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Sample records for lymphocyte granule tryptases

  1. Human mast cell tryptase in biology and medicine.

    Science.gov (United States)

    Vitte, Joana

    2015-01-01

    The most abundant prestored enzyme of human mast cell secretory granules is the serine-protease tryptase. In humans, there are four tryptase isoforms, but only two of them, namely the alpha and beta tryptases, are known as medically important. Low levels of continuous tryptase production as an immature monomer makes up the major part of the baseline serum tryptase levels, while transient release of mature tetrameric tryptase upon mast cell degranulation accounts for the anaphylactic rise of serum tryptase levels. Serum tryptase determination contributes to the diagnosis or monitoring of mast cell disorders including mast cell activation - induced anaphylaxis, mastocytosis and a number of myeloproliferative conditions with mast cell lineage involvement. Baseline serum tryptase levels are predictive of the severity risk in some allergic conditions.

  2. Expression and characterization of recombinant gamma-tryptase.

    Science.gov (United States)

    Yuan, Jing; Beltman, Jeri; Gjerstad, Erik; Nguyen, Margaret T; Sampang, Jun; Chan, Hedy; Janc, James W; Clark, James M

    2006-09-01

    Tryptases are trypsin-like serine proteases whose expression is restricted to cells of hematopoietic origin, notably mast cells. gamma-Tryptase, a recently described member of the family also known as transmembrane tryptase (TMT), is a membrane-bound serine protease found in the secretory granules or on the surface of degranulated mast cells. The 321 amino acid protein contains an 18 amino acid propeptide linked to the catalytic domain (cd), followed by a single-span transmembrane domain. gamma-Tryptase is distinguished from other human mast cell tryptases by the presence of two unique cysteine residues, Cys(26) and Cys(145), that are predicted to form an intra-molecular disulfide bond linking the propeptide to the catalytic domain to form the mature, membrane-anchored two-chain enzyme. We expressed gamma-tryptase as either a soluble, single-chain enzyme with a C-terminal His tag (cd gamma-tryptase) or as a soluble pseudozymogen activated by enterokinase cleavage to form a two-chain protein with an N-terminal His tag (tc gamma-tryptase). Both recombinant proteins were expressed at high levels in Pichia pastoris and purified by affinity chromatography. The two forms of gamma-tryptase exhibit comparable kinetic parameters, indicating the propeptide does not contribute significantly to the substrate affinity or activity of the protease. Substrate and inhibitor library screening indicate that gamma-tryptase possesses a substrate preference and inhibitor profile distinct from that of beta-tryptase. Although the role of gamma-tryptase in mast cell function is unknown, our results suggest that it is likely to be distinct from that of beta-tryptase.

  3. The nature of the refractive granules in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Knowlton, N.P. Jr.; Hempelmann, L.H. [Los Alamos Scientific Lab., NM (United States)

    1949-04-19

    The number of refractive bodies in human lymphocytes increases in persons chronically exposed to low level doses of ionizing radiation. The observations of the optical properties, the histochemistry, and the method of formation of these bodies are described.

  4. Serglycin determines secretory granule repertoire and regulates natural killer cell and cytotoxic T lymphocyte cytotoxicity.

    Science.gov (United States)

    Sutton, Vivien R; Brennan, Amelia J; Ellis, Sarah; Danne, Jill; Thia, Kevin; Jenkins, Misty R; Voskoboinik, Ilia; Pejler, Gunnar; Johnstone, Ricky W; Andrews, Daniel M; Trapani, Joseph A

    2016-03-01

    The anionic proteoglycan serglycin is a major constituent of secretory granules in cytotoxic T lymphocyte (CTL)/natural killer (NK) cells, and is proposed to promote the safe storage of the mostly cationic granule toxins, granzymes and perforin. Despite the extensive defects of mast cell function reported in serglycin gene-disrupted mice, no comprehensive study of physiologically relevant CTL/NK cell populations has been reported. We show that the cytotoxicity of serglycin-deficient CTL and NK cells is severely compromised but can be partly compensated in both cell types when they become activated. Reduced intracellular granzyme B levels were noted, particularly in CD27(+) CD11b(+) mature NK cells, whereas serglycin(-/-) TCR-transgenic (OTI) CD8 T cells also had reduced perforin stores. Culture supernatants from serglycin(-/-) OTI T cells and interleukin-2-activated NK contained increased granzyme B, linking reduced storage with heightened export. By contrast, granzyme A was not significantly reduced in cells lacking serglycin, indicating differentially regulated trafficking and/or storage for the two granzymes. A quantitative analysis of different granule classes by transmission electronmicroscopy showed a selective loss of dense-core granules in serglycin(-/-) CD8(+) CTLs, although other granule types were maintained quantitatively. The findings of the present study show that serglycin plays a critical role in the maturation of dense-core cytotoxic granules in cytotoxic lymphocytes and the trafficking and storage of perforin and granzyme B, whereas granzyme A is unaffected. The skewed retention of cytotoxic effector molecules markedly reduces CTL/NK cell cytotoxicity, although this is partly compensated for as a result of activating the cells by physiological means.

