Sample records for activate human polymorphonuclear

  1. Effect of plastic catheters on the phagocytic activity of human polymorphonuclear leukocytes.

    López-López, G; Pascual, A; Perea, E J


    The effect of five kinds of plastic catheters (polyvinyl chloride, Teflon, polyurethane, Vialon and siliconized latex) on the phagocytic and bactericidal function of human polymorphonuclear leukocytes was evaluated. In the presence of the polyvinyl chloride, Teflon and siliconized latex catheters, superoxide radical production by polymorphonuclear leukocytes was significantly inhibited. The effect of the siliconized latex catheter was presumably mediated by products eluted from the catheter into the medium, since the incubation of polymorphonuclear leukocytes in eluates obtained from the incubation of this catheter in buffer induced a similar inhibitory effect. This phenomenon was not observed with polyurethane or Vialon catheters. Neither the catheters evaluated nor their eluates affected the uptake of opsonized Staphylococcus aureus by human polymorphonuclear leukocytes. It is concluded that the polyvinyl chloride, Teflon and siliconized latex catheters used in this study could impair the respiratory burst of human polymorphonuclear leukocytes. PMID:2164932

  2. Mechanism of arachidonic acid liberation in platelet-activating factor-stimulated human polymorphonuclear neutrophils

    Upon stimulation of human polymorphonuclear neutrophils with platelet-activating factor (PAF), arachidonic acid (AA) is released from membrane phospholipids. The mechanism for AA liberation, a key step in the synthesis of biologically active eicosanoids, was investigated. PAF was found to elicit an increase in the cytoplasmic level of free Ca2+ as monitored by fluorescent indicator fura 2. When [3H] AA-labeled neutrophils were exposed to PAF, the enhanced release of AA was observed with a concomitant decrease of radioactivity in phosphatidylinositol and phosphatidylcholine fractions. The inhibitors of phospholipase A2, mepacrine and 2-(p-amylcinnamoyl)-amino-4-chlorobenzoic acid, effectively suppressed the liberation of [3H]AA from phospholipids, indicating that liberation of AA is mainly catalyzed by the action of phospholipase A2. The extracellular Ca2+ is not required for AA release. However, intracellular Ca2+ antagonists, TMB-8 and high dose of quin 2/AM drastically reduced the liberation of AA induced by PAF, indicating that Ca2+ is an essential factor for phospholipase A2 activation. PAF raised the fluorescence of fura 2 at concentrations as low as 8 pM which reached a maximal level about 8 nM, whereas more than nM order concentrations of PAF was required for the detectable release of [3H]AA. Pretreatment of neutrophils with pertussis toxin resulted in complete abolition of AA liberation in response to PAF. However, the fura 2 response to PAF was not effectively inhibited by toxin treatment. In human neutrophil homogenate and membrane preparations, guanosine 5'-O-(thiotriphosphate) stimulated AA release and potentiated the action of PAF. Guanosine 5'-O-(thiodiphosphate) inhibited the effects of guanosine 5'-O-(thiotriphosphate)

  3. Regulation of polymorphonuclear cell activation by thrombopoietin.

    Brizzi, M F; Battaglia, E.; Rosso, A.; Strippoli, P; Montrucchio, G; Camussi, G.; Pegoraro, L


    Thrombopoietin (TPO) regulates early and late stages of platelet formation as well as platelet activation. TPO exerts its effects by binding to the receptor, encoded by the protooncogene c-mpl, that is expressed in a large number of cells of hematopoietic origin. In this study, we evaluated the expression of c-Mpl and the effects of TPO on human polymorphonuclear cells (PMN). We demonstrate that PMN express the TPO receptor c-Mpl and that TPO induces STAT1 tyrosine phosphorylation and the for...

  4. A Novel Murine Anti-Lactoferrin Monoclonal Antibody Activates Human Polymorphonuclear Leukocytes through Membrane-Bound Lactoferrin and TLR4

    Xiao-Min Hu


    Full Text Available Soluble lactoferrin (LTF is a versatile molecule that not only regulates the iron homeostasis, but also harbors direct microbicidal and immunomodulating abilities in mammalian body fluids. In contrast, little is known about the function of membrane-bound LTF (mbLTF, although its expression on human polymorphonuclear leukocytes (huPMNs has been reported for decades. Given that LTF/anti-LTF antibodies represent a potential diagnostic/prognostic biomarker and a therapeutic target in patients with immune disorders, we wished, in the present study, to generate a novel human LTF- (huLTF- specific mAb suitable for detailed analyses on the expression and function of mbLTF as well as for deciphering the underlying mechanisms. By using the traditional hybridoma cell fusion technology, we obtained a murine IgG1 (kappa mAb, M-860, against huLTF. M-860 recognizes a conformational epitope of huLTF as it binds to natural, but not denatured, huLTF in ELISA. Moreover, M-860 detects mbLTF by FACS and captures endogenous huLTF in total cell lysates of huPMNs. Functionally, M-860 induces the activation of huPMNs partially through TLR4 but independently of phagocytosis. M-860 is thus a powerful tool to analyze the expression and function of human mbLTF, which will further our understanding of the roles of LTF in health and disease.

  5. Major histocompatibility complex class II (DR) antigen and costimulatory molecules on in vitro and in vivo activated human polymorphonuclear neutrophils

    Sandilands, Gavin P; McCrae, Jame; Hill, Kathryn; Perry, Martin; Baxter, Derek


    We have previously shown that normal human peripheral blood polymorphonuclear neutrophils (PMNs) contain cytoplasmic ‘stores’ of three key molecules normally associated with antigen presentation and T-cell costimulation, i.e. major histocompatibility complex class II (DR) antigen, CD80 (B7-1) and CD86 (B7-2). These cytoplasmic molecules were found to translocate to the cell surface within a few minutes following cross-linking (X-L) of Mac-1: an early neutrophil activation signal. In this study we have compared X-L of Mac −1 in parallel with four other well documented in vitro neutrophil activators: phorbol myristate acetate, N-formyl methionyl leucyl phenylalanine, lipopolysaccharide, and phagocytosis of immunoglobulin G–Latex particles. In addition, we have used paired samples of neutrophils obtained from peripheral blood (as a control) and synovial fluid from patients with rheumatoid arthritis as a source of in vivo activated cells. With the exception of phagocytosis, all activators resulted in the rapid (within 30 min) generation of two populations of activated neutrophils (designated P1 and P2) based on flow-cytometry measurements of size, granularity and phenotype. Significant up-regulation of DR and costimulatory molecules was observed, predominantly on P2 cells, with all activators except phagocytosis. CD80 and CD86 were noted to respond to the various activation signals in a different pattern suggesting that their intracellular granule location may be different. Dual-staining confocal laser microscopy studies showed that CD80 is largely confined to secretory vesicles (SVs) while CD86 appears to have a much wider distribution being found in SVs and within secondary (specific) and primary (azurophilic) granules. Increased surface expression of these antigens was also observed on P2 synovial fluid neutrophils appearing as large heterogeneous clusters on the cell surface when visualized by confocal laser microscopy. PMID:17034427


    Sudha Patil


    Full Text Available The objective of present study was to investigate Petroleum ether, ethyl acetate and hydroalcoholic extracts of B. racemosa fruits in vitro on human polymorphonuclear (PMN cells to screen their effects on phagocytosis and chemotaxis. Ethyl acetate extract of B. racemosa fruits was found to be a stimulant of PMN cell phagocytosis of Nitroblue tetrazolium (NBT dye and candida albicans. It also stimulated intracellur killing capacity of PMN cells. It was further found to increase the chemotaxis of human PMN cells. While, petroleum ether extract and hydroalcoholic extract were lesser active as far as these activities are concerned.

  7. Differential effect of extracellular calcium on the Na(+)-K+ pump activity in intact polymorphonuclear leucocytes and erythrocytes

    Petersen, R H; Knudsen, T; Johansen, Torben


    The effect of extracellular calcium on the Na(+)-K+ pump activity in human polymorphonuclear leucocytes and erythrocytes was studied and compared with the activity in mixed peritoneal leucocytes from rats. While there was maximal decrease in the pump activity (25-30%) of leucocytes from both rat ...

  8. Uptake of antibiotics by human polymorphonuclear leukocyte cytoplasts

    Hand, W.L.; King-Thompson, N.L. (Veterans Administration Medical Center (Atlanta), Decatur, GA (USA))


    Enucleated human polymorphonuclear leukocytes (PMN cytoplasts), which have no nuclei and only a few granules, retain many of the functions of intact neutrophils. To better define the mechanisms and intracellular sites of antimicrobial agent accumulation in human neutrophils, we studied the antibiotic uptake process in PMN cytoplasts. Entry of eight radiolabeled antibiotics into PMN cytoplasts was determined by means of a velocity gradient centrifugation technique. Uptakes of these antibiotics by cytoplasts were compared with our findings in intact PMN. Penicillin entered both intact PMN and cytoplasts poorly. Metronidazole achieved a concentration in cytoplasts (and PMN) equal to or somewhat less than the extracellular concentration. Chloramphenicol, a lipid-soluble drug, and trimethoprim were concentrated three- to fourfold by cytoplasts. An unusual finding was that trimethroprim, unlike other tested antibiotics, was accumulated by cytoplasts more readily at 25 degrees C than at 37 degrees C. After an initial rapid association with cytoplasts, cell-associated imipenem declined progressively with time. Clindamycin and two macrolide antibiotics (roxithromycin, erythromycin) were concentrated 7- to 14-fold by cytoplasts. This indicates that cytoplasmic granules are not essential for accumulation of these drugs. Adenosine inhibited cytoplast uptake of clindamycin, which enters intact phagocytic cells by the membrane nucleoside transport system. Roxithromycin uptake by cytoplasts was inhibited by phagocytosis, which may reduce the number of cell membrane sites available for the transport of macrolides. These studies have added to our understanding of uptake mechanisms for antibiotics which are highly concentrated in phagocytes.

  9. The essential oil of bergamot stimulates reactive oxygen species production in human polymorphonuclear leukocytes.

    Cosentino, Marco; Luini, Alessandra; Bombelli, Raffaella; Corasaniti, Maria T; Bagetta, Giacinto; Marino, Franca


    Bergamot (Citrus aurantium L. subsp. bergamia) essential oil (BEO) is used in folk medicine as an antiseptic and anthelminthic and to facilitate wound healing. Evidence indicates that BEO has substantial antimicrobial activity; however its effects on immunity have never been examined. We studied the effects of BEO on reactive oxygen species (ROS) production in human polymorphonuclear leukocytes (PMN) and the role of Ca(2+) in the functional responses evoked by BEO in these cells. Results show that BEO increased intracellular ROS production in human PMN, an effect that required the contribution of extracellular (and, to a lesser extent, of intracellular) Ca(2+) . Bergamot essential oil also significantly increased ROS production induced by the chemotactic peptide N-formyl-Met-Leu-Phe and reduced the response to the protein kinase C activator phorbol myristate acetate. In conclusion, this is the first report showing the ability of BEO to increase ROS production in human PMN. This effect could both contribute to the activity of BEO in infections and in tissue healing as well as underlie an intrinsic proinflammatory potential. The relevance of these findings for the clinical uses of BEO needs careful consideration. PMID:24458921

  10. Localization of NADH oxidase on the surface of human polymorphonuclear leukocytes by a new cytochemical method.

    Briggs, R T; Drath, D B; Karnovsky, M L; Karnovsky, M J


    The ultrastructural localization of NADH oxidase, a possible enzyme in the increased oxidative activity of polymorphonuclear leukocytes (PMN) during phagocytosis, was studied. A new cytochemical technique for the localization of H2O2, a product of NADH oxidase activity, was developed. Cerous ions, in the presence of peroxide, form an electron-dense precipitate. Resting and phagocytically stimulated PMN were exposed to cerous ions at pH 7.5 to demonstrate sites of NADH-dependent, cyanide-insensitive H2O2 production. Resting PMN exhibites slight activity on the plasma membrane; phagocytizing PMN had extensive deposits of reaction product localized within the phagosome and on the plasma membrane. Peroxide involvement was demonstrated by the inhibitory effect of catalase on cerium precipitation; the surface localization of the enzyme responsible was confirmed by using nonpenetrating inhibitors of enzymatic activity. A correlative study was performed with an NADH-dependent, tetrazolium-reduction system. As with cerium, formazan deposition on the surface of the cell was NADH dependent, cyanide insensitive, and stimulated by phagocytosis. Superoxide dismutase did not inhibit tetrazolium reduction, as observed cytochemically, indicating direct enzymatic dye reduction without superoxide interposition. These findings, combined with oxygen consumption studies on resting and stimulated PMN in the presence or absence of NADH, indicate that NADH oxidase is a surface enzyme in human PMN. It is internalized during phagocytosis and retains its peroxide-generating capacity within the phagocytic vacuole. PMID:407

  11. Fucose-binding Lotus tetragonolobus lectin binds to human polymorphonuclear leukocytes and induces a chemotactic response.

    VanEpps, D E; Tung, K S


    Fucose-binding L. tetragonolobus lectin to the surface of human polymorphonuclear leukocytes (PMN) and induces a chemotactic response. Both surface binding and chemotaxis are inhibited by free fucose but not by fructose, mannose, or galactose. The lectin-binding sites on PMN are unrelated to the A, B, or O blood group antigen. Utilization of this lectin should be a useful tool in isolating PMN membrane components and in analyzing the mechanism of neutrophil chemotaxis. PMID:330752

  12. Viricidal effect of polymorphonuclear leukocytes on human immunodeficiency virus-1. Role of the myeloperoxidase system.

    Klebanoff, S J; Coombs, R W


    Myeloperoxidase (MPO), H2O2, and chloride form an antimicrobial system in neutrophilic polymorphonuclear leukocytes (PMN) effective against a variety of microorganisms. Normal human PMN, when stimulated with phorbol myristate acetate or opsonized zymosan, are viricidal to HIV-1. The viricidal effect was lost when chloride was replaced by sulfate and was inhibited by the peroxidase inhibitor azide and by catalase, but not by heated catalase or superoxide dismutase, implicating H2O2. Stimulated...

  13. Effect of human polymorphonuclear and mononuclear leukocytes on chromosomal and plasmid DNA of Escherichia coli. Role of acid DNase

    Phagocytosis and killing by polymorphonuclear and mononuclear leukocytes are important host resistance factors against invading microorganisms. Evidence showing that killing is rapidly followed by degradation of bacterial components is limited. Therefore, we studied the fate of Escherichia coli DNA following phagocytosis of E. coli by polymorphonuclear and mononuclear leukocytes. [3H]Thymidine-labeled, unencapsulated E. coli PC2166 and E. coli 048K1 were incubated in serum, washed, and added to leukocytes. Uptake and killing of the bacteria and degradation of DNA were measured. Although phagocytosis and killing by mononuclear leukocytes was less efficient than that by polymorphonuclear leukocytes, only mononuclear leukocytes were able to degrade E. coli PC2166 DNA. Within 2 h, 60% of the radioactivity added to mononuclear leukocytes was released into the supernate, of which 40% was acid soluble. DNA of E. coli 048K1 was not degraded. To further analyze the capacity of mononuclear leukocytes to degrade E. coli DNA, chromosomal and plasmid DNA was isolated from ingested bacteria and subjected to agarose gel-electrophoresis. Only chromosomal DNA was degraded after phagocytosis. Plasmid DNA of E. coli carrying a gene coding for ampicillin resistance remained intact for a 2-h period after ingestion, and was still able to transform recipient E. coli cells after this period. Although we observed no DNA degradation during phagocytosis by polymorphonuclear leukocytes, lysates of both polymorphonuclear and mononuclear leukocytes contained acid-DNase activity with a pH optimum of 4.9. However, the DNase activity of mononuclear leukocytes was 20 times higher than that of polymorphonuclear leukocytes. No difference was observed between DNase activity from polymorphonuclear and mononuclear leukocytes from a chronic granulomatous disease patient with DNase activity from control polymorphonuclear and mononuclear leukocytes

  14. Subcellular localisation and properties of histone phosphate phosphatase in human polymorphonuclear leukocytes: alterations in pregnancy and chronic granulocytic leukaemia and relationship to alkaline phosphatase

    Using [32P]histone as substrate, an assay for histone phosphate phosphatase was optimised for human polymorphonuclear leukocytes. Kinetic studies showed that the activity was optimal at pH 6.8, was stimulated by Mn2+ and Co2+, and inhibited by sodium sulphite and zinc chloride. The apparent Ksub(m) of the enzyme for histone phosphate was 0.89 μmol/l. (Auth.)

  15. Effect of aspirin on the metabolism of exogenous arachidonic acid in human polymorphonuclear leukocytes

    Punnonen, K.; Uotila, P.


    When human polymorphonuclear leukocytes (PMNL) were incubated with exogenous /sup 14/C-arachidonic acid (/sup 14/C-AA), both lipoxygenase and cyclo-oxygenase metabolites were detected. The amount of the 5-lipoxygenase metabolites formed, including 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE), was small. The amount of other mono-HETE's (migrating in the vicinity of 12-HETE) was greater, but this was obviously mainly due to the small amount of contaminating platelets. In the presence of calcium ionophore A23187 the rate of formation of 5-HETE was increased, but the formation of other metabolites remained unchanged. When PMNL were incubated with aspirin in the presence of A23187 the formation of the cyclo-oxygenase products was decreased but that of 5-HETE was unchanged. The present study indicates that the calcium ionophore A23187 stimulates specifically the 5-lipoxygenase in human PMNL and that aspirin has no effect on the formation of the 5-lipoxygenase metabolites of arachidonic acid in human PMNL.

  16. CD66 carcinoembryonic antigens mediate interactions between Opa-expressing Neisseria gonorrhoeae and human polymorphonuclear phagocytes.

    Gray-Owen, S D; Dehio, C; Haude, A; Grunert, F; Meyer, T F


    Colonization of urogenital tissues by the human pathogen Neisseria gonorrhoeae is characteristically associated with purulent exudates of polymorphonuclear phagocytes (PMNs) containing apparently viable bacteria. Distinct variant forms of the phase-variable opacity-associated (Opa) outer membrane proteins mediate the non-opsonized binding and internalization of N. gonorrhoeae by human PMNs. Using overlay assays and an affinity isolation technique, we demonstrate the direct interaction between Opa52-expressing gonococci and members of the human carcinoembryonic antigen (CEA) family which express the CD66 epitope. Gonococci and recombinant Escherichia coli strains synthesizing Opa52 showed specific binding and internalization by transfected HeLa cell lines expressing the CD66 family members BGP (CD66a), NCA (CD66c), CGM1 (CD66d) and CEA (CD66e), but not that expressing CGM6 (CD66b). Bacterial strains expressing either no opacity protein or the epithelial cell invasion-associated Opa50 do not bind these CEA family members. Consistent with their different receptor specificities, Opa52-mediated interactions could be inhibited by polyclonal anti-CEA sera, while Opa50 binding was instead inhibited by heparin. Using confocal laser scanning microscopy, we observed a marked recruitment of CD66 antigen by Opa52-expressing gonococci on both the transfected cell lines and infected PMNs. These data indicate that members of the CEA family constitute the cellular receptors for the interaction with, and internalization of, N. gonorrhoeae. PMID:9218786

  17. Effect of staphylococcal delta-toxin and bee venom peptide melittin on leukotriene induction and metabolism of human polymorphonuclear granulocytes.

    Raulf, M; Alouf, J E; König, W


    The abilities of delta-toxin from Staphylococcus aureus and melittin to induce and modulate the generation of leukotriene from human polymorphonuclear granulocytes (PMNs) were studied. Stimulation of PMNs with melittin (10 micrograms) induced leukotriene formation, whereas stimulation with delta-toxin did not. Preincubation of the PMNs with delta-toxin modulated the subsequent generation of leukotriene from PMNs induced by Ca ionophore A23187 or opsonized zymosan. The generation of leukotrien...

  18. beta. -Endorphin and related peptides suppress phorbol myristate acetate-induced respiratory burst in human polymorphonuclear leukocytes

    Diamant, M.; Henricks, P.A.J.; Nijkamp, F.P.; de Wied, D. (Univ. of Utrecht (Netherlands))


    In the present study, the immunomodulatory effect of {beta}-endorphin ({beta}-E) and shorter pro-opiomelancortin (POMC) fragments was evaluated by assessing their influence on respiratory burst in human polymorphonuclear leukocytes (PMN). The effect of the peptides on phorbol myristate acetate (PMA)-stimulated production of reactive oxygen metabolites was measured in a lucigenin-enhanced chemiluminescence (CL) assay. Both POMC peptides with opiate-like activity and their non-opioid derivatives were tested. With the exception of {alpha}-E, PMA-stimulated respiratory burst was suppressed by all POMC fragments tested. A U-shaped dose-response relation was observed. Doses lower than 10{sup {minus}17}M and higher than 10{sup {minus}8}M were without effect. {beta}-E and dT{beta}E both suppressed PMA-induced oxidative burst in human PMN at physiological concentrations. {gamma}-E and dT{gamma}E proved to be less potent inhibitors, reaching maximal effect at higher concentrations. DE{gamma}E exerted an even less pronounced but still significant suppressive effect at the concentration of 10{sup {minus}10}M. None of the endorphins tested was shown to affect resting oxidative metabolism in the PMN. The modulatory effects of the opioid peptides could not be blocked by the opioid antagonist naloxone.

  19. Potentiation of human polymorphonuclear leukocytes respiratory burst and phagocytosis by a standardized liver and spleen fraction of peptides.

    Cramer, R; Dri, P; Spessotto, P; Mittenzwei, H; Patriarca, P


    The effect of Factor AF2 (AF2), a xenogeneic fraction of peptides with a molecular weight of < 10,000 Dalton obtained from livers and spleens of newborn lambs, on the oxygen consumption and the phagocytic activity of human polymorphonuclear leukocytes (PMN) was studied. AF2 increased the oxygen uptake of PMN exposed both to serum-treated zymosan (STZ), a phagocytosable stimulus, and phorbol-myristate-acetate (PMA), a soluble stimulus. The potentiating effect of the drug was dose-dependent and more pronounced when suboptimal amounts of either stimulus were used. The phagocytic activity of PMN, as measured by the rate of mineral oil particles ingestion, was also increased by AF2 in a dose-dependent manner. These results suggest that the drug may influence PMN behaviour in at least two ways: 1. by increasing the rate of phagocytosis, and 2. by potentiating the respiratory burst induced by soluble and particulate stimuli. The results are discussed in relation to the beneficial effects of AF2 in cancer patients under chemotherapy or radiation treatment. PMID:8352824

  20. Possible in vivo tolerance of human polymorphonuclear neutrophil to low-grade exercise-induced endotoxaemia

    G. Camus


    Full Text Available To address the question of whether translocation of bacterial lipopolysaccharide (LPS into the blood could be involved in the process of exercise-induced polymorphonuclear neutrophil (PMN activation, 12 healthy male subjects who took part in a sprint triathlon (1.5 km river swim, 40 km bicycle race, 10 km road race were studied. While there was no detectable amount of endotoxin in the blood samples drawn at rest, exercise was followed by the appearance of circulating endotoxin molecules at the end of competition in four subjects, and after one and 24 h recovery in three and seven athletes, respectively. The concentrations of plasma granulocyte myeloperoxidase ([MPO], were significantly higher immediately after exercise and one hour later than baseline values (P<0.001. This variable returned to pre-race levels the day after exercise, despite the presence of detectable amounts of LPS, at that time, in seven athletes. The absence of significant correlation (r=0.26;P=0.383 and temporal association between [MPO]and plasma endotoxin levels led us to conclude that endotoxaemia was not involved in the process of exercise-induced PMN degranulation observed in our subjects.

