ppm TCE, to investigate the occurrence of an impairment of the mucousciliary/alveolar macrophagic (AM) removal system eventually correlated with epithelial damage. Nasopharyngeal and bronchopulmonary clearance patterns were obtained from the retention of a radio-labeled carnauba wax control aerosol, the rats inhaled 24 h after exposure to TCE. Sequential sacrifices, close together in time, were performed up to 24 h to detect the rapid clearance phase in all the different regions of the respiratory tract; from then on the retention was assessed in vivo by measuring the rats up to 600 h. A new mechanistic model was designed and applied to the retention data to achieve the parameters of relative deposition and the rates of clearance. Even if a major deposition in the bronchial region of the TCE test occurred, no significant differences were detected between all the parameters describing the clearance both of the bronchoalveolar and nasopharyngeal regions.

Numerical Investigation of Pressure Fluctuation Characteristics in a Centrifugal Pump with Variable Axial Clearance

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Lei Cao

2016-01-01

Full Text Available Clearance flows in the sidewall gaps of centrifugal pumps are unsteady as well as main flows in the volute casing and impeller, which may cause vibration and noise, and the corresponding pressure fluctuations are related to the axial clearance size. In this paper, unsteady numerical simulations were conducted to predict the unsteady flows within the entire flow passage of a centrifugal pump operating in the design condition. Pressure fluctuation characteristics in the volute casing, impeller, and sidewall gaps were investigated with three axial clearance sizes. Results show that an axial clearance variation affects the pressure fluctuation characteristics in each flow domain by different degree. The greatest pressure fluctuation occurs at the blade pressure surface and is almost not influenced by the axial clearance variation which has a certainly effect on the pressure fluctuation characteristics around the tongue. The maximum pressure fluctuation amplitude in the sidewall gaps is larger than that in the volute casing, and different spectrum characteristics show up in the three models due to the interaction between the clearance flow and the main flow as well as the rotor-stator interaction. Therefore, clearance flow should be taken into consideration in the hydraulic design of centrifugal pumps.

Glomerular filtration in kidney recipients measured by plasma clearance of 169Yb-DTPA

International Nuclear Information System (INIS)

Stribrna, J.; Oppelt, A.; Jirickova, E.; Janata, V.; Kocandrle, V.; Sup, I.; Woller, P.; Franke, W.G.

1986-01-01

Values of 169 Yb-DTPA clearance (C DTPA ) calculated after a single injection were compared in 26 recipients of kidneys with renal clearance of inulin (C in ), polyfructosan S (C pf ) and creatinine (C cr ). In 21 patients the examinations were made simultaneously, in 5 patients C DTPA was measured within a short interval after the examination of renal clearance. The mean C DTPA values did not significantly differ from C cr but were significantly higher (p in and C pf (by 33% on average). Investigation of changes in C DTPA as compared with C in and C pf showed no significant difference in glomerular filtration (GF). This was measured using inulin and polyfructosan. The results showed that the differing molecular weight of inulin and polyfructosan S had no detectable effect on the GF of kidney recipients. The plasma clearance of 169 Yb-DTPA similarly to C cr overestimates the GF measured by inulin and polyfructosan clearance. (author)

A computer program for unilateral renal clearance calculation by a modified Oberhausen method

International Nuclear Information System (INIS)

Brueggemann, G.

1980-01-01

A FORTAN program is presented which, on the basis of data obtained with NUKLEOPAN M, calculates the glomerular filtration rate with sup(99m)Tc-DTPA, the unilateral effective renal plasma flow with 131 I-hippuran, and the parameters for describing the isotope rephrogram (ING) with 131 I-hippuran. The results are calculated fully automatically upon entry of the data, and the results are processed and printed out. The theoretical fundamentals of ING and whole-body clearance calculation are presented as well as the methods available for unilateral clearance calculation, and the FORTAN program is described in detail. The standard values of the method are documented, as well as a comparative gamma camera study of 48 patients in order to determine the accuracy of unilateral imaging with the NUKLEOPAN M instrument, a comparison of unilateral clearances by the Oberhausen and Taplin methods, and a comparison between 7/17' plasma clearance and whole-body clearance. Problems and findings of the method are discussed. (orig./MG) [de

Clearance, a powerful tool in optimizing the volume of radioactive wastes

International Nuclear Information System (INIS)

Blommaert, W.; Teunckens, L.

1997-01-01

In the framework its activities in decommissioning nuclear installations, Belgoprocess applies the clearance practice in optimizing the volume of radioactive wastes. The applied clearance methodology is discussed with special emphasis to different types of materials and to the associated measurements. Four practical cases are elaborated, dealing with the decommissioning and decontamination of two small buildings up to green field conditions, the unconditional release of large quantities of slightly contaminated active carbon, the melting and clearance of stainless steel fuel racks and of aluminium heat exchangers. The attention is drawn on practical problems associated with sampling and measurement strategies, in relation to the proposed low limits for unconditional release. (author)

A review and comparison of international exemption and clearance levels

International Nuclear Information System (INIS)

Cooper, J.R.; Mobbs, S.F.