  5. Inhibition of tryptase and chymase induced nucleated cell infiltration by proteinase inhibitors

    Institute of Scientific and Technical Information of China (English)

    Shao-heng HE; Han-qiu CHEN; Jian ZHENG

    2004-01-01

    AIM: To investigate the ability of proteinase inhibitors to modulate nucleated cell infiltration into the peritoneum of mice induced by tryptase and chymase. METHODS: Human lung tryptase and skin chymase were purified by a similar procedure involving high salt extraction, heparin agarose affinity chromatography followed by S-200 Sephacryl gel filtration chromatography. The actions of proteinase inhibitors on tryptase and chymase induced nucleated cell accumulation were examined with a mouse peritoneum model. RESULTS: A selective chymase inhibitor Z-Ile-GluPro-Phe-CO2Me (ZIGPPF) was able to inhibit approximately 90% neutrophil, 73% eosinophil, 87% lymphocyte and 60% macrophage accumulation induced by chymase at 16 h following injection. Soy bean trypsin inhibitor (SBTI), chymostatin, and α1-antitrypsin showed slightly less potency than ZIGPPF in inhibition of the actions of chymase. While all tryptase inhibitors tested were able to inhibit neutrophil, eosinophil, and macrophage accumulation provoked by tryptase at 16 h following injection, only leupeptin, APC366, and aprotinin were capable of inhibiting tryptase induced lymphocyte accumulation. The inhibitiors of tryptase tested were also able to inhibit tryptase induced neutrophil and eosinophil accumulation at 6 h following injection. When being injected alone, all inhibitors of chymase and tryptase at the concentrations tested by themselves had no significant effect on the accumulation of nucleated cells in the peritoneum of mice at both 6 h and 16 h. CONCLUSION: Proteinase inhibitors significantly inhibited tryptase and chymase-induced nucleated cell accumulation in vivo, and therefore they are likely to be developed as a novel class of anti-inflammatory drugs.

  6. Syntaxin 8 is required for efficient lytic granule trafficking in cytotoxic T lymphocytes.

    Science.gov (United States)

    Bhat, Shruthi S; Friedmann, Kim S; Knörck, Arne; Hoxha, Cora; Leidinger, Petra; Backes, Christina; Meese, Eckart; Keller, Andreas; Rettig, Jens; Hoth, Markus; Qu, Bin; Schwarz, Eva C

    2016-07-01

    Cytotoxic T lymphocytes (CTL) eliminate pathogen-infected and cancerous cells mainly by polarized secretion of lytic granules (LG, containing cytotoxic molecules like perforin and granzymes) at the immunological synapse (IS). Members of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) family are involved in trafficking (generation, transport and fusion) of vesicles at the IS. Syntaxin 8 (Stx8) is expressed in LG and colocalizes with the T cell receptor (TCR) upon IS formation. Here, we report the significance of Stx8 for human CTL cytotoxicity. We found that Stx8 mostly localized in late, recycling endosomal and lysosomal compartments with little expression in early endosomal compartments. Down-regulation of Stx8 by siRNA resulted in reduced cytotoxicity. We found that following perforin release of the pre-existing pool upon target cell contact, Stx8 down-regulated CTL regenerate perforin pools less efficiently and thus release less perforin compared to control CTL. CD107a degranulation, real-time and end-point population cytotoxicity assays, and high resolution microscopy support our conclusion that Stx8 is required for proper and timely sorting and trafficking of cytotoxic molecules to functional LG through the endosomal pathway in human CTL.

  7. The combined action of mast cell chymase, tryptase and carboxypeptidase A3 protects against melanoma colonization of the lung

    DEFF Research Database (Denmark)

    Grujic, Mirjana; Paivandy, Aida; Gustafson, Ann-Marie

    2017-01-01

    Mast cell secretory granules are densely packed with various bioactive mediators including proteases of chymase, tryptase and CPA3 type. Previous studies have indicated that mast cells can affect the outcome of melanoma but the contribution of the mast cell granule proteases to such effects has n...