  1. Evaluation of human polymorphonuclear behavior on textured titanium and calcium-phosphate coated surfaces

    Few studies have evaluated the effects of titanium (Ti) surface modifications on polymorphonuclear neutrophils (PMNs). Human PMNs' viability and release of key mediators—such as IL1β, IL6, TNFα, IL12, IL10, IL4, TGFβ1, IL8, IP-10, and Mig—were evaluated on three different Ti surface treatments: (1) machined Ti; (2) alumina-blasted and acid-etched Ti (AB/AE); and (3) calcium phosphate coating of 300–500 nm by ion beam onto the AB/AE Ti surface (CaP). A polystyrene surface was used as a negative control. The PMNs were purified from whole human blood and cultured for 6 h. Cell viability was determined by flow cytometry, and the supernatant was evaluated to determine the levels of cytokines and chemokines. Results showed that the percentage of viable cells was significantly lower on the CaP surface compared to the control (p < 0.05) relative to the other groups. No differences in the levels of IL8, MIG, and IP10 were detected between groups. Significantly higher levels of IL1β (p = 0.046) and TNFα (p = 0.016) were detected for the CaP surfaces compared to AB/AE surface only. The levels of IL4, IL10, and TGFβ1 secreted from the PMNs in the CaP group were significantly lower than in the control and machined groups (p < 0.05) that were statistically comparable to AB/AE. Overall, the addition of a thin CaP coating to the AB/AE Ti surface influenced the secretion profile of pro-inflammatory cytokines due to the higher release of pro-inflammatory cytokines (IL1β and TNFα) on these surfaces. (paper)

  2. Resistance of Capnocytophaga canimorsus to killing by human complement and polymorphonuclear leukocytes.

    Shin, Hwain; Mally, Manuela; Meyer, Salome; Fiechter, Chantal; Paroz, Cécile; Zaehringer, Ulrich; Cornelis, Guy R


    Capnocytophaga canimorsus is a bacterium of the canine oral flora known since 1976 to cause rare but severe septicemia and peripheral gangrene in patients that have been in contact with a dog. It was recently shown that these bacteria do not elicit an inflammatory response (H. Shin, M. Mally, M. Kuhn, C. Paroz, and G. R. Cornelis, J. Infect. Dis. 195:375-386, 2007). Here, we analyze their sensitivity to the innate immune system. Bacteria from the archetype strain Cc5 were highly resistant to killing by complement. There was little membrane attack complex (MAC) deposition in spite of C3b deposition. Cc5 bacteria were as resistant to phagocytosis by human polymorphonuclear leukocytes (PMNs) as Yersinia enterocolitica MRS40, endowed with an antiphagocytic type III secretion system. We isolated Y1C12, a transposon mutant that is hypersensitive to killing by complement via the antibody-dependent classical pathway. The mutation inactivated a putative glycosyltransferase gene, suggesting that the Y1C12 mutant was affected at the level of a capsular polysaccharide or lipopolysaccharide (LPS) structure. Cc5 appeared to have several polysaccharidic structures, one being altered in Y1C12. The structure missing in Y1C12 could be purified by classical LPS purification procedures and labeled by tritiated palmitate, indicating that it is more likely to be an LPS structure than a capsule. Y1C12 bacteria were also more sensitive to phagocytosis by PMNs than wild-type bacteria. In conclusion, a polysaccharide structure, likely an LPS, protects C. canimorsus from deposition of the complement MAC and from efficient phagocytosis by PMNs. PMID:19307219

  3. Effects of Montelukast on free radical production in whole blood and isolated human polymorphonuclear neutrophils (PMNs) in asthmatic children

    Al Saadi, Muslim M.; Meo, Sultan Ayoub; Mustafa, Ali; Shafi, Ahmed; Tuwajri, Ali S. Al


    Montelukast is a highly selective leukotriene-receptor antagonist (LTRA). It is widely used in the treatment of bronchial asthma, primarily as an adjunct to corticosteroids. Reactive oxygen species (ROSs) play an important role in the pathogenesis of asthma and oxidative stress contributing to the initiation and worsening of inflammatory respiratory disorders, such as asthma. Antioxidant drugs may have a role in minimizing or preventing damage in asthmatic children. The aim of this study was to assess the antioxidant effect of montelukast on the production of free radicals in the whole blood and polymorphonuclear neutrophils (PMNs) in asthmatic children. A group of 48 (38 males and 10 females), apparently healthy asthmatic children were recruited with ages ranging between 6 and 14 years. In asthmatic children, base line (premedication) and post medication free radicals activity in the whole blood and polymorphonuclear neutrophils (PMNs) was determined by measuring chemiluminescence (CL) response through chemiluminescence luminometer. Free radical productions were significantly decreased in the whole blood, when stimulated with Phorbol Myristate Acetate (p < 0.04) and Opsonised Zymosan (p < 0.05). The free radicals were also significantly decreased in isolated polymorphonuclear neutrophils (PMNs) when stimulated with Opsonised Zymosan (p < 0.05) after the post medication treatment of montelukast in asthmatic children. Montelukast decreased the reactive oxygen species production, both in the whole blood as well as isolated PMNs in asthmatic children. PMID:23960762

  4. Altered polymorphonuclear leukocyte Fc gamma R expression contributes to decreased candicidal activity during intraabdominal sepsis

    We investigated the effects of untreated intraabdominal sepsis on polymorphonuclear leukocyte (PMN) candicidal activity. Two groups of swine were studied. Group I (n=6) underwent sham laparotomy, group II (n=7) underwent cecal ligation and incision. Untreated intraabdominal sepsis resulted in a progressive decrease in PMN candicidal activity. Concomitant rosetting and phagocytosis assays demonstrated a decrease in both the attachment and phagocytosis of Candida albicans opsonized with both normal and septic swine serum by PMNs in group II. Iodine 125-labeled swine immunoglobulin G (IgG) and fluorescein isothioalanate (FITC)-labeled swine IgG were used to investigate Fc gamma receptor ligand interactions. Scatchard analyses demonstrated a progressive decline in both the binding affinity constant and number of IgG molecules bound per PMN. Stimulation of the oxidative burst markedly reduced 125I-labeled IgG binding in both group I and group II, with a greater decrement being seen in animals with intraabdominal sepsis. Further, in group II, PMN recycling of the Fc gamma receptor to the cell surface after generation of the oxidative burst was reduced by postoperative day 4. Binding of monoclonal antibodies to Fc gamma receptor II, but not Fc gamma receptor I/III markedly reduced intracellular candicidal activity. Immunofluorescence studies revealed a homogeneous pattern of FITC-IgG uptake by nearly all group I PMNs, whereas by postoperative day 8 a substantial number of PMNs from group II failed to internalize the FITC-IgG. These studies suggest that untreated intraabdominal sepsis reduces PMN candicidal activity and that this is due, in part, to altered PMN Fc gamma receptor ligand interactions

  5. Effect of the histaminergic system on human polymorphonuclear leukocyte aggregation and respiratory burst in vitro

    Nosáľ, R.; Drábiková, K.; Jančinová, V.; Číž, Milan; Lojek, Antonín

    Singapore: World Scientific, 2002 - (Stanley, P.; Kricka, L.), s. 285-288 ISBN 981-238-156-2. [Symposium on Bioluminescence and Chemiluminescence /12./. Cambridge (GB), 05.04.2002-09.04.2002] R&D Projects: GA ČR GA524/00/1223 Grant ostatní: VEGA SR(SK) 2/1012/21 Keywords : histamine * dithiaden * polymorphonuclear leukocytes Subject RIV: BO - Biophysics

  6. Hydrogen peroxide signals E. coli phagocytosis by human polymorphonuclear cells; up-stream and down-stream pathway.

    Petropoulos, Michalis; Karamolegkou, Georgia; Rosmaraki, Eleftheria; Tsakas, Sotiris


    Hydrogen peroxide (Η2Ο2) is produced during a variety of cellular procedures. In this paper, the regulatory role of Η2Ο2, in Escherichia coli phagocytosis by the human polymorphonuclears, was investigated. White blood cells were incubated with dihydrorhodamine (DHR) in order to study H2O2 synthesis and E. coli-FITC to study phagocytosis. Flow cytometry revealed increased synthesis of H2O2 in polymorphonuclears which incorporated E. coli-FITC. The blocking of H2O2 synthesis by specific inhibitors, N-ethylmaleimide (ΝΕΜ) for NADPH oxidase and diethyldithiocarbamate (DDC) for superoxide dismutase (SOD), decreased E. coli phagocytosis, as well. Immunoblot analysis of white blood cell protein extracts revealed that the blocking of NADPH oxidase and SOD decreased ERK-1/2 phosphorylation, while it had no effect on JNK and p38. Confocal microscopy showed that phosphorylation of MAPKs and phagocytosis solely occur in the polymorphonuclear and not in mononuclear cells. The use of specific MAPKs inhibitors showed that all of them are necessary for phagocytosis, but only phospho-p38 affects H2O2 synthesis. The blocking of JNK phosphorylation, in the presence of E. coli, evoked a further decrease of cytoplasmic p47 thus increasing its translocation onto the plasma membrane for the assembly of NADPH oxidase. It appears that newly synthesised H2O2 invigorates the phosphorylation and action of ERK-1/2 in E. coli phagocytosis, while phospho-JNK and phospho-p38 appear to regulate H2O2 production. PMID:26204503

  7. Characterization of the interaction between recombinant human interferon-gamma and its receptor on human polymorphonuclear leukocytes

    The interaction of human recombinant interferon-gamma (rIFN-gamma) with human polymorphonuclear cells (PMN) was investigated. Bolton-Hunter radioiodinated rIFN-gamma bound to PMN in a specific and saturable manner. Eleven hundred binding sites were observed with a Ka of 0.56 x 10(10) M-1. Binding to PMN was rapid with a K1 of 9 x 10(5) M-1 sec-1 at 4 degree C. At 37 degree C binding was complete within 6 min. About 50% of bound ligand was internalized within 30 min at 37 degree C. The receptor demonstrated moderate lability at 37 degree C in culture. After 1 h at 37 degree C, PMN lost 80% of their 125I-rIFN-gamma binding sites. This loss was reversed in part by the presence of interleukin-1 in the culture, but not tumor necrosis factor. These studies provide a framework for further investigation into the signalling process of rIFN-gamma on PMN

  8. Modulation of polymorphonuclear leukocytes function by incubation with human serum from oxidant-challenged individuals

    E Hoffer; T Machamid; A Tabak; Y Baum; A Tamir; Y Lerman


    Polymorphonuclear leukocytes (PMN) from healthy donors were tested for stimulated release of superoxide anions after being incubated with serum of welders and of a group of unexposed individuals. These two groups were further subdivided either according to age or to smoking habits. The experiments showed that stimulated superoxide production from PMN was inhibited ( < 0.05) by serum from young smokers as compared to that of young nonsmokers, both from the unexposed group. Incubation of PMN with serum from elderly nonsmoking individuals decreased superoxide production as compared to incubation with serum from young nonsmoking individuals, both from the unexposed group. A decrease in superoxide production by incubation with serum of welders as compared to that of unexposed individuals was significant only when the comparison was carried out between the young, non-smoking subgroups. These findings suggest that age, smoking, and exposure to oxidants induce appearance in serum of factors that affect the PMN function.

  9. Effects of 60Co gamma radiation on defense function of human polymorphonuclear leukocytes

    The effects of radiation on defense function of polymorphonuclear leukocytes (PMN) were studied following irradiation with 60Co γ radiation (30 - 3,000 rad) using PMN separated from the peripheral blood of healthy volunteers. The migration distances for all three measures of chemotaxis to fMet-Leu-Phe (10-8 M), chemokinesis induced by fMet-Leu-Phe, and random migration tended to decrease with increasing dose, showing 0.0054 μm/rad (p -5 M) in conjunction with cytochalasin B (CB, 5 μg/ml) there was a significant dose trend, showing the dose effects of decreasing 0.0022 % release/rad for BGL and 0.0030 % release/rad for LYZ with increasing dose. In superoxide anion (O2-) production, a slight and marginally significant linear dose trend was found. These results suggest that the defense function of PMN is not so resistant to radiation as predicted from the fact that PMN in the peripheral blood are differentiated and mature. It is thought that radiation inflicts substantially harmful effects on the defense function of peripheral PMN. (author)

  10. In vitro phagocytosis of methicillin resistant and methicillin sensitive staphylococcus aureus by human polymorphonuclear leucocytes

    Staphylococcus aureus is a gram positive bacterium that causes a number of diseases such as abscesses, infective endocarditis, septic arthritis, etc. It is acquiring resistance against many antibiotics like methicillin; therefore its control is becoming increasingly difficult. Peripheral blood phagocytes particularly polymorphonuclear leucocytes play an important role in the protective mechanisms against these organisms. Phagocytes interact with bacteria and phagocytose these microorganisms to kill them. Phenotypically different isolates of Staphylococcus aureus including methicillin resistant Staphylococcus aureus (MRSA) and methicillin sensitive Staphylococcus aureus (MSSA) were collected from various hospitals of Lahore, Pakistan. Fresh polymorphonuclaer leucocytes were obtained from healthy individuals by centrifugation using Ficol-Hypaque gradient combined with dextran sedimentation. Microbiological method was used for the determination of phagocytic index of phenotypic variants of Staphylococcus aureus. A significant difference was observed between the phagocytic index of both bacterial groups. MSSA group showed the Mean+-SD of 79.46%+-3.9 while MRSA group showed 72.35%+-2.5. Significant difference in phagocytic index indicates that it can be one of the mechanisms of MRSA to evade host immune system as compare to MSSA. (author)

  11. Promotion of DNA strand breaks in cocultured mononuclear leukocytes by protein kinase C-dependent prooxidative interactions of benoxaprofen, human polymorphonuclear leukocytes, and ultraviolet radiation

    At concentrations of 5 micrograms/ml and greater the nonsteroidal antiinflammatory drug benoxaprofen caused dose-related activation of lucigenin-enhanced chemiluminescence in human polymorphonuclear leukocytes (PMNL). Benoxaprofen-mediated activation of lucigenin-enhanced chemiluminescence by PMNL was increased by UV radiation and was particularly sensitive to inhibition by the selective protein kinase C inhibitor H-7. To identify the molecular mechanism of the prooxidative activity of benoxaprofen, the effects of the nonsteroidal antiinflammatory drug on the activity of purified protein kinase C in a cell-free system were investigated. Benoxaprofen caused a dose-related activation of protein kinase C by interaction with the binding site for the physiological activator phosphatidylserine, but could not replace diacylglycerol. When autologous mononuclear leukocytes (MNL) were cocultured with PMNL and benoxaprofen in combination, but not individually, the frequency of DNA strand breaks in MNL was markedly increased. UV radiation significantly potentiated damage to DNA mediated by benoxaprofen and PMNL. Inclusion of superoxide dismutase, H-7, and, to a much lesser extent, catalase during exposure of MNL to benoxaprofen-activated PMNL prevented oxidant damage to DNA. These results clearly demonstrate that potentially carcinogenic prooxidative interactions, which are unlikely to be detected by conventional assays of mutagenicity, may occur between phagocytes, UV radiation, and certain pharmacological agents

  12. Promotion of DNA strand breaks in cocultured mononuclear leukocytes by protein kinase C-dependent prooxidative interactions of benoxaprofen, human polymorphonuclear leukocytes, and ultraviolet radiation

    Schwalb, G.; Beyers, A.D.; Anderson, R.; Nel, A.E.


    At concentrations of 5 micrograms/ml and greater the nonsteroidal antiinflammatory drug benoxaprofen caused dose-related activation of lucigenin-enhanced chemiluminescence in human polymorphonuclear leukocytes (PMNL). Benoxaprofen-mediated activation of lucigenin-enhanced chemiluminescence by PMNL was increased by UV radiation and was particularly sensitive to inhibition by the selective protein kinase C inhibitor H-7. To identify the molecular mechanism of the prooxidative activity of benoxaprofen, the effects of the nonsteroidal antiinflammatory drug on the activity of purified protein kinase C in a cell-free system were investigated. Benoxaprofen caused a dose-related activation of protein kinase C by interaction with the binding site for the physiological activator phosphatidylserine, but could not replace diacylglycerol. When autologous mononuclear leukocytes (MNL) were cocultured with PMNL and benoxaprofen in combination, but not individually, the frequency of DNA strand breaks in MNL was markedly increased. UV radiation significantly potentiated damage to DNA mediated by benoxaprofen and PMNL. Inclusion of superoxide dismutase, H-7, and, to a much lesser extent, catalase during exposure of MNL to benoxaprofen-activated PMNL prevented oxidant damage to DNA. These results clearly demonstrate that potentially carcinogenic prooxidative interactions, which are unlikely to be detected by conventional assays of mutagenicity, may occur between phagocytes, UV radiation, and certain pharmacological agents.

  13. The role of oxidative metabolism in human polymorphonuclear leucocyte functions mediated by the specific receptor for N-formyl peptides

    Studies on the effects of auto-oxidation on the function of human polymorphonuclear leucocytes (PMNL) were performed on PMNL purified on ficoll-metrizoate cushions at room temperature. Auto-oxidation of PMNL was simulated. N-formyl peptide-dependent chemotaxis, chemokinesis and respiratory burst were inhibited by PMNL auto-oxidation. The oxidising system caused iodination as well as sulphydryl oxidation of PMNL. These effects were all prevented and reversed by antioxidants. Lysozyme release as well as total binding of radiolabelled peptide were increased by PMNL auto-oxidation. Whole PMNL and specific granules were covalently linked to an iodinated N-formyl peptide. After electrophoresis and autoradiography a diffuse band was common to both PMNL and granules, while PMNL displayed three additional bands and granules one additional band. Pre-incubation of PMNL at 37 degrees Celsius revealed most intense labelling of the diffuse band. Thin-layer chromatography of radiolabelled N-formyl peptides revealed a methionine-independent structural alteration mediated by PMNL and supernatants from stimulated PMNL. Tritium, Carbon 14 and Iodine 125 were used in these experiments for radiolabelling compounds

  14. Effects of dietary supplementation of Chinese medicinal herbs on polymorphonuclear neutrophil immune activity and small intestinal morphology in weanling pigs.

    Huang, C W; Lee, T T; Shih, Y C; Yu, B


    The purpose of this study was to evaluate the effects of dietary Chinese medicinal herbs (CMH) supplementation composed of Panax ginseng, Dioscoreaceae opposite, Atractylodes macrocephala, Glycyrrhiza uralensis, Ziziphus jujube and Platycodon grandiflorum, on the performance, intestinal tract morphology and immune activity in weanling pigs. Two hundred and forty weaned pigs were assigned randomly to four dietary groups including the negative control (basal diet), 0.1% CMH, 0.3% CMH and 0.114% antibiotic (Chlortetracycline calcium Complex, Sulfathiazole and Procaine Penicillin G) supplementation groups for a 28-day feeding trial. Results indicated that both CMH supplementation groups had a better gain and feed/gain than control group (CT) during the first 2 weeks of the experimental period. The 0.3% CMH had a significant decrease in the diarrhoea score in first 10 days of experimental period when compared with other groups. The CMH supplementation groups had a higher villous height, increased lactobacilli counts in digesta of ileum and decreased coliform counts in colon compared with CT. The immune activities of polymorphonuclear leucocytes (PMNs), including the respiratory burst and Salmonella-killing ability, were significantly enhanced in CMH supplementation groups at day 7 of experiment period. The CMH and antibiotic supplementations increased the nutrient digestibility such as dietary dry matter, crude protein and gross energy in weanling pigs. In conclusion, the dietary CMH supplementation improved intestinal morphology and immune activities of PMNs, thus giving rise to nutrient digestibility and reduce diarrhoea frequency in weanling pigs. PMID:21535231

  15. Mode of action of staphylococcal leukocidin: effects of the S and F components on the activities of membrane-associated enzymes of rabbit polymorphonuclear leukocytes.

    Noda, M; Kato, I.; Hirayama, T; Matsuda, F.


    The cytotoxic action of the S component of leukocidin from Staphylococcus aureus on rabbit polymorphonuclear leukocytes was supported by the following observations, (i) Leukocytes displayed a large chemotactic response to the S component (10(-10) M) as well as to the chemotactic factor N-formylmethionylleucylphenylalanine (10(-11) M). (ii) The S component stimulated high levels of phospholipase A2 activity in the cell membranes, with concomitant synthesis and release of prostaglandins. (iii) ...

  16. Gene Expression in HL60 Granulocytoids and Human Polymorphonuclear Leukocytes Exposed to Candida albicans†

    Mullick, Alaka; Elias, Miria; Harakidas, Penelope; Marcil, Anne; Whiteway, Malcolm; Ge, Bing; Hudson, Thomas J.; Caron, Antoine W; Bourget, Lucie; Picard, Serge; Jovcevski, Orce; Massie, Bernard; Thomas, David Y.


    Candida albicans is an opportunistic human pathogen causing both superficial and disseminated diseases. It is a dimorphic fungus, switching between yeast and hyphal forms, depending on cues from its microenvironment. Hyphae play an important role in the pathogenesis of candidiasis. The host's response to Candida infection is multifaceted and includes the participation of granulocytes as key effector cells. The aim of this investigation was to study host gene expression during granulocyte-Cand...

  17. Leukotriene B4 modulates human polymorphonuclear leukocyte (PMN) phospholipid (PL) methylation

    Formation of phosphatidylcholine (PC) by methylation of phosphatidylethanolamine (PE) is required for transduction of chemotactic factor messages in phagocytic cells, including the development of a motile configuration and release of arachidonic acid (AA) from PL. The authors examined PL methylation in human peripheral blood PMN following stimulation by leukotriene B4 (LTB4), a potent chemotactic lipid metabolite of AA that is produced by human PMN. [3H]-methionine, in the presence or absence of LTB4, was added directly to the cells without a preloading period. [3H]-methyl mono- and di-methylated PE, PC and lyso PC were separated by thin layer chromatography. PL methylation in human PMN is dependent on time of incubation, LTB4 concentration and methionine concentration. The optimal LTB4 concentration is 10-7 M, the same concentration that induces a maximal chemotactic response in PMN. At early time points (2-10 min), formation of methylated PL is enhanced following LTB4 stimulation. In contrast, at later time points (20-60 min), methylated PL synthesis in LTB4 treated cells is depressed or the same as control cells. Synthesis of PC by the choline transferase pathway is not affected by LTB4 stimulation. This data shows that, at early time points following LTB4 stimulation, PL methylation is enhanced. This correlates with other reports of calcium mobilization and chemotaxis in PMN at early time points following LTB4 stimulation

  18. Immunosenescence of Polymorphonuclear Neutrophils

    Inga Wessels


    Full Text Available All immune cells are affected by aging, contributing to the high susceptibility to infections and increased mortality observed in the elderly. The effect of aging on cells of the adaptive immune system is well documented. In contrast, knowledge concerning age-related defects of polymorphonuclear neutrophils (PMN is limited. During the past decade, it has become evident that in addition to their traditional role as phagocytes, neutrophils are able to secrete a wide array of immunomodulating molecules. Their importance is underlined by the finding that genetic defects that lead to neutropenia increase susceptibility to infections. Whereas there is consistence about the constant circulating number of PMN throughout aging, the abilities of tissue infiltration, phagocytosis, and oxidative burst of PMN from aged donors are discussed controversially. Furthermore, there are numerous discrepancies between in vivo and in vitro results, as well as between results for murine and human PMN. Most of the reported functional changes can be explained by defective signaling pathways, but further research is required to get a detailed insight into the underlying molecular mechanisms. This could form the basis for drug development in order to prevent or treat age-related diseases, and thus to unburden the public health systems.

  19. A quantitative in vitro assay of polymorphonuclear leukocyte migraton through human amnion membrane utilizing 111In-oxine

    A modified amnion chemotaxis assay is described for measurement of polymorphonuclear leukocyte(s) (PMNL) migration (random and directed) into a viable membrane. The primary modifications are the use of 111In-oxine-labelled PMNL and replacement of the nitrocellulose 'trap' filter with a type I collagen sponge. The modifications resulted in four important benefits: (1) the quantification of PMNL migration was simplified; (2) reader subjectivity was eliminated; (3) the information gained of the migration process was enhanced; and (4) the assay time was decreased. The amnion chemotaxis assay with the modifications reported should provide the means of evaluating several aspects of the inflammatory response of PMNL. (Auth.)

  20. Myeloperoxidase modulates the phagocytic activity of polymorphonuclear neutrophil leukocytes. Studies with cells from a myeloperoxidase-deficient patient.

    Stendahl, O.; Coble, B I; Dahlgren, C; Hed, J; Molin, L.


    Patients lacking the primary granulae enzyme, myeloperoxidase (MPO), do not usually show any increased susceptibility to infection or altered inflammatory response, in contrast to several other biochemical defects in polymorphonuclear neutrophils. We have now evaluated the role of MPO on phagocyte function in a patient with complete MPO deficiency suffering from generalized pustular psoriasis. We found that the MPO-deficient neutrophils showed enhanced phagocytosis (greater than 200% of norma...

  1. Effect of etizolam (Depas) on production of superoxide anion by platelet-activating factor and N-formyl-methionyl-leucyl-phenylalanine-stimulated guinea pig polymorphonuclear leukocytes.

    Aratani, H; Nishida, Y; Terasawa, M; Maruyama, Y


    Effect of etizolam on platelet activating factor (PAF) and N-formyl-methionyl-leucyl-phenylalanine (FMLP)-induced superoxide anion (O2-) production in guinea pig polymorphonuclear leukocytes (PMNL) was investigated. Etizolam showed the inhibitory effect on PAF-induced O2- production concentration dependently, with an IC50 value of 4.7 microM, but it had no inhibitory effect on FMLP-induced O2- production at 100 microM. These results suggest that etizolam has a selectively strong inhibitory effect on PAF-induced O2- production in guinea pig PMNL. PMID:2848961

  2. Measurement of arachidonic acid release from human polymorphonuclear neutrophils and platelets: comparison between gas chromatographic and radiometric assays

    a simple gas chromatographic method for the assay of phospholipase A2 (PLA2) has been described in which arachidonic acid released from endogenous phospholipid pools is measured following its extraction and derivatization to pentafluorobenzyl esters. Using this assay, PLA2 activities in control and calcium ionophore-stimulated human neutrophils, as well as in control, thrombin, and calcium ionophore stimulated human platelets, have been measured. These values are compared with those obtained by monitoring the release of radioactivity from 3H- or 14Carachidonic acid prelabeled cells. While the radiometric assay measures only the release of exogenously incorporated radioactive arachidonic acid, the gas chromatographic assay measures arachidonic acid released from all the endogenous pools. Thus, the apparent increase in PLA2 activity in stimulated cells measured by the gas chromatographic assay is four- to fivefold higher than that by the radiometric assay. Inclusion of fatty acid free bovine serum albumin in the reaction buffer significantly increases the amount of arachidonic acid that is measured by gas chromatography. The gas chromatographic method has also been successfully utilized for measuring PLA2 activity in cell-free preparations derived from physically disrupted human neutrophils

  3. Study of the inhibition by polymorphonuclear leukocytes of TNF-α release from human mononuclear cells and its mechanism


    The present study was undertaken to investigate the effect of human PMNs on the production of TNF-α by the human peripheral blood mononuclear cells (PBMCs) and to elucidate its tentative mechanism. Human PMNs and PBMCs were isolated from the venous blood of healthy donors by dextran sedimentation and density gradient centrifugation. In the presence of lipopolysaccharide (LPS), PMNs and PBMCs were cocultured at the ratio of 2:1 for 20 h and the concentration of TNF-α in the supernatant was measured by enzyme-linked immunosorbent assay. The binding rate of monocytes with the fluorescein isothiocyanate-labeled LPS (FITC-LPS) and the mean surface fluorescence intensity of monocytes were analyzed by flow cytometry. Results showed that PMNs were capable of inhibiting the TNF-α release from PBMCs (P<0.05). PMNs suppressed the TNF-α release from PBMCs by 45% on average when PMNs and PBMCs cocultured at the ratio of 2:1. Paraformaldehyde-fixed PMNs still demonstrated the same inhibition (P<0.05),which proved that the inhibition was dependent on cell-to-cell contact and suggested that effector molecules responsible for this effect existed on the cell surface of PMNs. In the presence of PMNs, the binding rate of monocytes with the FITC-LPS and the mean surface fluorescence intensity of monocytes were not affected compared with PBMCs alone (P>0.05). As incubation time was prolonged, the binding of FITC-LPS to monocytes increased (P<0.05). Thus PMNs did not block the binding of LPS with monocytes. It was concluded that PMNs suppressed the TNF-α release from PBMCs via cell-to-cell interaction. In a cell-contact dependent manner, PMNs might interfere with the signal transduction pathway through which LPS activated PBMCs, thus attenuating the response of PBMCs to LPS and downregulating the TNF-α release.

  4. Myeloid derived suppressor cells (MDSCs are increased and exert immunosuppressive activity together with polymorphonuclear leukocytes (PMNs in chronic myeloid leukemia patients.

    Cesarina Giallongo

    Full Text Available Tumor immune tolerance can derive from the recruitment of suppressor cell population, including myeloid derived suppressor cells (MDSCs, able to inhibit T cells activity. We identified a significantly expanded MDSCs population in chronic myeloid leukemia (CML patients at diagnosis that decreased to normal levels after imatinib therapy. In addition, expression of arginase 1 (Arg1 that depletes microenvironment of arginine, an essential aminoacid for T cell function, resulted in an increase in patients at diagnosis. Purified CML CD11b+CD33+CD14-HLADR- cells markedly suppressed normal donor T cell proliferation in vitro. Comparing CML Gr-MDSCs to autologous polymorphonuclear leukocytes (PMNs we observed a higher Arg1 expression and activity in PMNs, together with an inhibitory effect on T cells in vitro. Our data indicate that CML cells create an immuno-tolerant environment associated to MDSCs expansion with immunosuppressive capacity mediated by Arg1. In addition, we demonstrated for the first time also an immunosuppressive activity of CML PMNs, suggesting a strong potential immune escape mechanism created by CML cells, which control the anti-tumor reactive T cells. MDSCs should be monitored in imatinib discontinuation trials to understand their importance in relapsing patients.

  5. Effect of Ciprofloxacin on Killing of Actinobacillus actinomycetemcomitans by Polymorphonuclear Leukocytes

    Cacchillo, David A.; Walters, John D.


    Actinobacillus actinomycetemcomitans, a pathogen associated with aggressive periodontitis, resists phagocytic killing by polymorphonuclear leukocytes (PMNs). It is susceptible to ciprofloxacin, which PMNs actively accumulate. This study tested the hypothesis that ciprofloxacin-loaded PMNs are more effective at killing A. actinomycetemcomitans than control PMNs. Isolated human PMNs were loaded by brief incubation with 0.5 μg of ciprofloxacin/ml. Opsonized bacteria (ATCC 43718) were incubated a...