1997-01-01

The publication of new European Basic Safety Standards by the European Commission and of new International Basic Safety Standards by the IAEA together with other international agencies, has led to increased interest in the application of the concepts of exemption and clearance. This paper discusses the derivation of radionuclide-specific exemption and clearance values for application in various areas of the regulation of radioactive materials. (author)

Effects of 6-methyl-uracil upon the phagocytic activity in mice following whole-body X-irradiation or 2,4,6,-triethyleneimino-s-triazine treatment

International Nuclear Information System (INIS)

Raake, W.; Tempel, K.

1977-01-01

1. Phagocytic activity measured by means of the intravasal clearence of a soot dispersion in male NMRI-mice was increased six to ten days after whole-body X-irradiation (640 R) and decreased during the same period after i.v. administration of 2,4,6-triethyleneimino-s-triazine (TEM 2.0 mg/kg). 2. By means of 6-methyl-uracil food admixtures (200 to 400 ppm during 2 or 3 weeks) or by repeated intravenous injections of a N-methyl-D-glucosamine-6-methyluracil complex (62.5 to 250 mg/kg daily during five days), a significant augmentation of the phagocytic index being related to time and dosage was obtained in otherwise untreated mice. Comparable results were seen using cytidine and cytidine-5'-phosphate, whereas guanosine-5'-phosphate remained ineffective. 3. Whilst stimulating effects of 6-methyl-uracil or its N-methyl-D-glucosamine complex on X-irradiated mice were suspended, an increase up to supernormal values of the phagocytic index was produced by the pyrimidine base in animals treated with TEM. In accordance to this the survival rate of lethally X-irradiated mice (960 R) could not be increased; with animals given lethal TEM-doses, however, a significantly increased survival rate was obtained. 4. The present investigations as well as former biochemical analyses confirm the assumption that 6-methyluracil produces its regeneration effects, to some extent at least, by specific pathways influencing the reticuloendothelium. Different results from X-irradiated and TEM-treated mice are referring to the different points of attack of the two noxa. (orig.) [de

Clearance measurements on activated parts of accelerators by combined methods; Verfahrenskombinierte Freigabemessung aktivierter Beschleunigerteile

Energy Technology Data Exchange (ETDEWEB)

Jansen, S.; Friedemann, S. [VKTA, Dresden (Germany); Enghardt, W. [Technische Univ. Dresden (Germany). OncoRay

2016-07-01

The process of clearance of radioactive materials according to paragraph 29 StrlSchV contents the comparison of activity to mass and surface of the material. To avoid a borderless assessment of activity of activation it is often necessary to use combined measurement methods: For clearance of collimators of a medical proton accelerator (energy range up to 200 MeV) it needs to know the nuclide composition. The energetical and geometrical calibration was fixed by experiments. The clearance based on measurements of activity distribution, gammaspectroscopy verification of nuclide composition and gamma-counting detectors. Parts of medical electron-accelerators achieved its clearance by combination of abovementioned methods and in-situ-gammaspectroscopy. Activated und contaminated lead stones achieved its clearance by measurements of fluence, laboratory evaluation of samples, in-situ-gammaspectroscopy and wipe tests.

Comparison of gas clearance and radioactive microspheres for pancreatic blood flow measurement

International Nuclear Information System (INIS)

DeMar, A.R.; Graham, L.S.; Lake, R.; Fink, A.S.

1989-01-01

Measurement of pancreatic blood flow (PBF) is technically demanding. Although radiolabeled microspheres are considered the gold standard for PBF assessment, they have practical limitations. In the current study, H 2 and xenon-133 gas clearance techniques were adapted to PBF measurement and compared to radiolabeled microsphere techniques. Simultaneous measurements of PBF were made using either hydrogen or xenon gas washout and radiolabeled microspheres. Measurements were made under basal, vasoconstricted (vasopressin 2U i.v. or nicotine 4 micrograms/kg/h) and stimulated (secretin 125 ng/kg/h or 2 U/kg i.v.) conditions (random order). Mean PBF was 26.9 +/- 5.3, 50.5 +/- 2.3 and 27.6 +/- 5.2 ml/min/100 g basally, 36.9 +/- 8.0, 90.1 +/- 18.9, and 81.7 +/- 14.5 ml/min/100 g in the stimulated state, and 24.2 +/- 7.8, 25.0 +/- 3.5, and 14.9 +/- 7.5 ml/min/100 g in the vasoconstricted state for hydrogen gas clearance, xenon gas clearance, and radiolabeled microspheres, respectively. The H 2 clearance technique resulted in tissue trauma, was complicated by frequent electrode displacement, and correlated poorly (r2 = 0.36, p greater than 0.05) with microsphere values. In contrast, xenon clearance measurement had no apparent effect on the pancreas and correlated well (r2 = 0.83, p less than 0.01) with microsphere data. We conclude that xenon clearance offers an attractive, validated alternative to radiolabeled microspheres for measuring pancreatic blood flow