  8. Serum tryptase levels in adverse drug reactions.

    Science.gov (United States)

    Ordoqui, E; Zubeldia, J M; Aranzábal, A; Rubio, M; Herrero, T; Tornero, P; Rodríguez, V M; Prieto, A; Baeza, M L

    1997-11-01

    We evaluated the usefulness of individual tryptase levels and variations after adverse drug reactions in 64 patients. Our aim was to find a tool for the diagnosis of drug allergy. Thirty-seven subjects were confirmed to have drug allergy, 12 had nonsteroidal anti-inflammatory drug (NSAID) reactions, five had negative controlled drug challenges (NAAR), and 10 had symptoms after placebo intake (PLA). Serum tryptase levels greatly increased after anaphylactic shocks (2242%) and anaphylaxis (710.5%). Patients with allergic urticaria and those with idiosyncratic responses to acetylsalicylic acid (ASA) exhibited a small increase in serum tryptase (49.5% and 38.2%, respectively). In the other two groups (NAAR and PLA), no variation in this serum protease was observed. The time of appearance of the serum tryptase peak differed considerably among patients with similar clinical reactions (from 30 min to 6 h) and was independent of the latent period, severity of symptoms, or the amount of tryptase released. We conclude that serum tryptase determinations are helpful in the diagnosis of anaphylactic shock and anaphylaxis, but serial measurements may be needed to confirm mast-cell participation in milder reactions.

  9. Endocytosis of Cytotoxic Granules Is Essential for Multiple Killing of Target Cells by T Lymphocytes.

    Science.gov (United States)

    Chang, Hsin-Fang; Bzeih, Hawraa; Schirra, Claudia; Chitirala, Praneeth; Halimani, Mahantappa; Cordat, Emmanuelle; Krause, Elmar; Rettig, Jens; Pattu, Varsha

    2016-09-15

    CTLs are serial killers that kill multiple target cells via exocytosis of cytotoxic granules (CGs). CG exocytosis is tightly regulated and has been investigated in great detail; however, whether CG proteins are endocytosed following exocytosis and contribute to serial killing remains unknown. By using primary CTLs derived from a knock-in mouse of the CG membrane protein Synaptobrevin2, we show that CGs are endocytosed in a clathrin- and dynamin-dependent manner. Following acidification, endocytosed CGs are recycled through early and late, but not recycling endosomes. CGs are refilled with granzyme B at the late endosome stage and polarize to subsequent synapses formed between the CTL and new target cells. Importantly, inhibiting CG endocytosis in CTLs results in a significant reduction of their cytotoxic activity. Thus, our data demonstrate that continuous endocytosis of CG membrane proteins is a prerequisite for efficient serial killing of CTLs and identify key events in this process.

  10. Liver tryptase-positive mast cells and fibrosis in children with hepatic echinococcosis

    Directory of Open Access Journals (Sweden)

    Gulubova Maya

    2005-01-01

    Full Text Available The hepatic echinococcosis in children is a serious surgical problem. The aim of this study is to investigate the participation of mast cells in liver inflammatory reactions triggered by echinococcal cysts. Liver biopsy samples were collected from the tissue surrounding the cysts from 16 sick children (11 boys and 5 girls in the course of abdominal surgery and from 5 controls. Light and ultrastructural immunocytochemistry was performed using monoclonal antibody against tryptase. Light microscopical immunocytochemistry revealed abundance of tryptase-positive (MCT mast cells in the capsules of the cysts (43.58 cells/mm2. There were also observed greatly increased numbers of mast cells in portal tracts surrounding the cyst, compared to those of control biopsies (26.49 vs. 1.78 cells/mm2, p=0.0009, Mann-Whitney U test. Based on the ultrastructural appearance of tryptase-positive mast cell granules, morphological sings of activation of most of the mast cells were distinguished. In conclusion, we suggest that the accumulated and activated tryptase-positive mast cells in liver tissues surrounding the echinococcal cysts play a crucial role in modulation of the inflammatory liver response and could induce chronic inflammation and fibrogenesis, resulting in serious liver injury such as nonspecific reactive hepatitis.