  6. Mannose binding lectin plays a crucial role in innate immunity against yeast by enhanced complement activation and enhanced uptake of polymorphonuclear cells

    Herpers Bjorn L


    Full Text Available Abstract Background Mannose binding lectin (MBL is an important host defence protein against opportunistic fungal pathogens. This carbohydrate-binding protein, an opsonin and lectin pathway activator, binds through multiple lectin domains to the repeating sugar arrays displayed on the surface of a wide range of clinically relevant microbial species. We investigated the contribution of MBL to antifungal innate immunity towards C. parapsilosis in vitro. Results High avidity binding was observed between MBL and C. albicans and C. parapsilosis. Addition of MBL to MBL deficient serum increased the deposition of C4 and C3b and enhanced the uptake of C. albicans, C. parapsilosis and acapsular C. neoformans by polymorphonuclear cells (PMNs. Compared to other microorganisms, such as Escherichia coli, Staphylococcus aureus and Cryptococcus neoformans, C. parapsilosis and Candida albicans were potent activators of the lectin pathway. Conclusion Our results suggest that MBL plays a crucial role in the innate immunity against infections caused by yeast by increasing uptake by PMN.

  7. ADAM9 Is a Novel Product of Polymorphonuclear Neutrophils

    Roychaudhuri, Robin; Hergrueter, Anja H; Polverino, Francesca;


    A disintegrin and a metalloproteinase domain (ADAM) 9 is known to be expressed by monocytes and macrophages. In this study, we report that ADAM9 is also a product of human and murine polymorphonuclear neutrophils (PMNs). ADAM9 is not synthesized de novo by circulating PMNs. Rather, ADAM9 protein is...... stored in the gelatinase and specific granules and the secretory vesicles of human PMNs. Unstimulated PMNs express minimal quantities of surface ADAM9, but activation of PMNs with degranulating agonists rapidly (within 15 min) increases PMN surface ADAM9 levels. Human PMNs produce small quantities of...... soluble forms of ADAM9. Surprisingly, ADAM9 degrades several extracellular matrix (ECM) proteins, including fibronectin, entactin, laminin, and insoluble elastin, as potently as matrix metalloproteinase-9. However, ADAM9 does not degrade types I, III, or IV collagen or denatured collagens in vitro. To...

  8. Effect of diclofenac alone or in combination with alpha-tocopherol on the oxidative activity of polymorphonuclear leukocytes in healthy and osteoartheritic individuals

    To ivestigate the effects of diclofenac alone or when combined with alpha-tocopherol on the oxidative activity of polymorphonuclear leukocytes (PMNs) in healthy and osteoartheritic (OA) patients. The study was carried out at the College of Medicine, King Saud University, Riyadh, KIgdom of Saudi Arabia, over the period 1999 to 2000. 12 healthy controls and 12 osteoartheritic patients were recruited to the study. They were given diclofenac 50mg thricedaily orally, initially for 5 days then alpha-tocopherol at 200mg thrice daily orally, was added for another 5 days. Blood samples were drawn before the start of study and at 5 days following treatmentwith diclofenac alone and 10 days following treatment with diclophenac and alpha-tocopherol. Chemiluminescence (CL)reponse was measured for wohle blood and isolated (PMNs) on all samples. Diclofenac enhanced CL response of whole blood and PMNs of healthy controls when stimulated with phorbol myristate acetate (PMA) and opsonized zymosan (OPZ). Cotreatment with alpha-tocopherol resulted in no appreciable change in the CL response of whole blood when stimulated with PMA or OPZ but a further significant enhancement of CL response of isolated PMNs when these cells were stimulated by either PMA or OPZ. In osteoartheritic patients, diclofenac alone and when combined with alpha-tocopherol showed no significant change in CL response of the whole blood.The CL response of PMNs from OA patients was decreased by diclofenac alone. However the inhibitory effect was not observed when alpha-tocopherol was used together with diclofenac. The effect of diclofenac alone or in combination with alpha-tocopherol did not produce a consistent effect on the CL response of whole blood or isolated PMNs of healthy or osteoartheritic patients. (author)

  9. Sjogren's Syndrome Antigen B Acts as an Endogenous Danger Molecule to Induce Interleukin-8 Gene Expression in Polymorphonuclear Neutrophils.

    Cheng-Han Wu

    Full Text Available Sjögren's syndrome antigen B is expressed in the nucleus and surface membrane of human polymorphonuclear neutrophils and is released after cell death. However, its biological role is not clear. This study is aimed to investigate the effect of Sjögren's syndrome antigen B on human polymorphonuclear neutrophils.Human recombinant Sjögren's syndrome antigen B (rSSB purified from E. coli was incubated with human polymorphonuclear neutrophils as well as retinoid acid-induced granulocytic differentiated HL-60 cells, HL-60 (RA. Interleukin (IL-8 protein production and mRNA expressions were measured by enzyme-linked immunosorbent assay and quantitative-polymerase chain reaction, respectively. Uptake of fluorescein isothiocyanate (FITC-rSSB was assessed by flow cytometry and fluorescence microscopy. Moreover, mitogen-activated protein kinase (MAPK pathways and nuclear factor-kappaB activation were investigated.Human rSSB stimulated IL-8 production from normal human neutrophils and HL-60 (RA cells in a time- and dose-dependent manner. This IL-8-stimulated activity was blocked by chloroquine and NH4Cl, indicating that endosomal acidification is important for this effect. We found rSSB activated both MAPK pathway and nuclear factor-kappaB signaling to transcribe the IL-8 gene expression of cells. Furthermore, tumor necrosis factor-α exerted an additive effect and rSSB-anti-SSB immune complex exhibited a synergistic effect on rSSB-induced IL-8 production.Sjögren's syndrome antigen B might act as an endogenous danger molecule to enhance IL-8 gene expression in human polymorphonuclear neutrophils.

  10. Killing of Proteus mirabilis by polymorphonuclear leukocyte granule proteins: evidence for species specificity by antimicrobial proteins.

    Shafer, W M; Engle, S A; Martin, L E; Spitznagel, J K


    Low-molecular-weight (Mr, ca. 3,800) polypeptides containing human defensins HNP-1 and HNP-2 (T. Ganz, M. S. Selsted, D. Szlarek, S. L. Harwig, K. Daher, D. F. Bainton, and R. I. Lehrer, J. Clin. Invest. 76:1427-1434, 1985) prepared in our laboratory from acid extracts of human polymorphonuclear granulocyte granules and purified human defensins were found to exert potent bactericidal action against Proteus mirabilis. The antimicrobial action of the extracts of human polymorphonuclear leukocyt...

  11. Comparison of adherent and non-adherent staphylococci in the induction of polymorphonuclear leukocyte activation in vitro

    Riber, U; Espersen, F; Kharazmi, A


    the induction of chemiluminescence by planktonic bacteria, S. epidermidis induced a lower response than S. aureus, while when adherent to the catheter segments the bacteria induced similar responses. These responses were only 15 to 20% of those induced by planktonic bacteria and only slightly higher......The ability to consume complement and activate neutrophils was investigated for staphylococci adherent to silicone surfaces and non-adherent staphylococci. Staphylococcus epidermidis strain ATCC 14990 and Staphylococcus aureus strain E 2371 were used in this study. The bacteria were allowed to...... 37 degrees C. The bacteria consumed complement to approximately the same extent when adherent to the catheter segments, but more slowly in comparison with planktonic bacteria. When planktonic bacteria were compared, complement was consumed more quickly by S. epidermidis than by S. aureus. Measuring...

  12. Faster activation of polymorphonuclear neutrophils in resistant mice during early innate response to Pseudomonas aeruginosa lung infection

    Jensen, P Ø; Moser, C; Kobayashi, O;


    bacterial clearance in the lungs of C3H/HeN mice could be explained by faster activation of the PMNs, as indicated by the higher up-regulation of CD11b. The severe lung inflammation in BALB/c mice may be caused by the early higher content of G-CSF in the sera mobilizing PMNs from the bone marrow and the...... decreased 1 day after bacterial challenge, whereas the expression was increased after 2 days of challenge on PMNs of C3H/HeN mice only. These changes were accompanied by a more severe lung inflammation in BALB/c mice and faster clearance of the bacteria in C3H/HeN mice. In conclusion, the rapid early...

  13. Kinetics of staphylococcal opsonization, attachment, ingestion and killing by human polymorphonuclear leukocytes: a quantitative assay using [3H]thymidine labelled bacteria

    A method has been developed for studying quantitatively the separate processes of bacterial opsonization, phagocytosis and killing by hyman polymorphonuclear leukocytes using [3H]thymidine labelled staphylococcus aureus. Phagocytosis is determined by assaying for leukocytes-associated radioactivity after different centrifugation and washing the leukoctes. Opsonization is studied by incubating bacteria with an opsonic source for varying durations and then adding leukocytes. By treatment of samples with the muralytic enzyme, lysostaphin, the attachment and ingestion phases of phagocytosis can be separated. Sampling for colony forming units after disruption of the leukocytes permits the measurement of gacterial killing. Using this method, differences in the kinetics of staphylococcal opsonization by normal and C2 deficient sera were defined, opsonic influences on the attachment and ingestion phases of phagocytosis were delineated, and the influences of different opsonins and leukocyte populations on killing were determined

  14. Respiratory burst facilitates the digestion of Escherichia coli killed by polymorphonuclear leukocytes.

    Weiss, J; Kao, L; Victor, M; Elsbach, P


    We examined factors that may limit degradation of bacterial protein of Escherichia coli S15 killed by polymorphonuclear leukocytes (PMN). Both human and rabbit PMN degraded up to 40% of [14C]amino acid-labeled protein of ingested and killed E. coli in 2 h as determined by loss of acid-precipitable radioactivity. In contrast, equally bactericidal broken-PMN preparations or isolated granules degraded only about 10% of bacterial protein regardless of pH. To determine whether activation of the re...

  15. High Intracellular Concentrations of Posaconazole Do Not Impact on Functional Capacities of Human Polymorphonuclear Neutrophils and Monocyte-Derived Macrophages In Vitro.

    Farowski, Fedja; Cornely, Oliver A; Hartmann, Pia


    Posaconazole is a commonly used antifungal for the prophylaxis and treatment of invasive fungal infections. We previously demonstrated that the intracellular concentration of posaconazole in peripheral blood mononuclear cells (PBMCs) and polymorphonuclear neutrophils (PMNs) was greatly increased compared to the plasma concentration. As these professional phagocytes are crucial to combat fungal infections, we set out to investigate if and how, beneficial or deleterious, this high loading of intracellular posaconazole impacts the functional capacities of these cells. Here, we show that high intracellular concentrations of posaconazole do not significantly impact PMN and monocyte-derived macrophage function in vitro In particular, killing capacity and cytoskeletal features of PMN, such as migration, are not affected, indicating that these cells serve as vehicles for posaconazole to the site of infection. Moreover, since posaconazole as such slowed the germination of Aspergillus fumigatus conidia, infected neutrophils released less reactive oxygen species (ROS). Based on these findings, we propose that the delivery of posaconazole by neutrophils to the site of Aspergillus species infection warrants control of the pathogen and preservation of tissue integrity at the same time. PMID:27021317

  16. Labeled polymorphonuclear leukocytes: a comparison of methodology

    Polymorphonuclear neutrophilic granulocytes were separated from anti-coagulated whole blood using three techniques. The methods employed included volex sedimentation (VS), volex sedimentation with hypotonic lysis (VSHL), and Ficoll-Hypaque gradient separation (FH). The cells were labeled with 111In-oxine and 111In-tropolone. Studies were done with both blood from normal human volunteers and with canine blood. From the cell counts and differential, the harvested granulocytes, platelets, and red blood cells per milliliter of whole blood were calculated. Using the granulocyte chemotactic response to E. coli in agarose plates, the ratio of chemotactic migration to random migration (c./r.m.) was determined. Survival time for 111In labeled granulocytes were also determined in a canine model. The studies demonstrated that all procedures yielded 100% viability by the Trypan blue exclusion test. Chemotactic migration and leukocyte survival times were similar amongst all techniques. With the VSHL technique, there were significantly fewer red blood cells and platelets in the final preparation approaching the results of FH separation. The results suggest that, for a relatively pure granulocyte preparation, VSHL is an acceptable alternative to FH. (author)

  17. The small breathing amplitude at the upper lobes favours the attraction of polymorphonuclear neutrophils to Mycobacterium tuberculosis lesions and helps to understand the evolution towards active disease in an individual-based model

    Pere-Joan eCardona


    Full Text Available Infection with Mycobacterium tuberculosis (Mtb can induce two kinds of lesions, namely proliferative and exudative. The former are based on the presence of macrophages with controlled induction of intragranulomatous necrosis, and are even able to stop its physical progression, thus avoiding the induction of active tuberculosis (TB. In contrast, the most significant characteristic of exudative lesions is their massive infiltration with polymorphonuclear neutrophils (PMNs, which favour enlargement of the lesions and extracellular growth of the bacilli. We have built an individual-based model (IBM (known as TBPATCH using the NetLogo interface to better understand the progression from Mtb infection to TB. We have tested four main factors previously identified as being able to favour the infiltration of Mtb-infected lesions with PMNs, namely the tolerability of infected macrophages to the bacillary load; the capacity to modulate the Th17 response; the breathing amplitude (large or small in the lower and upper lobes respectively, which influences bacillary drainage at the alveoli; and the encapsulation of Mtb-infected lesions by the interlobular septae that structure the pulmonary parenchyma into secondary lobes. Overall, although all the factors analysed play some role, the small breathing amplitude is the major factor determining whether Mtb-infected lesions become exudative, and thus induce TB, thereby helping to understand why this usually takes place in the upper lobes. This information will be very useful for the design of future prophylactic and therapeutic approaches against TB.

  18. The Small Breathing Amplitude at the Upper Lobes Favors the Attraction of Polymorphonuclear Neutrophils to Mycobacterium tuberculosis Lesions and Helps to Understand the Evolution toward Active Disease in An Individual-Based Model

    Cardona, Pere-Joan; Prats, Clara


    Infection with Mycobacterium tuberculosis (Mtb) can induce two kinds of lesions, namely proliferative and exudative. The former are based on the presence of macrophages with controlled induction of intragranulomatous necrosis, and are even able to stop its physical progression, thus avoiding the induction of active tuberculosis (TB). In contrast, the most significant characteristic of exudative lesions is their massive infiltration with polymorphonuclear neutrophils (PMNs), which favor enlargement of the lesions and extracellular growth of the bacilli. We have built an individual-based model (IBM) (known as “TBPATCH”) using the NetLogo interface to better understand the progression from Mtb infection to TB. We have tested four main factors previously identified as being able to favor the infiltration of Mtb-infected lesions with PMNs, namely the tolerability of infected macrophages to the bacillary load; the capacity to modulate the Th17 response; the breathing amplitude (BAM) (large or small in the lower and upper lobes respectively), which influences bacillary drainage at the alveoli; and the encapsulation of Mtb-infected lesions by the interlobular septae that structure the pulmonary parenchyma into secondary lobes. Overall, although all the factors analyzed play some role, the small BAM is the major factor determining whether Mtb-infected lesions become exudative, and thus induce TB, thereby helping to understand why this usually takes place in the upper lobes. This information will be very useful for the design of future prophylactic and therapeutic approaches against TB. PMID:27065951

  19. Pulmonary accumulation of polymorphonuclear leukocytes in the adult respiratory distress syndrome

    The polymorphonuclear leukocyte (PMN) plays an integral role in the development of permeability pulmonary edema associated with the adult respiratory distress syndrome (ARDS). This report describes 3 patients with ARDS secondary to systemic sepsis who demonstrated an abnormal diffuse accumulation of Indium (111In)-labeled PMNs in their lungs, without concomitant clinical or laboratory evidence of a primary chest infection. In one patient, the accumulation of the pulmonary activity during an initial pass suggested that this observation was related to diffuse leukoaggregation within the pulmonary microvasculature. A 4th patient with ARDS was on high-dose corticosteroids at the time of a similar study, and showed no pulmonary accumulation of PMNs, suggesting a possible reason for the reported beneficial effect of corticosteroids in human ARDS

  20. File list: Pol.Bld.20.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

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  18. Antibody-dependent cytolysis of Trypanosoma cruzi by polymorphonuclear leucocytes: dependence on the respiratory burst

    Human polymorphonuclear leucocytes (PMN) lysed antibody-coated Trypanosoma cruzi epimastigotes under in vitro conditions. Cytotoxicity mediated by PMN, evaluated by the release of 3H-uridine-labelled RNA from T. cruzi, required specific, anti-T. cruzi antibody for target binding and triggering of the cytotoxic response. Cytotoxicity was negligible in the absence of serum. To determine if the respiratory burst and active oxygen species production could be triggered by contact with antibody-coated T. cruzi epimastigotes, oxygen consumption, superoxide anion and hydrogen peroxide release were measured under conditions of T. cruzi lysis by PMN. All three parameters of activation of the respiratory burst were increased in the presence of antibody-coated T. cruzi epimastigotes. Antibody or T. cruzi, added separately, caused no significant activation. An increase in the O2 consumption was also observed when human PMN were incubated in the presence of T. cruzi trypomastigotes coated with antibody present in the serum of chronic Chagas' disease patients. Electron microscopy examination of PMN exposed to diaminobenzidine and T. cruzi showed the parasites inside the PMN phagosomes and an electron-dense reaction product between the two membranes which reveals the presence of myeloperoxidase and H2O2. The reaction product was blocked by aminotriazole and cyanide. These data indicate that oxygen-radical production by PMN was increased under conditions of T. cruzi cell killing. (author)

  19. Type 2 fimbrial lectin-mediated phagocytosis of oral Actinomyces spp. by polymorphonuclear leukocytes.

    Sandberg, A L; Mudrick, L L; Cisar, J O; Brennan, M J; Mergenhagen, S. E.; Vatter, A. E.


    Phagocytosis of Actinomyces viscosus T14V and A. naeslundii WVU45 by human polymorphonuclear leukocytes in the absence of antibody or complement was mediated by the lectin associated with the type 2 fimbriae of these bacteria. This effect was markedly enhanced by exogenous sialidase, an enzyme also secreted by these actinomyces. Since sialidase treatment of the bacteria did not result in increased phagocytosis, this enzyme presumably acts by unmasking receptors for the fimbrial lectin on phag...

  20. Membrane Potential Changes in Polymorphonuclear Leukocytes of Patients with Chronic Granulomatous Disease

    Matsuura, Ryoji; Kobayashi, Masao; Usui, Tomofusa


    The activation of NADPH oxidase on the plasma membranes of polymorphonuclear leukocytes (PMNL) follows the change of membrane potential. It is thought that the activation of NADPH oxidase is disturbed in the PMNL of patients with chronic granulomatous disease (CGD). The change of membrane potential was examined in the PMNL of normal subjects and patients with CGD, with a lipophilic probe, di-O-C5(3). There was a disturbance in phorbol myristate acetate (PMA) and formyl-methionyl-leucyl-phenyl...

  1. Effects of lead on the killing mechanisms of polymorphonuclear leukocytes

    The effects of lead on the killing mechanisms of rat polymorphonuclear leukocytes (PMN) were investigated, using male Long-Evans rats exposed to 1% lead acetate in the drinking water for varying periods of time to achieve blood lead levels ranging from 20-200 μg/dl. Studies of PMN bacterial and fungal killing activity, chemotaxis and phagocytosis demonstrated that: 1) bactericidal activity of PMN from rats exposed to lead was not altered; 2) chemotactic activity remained within normal limits; 3) the phagocytic ability of the PMN also remained unaltered. In addition to these normal findings, one major abnormality was demonstrated: a significant decrease in the ability of PMN from rats exposed to lead to kill Candida albicans. This defect was not related to age or to length of exposure. It could not be produced by addition of lead to the test system in vitro. Further investigation revealed significant decreases in PMN glucose-6-phosphate dehydrogenase, catalase, and myeloperoxidase activities. These data support two possible mechanisms for the abnormal fungicidal activity of PMN from lead-exposed rats: decrease in ability to reduce oxygen to active metabolites, or reduction in myeloperoxidase activity due to diminshed synthesis of the heme moiety required for its function

  2. Putative glycoprotein and glycolipid polymorphonuclear leukocyte receptors for the Actinomyces naeslundii WVU45 fimbrial lectin.

    Sandberg, A L; Ruhl, S; Joralmon, R A; Brennan, M J; Sutphin, M J; Cisar, J O


    Recognition of receptors on sialidase-treated polymorphonuclear leukocytes (PMNs) by the Gal/GalNAc lectin associated with the type 2 fimbriae of certain strains of actinomyces results in activation of the PMNs, phagocytosis, and destruction of the bacteria. In the present study, plant lectins were utilized as probes to identify putative PMN receptors for the actinomyces lectin. The Gal-reactive lectin from Ricinus communis (RCAI), the Gal/GalNAc-reactive lectins from R. communis (RCAII) and ...

  3. Consolidated Human Activities Database (CHAD)

    U.S. Environmental Protection Agency — The Consolidated Human Activity Database (CHAD) contains data obtained from human activity studies that were collected at city, state, and national levels. CHAD is...

  4. Fagocitose por neutrófilos no Lúpus Eritematoso Sistêmico The phagocytosis by polymorphonuclear neutrophils in patients with systemic lupus erythematosus

    Wilma Carvalho Neves Forte


    Full Text Available OBJETIVO: Avaliar a presença de imunocomplexos e a atividade fagocitária de polimorfonucleares neutrofílicos em pacientes com Lúpus Eritematoso Sistêmico (LES com e sem sinais e sintomas de atividade da doença. MÉTODOS: Analisou-se o sangue periférico de 55 indivíduos, sendo 10 pacientes com forma ativa da doença, 15 fora de atividade e 30 indivíduos sadios. Foi utilizada imunodifusão radial para identificação de imunocomplexos e estudada a etapa de ingestão da fagocitose por neutrófilos com partículas de zimosan. RESULTADOS: Observou-se a presença de crioprecipitado constituído por IgM, IgG, IgA, componentes C3 e C4 do complemento nos pacientes com LES. As médias aritméticas da ingestão por neutrófilos de partículas de zimosan incubado com soro homólogo e zimosan incubado com soro autólogo mostraram uma diminuição significativa (pOBJECTIVE: To evaluate the presence of immune complexes and the phagocytes by polymorphonuclear neutrophils in patients with systemic lupus erythematosus, with and without disease activity. METHODS: The peripheral blood of 55 subjects was analyzed. Ten of those subjects had disease activity, 15 had not disease activity, and 30 were healthy. We used radial immune diffusion to detect immune complexes. The phagocytic function was estimated by the ingestion of zymosan by polymorphonuclear neutrophils. RESULTS: In this study we found the presence of immune complexes formatted of IgM, IgG, IgA, and complement component C3 and C4 in LES patients. The arithmetic average of zymosan particles ingested by the neutrophils incubated with homologous human serum and autologous human serum was significantly decreased (p<0.05 in the LES activity patients when we compare with the group without activity, and the control group. CONCLUSION: We conclude that there are immune complexes in the LES patients with and without disease activity, and there is a reduction in the digestive step of the phagocytes by

  5. Human activity recognition and prediction


    This book provides a unique view of human activity recognition, especially fine-grained human activity structure learning, human-interaction recognition, RGB-D data based action recognition, temporal decomposition, and causality learning in unconstrained human activity videos. The techniques discussed give readers tools that provide a significant improvement over existing methodologies of video content understanding by taking advantage of activity recognition. It links multiple popular research fields in computer vision, machine learning, human-centered computing, human-computer interaction, image classification, and pattern recognition. In addition, the book includes several key chapters covering multiple emerging topics in the field. Contributed by top experts and practitioners, the chapters present key topics from different angles and blend both methodology and application, composing a solid overview of the human activity recognition techniques. .

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  18. Differences in the effect of arachidonic acid on polymorphonuclear and mononuclear leukocyte function

    Nijkamp, F.P.; Henricks, P.A.J.; Tol, M.E. van der; Kats-Renaud, J. H. van; Verhoef, J.


    Incubation of human polymorphonuclear leukocytes with arachidonic acid resulted in a stimulation of the oxidative metabolism of the cells. Upon stimulation with 80 μM arachidonic acid, neutrophils (5·106 cells/ml) produced superoxide (53±8 nmol/5·106 cells per 15 min), generated chemiluminescence (1211 100±157 000 cpm) and consumed oxygen (20±1 nmol/106 cells per 5 min). The stimulation of the cell metabolism could be reduced 40–60% by prior incubation of the cells with 10 μM indomethacin. In...

  19. The effect of apomorphine on exocytosis and metabolic burst of polymorphonuclear leukocytes.

    Elferink, J G


    1 In rabbit polymorphonuclear leukocytes (PMNLs) apomorphine at 10-100 microM inhibits fMet-Leu-Phe and A23187-induced exocytosis, and the phorbol myristate acetate- and fMet-Leu-Phe-induced activation of the metabolic burst. The secretory response was not restored by washing the cells after pretreatment with apomorphine. 2 The inhibitory effect of apomorphine was not prevented by the dopamine receptor antagonists haloperidol and pimozide, nor did dopamine itself inhibit fMet-Leu-Phe-induced ...

  20. Evidence that endoplasmic reticulum (ER) stress and caspase-4 activation occur in human neutrophils

    Apoptosis can result from activation of three major pathways: the extrinsic, the intrinsic, and the most recently identified endoplasmic reticulum (ER) stress-mediated pathway. While the two former pathways are known to be operational in human polymorphonuclear neutrophils (PMNs), the existence of the ER stress-mediated pathway, generally involving caspase-4, has never been reported in these cells. Recently, we have documented that arsenic trioxide (ATO) induced apoptosis in human PMNs by a mechanism that needs to be further investigated. In this study, using immunofluorescence and electron microscopy, we present evidence of ER alterations in PMNs activated by the ER stress inducer arsenic trioxide (ATO). Several key players of the unfolded protein response, including GRP78, GADD153, ATF6, XBP1 and eIF2α are expressed and activated in PMNs treated with ATO or other ER stress inducers. Although caspase-4 is expressed and activated in neutrophils, treatment with a caspase-4 inhibitor did not attenuate the pro-apoptotic effect of ATO at a concentration that reverses caspase-4 processing and activation. Our results demonstrate for the first time that the ER stress-mediated apoptotic pathway operates in human neutrophils.

  1. Human telomerase activity regulation

    Wojtyla, Aneta; Gladych, Marta; Rubis, Blazej


    Telomerase has been recognized as a relevant factor distinguishing cancer cells from normal cells. Thus, it has become a very promising target for anticancer therapy. The cell proliferative potential can be limited by replication end problem, due to telomeres shortening, which is overcome in cancer cells by telomerase activity or by alternative telomeres lengthening (ALT) mechanism. However, this multisubunit enzymatic complex can be regulated at various levels, including expression control b...

  2. Polymorphonuclear leucocytes in Crohn's disease and ulcerative proctocolitis: association between enhanced adherence to nylon fibre and disease variables.

    Cason, J; Ainley, C C; Wolstencroft, R. A.; Thompson, R P


    The adherence of polymorphonuclear leucocytes (PMN) to nylon fibre was investigated in patients with Crohn's disease, ulcerative proctocolitis, and anorexia nervosa, and compared with changes of circulating PMNs, C reactive protein concentrations, erythrocyte sedimentation rates, and clinical assessment of disease activity. PMN adherence was in excess of the maximum value detected for healthy subjects in 14 of 25 patients with Crohn's disease and two of 10 with proctocolitis, but it was withi...

  3. Identification of Polymorphonuclear Leukocyte and HL-60 Cell Receptors for Adhesins of Streptococcus gordonii and Actinomyces naeslundii

    Ruhl, Stefan; Cisar, John O.; Sandberg, Ann L.


    Interactions of oral streptococci and actinomyces with polymorphonuclear leukocytes (PMNs), mediated by sialic acid- and Gal/GalNAc-reactive adhesins, respectively, result in activation of the PMNs and thereby may contribute to the initiation of oral inflammation. Sialidase treatment of PMNs or HL-60 cells abolished adhesion of Streptococcus gordonii but was required for adhesion of Actinomyces naeslundii. The same effects of sialidase were noted for adhesion of these bacteria to a major 150-...

  4. A new combined assay of phagocytosis and intracellular killing of Escherichia coli by polymorphonuclear leukocytes

    A new combined radiometric assay is described in which adherence, and phagocytosis and killing of Escherichia coli by human polymorphonuclear leucocytes (PMN) are simultaneously measured in the same sample. Pure monolayers of PMN in Petri dishes are allowed to ingest [14C]phenylalanine labelled E. coli and excess bacteria are removed by washing. A period of incubation allows intracellular killing to occur while polymyxin-B is added to half the dishes to kill extracellular bacteria. The remaining viable bacteria in all dishes are labelled with [3H]thymidine. The number of ingested bacteria and the percentage of intracellular organisms killed is determined from the 14C and 3H counts by a simple subtraction technique. By performing protein assays on representative monolayers, the number of PMN adhered in the monolayers and hence the mean bacterial uptake per PMN is estimated. The assay detected killing efficiencies reduced below the normal range, in monolayers treated with sodium azide, phenylbutazone, in polymorphonuclear leukocytes from patients with chronic granulomatous disease, and in immature neutrophils from the promyelocytic leukaemic cell line, HL60. The assay was adapted to measure phagocytosis and killing by cells in suspension. (Auth.)

  5. Combination of autoantibodies against different histone proteins influences complement-dependent phagocytosis of necrotic cell material by polymorphonuclear leukocytes in systemic lupus erythematosus

    Gullstrand, Birgitta; Lefort, Malin H; Tydén, Helena; Jönsen, Andreas; Lood, Christian; Johansson, Asa; Jacobsen, Søren; Truedsson, Lennart; Bengtsson, Anders A


    Polymorphonuclear leukocytes (PMN) with autoantibody-coated engulfed necrotic cell material (NC) are frequently seen in systemic lupus erythematosus (SLE). We evaluated the roles of complement, different antihistone antibodies (anti-H ab), and oxidative burst in the phagocytosis of NC by PMN, as...... well as association to disease activity and clinical phenotype in SLE....

  6. Arachidonic acid metabolism in polymorphonuclear leukocytes from patients with chronic granulomatous disease.

    Smith, D. M.; Walsh, C E; DeChatelet, L R; Waite, M.


    The effect of the calcium ionophore A23187 on the release and metabolism of [3H]arachidonic acid was examined in normal polymorphonuclear leukocytes and those obtained from patients with chronic granulomatous disease. The ionophore A23187 which stimulates oxidative metabolism in normal polymorphonuclear leukocytes was ineffective in increasing oxidative metabolism (chemiluminescence) in polymorphonuclear leukocytes from patients with chronic granulomatous disease. However, the ionophore A2318...

  7. INPO Assistance Activities: Human Resources

    The Institute of Nuclear Power Operations (INPO) has a number of ongoing activities designed to provide assistance to our members in the human resources area. These include the Educational Assistance Program and the ongoing facilitation of information exchange through Nuclear Network and INPO publications. INPO will continue to seek ways to assist its member utilities

  8. Physical activity and human health

    Paulina Wojciechowska


    Full Text Available Introduction: The dynamic development of the automotive industry, transport, and the media means that human life has become much easier. At the same time, the comfortable living conditions have decreased physical activity. Biologically conditioned, the need of activity has been minimised by the ever-increasing pace of life. As a result, it may lead to the loss of physical and mental health. Active recreation is not only an excellent source of activity, but also a source of satisfaction. Youths and adults should therefore spend their free time primarily on various forms of physical activity. Aim of the research : To evaluate the physical fitness of students who regularly practice physical exercise, those who occasionally practice, and those not practicing any form of physical activity. Material and methods : In the research we used a questionnaire of the Ruffier test and an orthostatic test. The study involved a group of 15 people aged 20–25 years. Participation in the study was entirely voluntary and anonymous. The study group consisted only of women. Results obtained from the questionnaire survey were fully reflected during exercise tests performed. Results and conclusions: Only regularly practiced physical activity has an effect on our body. Regular exercise increases our body’s physical capacity. Activity is the best means of prevention of lifestyle diseases. Youths and adults should spend their free time mainly doing various forms of physical activity.

  9. Locomotion forces generated by a polymorphonuclear leukocyte.

    Usami, S; Wung, S L; Skierczynski, B A; Skalak, R; Chien, S


    There have been very few studies which have measured the physical forces generated by cells during active movements. A special micropipette system has been designed to make it possible to observe cell motion within the pipette and to apply a pressure to counter the chemotactic migration of the cell. This provides a direct measure of the locomotion force generated by the cell. The average velocity of forward motion is 0.33 microns/s in the absence of counter-pressure. The application of a posi...

  10. 111In)oxine labelling of polymorphonuclear leucocytes: doubts concerning elution and effects on cell behaviour

    Sheehan, N.J.; Brown, K.A.; Camacho, A.; Dumonde, D.C.


    Polymorphonuclear leucocytes (PMN) from normal human subjects were labelled with (111In)oxine (20 muCi 10(8) cells). In the presence of 20% autologous serum (AS), dissociation of 111In from the cells resulted in mean losses of radioactivity of 13% at 3 h and 30% at 24 h. Adherence of 111In-labelled PMN to cultured porcine endothelial monolayers was increased by 40.7 +/- 31.6% after 60 min incubation in 20% AS at 37 degrees C when compared with unlabelled cells. Phagocytosis and intracellular killing of Candida albicans were unaltered by labelling. Elution of 111In from labelled PMN together with enhanced adhesiveness may have important implications for the study of PMN kinetics and the investigation of inflammatory disease.

  11. Chemotaxis of horse polymorphonuclear leukocytes to N-formyl-L-methionyl-L-leucyl-L-phenylalanine.

    Zinkl, J G; Brown, P D


    Horse polymorphonuclear leukocytes (PMN) isolated from horse blood by sedimentation and isotonic lysis and having about 25% accompanying lymphocytes were as effective at chemotaxis as nearly pure PMN isolated by density gradient techniques. N-Formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP), used as a representative of the formylmethionyl peptides (produced by prokaryocytic organisms), was effective as a chemoattractant only at the high concentration of 10(-4) M. When serum was preincubated with FMLP at concentrations as low as 10(-8) M, the serum attracted horse PMN. This activity was not generated when heat-inactivated (56 to 60 C for 30 minutes) serum was used. A combination of FMLP and zymosan was no more effective than zymosan alone in generating serum chemoattractants. The results of this study indicate that the FMLP is a weak chemoattractant for horse PMN, but that FMLP has the capability similar to that of zymosan to activate complement to produce PMN chemoattractants. PMID:7073083

  12. Double localization of F-actin in chemoattractant-stimulated polymorphonuclear leucocytes.

    Lepidi, H; Benoliel, A M; Mege, J L; Bongrand, P; Capo, C


    Uniform concentrations of chemoattractants such as formylpeptides induced a morphological polarization of human polymorphonuclear leucocytes (PMNs) and a concentration of F-actin at the cell front. They also induced a transient increase in filamentous actin (F-actin) which preceded the cell shape change. We combined fluorescence microscopy and image analysis to study the localization of F-actin, as revealed by a specific probe (bodipyTM phallacidin) in suspended PMNs stimulated by chemoattractants. F-actin exhibited remarkable concentration in focal points after a 30 s exposure to 10(-8) M formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe), although no shape change of PMNs was detectable. A 10-min incubation with formylpeptide (10(-6) to 10(-9) M) induced the morphological polarization of PMNs and the appearance of a principal focus of F-actin in the cell head region and a secondary focus in the cell posterior end. The distribution of F-actin-associated fluorescence in 2D images of polarized PMNs might be due to an actual concentration of F-actin in privileged areas, to a local concentration of plasma membrane drawing filamentous actin or to variations in the cell volume. Then, we studied the distribution of a cytoplasmic marker, fluorescein diacetate and a membrane probe, TMA-DPH, in unstimulated rounded PMNs and in spherical and morphologically polarized PMNs stimulated by formylpeptide. The distribution of neither of these probes was correlated with F-actin distribution, especially in rounded PMNs stimulated 30 s with 10(-8) M fMet-Leu-Phe, suggesting that F-actin was concentrated in two foci located in the cell head region and in the cell posterior end. In addition, zymosan-activated serum induced the morphological polarization of PMNs and the appearance of two foci of filamentous actin, demonstrating that binding of formylpeptide to its specific receptor was not required for F-actin reorganization. We conclude that the accumulation of F-actin probably

  13. Potential role of autophagy in the bactericidal activity of human PMNs for Bacillus anthracis.

    Ramachandran, Girish; Gade, Padmaja; Tsai, Pei; Lu, Wuyuan; Kalvakolanu, Dhananjaya V; Rosen, Gerald M; Cross, Alan S


    Bacillus anthracis, the causative agent of anthrax, is acquired by mammalian hosts from the environment, as quiescent endospores. These endospores must germinate inside host cells, forming vegetative bacilli, before they can express the virulence factors that enable them to evade host defenses and disseminate throughout the body. While the role of macrophages and dendritic cells in this initial interaction has been established, the role of polymorphonuclear leukocytes (PMNs) has not been adequately defined. We discovered that while B. anthracis 34F2 Sterne endospores germinate poorly within non-activated human PMNs, these phagocytes exhibit rapid microbicidal activity toward the outgrown vegetative bacilli, independent of superoxide and nitric oxide. These findings suggest that a non-free radical pathway kills B. anthracis bacilli. We also find in PMNs an autophagic mechanism of bacterial killing based on the rapid induction of LC-3 conversion, beclin-1 expression, sequestosome 1 (SQSTM1) degradation and inhibition of bactericidal activity by the inhibitor, 3-methyladenine. These findings extend to PMNs an autophagic bactericidal mechanism previously described for other phagocytes. PMID:26424808

  14. The effect of plant phenolics on the formation of 7,12-dimethylbenz[a]anthracene-DNA adducts and TPA-stimulated polymorphonuclear neutrophils chemiluminescence in vitro

    Phenolics, common plant constituents, form up an important part of human diet and are considered potential chemopreventive agents. In the present study, structurally diverse phenolics, such as tannic acid, protocatechuic acid, chlorogenic acid and resveratrol, were investigated for their inhibitory effects on covalent binding of 7,12-dimethylbenz[a]anthracene (DMBA) to DNA in vitro and the suppression of oxidative burst in 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated human polymorphonuclear neutrophils (PMNs). 32P-postlabeling analysis of DNA incubated with DMBA in the presence of 3-methylcholanthrene (3-MC)-induced microsomes produced three major adducts derived from anti-, syn- and anti-dihydrodiol epoxides through reactions with dGuo and dAdo, respectively. Phenolic compounds at the concentration of 150 μM reduced the levels of all DMBA-DNA adducts by 55-98%. The most dramatic effect was observed in case of tannic acid, which completely inhibited the formation of DMBA-dAdo adducts. Chlorogenic acid was the least effective inhibitor of DMBA-DNA adducts formation particularly syn-DMBADE-dAdo (20%). Human neutrophils showed a significant dose-related decrease of TPA-induced chemiluminescence after pretreatment with phenolic compounds. The most effective inhibitors were tannic acid and resveratrol with IC50=5.19 and 5.76 μM, respectively. These results suggest that the suppression of reactive oxygen species (ROS) and carcinogen-DNA adducts formation may be important for anticarcinogenic activity of the examined phenolics

  15. Telomerase activity in human cancer

    Griffith, J.


    The overall goal of this collaborative project was to investigate the role in malignant cells of both chromosome telomeres, and telomerase, the enzyme that replicates telomeres. Telomeres are highly conserved nucleoprotein complexes located at the ends of eucaryotic chromosomes. Telomere length in somatic cells is reduced by 40--50 nucleotide pairs with every cell division due to incomplete replication of terminal DNA sequences and the absence of telomerase, the ribonucleoprotein that adds telomere DNA to chromosome ends. Although telomerase is active in cells with extended proliferative capacities, including more than 85% of tumors, work performed under this contract demonstrated that the telomeres of human cancer cells are shorter than those of paired normal cells, and that the length of the telomeres is characteristic of particular types of cancers. The extent of telomere shortening ostensibly is related to the number of cell divisions the tumor has undergone. It is believed that ongoing cell proliferation leads to the accumulation and fixation of new mutations in tumor cell lineages.Therefore, it is not unreasonable to assume that the degree of phenotypic variability is related to the proliferative history of the tumor, and therefore to telomere length, implying a correlation with prognosis. In some human tumors, short telomeres are also correlated with genomic instabilities, including interstitial chromosome translocation, loss of heterozygosity, and aneuoploidy. Moreover, unprotected chromosome ends are highly recombinogenic and telomere shortening in cultured human cells correlates with the formation of dicentric chromosomes, suggesting that critically short telomeres not only identify, but also predispose, cells to genomic instability, again implying a correlation with prognosis. Therefore, telomere length or content could be an important predictor of metastatic potential or responsiveness to various therapeutic modalities.

  16. Phagocytosis-induced 45calcium efflux in polymorphonuclear leucocytes

    The role of calcium ions in regulating the structure and function of non-muscle cells is a subject of intense study. Several lines of evidence that calcium may be essential in the function of polymorphonuclear leucocytes (PMNL) and an important control element in the process of phagocytosis. Direct studies of calcium distribution and fluxes have only recently been undertaken. To our knowledge, no report of calcium movements during normal phagocytosis has been published. In the context of an overall study of calcium dynamics in the PMNL, we report here initial studies on 45Ca efflux in prelabelled guinea pig PMNL. The results demonstrate the energy-dependence of resting calcium efflux and an increased efflux upon addition of phagocytic particles which is not dependent on particle internalization

  17. Myeloperoxidase Activities in Polymorphonuclear Leukocytes in Lumbar Disc Disease

    Mehmet ŞENOĞLU; Ergul Belge KURUTAŞ; İdris ALTUN; Yalçın ATLI; Vedat NACİTARHAN


    Objectives: The exact pathogenesis of lumbar pain and radiculopathy is often poorly understood. Although nerve root entrapment resulting in mechanical pressure has been the most widely held concept to explain radiculopathy and lumbar pain, much of the recent research work increasingly supports an inflammatory reaction occurring in the lumbar intervertebral disc tissue. In this study, we aimed to show the role of Myeloperoxidase as an inflammatory marker and the correlation of inflammation wit...

  18. Re-evaluation of the culture condition of polymorphonuclear cells for the study of apoptosis induction.

    Hiroi, M; Tajima, M; Shimojima, T; Kashimata, M; Miyata, T; Sakagami, H


    The culture conditions of human peripheral blood polymorphonuclear leukocytes (PMN) in the study of apoptosis induction were re-evaluated. The changes in the relative viable cell number of PMNs after tumor necrosis factor (TNF) treatment were colorimetrically investigated using a cell counting kit. The relative potency of PMNs to produce the superoxide anion (O2-) was measured as the reduction of color intensity by addition of superoxide dismutase (SOD). When the PMNs were cultured in conventional RPMI1640 medium supplemented with 10% fetal bovine serum (FBS), the stimulation effect of TNF on O2- generation by PMNs was observed only for the first 6 hours. When FBS was replaced with human serum, the effect of TNF was maintained for longer incubation periods. Prolonged incubation of PMNs spontaneously produced large DNA fragments, and the extent of DNA fragmentation was relatively smaller in human serum-containing medium. TNF, LPS, hyperthermia or potassium thiocyanate slightly accelerated the production of large DNA fragments, as well as the induction of trace amounts of internucleosomal DNA cleavage in PMNs, which became detectable only after concentration by fractional isopropanol precipitation. The present study suggests the importance of the use of human serum rather than conventional FBS for the study of apoptosis induction in PMNs. PMID:9673409

  19. Human activities threaten coral reefs

    Research indicates that 58 per cent of the coral reefs of the world are threatened by human activities. Pollution and global heating represent some of the threats. Coral reefs just beneath the surface of the sea are very sensitive to temperature changes. Since 1979, mass death of coral reefs has been reported increasingly often. More than 1000 marine species live in the coral reefs, among these are one fourth of all marine species of fish. It is imperative that the coral reefs be preserved, as coastal communities all over the world depend on them as sources of food and as they are the raw materials for important medicines. The article discusses the threats to the coral reefs in general and does not single out any particular energy-related activity as the principal threat. For instance, the El-Nino phenomenon of the Pacific Ocean is probably involved in mass death of coral reefs and in the North Sea large parts of deep-water reefs have been crushed by heavy beam trawlers fishing for bottom fish

  20. Polymorphonuclear neutrophils in periodontitis and their possible modulation as a therapeutic approach.

    Nicu, Elena A; Loos, Bruno G


    The main focus of this review is polymorphonuclear neutrophilic granulocytes. Polymorphonuclear neutrophils play a pivotal role in normal host resistance to subgingival dental-plaque biofilm. Both hyper- and hypo-responsiveness of the immune system toward the microbial challenge in periodontitis have been described. We review polymorphonuclear neutrophil physiology with emphasis on the role of neutrophil functions and dysfunctions in periodontitis. Text boxes are given at the end of each subsection, which present the current knowledge on neutrophil-modulating agents as a potential therapeutic approach in periodontitis. PMID:27045435

  1. Regulation of normal human polyrnorphonuclear leucocytes by carnitine

    Andrea Fattorossi; Roberto Biselli; Anna Casciaro; Sonia Tzantzoglou; Claudio De Simone


    The effect of carnitine, a drug that plays an essential role in mitochondria metabolism, on some of the most important human polymorphonuclear leucocytes (PMN) activation steps including modulation of adhesion molecule density, reactive oxygen species production, and tumour necrosis factor-α (TNFα) production was investigated. The capability of carnitine in protecting PMN from deter ioration on storage was also studied. Data shows that carnitine exerts considerable effects on all PMN function...

  2. Bovine polymorphonuclear neutrophil-mediated phagocytosis and an immunoglobulin G2 protease produced by Porphyromonas levii.

    Lobb, D A; Loeman, H J; Sparrow, D G; Morck, D. W.


    Acute interdigital phlegmon (AIP) is a commonly occurring anaerobic bacterial infection in cattle. This study examined in vitro the interaction of bovine polymorphonuclear granulocytic neutrophils (PMN) from blood with bacterial species involved in AIP. Polymorphonuclear neutrophils were purified from whole bovine blood, exposed to one of the three putative etiologic agents of AIP and comparatively assessed for phagocytosis using light microscopy. Fusobacterium necrophorum and Prevotella inte...

  3. Effects of in vivo dexamethasone administration on in vitro bovine polymorphonuclear leukocyte function.

    Roth, J A; Kaeberle, M L


    Polymorphonuclear leukocyte function was evaluated in vitro after in vivo administration of a single dose of dexamethasone to cattle. Purified polymorphonuclear leukocytes from dexamethasone-treated cattle displayed enhanced random migration under agarose but impaired ingestion of Staphylococcus aureus, Nitro Blue Tetrazolium reduction, chemiluminescence, iodination, and antibody-dependent, cell-mediated cytotoxicity. The depression of iodination may have been related to a drop in the proport...

  4. Complement activation in experimental human malaria infection.

    Roestenberg, M.; McCall, M.B.B.; Mollnes, T.E.; Deuren, M. van; Sprong, T.; Klasen, I.S.; Hermsen, C.C.; Sauerwein, R.W.; Ven, A.J.A.M. van der


    The objective of this study was to investigate complement activation in uncomplicated, early phases of human malaria. Fifteen healthy volunteers were experimentally infected with Plasmodium falciparum malaria. Parasitemia and complement activation products were assessed. During blood stage parasitem

  5. Histamine-induced inhibition of leukotriene biosynthesis in human neutrophils: involvement of the H2 receptor and cAMP

    Flamand, Nicolas; Plante, Hendrick; Picard, Serge; Laviolette, Michel; Borgeat, Pierre


    Histamine is generally regarded as a pro-inflammatory mediator in diseases such as allergy and asthma. A growing number of studies, however, suggest that this autacoid is also involved in the downregulation of human polymorphonuclear leukocyte (PMN) functions and inflammatory responses through activation of the Gs-coupled histamine H2 receptor.We report here that histamine inhibits thapsigargin- and ligand (PAF and fMLP)-induced leukotriene (LT) biosynthesis in human PMN in a dose-dependent m...

  6. A possible role for polymorphonuclear leucocytes in the defence against recrudescent herpes simplex virus infection in man

    A 51Cr release assay has been used to demonstrate that human polymorphonuclear leucocytes (PMNL) can damage herpes simplex infected target cells sensitized with antiviral antibody. Effective sensitizing antibodies were found in both serum and saliva of all those persons tested who were subject to recurrent cold sores. PMNL were much less effective as killer cells than peripheral blood mononuclear cells, but as they are the predominant inflammatory cell within the HSVl lesion they may be, quantitatively, more important. The cytotoxic effects of both PMNL and mononuclear cells were significantly reduced by prostaglandin El as well as by several drugs that were tested. It is suggested that antibody dependent PMNL-mediated cytotoxicity may play a role in the human host defences against recrudescent herpes simplex infection. (author)

  7. Kinetics of leukotriene A4 synthesis by 5-lipoxygenase from rat polymorphonuclear leukocytes

    When arachidonic acid is added to lysates of rat polymorphonuclear leukocytes, it is oxidized to (5S)-hydroperoxy-6(E),8(Z),11(Z),14(Z)-eicosatetraenoic acid (5-HPETE). The 5-HPETE then partitions between reduction to the 5-hydroxyeicosanoid and conversion to leukotriene A4 (LTA4). Both steps in the formation of LTA4 are catalyzed by the enzyme 5-lipoxygenase. When [3H]arachidonic acid and unlabeled 5-HPETE were incubated together with 5-lipoxygenase, approximately 20% of the arachidonic acid oxidized at low enzyme concentrations was converted to LTA4 without reduction of the specific radioactivity of the LTA4 by the unlabeled 5-HPETE. A significant fraction of the [3H]-5-HPETE intermediate that is formed from arachidonic acid must therefore be converted directly to LTA4 without dissociation of the intermediate from the enzyme. This result predicts that even in the presence of high levels of peroxidase activity, which will trap any free 5-HPETE by reduction, the minimum efficiency of conversion of 5-HPETE to LTA4 will be approximately 20%, and this prediction was confirmed. 5-HPETE was found to be a competitive substrate relative to arachidonic acid, so that it is likely that the two substrates share a common active site

  8. CD44 mediates polymorphonuclear leukocyte motility on hyaluronan

    To investigate the behavior of polymorphonuclear (PMN) leukocytes on the extracellular matrix carbohydrate component hyaluronan(HA) in the presense and absence of the chemokine ,iterleukin-8(IL).The present study was conducted at the Department of Hematology, University of Liverpool, United Kingdom between the period 2000 to 2001. Polmorphonuclear cells were isolated from whole venous blood using Mono-Poly-Resolving Medium. Purified PMN were added alone or with IL-8 to HA-coated plates and the behavior of these cells monitored by time-lapse video microscopy over a period of 40 minutes. For the identification of surface receptor(s) mediating PMN migration on HA, PMN were incubated with blocking non-blocking antibodies against cluster of differntiation 44 (CD44) and Receptor for Hyaluronan Mediated Motility (RHAMM) prior to addition to HA-coated surfaces. Approximately 55% of PMN were found to interact and migrate on HA-coated plates with a mean speed of 6.4+-0.7um/min. Addition of IL-8 reduced both the percentage moving cells (7.5%) and the average speed of the remaining moving cells(2.0+-0.3um/min). The inhibitory effect of IL-8 on PMN migration was associated with organization of the cytoplasmic fibrillar form of action. Anti-CD44 blocking antibody substantially reduced the speed of PMN (2.5+-0.9um/min), while non-blocking anti-CD44and anti-RHAAM antibodies had no effect. The present study demonstrates for the first time that PMN are able to interact and migrate on the widely distributed extracellular matrix component ,HA, using the cell surface receptor,CD44.Such interaction is modified by the chemokine, IL-8 in a way that optimizes the host defence against invading pathogens. (author)

  9. Uptake and Intracellular Activity of Moxifloxacin in Human Neutrophils and Tissue-Cultured Epithelial Cells

    Pascual, Alvaro; García, Isabel; Ballesta, Sofía; Perea, Evelio J.


    The penetration by moxifloxacin of human neutrophils (polymorphonuclear leukocytes [PMN]) and tissue-cultured epithelial cells (McCoy cells) was evaluated by a fluorometric assay. At extracellular concentrations of 5 mg/liter, the cellular-to-extracellular concentration ratios (C/E) of moxifloxacin in PMN and McCoy cells were 10.9 ± 1.0 and 8.7 ± 1.0, respectively (20 min; 37°C). The uptake of moxifloxacin by PMN was rapid, reversible, nonsaturable (at extracellular concentrations ranging fro...

  10. Sensing Human Activity: GPS Tracking

    Remco de Haan


    Full Text Available The enhancement of GPS technology enables the use of GPS devices not only as navigation and orientation tools, but also as instruments used to capture travelled routes: as sensors that measure activity on a city scale or the regional scale. TU Delft developed a process and database architecture for collecting data on pedestrian movement in three European city centres, Norwich, Rouen and Koblenz, and in another experiment for collecting activity data of 13 families in Almere (The Netherlands for one week. The question posed in this paper is: what is the value of GPS as ‘sensor technology’ measuring activities of people? The conclusion is that GPS offers a widely useable instrument to collect invaluable spatial-temporal data on different scales and in different settings adding new layers of knowledge to urban studies, but the use of GPS-technology and deployment of GPS-devices still offers significant challenges for future research.