  11. Effect of general anesthesia and orthopedic surgery on serum tryptase

    DEFF Research Database (Denmark)

    Garvey, Lene H; Bech, Birgitte Louise; Mosbech, Holger

    2010-01-01

    Mast cell tryptase is used clinically in the evaluation of anaphylaxis during anesthesia, because symptoms and signs of anaphylaxis are often masked by the effect of anesthesia. No larger studies have examined whether surgery and anesthesia affect serum tryptase. The aim of this study...... was to investigate the effect of anesthesia and surgery on serum tryptase in the absence of anaphylaxis....

  12. Effect of general anesthesia and orthopedic surgery on serum tryptase

    DEFF Research Database (Denmark)

    Garvey, Lene H; Bech, Birgitte Louise; Mosbech, Holger

    2010-01-01

    Mast cell tryptase is used clinically in the evaluation of anaphylaxis during anesthesia, because symptoms and signs of anaphylaxis are often masked by the effect of anesthesia. No larger studies have examined whether surgery and anesthesia affect serum tryptase. The aim of this study...... was to investigate the effect of anesthesia and surgery on serum tryptase in the absence of anaphylaxis....

  13. Factors influencing serum total tryptase concentrations in a general adult population

    DEFF Research Database (Denmark)

    Gonzalez-Quintela, Arturo; Vizcaino, Luis; Gude, Francisco;

    2010-01-01

    Serum tryptase measurements are increasingly being used in clinical practice. However, there is a paucity of studies focused on factors that influence tryptase concentrations. We investigated the relationships between total tryptase concentrations and age, gender, atopy, alcohol consumption, smok...

  14. Factors influencing serum total tryptase concentrations in a general adult population

    DEFF Research Database (Denmark)

    Gonzalez-Quintela, Arturo; Vizcaino, Luis; Gude, Francisco;

    2010-01-01

    Serum tryptase measurements are increasingly being used in clinical practice. However, there is a paucity of studies focused on factors that influence tryptase concentrations. We investigated the relationships between total tryptase concentrations and age, gender, atopy, alcohol consumption...

  15. Effect of general anesthesia and orthopedic surgery on serum tryptase

    DEFF Research Database (Denmark)

    Garvey, Lene H; Bech, Birgitte Louise; Mosbech, Holger;

    2010-01-01

    Mast cell tryptase is used clinically in the evaluation of anaphylaxis during anesthesia, because symptoms and signs of anaphylaxis are often masked by the effect of anesthesia. No larger studies have examined whether surgery and anesthesia affect serum tryptase. The aim of this study was to inve...

  16. Raised tryptase without anaphylaxis or mastocytosis: heterophilic antibody interference in the serum tryptase assay.

    Science.gov (United States)

    Sargur, R; Cowley, D; Murng, S; Wild, G; Green, K; Shrimpton, A; Egner, W

    2011-03-01

    Mast cell tryptase (MCT) is a key diagnostic test for mastocytosis and anaphylaxis. High serum tryptase levels are also one of the risk factors for adverse reaction in venom immunotherapy, yet occasional patients are seen with raised levels in the absence of either diagnosis. False positive results can be due to assay interference by heterophilic antibodies such as rheumatoid factor (RF) and human anti-mouse antibodies (HAMA). We therefore investigated heterophilic antibody interference by rheumatoid factor activity and HAMA as a cause of raised MCT results in the Phadia tryptase assay. Serum samples from 83 patients were assayed for MCT and rheumatoid factor before and after the use of heterophilic antibody blocking tubes (HBT). Samples with more than 17% reduction in MCT with detectable RF were then assayed for HAMA. Fourteen (17%) of the 83 samples with positive RF showed a >17% decrease in mast cell tryptase after HBT blocking. Post-HBT, eight of 14 (57%) reverted from elevated to normal range values with falls of up to 98%. RF levels were also decreased significantly (up to 75%). Only one of the 83 tested was apparently affected by HAMA in the absence of detectable IgM RF. In conclusion, any suspicious MCT result should be checked for heterophilic antibodies to evaluate possible interference. False positive MCT levels can be caused by rheumatoid factor. We suggest a strategy for identifying assay interference, and show that it is essential to incorporate this caveat into guidance for interpretation of MCT results. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.

  17. Serum concentrations of mast cell tryptase are reduced in heavy drinkers

    DEFF Research Database (Denmark)

    Beceiro, Carmen; Campos, Joaquín; Valcarcel, Maria-Angeles;

    2015-01-01

    BACKGROUND: Baseline serum tryptase concentrations are commonly used in clinical practice as a marker of the body's mast cell burden. This study aimed to investigate serum tryptase concentrations in heavy drinkers. METHODS: Serum tryptase concentrations were determined in 126 heavy drinkers (75...... test positivity) was not associated with serum tryptase concentrations in heavy drinkers. CONCLUSIONS: Serum concentrations of mast cell tryptase are lower in heavy drinkers than in healthy controls....