  11. Activation of human B lymphocytes

    The differential effect of various doses of irradiation on subpopulations of human peripheral blood lymphoid cells involved in the pokeweed mitogen induced PFC response against sheep red blood cells was studied. The plaque forming B cells were quite sensitive to low doses of irradiation with complete suppression of responses at 300 to 500 rad. On the contrary, helper T-cell function was resistant to 2000 rad. Co-culture of irradiated T cells with autologous or allogeneic B cells resulted in marked enhancement of PFC responses consistent with the suppression of naturally occurring suppressor cells with a resulting pure helper effect. Irradiated T-cell-depleted suspensions failed to produce this effect as did heat killed T cells, whereas mitomycin C treated T cells gave effects similar to irradiated T cells. These findings are consistent with a lack of requirement of cell division for a T-cell helper effect and a requirement of mitosis or another irradiation sensitive, mitomycin C sensitive process for a T-suppressor cell effect. These studies have potential relevance in the evaluation of subpopulations of human lymphoid cells involved in antibody production in normal individuals and in disease states. (author)

  12. Polymorphonuclear leucocytes in Crohn's disease and ulcerative proctocolitis: association between enhanced adherence to nylon fibre and disease variables.

    Cason, J; Ainley, C C; Wolstencroft, R A; Thompson, R P


    The adherence of polymorphonuclear leucocytes (PMN) to nylon fibre was investigated in patients with Crohn's disease, ulcerative proctocolitis, and anorexia nervosa, and compared with changes of circulating PMNs, C reactive protein concentrations, erythrocyte sedimentation rates, and clinical assessment of disease activity. PMN adherence was in excess of the maximum value detected for healthy subjects in 14 of 25 patients with Crohn's disease and two of 10 with proctocolitis, but it was within the normal range for all eight with anorexia nervosa. High adherence in Crohn's disease, however, was not associated with quantitative or qualitative changes of PMN populations, absolute concentrations of C reactive protein, erythrocyte sedimentation rates, disease severity, drug regimens, malnutrition, or zinc deficiency. High PMN adherence in Crohn's disease may therefore reflect the activation in vivo of normal PMN by humoral factors. PMID:3360954

  13. Human filarial Wolbachia lipopeptide directly activates human neutrophils in vitro.

    Tamarozzi, F; Wright, H L; Johnston, K L; Edwards, S W; Turner, J D; Taylor, M J


    The host inflammatory response to the Onchocerca volvulus endosymbiont, Wolbachia, is a major contributing factor in the development of chronic pathology in humans (onchocerciasis/river blindness). Recently, the toll-like pattern recognition receptor motif of the major inflammatory ligands of filarial Wolbachia, membrane-associated diacylated lipoproteins, was functionally defined in murine models of pathology, including mediation of neutrophil recruitment to the cornea. However, the extent to which human neutrophils can be activated in response to this Wolbachia pattern recognition motif is not known. Therefore, the responses of purified peripheral blood human neutrophils to a synthetic N-terminal diacylated lipopeptide (WoLP) of filarial Wolbachia peptidoglycan-associated lipoprotein (PAL) were characterized. WoLP exposure led to a dose-dependent activation of healthy, human neutrophils that included gross morphological alterations and modulation of surface expressed integrins involved in tethering, rolling and extravasation. WoLP exposure induced chemotaxis but not chemokinesis of neutrophils, and secretion of the major neutrophil chemokine, interleukin 8. WoLP also induced and primed the respiratory burst, and enhanced neutrophil survival by delay of apoptosis. These results indicate that the major inflammatory motif of filarial Wolbachia lipoproteins directly activates human neutrophils in vitro and promotes a molecular pathway by which human neutrophils are recruited to sites of Onchocerca parasitism. PMID:24909063

  14. Fracture initiates systemic inflammatory response syndrome through recruiting polymorphonuclear leucocytes.

    Li, Haipeng; Liu, Jia; Yao, Jianhua; Zhong, Jianfeng; Guo, Lei; Sun, Tiansheng


    Fracture, a common type injury in trauma patients, often results in the development of the systemic inflammatory response syndrome (SIRS). Though the mechanism of the fracture-initiated SIRS still remains not well characterized, it is well documented that the polymorphonuclear leucocytes (PMN) play an important role in the inflammatory process. We hypothesize that fractures recruit PMN to the local tissue, which is followed by an increase in the number of peripheral PMN and initiation of SIRS. In the current study, we established a closed femoral fracture rat model. We evaluated the levels of MPO, IL-1β and CINC-1 in fractured tissue homogenate, and we measured the levels of IL-6 and IL-10, the biomarkers for systemic inflammatory response, in the rat sera. In clinical part of the study, we collected blood from patients with isolated closed femoral fractures and evaluated PMN-related chemoattractants (IL-8, IL-1β and G-CSF) and the number of peripheral PMN. We further evaluated the level of mitochondrial DNA in the local haematoma of fracture and the circulating plasma of the patients with fracture. In the animal model of closed femoral fracture, we found a significant recruitment of PMN to the local tissue after fracture, which correlates with the elevated MPO level. We also showed that the concentration of IL-1β and CINC-1 in local tissue is significantly increased and might be responsible for the PMN recruitment. Recruitment of PMN to the local tissue was accompanied with a significant increase in the systemic levels of IL-6 and IL-10 in serum. In the patients with closed femoral fracture, we observed an increase in the number of peripheral PMN and PMN-related chemoattractants, including IL-8, IL-1β and G-CSF. The level of mitochondrial DNA in the local haematoma of fracture and the circulating plasma of patients were significantly higher compared to the healthy volunteers. Our data suggest that fracture released mitochondrial DNA into the local haematoma of

  15. Human activities affecting trace gases and climate

    The Earth's climate has been in a constant state of change throughout geologic time due to natural perturbations in the global geobiosphere. However, various human activities have the potential to cause future global warming over a relatively short amount of time. These activities, which affect the Earth's climate by altering the concentrations of trace gases in the atmosphere, include energy consumption, particularly fossil-fuel consumption; industrial processes (production and use of chlorofluorocarbons, halons, and chlorocarbons, landfilling of wastes, and cement manufacture); changes in land use patterns, particularly deforestation and biomass burning; and agricultural practices (waste burning, fertilizer usage, rice production, and animal husbandry). Population growth is an important underlying factor affecting the level of growth in each activity. This paper describes how the human activities listed above contribute to atmospheric change, the current pattern of each activity, and how levels of each activity have changed since the early part of this century

  16. Cholesterol esterase activity of human intestinal mucosa

    It has been suggested that cholesterol absorption in humans is dependent on bile acid pool composition and that expansion of the cholic acid pool size is followed by an increase of the absorption values. Similar observations were reported in rats. In the present study, therefore, the authors investigated some general properties of human intestinal cholesterol esterase, with particular emphasis on the effect of bile acids on this enzymatic activity. Twenty-nine segments of small intestine were taken during operations; the enzymatic activity was studied by using mucosal homogenate as a source of enzyme and oleic acid, cholesterol, and 14C-labeled cholesterol as substrates. The time-activity relationship was linear within the first two hours; optimal pH for esterification ranged between 5 and 6.2. There was little difference between the esterifying activity of the jejunal and ileal mucosa. Esterification of cholesterol was observed with all the investigated fatty acids but was maximal with oleic acid. Bile acids did not affect cholesterol esterase activity when present in the incubation mixture at 0.1 and 1.0 mM; the enzymatic activity, however, was significantly inhibited when bile acids were added at 20 mM. In conclusion, this study has shown that the human intestinal mucosa possesses a cholesterol esterase activity; at variance with the rat, however, the human enzyme does not seem to be stimulated by trihydroxy bile acids

  17. Novel anti-bacterial activities of β-defensin 1 in human platelets: suppression of pathogen growth and signaling of neutrophil extracellular trap formation.

    Bjoern F Kraemer


    Full Text Available Human β-defensins (hBD are antimicrobial peptides that curb microbial activity. Although hBD's are primarily expressed by epithelial cells, we show that human platelets express hBD-1 that has both predicted and novel antibacterial activities. We observed that activated platelets surround Staphylococcus aureus (S. aureus, forcing the pathogens into clusters that have a reduced growth rate compared to S. aureus alone. Given the microbicidal activity of β-defensins, we determined whether hBD family members were present in platelets and found mRNA and protein for hBD-1. We also established that hBD-1 protein resided in extragranular cytoplasmic compartments of platelets. Consistent with this localization pattern, agonists that elicit granular secretion by platelets did not readily induce hBD-1 release. Nevertheless, platelets released hBD-1 when they were stimulated by α-toxin, a S. aureus product that permeabilizes target cells. Platelet-derived hBD-1 significantly impaired the growth of clinical strains of S. aureus. hBD-1 also induced robust neutrophil extracellular trap (NET formation by target polymorphonuclear leukocytes (PMNs, which is a novel antimicrobial function of β-defensins that was not previously identified. Taken together, these data demonstrate that hBD-1 is a previously-unrecognized component of platelets that displays classic antimicrobial activity and, in addition, signals PMNs to extrude DNA lattices that capture and kill bacteria.

  18. Deep Human Parsing with Active Template Regression.

    Liang, Xiaodan; Liu, Si; Shen, Xiaohui; Yang, Jianchao; Liu, Luoqi; Dong, Jian; Lin, Liang; Yan, Shuicheng


    In this work, the human parsing task, namely decomposing a human image into semantic fashion/body regions, is formulated as an active template regression (ATR) problem, where the normalized mask of each fashion/body item is expressed as the linear combination of the learned mask templates, and then morphed to a more precise mask with the active shape parameters, including position, scale and visibility of each semantic region. The mask template coefficients and the active shape parameters together can generate the human parsing results, and are thus called the structure outputs for human parsing. The deep Convolutional Neural Network (CNN) is utilized to build the end-to-end relation between the input human image and the structure outputs for human parsing. More specifically, the structure outputs are predicted by two separate networks. The first CNN network is with max-pooling, and designed to predict the template coefficients for each label mask, while the second CNN network is without max-pooling to preserve sensitivity to label mask position and accurately predict the active shape parameters. For a new image, the structure outputs of the two networks are fused to generate the probability of each label for each pixel, and super-pixel smoothing is finally used to refine the human parsing result. Comprehensive evaluations on a large dataset well demonstrate the significant superiority of the ATR framework over other state-of-the-arts for human parsing. In particular, the F1-score reaches 64.38 percent by our ATR framework, significantly higher than 44.76 percent based on the state-of-the-art algorithm [28]. PMID:26539846

  19. Integrated Extravehicular Activity Human Research Plan: 2016

    Abercromby, Andrew F. J.; Ross, Amy J.; Cupples, J. Scott; Rajulu, Sudhakar; Norcross, Jason R.; Chappell, Steven P.


    Multiple organizations within NASA and outside of NASA fund and participate in research related to extravehicular activity (EVA). In October 2015, representatives of the EVA Office, the Crew and Thermal Systems Division (CTSD), and the Human Research Program (HRP) at NASA Johnson Space Center agreed on a formal framework to improve multi-year coordination and collaboration in EVA research. At the core of the framework is an Integrated EVA Human Research Plan and a process by which it will be annually reviewed and updated. The over-arching objective of the collaborative framework is to conduct multi-disciplinary cost-effective research that will enable humans to perform EVAs safely, effectively, comfortably, and efficiently, as needed to enable and enhance human space exploration missions. Research activities must be defined, prioritized, planned and executed to comprehensively address the right questions, avoid duplication, leverage other complementary activities where possible, and ultimately provide actionable evidence-based results in time to inform subsequent tests, developments and/or research activities. Representation of all appropriate stakeholders in the definition, prioritization, planning and execution of research activities is essential to accomplishing the over-arching objective. A formal review of the Integrated EVA Human Research Plan will be conducted annually. External peer review of all HRP EVA research activities including compilation and review of published literature in the EVA Evidence Report is will also continue at a frequency determined by HRP management. Coordination with stakeholders outside of the EVA Office, CTSD, and HRP is already in effect on a study-by-study basis; closer coordination on multi-year planning with other EVA stakeholders including academia is being actively pursued. Details of the current Integrated EVA Human Research Plan are presented including description of ongoing and planned research activities in the areas of

  20. Evidence for lipoxin formation by bovine polymorphonuclear leukocytes via triple dioxygenation of arachidonic acid

    Vliegenthart, J.F.G.; Walstra, P.; Verhagen, J.; Vermeer, M.A.; Klerks, J.P.M.; Veldink, G.A.


    Incubation of bovine polymorphonuclear leukocytes (PMNs) with arachidonic acid leads to the formation of four lipoxins. The same lipoxins are also formed upon incubation of bovine PMNs with 5(S)-hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic acid, 5-hydroxy-6-trans-8,11,14-cis-eicosatetraenoic aci

  1. Scaling behavior of online human activity

    Zhao, Zhi-Dan; Cai, Shi-Min; Huang, Junming; Fu, Yan; Zhou, Tao


    The rapid development of the Internet technology enables humans to explore the web and record the traces of online activities. From the analysis of these large-scale data sets (i.e., traces), we can get insights about the dynamic behavior of human activity. In this letter, the scaling behavior and complexity of human activity in the e-commerce, such as music, books, and movies rating, are comprehensively investigated by using the detrended fluctuation analysis technique and the multiscale entropy method. Firstly, the interevent time series of rating behaviors of these three types of media show similar scaling properties with exponents ranging from 0.53 to 0.58, which implies that the collective behaviors of rating media follow a process embodying self-similarity and long-range correlation. Meanwhile, by dividing the users into three groups based on their activities (i.e., rating per unit time), we find that the scaling exponents of the interevent time series in the three groups are different. Hence, these results suggest that a stronger long-range correlations exist in these collective behaviors. Furthermore, their information complexities vary in the three groups. To explain the differences of the collective behaviors restricted to the three groups, we study the dynamic behavior of human activity at the individual level, and find that the dynamic behaviors of a few users have extremely small scaling exponents associated with long-range anticorrelations. By comparing the interevent time distributions of four representative users, we can find that the bimodal distributions may bring forth the extraordinary scaling behaviors. These results of the analysis of the online human activity in the e-commerce may not only provide insight into its dynamic behaviors but may also be applied to acquire potential economic interest.

  2. Food & Fitness. Directory. Human Nutrition Activities.

    Department of Agriculture, Washington, DC.

    Activities of the following regulatory and food service agencies of the Department of Agriculture are described: (1) Agricultural Research Service; (2) Cooperative State Research Service; (3) Economic Research Service; (4) Human Nutrition Information Service; (5) Office of Grants and Program Systems; (6) Office of International Cooperation and…

  3. CTSS activation coexists with CD40 activation in human atheroma

    Černe, Andreja; Kržišnik-Zorman, Simona; ZORMAN, Darko; Kranjec, Igor; Černe, Darko; Marc, Janja; Štern, Irma


    Objectives: By the analysis of plasma mRNA levels, we tested the hypothesis that, in human atheroma, CTSS activation coexists with activation of CD40. Design and methods: mRNAs were isolated from plasma of patients with coronary atherosclerosis and quantified by real-time RT-PCR. Results: CTSS mRNA levels correlated with CD40 mRNA levels, independently of observed traditional risk factors for atherosclerosis and pharmacological treatment. Conclusions: Our results suggest that CTSS mediated at...

  4. Aldehyde oxidase activity in fresh human skin.

    Manevski, Nenad; Balavenkatraman, Kamal Kumar; Bertschi, Barbara; Swart, Piet; Walles, Markus; Camenisch, Gian; Schiller, Hilmar; Kretz, Olivier; Ling, Barbara; Wettstein, Reto; Schaefer, Dirk J; Pognan, Francois; Wolf, Armin; Litherland, Karine


    Human aldehyde oxidase (AO) is a molybdoflavoenzyme that commonly oxidizes azaheterocycles in therapeutic drugs. Although high metabolic clearance by AO resulted in several drug failures, existing in vitro-in vivo correlations are often poor and the extrahepatic role of AO practically unknown. This study investigated enzymatic activity of AO in fresh human skin, the largest organ of the body, frequently exposed to therapeutic drugs and xenobiotics. Fresh, full-thickness human skin was obtained from 13 individual donors and assayed with two specific AO substrates: carbazeran and zoniporide. Human skin explants from all donors metabolized carbazeran to 4-hydroxycarbazeran and zoniporide to 2-oxo-zoniporide. Average rates of carbazeran and zoniporide hydroxylations were 1.301 and 0.164 pmol⋅mg skin(-1)⋅h(-1), resulting in 13 and 2% substrate turnover, respectively, after 24 hours of incubation with 10 μM substrate. Hydroxylation activities for the two substrates were significantly correlated (r(2) = 0.769), with interindividual variability ranging from 3-fold (zoniporide) to 6-fold (carbazeran). Inclusion of hydralazine, an irreversible inhibitor of AO, resulted in concentration-dependent decrease of hydroxylation activities, exceeding 90% inhibition of carbazeran 4-hydroxylation at 100 μM inhibitor. Reaction rates were linear up to 4 hours and well described by Michaelis-Menten enzyme kinetics. Comparison of carbazeran and zoniporide hydroxylation with rates of triclosan glucuronidation and sulfation and p-toluidine N-acetylation showed that cutaneous AO activity is comparable to tested phase II metabolic reactions, indicating a significant role of AO in cutaneous drug metabolism. To our best knowledge, this is the first report of AO enzymatic activity in human skin. PMID:25249692

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



    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.


    Olga Yurievna Galiullina


    Full Text Available The article discusses the relationship of divergent thinking and achievement in learning activities. J. Guilford and some Russian scientists, divergent thinking is understood as a common creative ability. To be creators, to initiate and carry out initial practice and other forms of specifically human activity is to be subject. This ability – the main characteristic of subjectivity. Proved the importance of the relationship of divergent thinking and achievement in learning activities, for disclosure of subject student productivity. The study found «positive» relationship between divergent thinking and academic performance of students of the middle classes and the «negative» relationship among elementary school students. As we know from the writings of SL Rubinstein and N. Bernstein, training activities associated with the mastery of relevant skills. Formation of skills takes time. Therefore subjective productivity in educational activity is observed in the textbooks of the middle classes and does not manifest itself in elementary school students.

  7. Scaling behavior of online human activity

    Zhao, Zhi-Dan; Huang, Junming; Fu, Yan; Zhou, Tao; 10.1209/0295-5075/100/48004


    The rapid development of Internet technology enables human explore the web and record the traces of online activities. From the analysis of these large-scale data sets (i.e. traces), we can get insights about dynamic behavior of human activity. In this letter, the scaling behavior and complexity of human activity in the e-commerce, such as music, book, and movie rating, are comprehensively investigated by using detrended fluctuation analysis technique and multiscale entropy method. Firstly, the interevent time series of rating behaviors of these three type medias show the similar scaling property with exponents ranging from 0.53 to 0.58, which implies that the collective behaviors of rating media follow a process embodying self-similarity and long-range correlation. Meanwhile, by dividing the users into three groups based their activities (i.e., rating per unit time), we find that the scaling exponents of interevent time series in three groups are different. Hence, these results suggest the stronger long-rang...

  8. A human activity approach to User Interfaces

    Bødker, Susanne


    How can we understand why a bank teller has different needs for a user interface than those of casual users of a machine teller, or why a graphic designer needs a different user interface than a secretary? This article presents a framework for the design of user interfaces that originates from the...... work situations in which computer-based artifacts are used: The framework deals with the role of the user interface in purposeful human work. Human activity theory is used in this analysis. The purpose of this article is to make the reader curious and hopefully open his or her eyes to a somewhat...... different way of thinking about the user interface. The article applies examples of real-life interfaces to support this process, but it does not include a systematic presentation of empirical results. I focus on the role of the computer application in use. Thus, it is necessary to consider human...

  9. Polymorphonuclear leucocyte dysfunction during short term metabolic changes from normo- to hyperglycemia in type 1 (insulin dependent) diabetic patients

    Kjersem, H; Hilsted, J; Madsbad, S; Wandall, Johan; Johansen, K S; Borregaard, N


    Polymorphonuclear leucocyte (PMN) ingestion of particles coated with lipopolysaccharide (LPS) from Escherichia coli was compared to other PMN functions in seven patients with insulin dependent diabetes mellitus (IDDM) during short-term controlled metabolic changes from normo- to hyperglycemia wit...

  10. Phagocytosis of Pseudomonas aeruginosa by polymorphonuclear leukocytes and monocytes: effect of cystic fibrosis serum.

    Thomassen, M J; Demko, C A; Wood, R E; Sherman, J. M.


    It has been shown previously that serum from chronically infected patients with cystic fibrosis inhibits the phagocytosis of Pseudomonas aeruginosa by both normal and cystic fibrosis alveolar macrophages. In the present study, the ability of peripheral monocytes and polymorphonuclear leukocytes from normal volunteers and cystic fibrosis patients to phagocytize P. aeruginosa was shown not to be inhibited in the presence of serum from cystic fibrosis patients.

  11. Polymorphonuclear leucocyte function and previous yersinia arthritis: correlation of enhanced superoxide production with late manifestations.

    Repo, H; Koivuranta-Vaara, P; Leirisalo-Repo, M


    Polymorphonuclear leucocyte (PMN) functions (migration in vitro, chemiluminescence, O-2 production, and aggregation) were studied in 32 patients with previous yersinia arthritis (YA). PMNs of 11 HLA-B27 positive patients who had chronic or recurrent inflammatory symptoms showed O-2 production significantly higher than that of PMNs of 11 HLA-B27 positive patients without late manifestations. Also, PMNs of both HLA-B27 positive and negative patients tended to show chemotactic and chemokinetic m...

  12. Effect of staphylococcal alpha-toxin on intracellular Ca2+ in polymorphonuclear leukocytes.

    Suttorp, N; Habben, E


    Staphylococcal alpha-toxin, a channel-forming protein, stimulates leukotriene B4 formation in rabbit polymorphonuclear leukocytes (PMN) (N. Suttorp, W. Seeger, J. Zucker-Reimann, L. Roka, and S. Bhakdi, Infect. Immun. 55:104-110, 1987). The concept was advanced that transmembrane toxin pores act as Ca2+ gates allowing passive Ca2+ influx into the cell, thus initiating stimulus response coupling. A critical step in this hypothesis is the demonstration of an increase in the cytosolic free Ca2+ ...

  13. Understanding Usability Work as a Human Activity

    Nørgaard, Mie

    Three core themes are explored in eight papers: Usability work as a human activity, usability practice and methods, and persuasiveness of evaluation results and feedback. We explore how usability work is much more than methods and work procedures, and argue that maturing our understanding...... systems struggle with making methods meet practical realities and demands, and that the concept of usability in games is not satisfactorily covered by for example the ISO 9241-11. With this in mind we call for future work that broadens the concept of usability to include concepts more relevant to games...... of usability work to include a human perspective, is crucial to downstream utility—how usability work impacts the on-going development process. Our work shows that cross-professional collaboration is subject to challenges that arise from stakeholders having conflicting priorities, procedures and personalities...

  14. Neutron activation analysis of human hair

    In an attempt to study the availability and limitation of analytical data of human hair as an indicator of environmental pollution and/or of human health effect, concentrations of elements in 202 scalp hair samples collected from local population in the Tokyo Metropolitan area were determined by instrumental neutron activation analysis. The correlation coefficients between concentrations of 13 elements in each sex and in each age group were calculated and discussed. There were significant correlations between some pairs of elements, i.e. Na-K, Br-Cl, Ca-Zn and Ca-Mg, in all five age classes in both of male and female, indicating that the correlations were consistent. Ca was observed to be reversely correlated with Cl. No significant correlation was apparent between Hg and Se, when the correlation coefficient was calculated using logarithmic converted concentration data. (author)

  15. Physical Human Activity Recognition Using Wearable Sensors

    Ferhat Attal


    Full Text Available This paper presents a review of different classification techniques used to recognize human activities from wearable inertial sensor data. Three inertial sensor units were used in this study and were worn by healthy subjects at key points of upper/lower body limbs (chest, right thigh and left ankle. Three main steps describe the activity recognition process: sensors’ placement, data pre-processing and data classification. Four supervised classification techniques namely, k-Nearest Neighbor (k-NN, Support Vector Machines (SVM, Gaussian Mixture Models (GMM, and Random Forest (RF as well as three unsupervised classification techniques namely, k-Means, Gaussian mixture models (GMM and Hidden Markov Model (HMM, are compared in terms of correct classification rate, F-measure, recall, precision, and specificity. Raw data and extracted features are used separately as inputs of each classifier. The feature selection is performed using a wrapper approach based on the RF algorithm. Based on our experiments, the results obtained show that the k-NN classifier provides the best performance compared to other supervised classification algorithms, whereas the HMM classifier is the one that gives the best results among unsupervised classification algorithms. This comparison highlights which approach gives better performance in both supervised and unsupervised contexts. It should be noted that the obtained results are limited to the context of this study, which concerns the classification of the main daily living human activities using three wearable accelerometers placed at the chest, right shank and left ankle of the subject.

  16. Novel innate cancer killing activity in humans

    Lovato James


    Full Text Available Abstract Background In this study, we pilot tested an in vitro assay of cancer killing activity (CKA in circulating leukocytes of 22 cancer cases and 25 healthy controls. Methods Using a human cervical cancer cell line, HeLa, as target cells, we compared the CKA in circulating leukocytes, as effector cells, of cancer cases and controls. The CKA was normalized as percentages of total target cells during selected periods of incubation time and at selected effector/target cell ratios in comparison to no-effector-cell controls. Results Our results showed that CKA similar to that of our previous study of SR/CR mice was present in human circulating leukocytes but at profoundly different levels in individuals. Overall, males have a significantly higher CKA than females. The CKA levels in cancer cases were lower than that in healthy controls (mean ± SD: 36.97 ± 21.39 vs. 46.28 ± 27.22. Below-median CKA was significantly associated with case status (odds ratio = 4.36; 95% Confidence Interval = 1.06, 17.88 after adjustment of gender and race. Conclusions In freshly isolated human leukocytes, we were able to detect an apparent CKA in a similar manner to that of cancer-resistant SR/CR mice. The finding of CKA at lower levels in cancer patients suggests the possibility that it may be of a consequence of genetic, physiological, or pathological conditions, pending future studies with larger sample size.

  17. The spatial structure of transnational human activity.

    Deutschmann, Emanuel


    Starting from conflictive predictions of hitherto disconnected debates in the natural and social sciences, this article examines the spatial structure of transnational human activity (THA) worldwide (a) across eight types of mobility and communication and (b) in its development over time. It is shown that the spatial structure of THA is similar to that of animal displacements and local-scale human motion in that it can be approximated by Lévy flights with heavy tails that obey power laws. Scaling exponent and power-law fit differ by type of THA, being highest in refuge-seeking and tourism and lowest in student exchange. Variance in the availability of resources and opportunities for satisfying associated needs appears to explain these differences. Over time (1960-2010), the Lévy-flight pattern remains intact and remarkably stable, contradicting the popular notion that socio-technological trends lead to a "death of distance." Humans have not become more "global" over time, they rather became more mobile in general, i.e. they move and communicate more at all distances. Hence, it would be more adequate to speak of "mobilization" than of "globalization." Longitudinal change occurs only in some types of THA and predominantly at short distances, indicating regional rather than global shifts. PMID:27480376

  18. Activities induced in the human body by thermal neutrons

    Activities of 17 radionuclides induced in the human body by the activation of 14 elements with thermal neutrons were calculated. Resulting dependences of these activities on the activation time are shown in graphs. (author)

  19. Cholinesterase activity in some human lymphatic organs.

    Rakhawy, M T; Tarkhan, A A; Zakaria, A M


    (1) Cholinesterase activity was investigated in some human lymphatic organs (palatine tonsil, 'normal' spleen, 'bilharzial' spleen, thymus, lymph node and appendix) using GOMORI'S modification of KOELLE and FRIEDENWALD'S thiocholine iodide method, hydrolyzing acetylthiocholine iodide and butyrylthiocholine iodide. (a) Acetyl- and butyrylcholinesterases seemed to be different enzymes; but when they have the same pattern of activity, the latter generally offers a weaker reaction. (b) All the lymphatic follicles of the tonsil, those found in the cortex of the cervical lymph nodes as well as those present in the appendix, were stainable with both acetyl- and butyrylcholinesterase. (c) Acetylcholinesterase activity was not demonstrated in the Malpighian bodies of the 'normal' spleen, but the reaction was strongly present in the blood vessels (including the central arterioles) as well as in the capsule and the different components of the trabecular system. (d) In 'bilharzial' splenomegaly a relatively strong activity started to appear in the Malpighian corpuscles, manifested as a brownish precipitate in their centres. Also some patchy positive areas began to make their appearance in the tissue of the red pulp and had a particular arrangement around the Malpighian corpuscules, in such a way as to 'wall them off' from the tissue of the red pulp. (e) In the thymus no acetylcholinesterase activity was encountered, except in Hassal's corpuscles and in the trabeculae between the thymic lobules. (2) The data obtained in this work were discussed in relation to previous works in other laboratories and it seems that a species difference exists. (3) Cholinesterases may be present in the lymphatic tissue in order to get rid of some potentially toxic esters resulting from the necrobiotic phenomena accompanying the high mitotic activity found especially in the germinal centres of the lymphoid follicles. (4) There are many unanswered questions about the coexistence of the phosphatases

  20. Activation of Human T Cells in Hypertension: Studies of Humanized Mice and Hypertensive Humans.

    Itani, Hana A; McMaster, William G; Saleh, Mohamed A; Nazarewicz, Rafal R; Mikolajczyk, Tomasz P; Kaszuba, Anna M; Konior, Anna; Prejbisz, Aleksander; Januszewicz, Andrzej; Norlander, Allison E; Chen, Wei; Bonami, Rachel H; Marshall, Andrew F; Poffenberger, Greg; Weyand, Cornelia M; Madhur, Meena S; Moore, Daniel J; Harrison, David G; Guzik, Tomasz J


    Emerging evidence supports an important role for T cells in the genesis of hypertension. Because this work has predominantly been performed in experimental animals, we sought to determine whether human T cells are activated in hypertension. We used a humanized mouse model in which the murine immune system is replaced by the human immune system. Angiotensin II increased systolic pressure to 162 versus 116 mm Hg for sham-treated animals. Flow cytometry of thoracic lymph nodes, thoracic aorta, and kidney revealed increased infiltration of human leukocytes (CD45(+)) and T lymphocytes (CD3(+) and CD4(+)) in response to angiotensin II infusion. Interestingly, there was also an increase in the memory T cells (CD3(+)/CD45RO(+)) in the aortas and lymph nodes. Prevention of hypertension using hydralazine and hydrochlorothiazide prevented the accumulation of T cells in these tissues. Studies of isolated human T cells and monocytes indicated that angiotensin II had no direct effect on cytokine production by T cells or the ability of dendritic cells to drive T-cell proliferation. We also observed an increase in circulating interleukin-17A producing CD4(+) T cells and both CD4(+) and CD8(+) T cells that produce interferon-γ in hypertensive compared with normotensive humans. Thus, human T cells become activated and invade critical end-organ tissues in response to hypertension in a humanized mouse model. This response likely reflects the hypertensive milieu encountered in vivo and is not a direct effect of the hormone angiotensin II. PMID:27217403

  1. Human activity and rest in situ.

    Roenneberg, Till; Keller, Lena K; Fischer, Dorothee; Matera, Joana L; Vetter, Céline; Winnebeck, Eva C


    Our lives are structured by the daily alternation of activity and rest, of wake and sleep. Despite significant advances in circadian and sleep research, we still lack answers to many of the most fundamental questions about this conspicuous behavioral pattern. We strongly believe that investigating this pattern in entrained conditions, real-life and daily contexts-in situ-will help the field to elucidate some of these central questions. Here, we present two common approaches for in situ investigation of human activity and rest: the Munich ChronoType Questionnaire (MCTQ) and actimetry. In the first half of this chapter, we provide detailed instructions on how to use and interpret the MCTQ. In addition, we give an overview of the main insights gained with this instrument over the past 10 years, including some new findings on the interaction of light and age on sleep timing. In the second half of this chapter, we introduce the reader to the method of actimetry and share our experience in basic analysis techniques, including visualization, smoothing, and cosine model fitting of in situ recorded data. Additionally, we describe our new approach to automatically detect sleep from activity recordings. Our vision is that the broad use of such easy techniques in real-life settings combined with automated analyses will lead to the creation of large databases. The resulting power of big numbers will promote our understanding of such fundamental biological phenomena as sleep. PMID:25707281

  2. Recruitment of 99m-technetium- or 111-indium-labelled polymorphonuclear leucocytes in experimentally induced pyogranulomas in lambs

    The recruitment of polymorphonuclear leucocytes (PMNs) during the development of experimental pyogranulomas induced by Corynebacterium pseudotuberculosis was followed in nine male lambs by scintigraphic examination. Autologous blood PMNs were labelled with 99m-technetium or 111-indium and were re-injected intravenously into infected lambs. The functional properties of the labelled cells were monitored (1) in vitro by measuring their phagocytic and bactericidal activity against C. pseudotuberculosis and their chemotaxis under agarose, and (2) in vivo by following scintigraphically their capacity to accumulate in an inflammatory focus induced by intradermal injection of latex beads coated with Salmonella abortus equi lipopolysaccharide. Following inoculation of corynebacteria into the right ear of lambs, radioactive foci were observed to be localized in the right ear and in the draining lymph nodes during the 4 days following inoculation. Histopathological examination performed 32 h after inoculation confirmed the intense accumulation of PMNs at these sites. With the exception of one animal, which presented visible foci in the neck 14 days postinoculation, no radioactive foci were observed during the later phases of experimental infection, despite the presence of multiple pyogranulomas which were confirmed by bacteriological examination after necropsy of the lambs. Histopathological examination of these lesions revealed layers of fibroblasts, lymphocytes, and macrophages surrounding a necrotic centre. The results of these studies suggest that the contribution of PMNs during the chronic phase of inflammation is considerably reduced in comparison with the acute inflammatory phase of the infectious process

  3. Determination of phagocytosis of 32P-labeled Staphylococcus aureus by bovine polymorphonuclear leukocytes

    A procedure for the measurement of phagocytosis by bovine polymorphonuclear leukocytes (PMN) of 32P-labeled Staphylococcus aureus was modified so that a larger number of samples could be compared in a single run, and smaller volumes of sample, PMN, and 32P-labeled S aureus could be used. Results were highly reproducible, with a coefficient of variation between duplicate determinations of less than or equal to 2%. Lysostaphin was prepared from the supernatant of S staphylolyticus and was compared with a commercially available preparation. Effects of lysostaphin on PMN and influence of incubation media on release of 32P from 32P-labeled S aureus by lysostaphin were examined

  4. Nitric oxide production by polymorphonuclear leukocytes in infected cystic fibrosis sputum consumes oxygen

    Kolpen, Mette; Bjarnsholt, Thomas; Moser, Claus Ernst;


    Chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients is characterized by persisting mucoid biofilms in hypoxic endobronchial mucus. These biofilms are surrounded by numerous polymorphonuclear leucocytes (PMNs), which consume a major part of present molecular oxygen (O(2...... reactive oxygen species, the PMNs in CF sputum also consume O(2) for production of NO.......)) due to production of superoxide (O(2)(-)). In this study, we show that the PMNs also consume O(2) for production of nitric oxide (NO) by the nitric oxide synthases (NOS) in the infected endobronchial mucus. Fresh expectorated sputum samples (n = 28) from chronically infected CF patients (n = 22) were...

  5. Synthesis and Biological Activity of Arylspiroborate Salts Derived from Caffeic Acid Phenethyl Ester

    Martin J. G. Hébert


    Full Text Available Two novel boron compounds containing caffeic acid phenethyl ester (CAPE derivatives have been prepared and characterized fully. These new compounds and CAPE have been investigated for potential antioxidant and antimicrobial properties and their ability to inhibit 5-lipoxygenase and whether chelation to boron improves their biological activity. Sodium salt 4 was generally more active than ammonium salt 5 in the biological assays and surpassed the radical scavenging ability of CAPE. Compounds 4 and 5 were more active than CAPE and Zileuton in human polymorphonuclear leukocytes. These results clearly show the effectiveness of the synthesized salts as transporter of CAPE.

  6. The climatic change induced by human activities

    The climate of the Earth is a changing climate. Along their history many natural climate changes have existed in all time scales. At the present time we use the term climate changes have existed in all time scales. At the present time we use the term climate change in a restricted way, understanding that we have referring to a singular change that has their origin in the modification of the natural composition of the atmosphere. The increase of greenhouse gases from the second half the XVIII century, is due to the human activities of fossil fuels burning to obtain energy and to industrial and agricultural activities needing for the development of a world which population has been duplicated between 1960 and 2000, until overcoming the 6,000 million inhabitants. In particular, the concentrations of carbon dioxide-CO2 have increased in a 34%. The more recent emission scenarios proposed by the IPCC (SRES, 2000) are based on hypothesis about the population evolution, the energy consumption and the word patterns of development, which are grouped in four families dominated as A1, A2, B1 and B2. The answer for these scenarios from a range of climate models results in an increase of the world average surface atmospheric temperature between 1,4 degree centigrade and 5,8 degree centigrade and a corresponding sea level rise understood between 9 cm and 88 cm. The changes in the precipitation patterns show us that could be above to the current one in high and media latitudes and below in subtropical latitudes, with exceptions highly depending of the model used. (Author)

  7. New activity pattern in human interactive dynamics

    Formentin, Marco; Lovison, Alberto; Maritan, Amos; Zanzotto, Giovanni


    We investigate the response function of human agents as demonstrated by written correspondence, uncovering a new pattern for how the reactive dynamics of individuals is distributed across the set of each agent’s contacts. In long-term empirical data on email, we find that the set of response times considered separately for the messages to each different correspondent of a given writer, generate a family of heavy-tailed distributions, which have largely the same features for all agents, and whose characteristic times grow exponentially with the rank of each correspondent. We furthermore show that this new behavioral pattern emerges robustly by considering weighted moving averages of the priority-conditioned response-time probabilities generated by a basic prioritization model. Our findings clarify how the range of priorities in the inputs from one’s environment underpin and shape the dynamics of agents embedded in a net of reactive relations. These newly revealed activity patterns might be universal, being present in other general interactive environments, and constrain future models of communication and interaction networks, affecting their architecture and evolution.

  8. Human Activity Detection and Recognition Algorithm from Video Surveillances

    Kanchan Gaikwad


    Full Text Available This paper presents a novel approach for automatic recognition of human activities from video sequences. Visual study of human motion is currently one of the most active research topics in computer vision. This strong interest is determined by a wide spectrum of promising applications in many areas such as virtual reality, smart surveillance, perceptual interface, etc. Human motion analysis concerns the detection, tracking and recognition of people. This paper includes the tracking of human activity from video sequencing images. Here we first make frames from video and apply GMM on it. Using HMM we classify the activity and detect the activity. The importance is on three major issues involved in a general human motion analysis system, namely human detection, tracking and activity understanding.

  9. Visualizing signatures of human activity in cities across the globe

    Kondor, Dániel; Thebault, Pierrick; Grauwin, Sebastian; Gódor, István; Moritz, Simon; Sobolevsky, Stanislav; Ratti, Carlo


    The availability of big data on human activity is currently changing the way we look at our surroundings. With the high penetration of mobile phones, nearly everyone is already carrying a high-precision sensor providing an opportunity to monitor and analyze the dynamics of human movement on unprecedented scales. In this article, we present a technique and visualization tool which uses aggregated activity measures of mobile networks to gain information about human activity shaping the structur...

  10. Reshaping Human Antibodies: Grafting an Antilysozyme Activity

    Verhoeyen, Martine; Milstein, Cesar; Winter, Greg


    The production of therapeutic human monoclonal antibodies by hybridoma technology has proved difficult, and this has prompted the ``humanizing'' of mouse monoclonal antibodies by recombinant DNA techniques. It was shown previously that the binding site for a small hapten could be grafted from the heavy-chain variable domain of a mouse antibody to that of a human myeloma protein by transplanting the hypervariable loops. It is now shown that a large binding site for a protein antigen (lysozyme) can also be transplanted from mouse to human heavy chain. The success of such constructions may be facilitated by an induced-fit mechanism.

  11. Selective activation of neuromuscular compartments within the human trapezius muscle

    Holtermann, A; Roeleveld, K; Mork, P J;


    was to investigate whether subdivisions within the human trapezius can be independently activated by voluntary command using biofeedback guidance. Bipolar electromyographical electrodes were situated on four subdivisions of the trapezius muscle. The threshold for "active" and "rest" for each...

  12. Enhanced casein kinase II activity in human tumour cell cultures

    Prowald, K; Fischer, H; Issinger, O G


    Casein kinase II (CKII) activity is enhanced as much as 2-3 fold in established and 4-5-fold in transformed human cell lines when compared to that of fibroblasts and primary human tumour cell cultures where CKII activity never exceeded a basic level. The high activity of CKII in transformed cells...... and in established cell lines was reduced to about the same basic level after treatment with heparin, a highly specific inhibitor of CKII activity. The activity of the cAMP-dependent protein kinase was virtually the same in fibroblasts and various human tumour cell lines investigated....

  13. C-Reactive Protein Activates Complement in Infarcted Human Myocardium

    Nijmeijer, Remco; Lagrand, Wim K.; Lubbers, Yvonne T. P.; Visser, Cees A.; Meijer, Chris J.L.M.; Niessen, Hans W. M.; Hack, C. Erik


    Circulating levels of C-reactive protein (CRP) constitute a cardiovascular risk marker. Immunohistochemical studies have revealed co-localization of CRP and activated complement in human infarcted myocardium suggesting CRP to enhance inflammation in ischemic myocardium by inducing local complement activation. The aim was to establish whether CRP activates complement in infarcted human myocardium and to assess the relationship between this activation and the duration of infarction. Myocardial ...

  14. Recombinant human interleukin 5 is a selective activator of human eosinophil function


    Human rIL-5 was found to selectively stimulate morphological changes and the function of human eosinophils. This molecule is thus a prime candidate for the selective eosinophilia and eosinophil activation seen in disease.

  15. Activities of Human Gene Nomenclature Committee



    The objective of this project, shared between NIH and DOE, has been and remains to enable the medical genetics communities to use common names for genes that are discovered by different gene hunting groups, in different species. This effort provides consistent gene nomenclature and approved gene symbols to the community at large. This contributes to a uniform and consistent understanding of genomes, particularly the human as well as functional genomics based on comparisons between homologous genes in related species (human and mice).

  16. Aryl hydrocarbon mono-oxygenase activity in human lymphocytes

    Griffin, G.D.; Schuresko, D.D.


    Aryl hydrocarbon mono-oxygenase (AHM), an enzyme of key importance in metabolism of xenobiotic chemicals such as polynuclear aromatic hydrocarbons (PNA), is present in human lymphocytes. Studies investing the relation of activity of AHM in human lymphocytes to parameters such as disease state, PNA exposure, in vitro mitogen stimulation, etc. have been summarized in this report. Some studies have demonstrated increased AHM activity in lymphocytes from cigarette smokers (compared to nonsmokers), and in lung cancer patients when compared to appropriate control groups. These observations are confused by extreme variability in human lymphocyte AHM activities, such variability arising from factors such as genetic variation in AHM activity, variation in in vitro culture conditions which affect AHM activity, and the problematical relationship of common AHM assays to actual PNA metabolism taking place in lymphocytes. If some of the foregoing problems can be adequately addressed, lymphocyte AHM activity could hold the promise of being a useful biomarker system for human PNA exposure.

  17. Human Activity Recognition in AAL Environments Using Random Projections

    Robertas Damaševičius


    Full Text Available Automatic human activity recognition systems aim to capture the state of the user and its environment by exploiting heterogeneous sensors attached to the subject’s body and permit continuous monitoring of numerous physiological signals reflecting the state of human actions. Successful identification of human activities can be immensely useful in healthcare applications for Ambient Assisted Living (AAL, for automatic and intelligent activity monitoring systems developed for elderly and disabled people. In this paper, we propose the method for activity recognition and subject identification based on random projections from high-dimensional feature space to low-dimensional projection space, where the classes are separated using the Jaccard distance between probability density functions of projected data. Two HAR domain tasks are considered: activity identification and subject identification. The experimental results using the proposed method with Human Activity Dataset (HAD data are presented.

  18. Soluble Pityrosporum-derived chemoattractant for polymorphonuclear leukocytes of psoriatic patients.

    Bunse, T; Mahrle, G


    The chemoattraction of polymorphonuclear leukocytes (PMNs) from psoriatic patients, atopic patients and healthy control persons by Pityrosporum orbicularelovale was investigated using the Boyden chamber method. The chemotactical attraction of PMNs from psoriatic patients by Pityrosporum (stimulation index SI = 58 +/- 50) was significantly increased (p < 0.05) compared to PMNs from atopic patients (SI = 20 +/- 17) and control persons (SI = 26 +/- 24). This effect seems to be specific for Pityrosporum, since the chemotactical response to Staphylococcus epidermidis was not increased in psoriasis. The chemotactical factor produced by Pityrosporum is hydrophilic and is destroyed by acid hydrolysis, indicating its protein nature. The yeast Pityrosporum may thus play a role in the koebnerization of psoriasis. PMID:8721481

  19. Determination of phagocytosis of /sup 32/P-labeled Staphylococcus aureus by bovine polymorphonuclear leukocytes

    Dulin, A.M.; Paape, M.J.; Weinland, B.T.


    A procedure for the measurement of phagocytosis by bovine polymorphonuclear leukocytes (PMN) of /sup 32/P-labeled Staphylococcus aureus was modified so that a larger number of samples could be compared in a single run, and smaller volumes of sample, PMN, and /sup 32/P-labeled S aureus could be used. Results were highly reproducible, with a coefficient of variation between duplicate determinations of less than or equal to 2%. Lysostaphin was prepared from the supernatant of S staphylolyticus and was compared with a commercially available preparation. Effects of lysostaphin on PMN and influence of incubation media on release of /sup 32/P from /sup 32/P-labeled S aureus by lysostaphin were examined.

  20. High affinity capture and concentration of quinacrine in polymorphonuclear neutrophils via vacuolar ATPase-mediated ion trapping: Comparison with other peripheral blood leukocytes and implications for the distribution of cationic drugs

    Roy, Caroline; Gagné, Valérie; Fernandes, Maria J.G.; Marceau, François, E-mail:


    trapping. • Human peripheral blood leukocytes capture and concentrate quinacrine. • Polymorphonuclear leukocytes do so with higher apparent affinity. • Polymorphonuclear are also more competent than lymphocytes for pinocytosis.

  1. Window Size Impact in Human Activity Recognition

    Oresti Banos


    Full Text Available Signal segmentation is a crucial stage in the activity recognition process; however, this has been rarely and vaguely characterized so far. Windowing approaches are normally used for segmentation, but no clear consensus exists on which window size should be preferably employed. In fact, most designs normally rely on figures used in previous works, but with no strict studies that support them. Intuitively, decreasing the window size allows for a faster activity detection, as well as reduced resources and energy needs. On the contrary, large data windows are normally considered for the recognition of complex activities. In this work, we present an extensive study to fairly characterize the windowing procedure, to determine its impact within the activity recognition process and to help clarify some of the habitual assumptions made during the recognition system design. To that end, some of the most widely used activity recognition procedures are evaluated for a wide range of window sizes and activities. From the evaluation, the interval 1–2 s proves to provide the best trade-off between recognition speed and accuracy. The study, specifically intended for on-body activity recognition systems, further provides designers with a set of guidelines devised to facilitate the system definition and configuration according to the particular application requirements and target activities.

  2. ActivityNet: A Large-Scale Video Benchmark for Human Activity Understanding

    Heilbron, Fabian Caba


    In spite of many dataset efforts for human action recognition, current computer vision algorithms are still severely limited in terms of the variability and complexity of the actions that they can recognize. This is in part due to the simplicity of current benchmarks, which mostly focus on simple actions and movements occurring on manually trimmed videos. In this paper we introduce ActivityNet, a new largescale video benchmark for human activity understanding. Our benchmark aims at covering a wide range of complex human activities that are of interest to people in their daily living. In its current version, ActivityNet provides samples from 203 activity classes with an average of 137 untrimmed videos per class and 1.41 activity instances per video, for a total of 849 video hours. We illustrate three scenarios in which ActivityNet can be used to compare algorithms for human activity understanding: untrimmed video classification, trimmed activity classification and activity detection.

  3. Human-induced soil degradation activities

    Oldeman L.R.; Van Baren J.H. V.


    Soil degradation is occurring over vast areas. The GLASOD and ASSOD projects reflect the present status of human-induced soil degradation and its impact on food productivity related to productivity changes observed in the recent past. However, there is a great need for well-documented, reliable soil information and other related data at national and regional levels to better understand and qualify the impact of changing soil conditions or biomass production.

  4. Mapping human brain activity in vivo.

    Mazziotta, J.C.


    A wide range of structural and functional techniques now exists to map the human brain in health and disease. These approaches span the gamut from external tomographic imaging devices (positron-emission tomography, single photon-emission computed tomography, magnetic resonance imaging, computed tomography), to surface detectors (electroencephalography, magnetoencephalography, transcranial magnetic stimulation), to measurements made directly on the brain's surface or beneath it (intrinsic sign...

  5. Type IV collagen-degrading enzyme activity in human serum.



    Full Text Available Type IV collagen-degrading enzyme activity was detected in human serum. Serum was preincubated with 4-aminophenylmercuric acetate and trypsin to activate the enzyme prior to assay. Type IV collagen, purified from human placentas and radiolabeled with [1-14C] acetic anhydride, was used as the substrate. The enzyme activity was measured at pH 7.5 and inhibited by treatment with ethylenediaminetetraacetic acid or heat. The assay of type IV collagen-degrading enzyme in human serum might be useful for estimating the degradation of type IV collagen.

  6. Type IV collagen-degrading enzyme activity in human serum.

    Hashimoto, Noriaki; Kobayashi,Michio; Watanabe,Akiharu; Higashi,Toshiro; Tsuji, Takao


    Type IV collagen-degrading enzyme activity was detected in human serum. Serum was preincubated with 4-aminophenylmercuric acetate and trypsin to activate the enzyme prior to assay. Type IV collagen, purified from human placentas and radiolabeled with [1-14C] acetic anhydride, was used as the substrate. The enzyme activity was measured at pH 7.5 and inhibited by treatment with ethylenediaminetetraacetic acid or heat. The assay of type IV collagen-degrading enzyme in human serum might be useful...

  7. Activation of human immunodeficiency virus by radiation

    It was recently demonstrated that ultraviolet radiation (UVR) can induce the HIV promoter as well as activate the complete virus in cultured cells (Valerie et al., 1988). This and subsequent observations, reviewed in this article, suggest a possibility that radiation exposure may accelerate development of AIDS in HIV-infected individuals. They also indicate that studies on HIV activation by stressors, including radiation, may advance our understanding of some phenomena that follow HIV infection. (author)

  8. Effect of Legionella pneumophila sonicate on killing of Listeria monocytogenes by human polymorphonuclear neutrophils and monocytes

    Rechnitzer, C; Bangsborg, Jette Marie; Shand, G H


    Legionella pneumophila shares with other intracellular pathogens the ability to resist intracellular killing within phagocytes. An increasing number of cellular components of L. pneumophila are proposed as pathogenic factors of the organism. At the site of infection, the phagocytic cells will be ...


    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...


    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  11. Supporting Human Activities - Exploring Activity-Centered Computing

    Christensen, Henrik Bærbak; Bardram, Jakob


    -hoc collaboration based on shared material, and organized in terms of well-defined, recurring, work activities. We propose that this kind of work can be supported by a pervasive computing infrastructure together with domain-specific services, both designed from a perspective where work activities are first class......In this paper we explore an activity-centered computing paradigm that is aimed at supporting work processes that are radically different from the ones known from office work. Our main inspiration is healthcare work that is characterized by an extreme degree of mobility, many interruptions, ad...

  12. Cercarial glycocalyx of Schistosoma mansoni activates human complement.

    Samuelson, J C; Caulfield, J. P.


    Human complement activation by cercariae and schistosomula of the human parasite Schistosoma mansoni was studied in vitro. Cercariae are composed of tails which are shed after infection of the host and bodies which transform into the larvae or schistosomula after infection. After incubation in fresh normal human serum (NHS), cercarial tails bound more anti-C3 antibodies than did cercarial bodies (CB), and the tails were rapidly lysed, while the attached CB remained intact. Complement activati...

  13. Human activities change marine ecosystems by altering predation risk.

    Madin, Elizabeth M P; Dill, Lawrence M; Ridlon, April D; Heithaus, Michael R; Warner, Robert R


    In ocean ecosystems, many of the changes in predation risk - both increases and decreases - are human-induced. These changes are occurring at scales ranging from global to local and across variable temporal scales. Indirect, risk-based effects of human activity are known to be important in structuring some terrestrial ecosystems, but these impacts have largely been neglected in oceans. Here, we synthesize existing literature and data to explore multiple lines of evidence that collectively suggest diverse human activities are changing marine ecosystems, including carbon storage capacity, in myriad ways by altering predation risk. We provide novel, compelling evidence that at least one key human activity, overfishing, can lead to distinct, cascading risk effects in natural ecosystems whose magnitude exceeds that of presumed lethal effects and may account for previously unexplained findings. We further discuss the conservation implications of human-caused indirect risk effects. Finally, we provide a predictive framework for when human alterations of risk in oceans should lead to cascading effects and outline a prospectus for future research. Given the speed and extent with which human activities are altering marine risk landscapes, it is crucial that conservation and management policy considers the indirect effects of these activities in order to increase the likelihood of success and avoid unfortunate surprises. PMID:26448058

  14. Impact of the spatial context on human communication activity

    Dashdorj, Zolzaya; Sobolevsky, Stanislav


    Technology development produces terabytes of data generated by hu- man activity in space and time. This enormous amount of data often called big data becomes crucial for delivering new insights to decision makers. It contains behavioral information on different types of human activity influenced by many external factors such as geographic infor- mation and weather forecast. Early recognition and prediction of those human behaviors are of great importance in many societal applications like hea...

  15. Random isolation of gene activator elements from the human genome.

    Hamada, H


    Long-range-acting gene activator elements were randomly isolated from the human genome by functional selection. HeLa cells were transfected with an enhancer trap, a plasmid containing an enhancerless xanthine-guanosine phosphoribosyltransferase (gpt) gene transcribed from the simian virus 40 early promoter, and stably transformed GPT+ cells were selected. From several transformants, human DNA sequences flanking the enhancer trap were cloned. Two gene activators (GA1 and GA2) were found in the...

  16. Invading the Mediterranean Sea: biodiversity patterns shaped by human activities

    Katsanevakis, Stelios; Coll, Marta; Piroddi, Chiara; STEENBEEK Jeroen; Ben Rais Lasram, Frida; Zenetos, Argyro; Cardoso, Ana Cristina


    Human activities, such as shipping, aquaculture, and the opening of the Suez Canal, have caused the introduction of nearly 1,000 alien species in the Mediterranean Sea. We investigated how human activities, offering pathways for the introduction of alien species, may shape the biodiversity patterns in the Mediterranean. Richness of Red Sea species introduced through the Suez Canal (Lessepsian species) is very high along the eastern Mediterranean coastline, reaching a maximum of 129 species pe...

  17. Telomere elongation in immortal human cells without detectable telomerase activity.

    Bryan, T M; Englezou, A; J Gupta; Bacchetti, S; Reddel, R. R.


    Immortalization of human cells is often associated with reactivation of telomerase, a ribonucleoprotein enzyme that adds TTAGGG repeats onto telomeres and compensates for their shortening. We examined whether telomerase activation is necessary for immortalization. All normal human fibroblasts tested were negative for telomerase activity. Thirteen out of 13 DNA tumor virus-transformed cell cultures were also negative in the pre-crisis (i.e. non-immortalized) stage. Of 35 immortalized cell line...

  18. Dietary methanol regulates human gene activity.

    Anastasia V Shindyapina

    Full Text Available Methanol (MeOH is considered to be a poison in humans because of the alcohol dehydrogenase (ADH-mediated conversion of MeOH to formaldehyde (FA, which is toxic. Our recent genome-wide analysis of the mouse brain demonstrated that an increase in endogenous MeOH after ADH inhibition led to a significant increase in the plasma MeOH concentration and a modification of mRNA synthesis. These findings suggest endogenous MeOH involvement in homeostasis regulation by controlling mRNA levels. Here, we demonstrate directly that study volunteers displayed increasing concentrations of MeOH and FA in their blood plasma when consuming citrus pectin, ethanol and red wine. A microarray analysis of white blood cells (WBC from volunteers after pectin intake showed various responses for 30 significantly differentially regulated mRNAs, most of which were somehow involved in the pathogenesis of Alzheimer's disease (AD. There was also a decreased synthesis of hemoglobin mRNA, HBA and HBB, the presence of which in WBC RNA was not a result of red blood cells contamination because erythrocyte-specific marker genes were not significantly expressed. A qRT-PCR analysis of volunteer WBCs after pectin and red wine intake confirmed the complicated relationship between the plasma MeOH content and the mRNA accumulation of both genes that were previously identified, namely, GAPDH and SNX27, and genes revealed in this study, including MME, SORL1, DDIT4, HBA and HBB. We hypothesized that human plasma MeOH has an impact on the WBC mRNA levels of genes involved in cell signaling.

  19. Telomerase Activity in Human Ovarian Carcinoma

    Counter, Christopher M.; Hirte, Hal W.; Bacchetti, Silvia; Harley, Calvin B.


    Telomeres fulfill the dual function of protecting eukaryotic chromosomes from illegitimate recombination and degradation and may aid in chromosome attachment to the nuclear membrane. We have previously shown that telomerase, the enzyme which synthesizes telomeric DNA, is not detected in normal somatic cells and that telomeres shorten with replicative age. In cells immortalized in vitro, activation of telomerase apparently stabilizes telomere length, preventing a critical destabilization of chromosomes, and cell proliferation continues even when telomeres are short. In vivo, telomeres of most tumors are shorter than telomeres of control tissues, suggesting an analogous role for the enzyme. To assess the relevance of telomerase and telomere stability in the development and progression of tumors, we have measured enzyme activity and telomere length in metastatic cells of epithelial ovarian carcinoma. We report that extremely short telomeres are maintained in these cells and that tumor cells, but not isogenic nonmalignant cells, express telomerase. Our findings suggest that progression of malignancy is ultimately dependent upon activation of telomerase and that telomerase inhibitors may be effective antitumor drugs.

  20. Active ingredients against human epidermal aging.

    Lorencini, Márcio; Brohem, Carla A; Dieamant, Gustavo C; Zanchin, Nilson I T; Maibach, Howard I


    The decisive role of the epidermis in maintaining body homeostasis prompted studies to evaluate the changes in epidermal structure and functionality over the lifetime. This development, along with the identification of molecular mechanisms of epidermal signaling, maintenance, and differentiation, points to a need for new therapeutic alternatives to treat and prevent skin aging. In addition to recovering age- and sun-compromised functions, proper treatment of the epidermis has important esthetic implications. This study reviews active ingredients capable of counteracting symptoms of epidermal aging, organized according to the regulation of specific age-affected epidermal functions: (1) several compounds, other than retinoids and derivatives, act on the proliferation and differentiation of keratinocytes, supporting the protective barrier against mechanical and chemical insults; (2) natural lipidic compounds, as well as glycerol and urea, are described as agents for maintaining water-ion balance; (3) regulation of immunological pathogen defense can be reinforced by natural extracts and compounds, such as resveratrol; and (4) antioxidant exogenous sources enriched with flavonoids and vitamin C, for example, improve solar radiation protection and epidermal antioxidant activity. The main objective is to provide a functional classification of active ingredients as regulatory elements of epidermal homeostasis, with potential cosmetic and/or dermatological applications. PMID:24675046

  1. Broad-spectrum antimicrobial activity of human intestinal defensin 5.

    Porter, E M; van Dam, E; Valore, E V; Ganz, T


    Defensins are antibiotic peptides expressed in human and animal myeloid and epithelial cells. Due to the limited availability of natural peptides, the properties of human epithelial defensins have not been studied. We assayed the microbicidal activity of recombinant human intestinal defensin 5 (rHD-5) in the presence of salt (O to 150 mM NaCl) with varied pH (pH 5.5 to pH 8.5) and trypsin (25 and 250 microg/ml). rHD-5 exhibits microbicidal activity against Listeria monocytogenes, Escherichia ...

  2. Estudio de la migración y de la actividad metabólica de los polimofonucleares neutrófilos en pacientes con periodontitis juvenil localizada Migration and metabolic activity of polymorphonuclear neutrophils in patients with localized juvenile periodontitis

    Pablo Javier Patiño Grajales


    -family: Arial">Localized Juvenile periodontitis (LJP is characterized by a rapid loss of connective tissue insertion and of alveolar bone around the first molars and incisors of the permanent teeth. This research was carried out in order to establish a relationship between in vitro behavior of PMN and the different clinical types of the disease. Twenty-one patients were studied; they Included incipient, moderate and advanced LJP. Before any kind of dental treatment was applied PMN were isolated from each patient to determine their chemotaxis under agarose and their metabolic activity (luminoidependent- chemiluminiscence, LDCL. A group of healthy control individuals was similarly studied.


    Patients with advanced LJP had significantly lower chemotaxis (p=O.O23; on the other hand, LDCL of phorbol-myristate-acetate stimulated PMN was normalin the three groups as compared with controls; PMN stimulation with opsonized zimosan revealed significantly decreased metabolic activity in patients with incipient and advanced disease (p=O.O12. These findings indicate that patients with LJP behave as a heterogeneous group regarding PMN function. In order to define PMN response in each type of this disease It Is necessary to study the relationship between genetic components, environment and clinical phenotypes of the disease.

  3. Anticipating Human Activities Using Object Affordances for Reactive Robotic Response.

    Koppula, Hema S; Saxena, Ashutosh


    An important aspect of human perception is anticipation, which we use extensively in our day-to-day activities when interacting with other humans as well as with our surroundings. Anticipating which activities will a human do next (and how) can enable an assistive robot to plan ahead for reactive responses. Furthermore, anticipation can even improve the detection accuracy of past activities. The challenge, however, is two-fold: We need to capture the rich context for modeling the activities and object affordances, and we need to anticipate the distribution over a large space of future human activities. In this work, we represent each possible future using an anticipatory temporal conditional random field (ATCRF) that models the rich spatial-temporal relations through object affordances. We then consider each ATCRF as a particle and represent the distribution over the potential futures using a set of particles. In extensive evaluation on CAD-120 human activity RGB-D dataset, we first show that anticipation improves the state-of-the-art detection results. We then show that for new subjects (not seen in the training set), we obtain an activity anticipation accuracy (defined as whether one of top three predictions actually happened) of 84.1, 74.4 and 62.2 percent for an anticipation time of 1, 3 and 10 seconds respectively. Finally, we also show a robot using our algorithm for performing a few reactive responses. PMID:26656575


    Song Shunling


    @@ As an EFL teacher actively engaged in promoting communicative approach in teaching post-intermediate students I have been all the time aware of the risks involved in classroom discussion and debate in the target language. Despite elaborate preparations on thepart of both teacher and students and numerous encouraging cues from the teacher to induce an adequate interaction during the session, the end product is anything but satisfactory: few more able students may hog the show for a few minutes while the rest clamp up, then stony silence dominates and the teacher has recourse to monologue.

  5. Echocardiographic image of an active human heart


    Echocardiographic images provide quick, safe images of the heart as it beats. While a state-of-the art echocardiograph unit is part of the Human Research Facility on International Space Station, quick transmission of images and data to Earth is a challenge. NASA is developing techniques to improve the echocardiography available to diagnose sick astronauts as well as study the long-term effects of space travel on their health. Echocardiography uses ultrasound, generated in a sensor head placed against the patient's chest, to produce images of the structure of the heart walls and valves. However, ultrasonic imaging creates an enormous volume of data, up to 220 million bits per second. This can challenge ISS communications as well as Earth-based providers. Compressing data for rapid transmission back to Earth can degrade the quality of the images. Researchers at the Cleveland Clinic Foundation are working with NASA to develop compression techniques that meet imaging standards now used on the Internet and by the medical community, and that ensure that physicians receive quality diagnostic images.

  6. Structure activity relationships of human galactokinase inhibitors.

    Liu, Li; Tang, Manshu; Walsh, Martin J; Brimacombe, Kyle R; Pragani, Rajan; Tanega, Cordelle; Rohde, Jason M; Baker, Heather L; Fernandez, Elizabeth; Blackman, Burchelle; Bougie, James M; Leister, William H; Auld, Douglas S; Shen, Min; Lai, Kent; Boxer, Matthew B


    Classic Galactosemia is a rare inborn error of metabolism that is caused by deficiency of galactose-1-phosphate uridyltransferase (GALT), an enzyme within the Leloir pathway that is responsible for the conversion of galactose-1-phosphate (gal-1-p) and UDP-glucose to glucose-1-phosphate and UDP-galactose. This deficiency results in elevated intracellular concentrations of its substrate, gal-1-p, and this increased concentration is believed to be the major pathogenic mechanism in Classic Galactosemia. Galactokinase (GALK) is an upstream enzyme of GALT in the Leloir pathway and is responsible for conversion of galactose and ATP to gal-1-p and ADP. Therefore, it was hypothesized that the identification of a small-molecule inhibitor of human GALK would act to prevent the accumulation of gal-1-p and offer a novel entry therapy for this disorder. Herein we describe a quantitative high-throughput screening campaign that identified a single chemotype that was optimized and validated as a GALK inhibitor. PMID:25553891

  7. Natural radiation exposure modified by human activities

    We are now living in the radiation environment modified by our technology. It is usually called 'Technologically Enhanced Natural Radiation' and have been discussed in the UNSCEAR Reports as an important source of exposure. The terrestrial radionuclide concentrations as well as the intensity of cosmic rays are considered to have been constant after our ancestors came down from trees and started walking on their two feet. However, we have been changing our environment to be more comfortable for our life and consequently ambient radiation levels are nomore what used to be. In this paper exposures due to natural radiation modified by our following activities are discussed: housing, balneology, cave excursion, mountain climbing, skiing, swimming, smoking and usage of mineral water, well water, coal, natural gas, phosphate rocks and minerals. In the ICRP Publication No. 39, it is clearly mentioned that even natural radiation should be controlled as far as it is controllable. We have to pay more attention to our activities not to enhance the exposure due to unnecessary, avoidable radiation. (author)

  8. Neutron activation analysis of human hair

    As a part of IAEA research project, ''Activation analysis of hair as an indicator of contamination of man by environmental trace element pollutants'', a survey was carried out to elucidate the levels of various trace element concentration in hair of local population in the Tokyo Metropolitan areas, by applying instrumental neutron activation analysis. A total of 202 scalp hair samples were collected from the inhabitants classified by sex and five age classes. Irradiation was made in the Rikkyo University 100 kW TRIGA MARK-II reactor. Using several combinations of irradiation time, cooling time and counting time, forty elements were determined. The relationship between several trace element contents in hair and such factors as sex, age class, hair treatment, smoking habit and dental treatment, was analyzed by using the method of multiple regression. It was shown that (1) Hair treatment had a predominant effect on the contents of bromine, magnesium and calcium in hair, (2) Aging and amoking contributed increasing mercury content in hair, and hair treatment acted reversely. (author)

  9. Humpback Dolphin (Genus Sousa) Behavioural Responses to Human Activities.

    Piwetz, Sarah; Lundquist, David; Würsig, Bernd


    Humpback dolphins (genus Sousa) use shallow, near-shore waters throughout their range. This coastal distribution makes them vulnerable to recreational and commercial disturbances, especially near heavily populated and industrialized areas. Most research focusing on Sousa and human activities has emphasized direct impacts and threats, involving injury and death, with relatively little focus on indirect effects on dolphins, such as changes in behaviour that may lead to deleterious effects. Understanding behaviour is important in resolving human-wildlife conflict and is an important component of conservation. This chapter gives an overview of animal behavioural responses to human activity with examples from diverse taxa; reviews the scientific literature on behavioural responses of humpback dolphins to human activity throughout their range, including marine vessel traffic, dolphin tourism, cetacean-fishery interactions, noise pollution, and habitat alteration; and highlights information and data gaps for future humpback dolphin research to better inform behaviour-based management decisions that contribute to conservation efforts. PMID:26555621

  10. The cell-penetrating peptide domain from human heparin-binding epidermal growth factor-like growth factor (HB-EGF) has anti-inflammatory activity in vitro and in vivo

    Highlights: ► HBP sequence identified from HB-EGF has cell penetration activity. ► HBP inhibits the NF-κB dependent inflammatory responses. ► HBP directly blocks phosphorylation and degradation of IκBα. ► HBP inhibits nuclear translocation of NF-κB p65 subunit. -- Abstract: A heparin-binding peptide (HBP) sequence from human heparin-binding epidermal growth factor-like growth factor (HB-EGF) was identified and was shown to exhibit cell penetration activity. This cell penetration induced an anti-inflammatory reaction in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. HBP penetrated the cell membrane during the 10 min treatment and reduced the LPS-induced production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), and cytokines (TNF-α and IL-6) in a concentration-dependent manner. Additionally, HBP inhibited the LPS-induced upregulation of cytokines, including TNF-α and IL-6, and decreased the interstitial infiltration of polymorphonuclear leukocytes in a lung inflammation model. HBP inhibited NF-κB-dependent inflammatory responses by directly blocking the phosphorylation and degradation of IκBα and by subsequently inhibiting the nuclear translocation of the p65 subunit of NF-κB. Taken together, this novel HBP may be potentially useful candidate for anti-inflammatory treatments and can be combined with other drugs of interest to transport attached molecules into cells.

  11. Macrophages are stimulated by muramyl dipeptide to induce polymorphonuclear leukocyte accumulation in the peritoneal cavities of guinea pigs.

    Nagao, S; Nakanishi, M.; Kutsukake, H; Yagawa, K; Kusumoto, S; Shiba, T; Tanaka, A; Kotani, S.


    N-Acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide [MDP]) injected intraperitoneally significantly increased the number of cells entering the peritoneal cavity of guinea pigs primed with liquid paraffin or thioglycollate. There was a close relationship between peritoneal polymorphonuclear leukocyte (PMN) accumulation and the uptake of glucosamine by macrophages in guinea pigs treated with a variety of bacterial cell surface components such as cell wall peptidoglycan subunits and bacte...

  12. Activation of peroxisome proliferator-activated receptor-α enhances fatty acid oxidation in human adipocytes

    Highlights: → PPARα activation increased mRNA expression levels of adipocyte differentiation marker genes and GPDH activity in human adipocytes. → PPARα activation also increased insulin-dependent glucose uptake in human adipocytes. → PPARα activation did not affect lipid accumulation in human adipocytes. → PPARα activation increased fatty acid oxidation through induction of fatty acid oxidation-related genes in human adipocytes. -- Abstract: Peroxisome proliferator-activated receptor-α (PPARα) is a key regulator for maintaining whole-body energy balance. However, the physiological functions of PPARα in adipocytes have been unclarified. We examined the functions of PPARα using human multipotent adipose tissue-derived stem cells as a human adipocyte model. Activation of PPARα by GW7647, a potent PPARα agonist, increased the mRNA expression levels of adipocyte differentiation marker genes such as PPARγ, adipocyte-specific fatty acid-binding protein, and lipoprotein lipase and increased both GPDH activity and insulin-dependent glucose uptake level. The findings indicate that PPARα activation stimulates adipocyte differentiation. However, lipid accumulation was not changed, which is usually observed when PPARγ is activated. On the other hand, PPARα activation by GW7647 treatment induced the mRNA expression of fatty acid oxidation-related genes such as CPT-1B and AOX in a PPARα-dependent manner. Moreover, PPARα activation increased the production of CO2 and acid soluble metabolites, which are products of fatty acid oxidation, and increased oxygen consumption rate in human adipocytes. The data indicate that activation of PPARα stimulates both adipocyte differentiation and fatty acid oxidation in human adipocytes, suggesting that PPARα agonists could improve insulin resistance without lipid accumulation in adipocytes. The expected effects of PPARα activation are very valuable for managing diabetic conditions accompanied by obesity, because PPAR

  13. Brain Activation During Singing: "Clef de Sol Activation" Is the "Concert" of the Human Brain.

    Mavridis, Ioannis N; Pyrgelis, Efstratios-Stylianos


    Humans are the most complex singers in nature, and the human voice is thought by many to be the most beautiful musical instrument. Aside from spoken language, singing represents a second mode of acoustic communication in humans. The purpose of this review article is to explore the functional anatomy of the "singing" brain. Methodologically, the existing literature regarding activation of the human brain during singing was carefully reviewed, with emphasis on the anatomic localization of such activation. Relevant human studies are mainly neuroimaging studies, namely functional magnetic resonance imaging and positron emission tomography studies. Singing necessitates activation of several cortical, subcortical, cerebellar, and brainstem areas, served and coordinated by multiple neural networks. Functionally vital cortical areas of the frontal, parietal, and temporal lobes bilaterally participate in the brain's activation process during singing, confirming the latter's role in human communication. Perisylvian cortical activity of the right hemisphere seems to be the most crucial component of this activation. This also explains why aphasic patients due to left hemispheric lesions are able to sing but not speak the same words. The term clef de sol activation is proposed for this crucial perisylvian cortical activation due to the clef de sol shape of the topographical distribution of these cortical areas around the sylvian fissure. Further research is needed to explore the connectivity and sequence of how the human brain activates to sing. PMID:26966964

  14. Human activity recognition from object interaction in domestic scenarios

    Flores Vázquez, Carlos


    This work describes the recognition of human activity based on the interaction between people and objects in domestic settings, specifically in a kitchen. In order to achieve the aim of recognizing activity it is necessary to establish a procedure and essential equipment. Regarding the procedure, in a simplified manner, it is based on capturing local images where the activity takes place using a colour camera (RGB), and processing the above mentioned images to recognize the present objects an...

  15. GIS spatio-temporal modeling of human maritime activities

    Le Guyader, Damien; Gourmelon, Françoise


    Coastal seas are important for human societies with many and diverse activities. These space and resource consuming activities exert an increasing pressure on the environment and sometimes result in conflicting interactions. Understanding these interactions remains a challenge for research and civil society. A methodology is proposed to describe the spatio-temporal distribution of several activities in coastal seas. An application is developed in the Bay of Brest (Brittany, France). Spatial, ...

  16. A Competitive Approach for Human Activity Recognition on Smartphones

    Reiss, Attila; Hendeby, Gustaf; Stricker, Didier


    This paper describes a competitive approach developed for an activity recognition challenge. The competition was defined on a new and publicly available dataset of human activities, recorded with smartphone sensors. This work investigates different feature sets for the activity recognition task of the competition. Moreover, the focus is also on the introduction of a new, confidence-based boosting algorithm called ConfAda- Boost.M1. Results show that the new classification method outperforms c...

  17. Thermodynamic determination of beta-hexosaminidase isoenzymes in mononuclear and polymorphonuclear leukocyte populations.

    Casal, J Antonio; Chabás, Amparo; Tutor, J Carlos


    Isoenzymes of beta-hexosaminidase (Hex) were determined in mononuclear (MN) and polymorphonuclear (PMN) leukocytes, with a thermodynamic method using the chromogenic substrate sodio-3,3'-dichlorophenolsulfonphthaleinyl N-acetyl-beta-D-glucosaminide. Imprecision was very satisfactory, and the results are very much in agreement with those obtained using the fluorogenic substrates 4-methylumbelliferyl N-acetyl-beta-D-glucosaminide and 4-methylumbelliferyl N-acetyl-beta-D-glucosaminide 6-sulfate. In 163 healthy individuals we found, for the proportion as a percentage of the Hex A isoenzyme, significantly higher values (P < 0.001) in PMN than in MN cells (71.56 +/- 0.30% vs. 54.28 +/- 0.24%), meaning that it would not appear advisable to use total leukocyte lysates for evaluating this variable. The method is fast, precise, and highly suitable for the biochemical diagnosis and heterozygote screening of GM2 gangliosidoses, and would be applicable in cases of thermolabile Hex B and for detecting the B1 variant. PMID:12503097

  18. Function of irradiated polymorphonuclear leukocytes obtained by buffy-coat centrifugation

    Several studies suggest that transfusion of polymorphonuclear leukocytes (PMNs) may be beneficial in the treatment of septic neonatal patients. Because of expense, donor availability, and the technical effort involved in obtaining PMNs by intermittent or continuous flow leukapheresis, buffy coat centrifugation of whole blood has been suggested as an alternative source. An in vitro study was performed to determine whether PMNs collected by this method have adequate oxidative and migratory function measured by chemiluminescence (CL) and chemotaxis under agarose (CT), respectively. Whole blood samples from six adult volunteers were drawn into citrate-phosphate-dextrose-adenine-one and stored at 4 degrees C for 0 to 48 hours. One-half of each sample was irradiated with 1500 rads. PMNs isolated from the buffy coat of these samples had greater than 80 percent normal CT and CL following 0 to 28 hours of storage in whole blood. Irradiation caused no depression in function. Units of whole blood yielded 1.11 +/- 0.40 X 10(9) PMNs per unit. This study indicates that transfusion of radiated PMNs obtained from stored whole blood that is less than 28 hours old is reasonable to use in studies involving PMN transfusions

  19. Study on defense function of polymorphonuclear leukocytes in A-bomb survivors, 4

    Included in this study were 222 A-bomb survivors, consisting of the exposed group (104 exposed to 0.5-6.0 Gy estimated on the basis of T65 DR) and the non-exposed group (118 exposed to 0 Gy). Regarding superoxide anion production, such as O2-·CF and O2-·F, there were significant differences between the exposed and non-exposed groups. Chemotaxis, natural migration, and chemokinesis of polymorphonuclear leukocytes (PMN) tended to be increased in the exposed group. This was more marked in men than women. Chemotaxis, natural migration, and chemokinesis of PMN were significantly increased in A-bomb survivors aged 59 years or less (65.2±16.7 μml/45 min, 31.3±11.1, and 44.7±13.9, respectively) than those aged more than 59 years (59.5±18.5, 26.3±10.8, and 38.6±14.6, respectively). The group of patients aged 59 years or less tended to have higher values of O2-·CF and O2-·F. A significantly increased chemokinesis was associated with cigarette smoking. Regarding the other items, such as migration, chemotaxis, and superoxide anion production, the measurement values tended to be higher in the group of smokers than that of nonsmokers. (N.K.)

  20. Function of irradiated polymorphonuclear leukocytes obtained by buffy-coat centrifugation

    Wheeler, J.G.; Abramson, J.S.; Ekstrand, K.

    Several studies suggest that transfusion of polymorphonuclear leukocytes (PMNs) may be beneficial in the treatment of septic neonatal patients. Because of expense, donor availability, and the technical effort involved in obtaining PMNs by intermittent or continuous flow leukapheresis, buffy coat centrifugation of whole blood has been suggested as an alternative source. An in vitro study was performed to determine whether PMNs collected by this method have adequate oxidative and migratory function measured by chemiluminescence (CL) and chemotaxis under agarose (CT), respectively. Whole blood samples from six adult volunteers were drawn into citrate-phosphate-dextrose-adenine-one and stored at 4 degrees C for 0 to 48 hours. One-half of each sample was irradiated with 1500 rads. PMNs isolated from the buffy coat of these samples had greater than 80 percent normal CT and CL following 0 to 28 hours of storage in whole blood. Irradiation caused no depression in function. Units of whole blood yielded 1.11 +/- 0.40 X 10(9) PMNs per unit. This study indicates that transfusion of radiated PMNs obtained from stored whole blood that is less than 28 hours old is reasonable to use in studies involving PMN transfusions.

  1. CCL2 Promotes Colorectal Carcinogenesis by Enhancing Polymorphonuclear Myeloid-Derived Suppressor Cell Population and Function

    Eunyoung Chun


    Full Text Available Our study reveals a non-canonical role for CCL2 in modulating non-macrophage, myeloid-derived suppressor cells (MDSCs and shaping a tumor-permissive microenvironment during colon cancer development. We found that intratumoral CCL2 levels increased in patients with colitis-associated colorectal cancer (CRC, adenocarcinomas, and adenomas. Deletion of CCL2 blocked progression from dysplasia to adenocarcinoma and reduced the number of colonic MDSCs in a spontaneous mouse model of colitis-associated CRC. In a transplantable mouse model of adenocarcinoma and an APC-driven adenoma model, CCL2 fostered MDSC accumulation in evolving colonic tumors and enhanced polymorphonuclear (PMN-MDSC immunosuppressive features. Mechanistically, CCL2 regulated T cell suppression of PMN-MDSCs in a STAT3-mediated manner. Furthermore, CCL2 neutralization decreased tumor numbers and MDSC accumulation and function. Collectively, our experiments support that perturbing CCL2 and targeting MDSCs may afford therapeutic opportunities for colon cancer interception and prevention.

  2. Perceiving emotions in human-human and human-animal interactions: Hemodynamic prefrontal activity (fNIRS) and empathic concern.

    Vanutelli, Maria Elide; Balconi, Michela


    In the last years social neuroscience research attempted to identify the neural networks underlying the human ability to perceive others' emotions, a core process in establishing meaningful social bonds. A large amount of papers arose and identified common and specific empathy-based networks with respect to stimulus type and task. Despite the great majority of studies focused on human-human contexts, we do not establish relations with only other humans, but also with non-human animals. The aim of the present work was to explore the brain mechanisms involved in empathic concern for people who interacts with both peers and other species. Participants have been assessed by functional near-infrared spectroscopy (fNIRS) while viewing pictures depicting humans interacting with both other men and women (human-human condition: HH), or with dogs and cats (human-animal: HA). Results showed that aggressive HH interactions elicited greater prefrontal activity (PFC) than HA ones while, when considering HA interactions, friendly ones were related to higher cortical activity. Finally, oxy (O2Hb) and deoxyhemoglobin (HHb) increasing related to the processing of aggressive interactions positively correlated with different empathic measures, within more specific brain regions. Results were elucidated with respect to available evidence on emotion perception, empathic neural mechanisms and their functional meaning for human-animal contexts. PMID:26272301

  3. Modeling and Visualization of Human Activities for Multicamera Networks

    Aswin C. Sankaranarayanan


    Full Text Available Multicamera networks are becoming complex involving larger sensing areas in order to capture activities and behavior that evolve over long spatial and temporal windows. This necessitates novel methods to process the information sensed by the network and visualize it for an end user. In this paper, we describe a system for modeling and on-demand visualization of activities of groups of humans. Using the prior knowledge of the 3D structure of the scene as well as camera calibration, the system localizes humans as they navigate the scene. Activities of interest are detected by matching models of these activities learnt a priori against the multiview observations. The trajectories and the activity index for each individual summarize the dynamic content of the scene. These are used to render the scene with virtual 3D human models that mimic the observed activities of real humans. In particular, the rendering framework is designed to handle large displays with a cluster of GPUs as well as reduce the cognitive dissonance by rendering realistic weather effects and illumination. We envision use of this system for immersive visualization as well as summarization of videos that capture group behavior.

  4. Detection of cardiac activity changes from human speech

    Tovarek, Jaromir; Partila, Pavol; Voznak, Miroslav; Mikulec, Martin; Mehic, Miralem


    Impact of changes in blood pressure and pulse from human speech is disclosed in this article. The symptoms of increased physical activity are pulse, systolic and diastolic pressure. There are many methods of measuring and indicating these parameters. The measurements must be carried out using devices which are not used in everyday life. In most cases, the measurement of blood pressure and pulse following health problems or other adverse feelings. Nowadays, research teams are trying to design and implement modern methods in ordinary human activities. The main objective of the proposal is to reduce the delay between detecting the adverse pressure and to the mentioned warning signs and feelings. Common and frequent activity of man is speaking, while it is known that the function of the vocal tract can be affected by the change in heart activity. Therefore, it can be a useful parameter for detecting physiological changes. A method for detecting human physiological changes by speech processing and artificial neural network classification is described in this article. The pulse and blood pressure changes was induced by physical exercises in this experiment. The set of measured subjects was formed by ten healthy volunteers of both sexes. None of the subjects was a professional athlete. The process of the experiment was divided into phases before, during and after physical training. Pulse, systolic, diastolic pressure was measured and voice activity was recorded after each of them. The results of this experiment describe a method for detecting increased cardiac activity from human speech using artificial neural network.

  5. Activity of antiretroviral drugs in human infections by opportunistic agents

    Izabel Galhardo Demarchi; Daniela Maira Cardozo; Sandra Mara Alessi Aristides; Ricardo Alberto Moliterno; Thaís Gomes Verzignassi Silveira; Rosilene Fressatti Cardoso; Dennis Armando Bertolini; Terezinha Inez Estivalet Svidzinski; Jorge Juarez Vieira Teixeira; Maria Valdrinez Campana Lonardoni


    Highly active antiretroviral therapy (HAART) is used in patients infected with HIV. This treatment has been shown to significantly decrease opportunist infections such as those caused by viruses, fungi and particularly, protozoa. The use of HAART in HIV-positive persons is associated with immune reconstitution as well as decreased prevalence of oral candidiasis and candidal carriage. Antiretroviral therapy benefits patients who are co-infected by the human immunodeficiency virus (HIV), human ...

  6. Gastrointestinal-active oligosaccharides from human milk and functional foods

    Albrecht, S.A.


    Keywords: human milk oligosaccharides (HMOs), galacto-oligosaccharides (GOS), konjac glucomannan (KGM), breast milk, baby feces, gastrointestinal metabolization, blood-group specific conjugates, CE-LIF-MSn   Oligosaccharides, as present in human milk or supplemented to food, are renowned for their biological activity in the gastrointestinal tract. So far, little is known about the implication of oligosaccharide structures on their gastrointestinal fate. The influence of diet-related olig...

  7. Autoproteolytic Cleavage and Activation of Human Acid Ceramidase*

    Shtraizent, Nataly; Eliyahu, Efrat; Park, Jae-Ho; He, Xingxuan; Shalgi, Ruth; Schuchman, Edward H.


    Herein we report the mechanism of human acid ceramidase (AC; N-acylsphingosine deacylase) cleavage and activation. A highly purified, recombinant human AC precursor underwent self-cleavage into α and β subunits, similar to other members of the N-terminal nucleophile hydrolase superfamily. This reaction proceeded with first order kinetics, characteristic of self-cleavage. AC self-cleavage occurred most rapidly at acidic pH, but also at neutral pH. Site-directed mutagene...

  8. Multiple biological activities of human recombinant interleukin 1.

    Dinarello, C A; Cannon, J. G.; Mier, J W; Bernheim, H. A.; LoPreste, G; Lynn, D L; Love, R N; Webb, A C; Auron, P. E.; Reuben, R C


    Complementary DNA coding for human monocyte interleukin 1 (IL-1), pI 7 form, was expressed in Escherichia coli. During purification, IL-1 activity on murine T cells was associated with the recombinant protein. Homogeneous human recombinant IL-1 (hrIL-1) was tested in several assays to demonstrate the immunological and inflammatory properties attributed to this molecule. hrIL-1 induced proliferative responses in a cloned murine T cell in the presence of suboptimal concentrations of mitogen, wh...

  9. Human receptor activation by aroclor 1260, a polychlorinated biphenyl mixture.

    Wahlang, Banrida; Falkner, K Cameron; Clair, Heather B; Al-Eryani, Laila; Prough, Russell A; States, J Christopher; Coslo, Denise M; Omiecinski, Curtis J; Cave, Matthew C


    Polychlorinated biphenyls (PCBs) are persistent environmental toxicants, present in 100% of U.S. adults and dose-dependently associated with obesity and non-alcoholic fatty liver disease (NAFLD). PCBs are predicted to interact with receptors previously implicated in xenobiotic/energy metabolism and NAFLD. These receptors include the aryl hydrocarbon receptor (AhR), pregnane xenobiotic receptor (PXR), constitutive androstane receptor (CAR), peroxisome proliferator-activated receptors (PPARs), liver-X-receptor (LXRα), and farnesoid-X-receptor (FXR). This study evaluates Aroclor 1260, a PCB mixture with congener composition mimicking that of human adipose tissue, and selected congeners, as potential ligands for these receptors utilizing human hepatoma-derived (HepG2) and primate-derived (COS-1) cell lines, and primary human hepatocytes. Aroclor 1260 (20 μg/ml) activated AhR, and PCB 126, a minor component, was a potent inducer. Aroclor 1260 activated PXR in a simple concentration-dependent manner at concentrations ≥10 μg/ml. Among the congeners tested, PCBs 138, 149, 151, 174, 183, 187, and 196 activated PXR. Aroclor 1260 activated CAR2 and CAR3 variants at lower concentrations and antagonize CAR2 activation by the CAR agonist, CITCO, at higher concentrations (≥20 μg/ml). Additionally, Aroclor 1260 induced CYP2B6 in primary hepatocytes. At subtoxic doses, Aroclor 1260 did not activate LXR or FXR and had no effect on LXR- or FXR-dependent induction by the agonists T0901317 or GW4064, respectively. Aroclor 1260 (20 μg/ml) suppressed PPARα activation by the agonist nafenopin, although none of the congeners tested demonstrated significant inhibition. The results suggest that Aroclor 1260 is a human AhR, PXR and CAR3 agonist, a mixed agonist/antagonist for CAR2, and an antagonist for human PPARα. PMID:24812009

  10. The United Nations Human Space Technology Initiative (HSTI): Science Activities

    Niu, A; Haubold, H J; Doi, T


    The United Nations Human Space Technology Initiative (HSTI) aims at promoting international cooperation in human spaceflight and space exploration-related activities; creating awareness among countries on the benefits of utilizing human space technology and its applications; and building capacity in microgravity education and research. HSTI has been conducting various scientific activities to promote microgravity education and research. The primary science activity is called 'Zero-gravity Instrument Distribution Project', in which one-axis clinostats will be distributed worldwide. The distribution project will provide unique opportunities for students and researchers to observe the growth of indigenous plants in their countries in a simulated microgravity condition and is expected to create a huge dataset of plant species with their responses to gravity.

  11. Identification of a cell-penetrating peptide domain from human beta-defensin 3 and characterization of its anti-inflammatory activity

    Lee JY


    Full Text Available Jue Yeon Lee,1,* Jin Sook Suh,2,* Jung Min Kim,1 Jeong Hwa Kim,1 Hyun Jung Park,1 Yoon Jeong Park,1,2 Chong Pyoung Chung1 1Central Research Institute, Nano Intelligent Biomedical Engineering Corporation (NIBEC, Chungcheongbuk-do, Republic of Korea; 2Dental Regenerative Biotechnology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea *These authors contributed equally to this work Abstract: Human beta-defensins (hBDs are crucial factors of intrinsic immunity that function in the immunologic response to a variety of invading enveloped viruses, bacteria, and fungi. hBDs can cause membrane depolarization and cell lysis due to their highly cationic nature. These molecules participate in antimicrobial defenses and the control of adaptive and innate immunity in every mammalian species and are produced by various cell types. The C-terminal 15-mer peptide within hBD3, designated as hBD3-3, was selected for study due to its cell- and skin-penetrating activity, which can induce anti-inflammatory activity in lipopolysaccharide-treated RAW 264.7 macrophages. hBD3-3 penetrated both the outer membrane of the cells and mouse skin within a short treatment period. Two other peptide fragments showed poorer penetration activity compared to hBD3-3. hBD3-3 inhibited the lipopolysaccharide-induced production of inducible nitric oxide synthase, nitric oxide, and secretory cytokines, such as interleukin-6 and tumor necrosis factor in a concentration-dependent manner. Moreover, hBD3-3 reduced the interstitial infiltration of polymorphonuclear leukocytes in a lung inflammation model. Further investigation also revealed that hBD3-3 downregulated nuclear factor kappa B-dependent inflammation by directly suppressing the degradation of phosphorylated-IκBα and by downregulating active nuclear factor kappa B p65. Our findings indicate that hBD3-3 may be conjugated with drugs of interest to ensure their proper translocation to

  12. Protein composition of catalytically active human telomerase from immortal cells

    Cohen, Scott B; Graham, Mark E; Lovrecz, George O;


    Telomerase is a ribonucleoprotein enzyme complex that adds 5'-TTAGGG-3' repeats onto the ends of human chromosomes, providing a telomere maintenance mechanism for approximately 90% of human cancers. We have purified human telomerase approximately 10(8)-fold, with the final elution dependent on the...... enzyme's ability to catalyze nucleotide addition onto a DNA oligonucleotide of telomeric sequence, thereby providing specificity for catalytically active telomerase. Mass spectrometric sequencing of the protein components and molecular size determination indicated an enzyme composition of two molecules...... each of telomerase reverse transcriptase, telomerase RNA, and dyskerin....

  13. CRISPR RNA-guided activation of endogenous human genes

    Maeder, Morgan L.; Linder, Samantha J; Cascio, Vincent M.; Fu, Yanfang; Ho, Quan H; Joung, J Keith


    Catalytically inactive CRISPR-associated 9 nuclease (dCas9) can be directed by short guide RNAs (gRNAs) to repress endogenous genes in bacteria and human cells. Here we show that a dCas9-VP64 transcriptional activation domain fusion protein can be directed by single or multiple gRNAs to increase expression of specific endogenous human genes. These results provide an important proof-of-principle that CRISPR-Cas systems can be used to target heterologous effector domains in human cells.

  14. Bacterial expression of human kynurenine 3-monooxygenase: solubility, activity, purification.

    Wilson, K; Mole, D J; Binnie, M; Homer, N Z M; Zheng, X; Yard, B A; Iredale, J P; Auer, M; Webster, S P


    Kynurenine 3-monooxygenase (KMO) is an enzyme central to the kynurenine pathway of tryptophan metabolism. KMO has been implicated as a therapeutic target in several disease states, including Huntington's disease. Recombinant human KMO protein production is challenging due to the presence of transmembrane domains, which localise KMO to the outer mitochondrial membrane and render KMO insoluble in many in vitro expression systems. Efficient bacterial expression of human KMO would accelerate drug development of KMO inhibitors but until now this has not been achieved. Here we report the first successful bacterial (Escherichia coli) expression of active FLAG™-tagged human KMO enzyme expressed in the soluble fraction and progress towards its purification. PMID:24316190

  15. Fish oil supplementation alters levels of lipid mediators of inflammation in microenvironment of acute human wounds

    McDaniel, Jodi C.; Massey, Karen; Nicolaou, Anna


    Chronic wounds often result from prolonged inflammation involving excessive polymorphonuclear leukocyte activity. Studies show that the ω-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish oils generate bioactive lipid mediators that reduce inflammation and polymorphonuclear leukocyte recruitment in numerous inflammatory disease models. This study’s purpose was to test the hypotheses that boosting plasma levels of EPA and DHA with oral suppl...

  16. Impact of the human activities on the climate

    In the framework of the A2 scenario of the GIEC, the possible impacts on the french climate, of the human activities are examined. It seems that the human activities imposed and will be able to impose a faster change of the climate than the natural changes. For the hundred coming years the main characteristics could be: an increase of the temperature, an increase of the rains in winter and a decrease in summer, a decrease of the water in soils expected in freezing areas and an increase of the drought periods. (A.L.B.)

  17. Chloride transport in human fibroblasts is activated by hypotonic shock

    Incubation of human skin fibroblasts in hypotonic media induced the activation of 36Cl- efflux which was roughly proportional to the decrease in the osmolality of the media. The efflux of 36Cl- was insensitive to DIDS plus furosemide and inhibited by addition of a Cl- channel blocker such as 5-nitro-2-(3-phenyl propylamino) benzoic acid (NPPB). We propose that a conductive pathway for Cl- transport, almost silent in isotonic conditions, is activated by exposing human fibroblasts to hypotonic shock, this conclusion being supported by evidence that also 36Cl- influx was enhanced by hypotonic medium

  18. Modulation of ROS production in human leukocytes by ganglioside micelles

    M. Gavella


    Full Text Available Recent studies have reported that exogenous gangliosides, the sialic acid-containing glycosphingolipids, are able to modulate many cellular functions. We examined the effect of micelles of mono- and trisialoganglioside GM1 and GT1b on the production of reactive oxygen species by stimulated human polymorphonuclear neutrophils using different spectroscopic methods. The results indicated that exogenous gangliosides did not influence extracellular superoxide anion (O2.- generation by polymorphonuclear neutrophils activated by receptor-dependent formyl-methionyl-leucyl-phenylalanine. However, when neutrophils were stimulated by receptor-bypassing phorbol 12-myristate 13-acetate (PMA, gangliosides above their critical micellar concentrations prolonged the lag time preceding the production in a concentration-dependent way, without affecting total extracellular O2.- generation detected by superoxide dismutase-inhibitable cytochrome c reduction. The effect of ganglioside GT1b (100 µM on the increase in lag time was shown to be significant by means of both superoxide dismutase-inhibitable cytochrome c reduction assay and electron paramagnetic resonance spectroscopy (P < 0.0001 and P < 0.005, respectively. The observed phenomena can be attributed to the ability of ganglioside micelles attached to the cell surface to slow down PMA uptake, thus increasing the diffusion barrier and consequently delaying membrane events responsible for PMA-stimulated O2.- production.

  19. Tuberculin skin test and interferon-gamma release assay values are associated with antimicrobial peptides expression in  polymorphonuclear cells during latent tuberculous infection

    Julio E Castañeda-Delgado


    Full Text Available It has been reported that patients with progressive tuberculosis (TB express abundant amounts of the antimicrobial peptides (AMPs cathelicidin (LL-37 and human neutrophil peptide-1 (HNP-1 in circulating cells, whereas latent TB infected donors showed no differences when compared with purified protein derivative (PPD and QuantiFERON®-TB Gold (QFT-healthy individuals. The aim of this study was to determine whether LL-37 and HNP-1 production correlates with higher tuberculin skin test (TST and QFT values in TB household contacts. Twenty-six TB household contact individuals between 26-58 years old TST and QFT positive with at last two years of latent TB infection were recruited. AMPs production by polymorphonuclear cells was determined by flow cytometry and correlation between TST and QFT values was analysed. Our results showed that there is a positive correlation between levels of HNP-1 and LL-37 production with reactivity to TST and/or QFT levels. This preliminary study suggests the potential use of the expression levels of these peptides as biomarkers for progression in latent infected individuals.

  20. Implications of Special Regions to Conducting Human Activities on Mars

    Rummel, J. D.; Barlow, N. G.; Beaty, D. W.; Jones, M. A.; Hipkin, V.


    A MEPAG Science Analysis Group (SAG) has undertaken an analysis of Special Regions (SR) on Mars—regions where indigenous martian life could exist or where Earth microbes, if introduced, could survive and reproduce. The SR-SAG has considered the impact of SR on future human activities on the martian surface. Human exploration requires access to in-situ resources, some of which may be found in SR. Water and oxygen for ISRU are found in the atmosphere, surface/near-surface ice, hydrated minerals, and perchlorates. Water ice is most abundant at latitudes poleward of ~60 degrees, but polar darkness, cold temperatures, and CO2 degassing present hazards to human operations in these regions. Accessible water is more limited toward the equator, though temperature and solar energy conditions become more favorable. The possible presence of liquid water in Recurring Slope Lineae and active gullies leads to their treatment as SR. Fuel for surface operations and propellants for crew ascent could be manufactured from the martian atmosphere and surface materials, but dust in the atmosphere may clog ISRU equipment and perchlorate is toxic to humans. Power may be produced from solar or nuclear energy. Reliance on solar energy limits operations to the equatorial zone where easily accessible ice resources are limited. Nuclear power allows surface operations at a range of latitudes, but waste heat could convert some non-SR into SR. Radiation shielding is necessary for long-term human operations on Mars and could be obtained by deposition of regolith or by water storage in tanks or as ice around habitats, or the use of underground habitats. SR-SAG recognizes that it will be impossible for all human-associated processes and operations to be conducted within entirely closed systems. Protocols need to be established so (1) human missions to Mars will not contaminate SR nor be contaminated by materials from them, and (2) human activities on Mars will avoid converting areas into SR.

  1. Magnetogastrographic detection of gastric electrical response activity in humans

    The detection and characterization of gastric electrical activity has important clinical applications, including the early diagnosis of gastric diseases in humans. In mammals, this phenomenon has two important features: an electrical control activity (ECA) that manifests itself as an electric slow wave (with a frequency of 3 cycles per minute in humans) and an electrical response activity (ERA) that is characterized by spiking potentials during the plateau phase of the ECA. Whereas the ECA has been recorded in humans both invasively and non-invasively (magnetogastrography-MGG), the ERA has never been detected non-invasively in humans before. In this paper, we report on our progress towards the non-invasive detection of ERA from the human stomach using a procedure that involves the application of principal component analysis to MGG recordings, which were acquired in our case from ten normal human patients using a Superconducting QUantum Interference Device (SQUID) magnetometer. Both pre- and post-prandial recordings were acquired for each patient and 20 min of recordings (10 min of pre-prandial and 10 min of post-prandial data) were analysed for each patient. The mean percentage of ECA slow waves that were found to exhibit spikes of suspected ERA origin was 41% and 61% for pre- and post-prandial recordings, respectively, implying a 47% ERA increase post-prandially (P < 0.0001 at a 95% confidence level). The detection of ERA in humans is highly encouraging and points to the possible use of non-invasive ERA recordings as a valuable tool for the study of human gastric disorders

  2. Accumulation of polymorphonuclear leukocytes in reperfused ischemic canine myocardium: relation with tissue viability assessed by fluorine-18-2-deoxyglucose uptake

    Polymorphonuclear leukocytes may participate in reperfusion injury. Whether leukocytes affect viable or only irreversibly injured tissue is not known. Therefore, we assessed the accumulation of 111In-labeled leukocytes in tissue samples characterized as either ischemic but viable or necrotic by metabolic, histochemical, and ultrastructural criteria. Six open-chest dogs received left anterior descending coronary occlusion for 2 hr followed by 4 hr reperfusion. Myocardial blood flow was determined by microspheres and autologous 111In-labeled leukocytes were injected intravenously. Fluorine-18-2-deoxyglucose, a tracer of exogenous glucose utilization, was injected 3 hr after reperfusion. The dogs were killed 4 hr after reperfusion. The risk and the necrotic regions were assessed following in vivo dye injection and postmortem tetrazolium staining. Myocardial samples were obtained in the ischemic but viable, necrotic and normal zones, and counted for 111In and 18F activity. Compared to normal, leukocytes were entrapped in necrotic regions (111In activity: 207 +/- 73%) where glucose uptake was decreased (26 +/- 15%). A persistent glucose uptake, marker of viability, was mainly seen in risk region (135 +/- 85%) where leukocytes accumulation was moderate in comparison to normal zone (146 +/- 44%). Thus, the glucose uptake observed in viable tissue is mainly related to myocytes metabolism and not to leukocytes metabolism

  3. Characterization of acid sphingomyelinase activity in human cerebrospinal fluid.

    Christiane Mühle

    Full Text Available BACKGROUND: As a key enzyme in sphingolipid metabolism, acid sphingomyelinase (ASM is involved in the regulation of cell fate and signaling via hydrolysis of sphingomyelin to form ceramide. While increased activity of the lysosomal form has been associated with various pathological conditions, there are few studies on secretory ASM limited only to cell models, plasma or serum. METHODS: An optimized assay based on a fluorescent substrate was applied to measure the ASM activity in cerebrospinal fluid (CSF collected from mice and from 42 patients who were classified as controls based on normal routine CSF values. RESULTS: We have detected ASM activity in human CSF, established a sensitive quantitative assay and characterized the enzyme's properties. The enzyme resembles plasmatic ASM including protein stability and Zn(2+-dependence but the assays differ considerably in the optimal detergent concentration. Significantly increased activities in the CSF of ASM transgenic mice and undetectable levels in ASM knock-out mice prove that the measured ASM activity originates from the ASM-encoding gene SMPD1. CSF localized ASM activities were comparable to corresponding serum ASM levels at their respective optimal reaction conditions, but no correlation was observed. The large variance in ASM activity was independent of sex, age or analyzed routine CSF parameters. CONCLUSIONS: Human and mouse CSF contain detectable levels of secretory ASM, which are unrelated to serum ASM activities. Further investigations in humans and in animal models will help to elucidate the role of this enzyme in human disease and to assess its value as a potential biomarker for disease type, severity, progress or therapeutic success.

  4. Human ECG signal parameters estimation during controlled physical activity

    Maciejewski, Marcin; Surtel, Wojciech; Dzida, Grzegorz


    ECG signal parameters are commonly used indicators of human health condition. In most cases the patient should remain stationary during the examination to decrease the influence of muscle artifacts. During physical activity, the noise level increases significantly. The ECG signals were acquired during controlled physical activity on a stationary bicycle and during rest. Afterwards, the signals were processed using a method based on Pan-Tompkins algorithms to estimate their parameters and to test the method.

  5. Antibacterial activity of mangrove leaf extracts against human pathogens

    G. Sahoo; N. S. S. Mulla; Ansari, Z.A.; Mohandass, C.


    The antibacterial activity of leaf extract of mangroves, namely, Rhizophora mucronata, Sonneratia alba and Exoecaria agallocha from Chorao island, Goa was investigated against human bacterial pathogens Staphylococcus aureus, Streptococcus sp., Salmonella typhi, Proteus vulgaris and Proteus mirabilis. As compared to aqueous, ethanol extract showed broad-spectrum activity. The multidrug-resistant (MDR) bacteria Salmonella typhi was inhibited by the ethanol extract of S. alba leaf whereas the ot...

  6. Recognition of Human Activities Using Continuous Autoencoders with Wearable Sensors

    Lukun Wang


    This paper provides an approach for recognizing human activities with wearable sensors. The continuous autoencoder (CAE) as a novel stochastic neural network model is proposed which improves the ability of model continuous data. CAE adds Gaussian random units into the improved sigmoid activation function to extract the features of nonlinear data. In order to shorten the training time, we propose a new fast stochastic gradient descent (FSGD) algorithm to update the gradients of CAE. The recons...

  7. Human brain activity with functional NIR optical imager

    Luo, Qingming


    In this paper we reviewed the applications of functional near infrared optical imager in human brain activity. Optical imaging results of brain activity, including memory for new association, emotional thinking, mental arithmetic, pattern recognition ' where's Waldo?, occipital cortex in visual stimulation, and motor cortex in finger tapping, are demonstrated. It is shown that the NIR optical method opens up new fields of study of the human population, in adults under conditions of simulated or real stress that may have important effects upon functional performance. It makes practical and affordable for large populations the complex technology of measuring brain function. It is portable and low cost. In cognitive tasks subjects could report orally. The temporal resolution could be millisecond or less in theory. NIR method will have good prospects in exploring human brain secret.

  8. The interaction between ICT and human activity-travel behavior

    Kwan, M.P.; Dijst, M.J.; Schwanen, T.


    The interaction between information and communication technologies (ICT) and human activity-travel behavior has been an important theme in transportation research in recent years. Researchers have recognized that an increase in the use of ICT may lead to changes in the location, timing and duration

  9. Activation of the insular cortex during dynamic exercise in humans

    Williamson, James; Nobrega, A C; McColl, R;


    role as a site for regulation of autonomic activity. 2. Eight subjects were studied during voluntary active cycling and passively induced cycling. Additionally, four of the subjects underwent passive movement combined with electrical stimulation of the legs. 3. Increases in regional cerebral blood flow...... during active, but not passive cycling. There were no significant changes in rCBF for the right insula. Also, the magnitude of rCBF increase for leg primary motor areas was significantly greater for both active cycling and passive cycling combined with electrical stimulation compared with passive cycling...... alone. 5. These findings provide the first evidence of insular activation during dynamic exercise in humans, suggesting that the left insular cortex may serve as a site for cortical regulation of cardiac autonomic (parasympathetic) activity. Additionally, findings during passive cycling with electrical...

  10. Corticospinal contribution to arm muscle activity during human walking

    Barthélemy, Dorothy; Nielsen, Jens Bo


    When we walk, our arm muscles show rhythmic activity suggesting that the central nervous system contributes to the swing of the arms. The purpose of the present study was to investigate whether corticospinal drive plays a role in the control of arm muscle activity during human walking. Motor evoked...... potentials (MEPs) elicited in the posterior deltoid muscle (PD) by transcranial magnetic stimulation (TMS) were modulated during the gait cycle in parallel with changes in the background EMG activity. There was no significant difference in the size of the MEPs at a comparable level of background EMG during...... inhibitory interneurones, the suppression is in all likelihood caused by removal of a corticospinal contribution to the ongoing EMG activity. The data thus suggest that the motor cortex makes an active contribution, through the corticospinal tract, to the ongoing EMG activity in arm muscles during walking....