  18. Inhibition of tryptase release from human colon mast cells by protease inhibitors

    Institute of Scientific and Technical Information of China (English)

    Shao-Heng He; Hua Xie

    2004-01-01

    AIM: To investigate the ability of protease inhibitors to modulate tryptase release from human colon mast cells.METHODS: Enzymatically dispersed cells from human colon were challenged with anti-IgE or calcium ionophore A23187 in the absence or presence of tryptase and chymase inhibitors,and tryptase release was determined.RESULTS: IgE dependent tryptase release from colon mast cells was inhibited by up to approximately 37%, 40% and 36.6% by chymase inhibitors Z-Ile-Glu-Pro-Phe-CO2Me (ZIGPFM), N-tosyl-L-phenylalanyl-chloromethyl ketone (TPCK), and α1-antitrypsin, respectively. Similarly, the inhibitors of tryptase leupeptin, N-tosyl-L-lysine chloromethyl ketone (TLCK) and lactoferrin were also able to inhibit anti-IgE induced tryptase release by a maximum of 39.4%,47.6% and 36.6%, respectively. The inhibitory actions of chymase inhibitors, but not tryptase inhibitors on colon mast cells were enhanced by preincubation of them with cells for 20 min before challenged with anti-IgE. At a concentration of 10 μg/mL, protamine was able to inhibit anti-IgE and calcium ionophore induced tryptase release. However, at 100 μg/mL, protamine elevated tryptase levels in supernatants.A specific inhibitor of aminopeptidase amastatin had no effect on anti-IgE induced tryptase release. The significant inhibition of calcium ionophore induced tryptase release was also observed with the inhibitors of tryptase and chymase examined. The inhibitors tested by themselves did not stimulate tryptase release from colon mast cells.CONCLUSION: It was demonstrated for the first time that both tryptase and chymase inhibitors could inhibit IgE dependent and calcium ionophore induced tryptase release from dispersed colon mast cells in a concentration dependent of manner, which suggest that they are likely to be developed as a novel class of anti-inflammatory drugs to treat chronic of colitis in man.

  19. Ctr2 Regulates Mast Cell Maturation by Affecting the Storage and Expression of Tryptase and Proteoglycans.

    Science.gov (United States)

    Öhrvik, Helena; Logeman, Brandon; Noguchi, Glyn; Eriksson, Inger; Kjellén, Lena; Thiele, Dennis J; Pejler, Gunnar

    2015-10-15

    Copper (Cu) is essential for multiple cellular functions. Cellular uptake of Cu(+) is carried out by the Ctr1 high-affinity Cu transporter. The mobilization of endosomal Cu pools is regulated by a protein structurally similar to Ctr1, called Ctr2. It was recently shown that ablation of Ctr2 caused an increase in the concentration of Cu localized to endolysosomes. However, the biological significance of excess endolysosomal Cu accumulation has not been assessed. In this study, we addressed this issue by investigating the impact of Ctr2 deficiency on mast cells, a cell type unusually rich in endolysosomal organelles (secretory granules). We show that Ctr2(-/-) mast cells have increased intracellular Cu concentrations and that the absence of Ctr2 results in increased metachromatic staining, the latter indicating an impact of Ctr2 on the storage of proteoglycans in the secretory granules. In agreement with this, the absence of Ctr2 caused a skewed ratio between proteoglycans of heparin and chondroitin sulfate type, with increased amounts of heparin accompanied by a reduction of chondroitin sulfate. Moreover, transmission electron microscopy analysis revealed a higher number of electron-dense granules in Ctr2(-/-) mast cells than in wild-type cells. The increase in granular staining and heparin content is compatible with an impact of Ctr2 on mast cell maturation and, in support of this, the absence of Ctr2 resulted in markedly increased mRNA expression, storage, and enzymatic activity of tryptase. Taken together, the present study introduces Ctr2 and Cu as novel actors in the regulation of mast cell maturation and granule homeostasis.

  20. RNA granules

    OpenAIRE

    Anderson, Paul; Kedersha, Nancy

    2006-01-01

    Cytoplasmic RNA granules in germ cells (polar and germinal granules), somatic cells (stress granules and processing bodies), and neurons (neuronal granules) have emerged as important players in the posttranscriptional regulation of gene expression. RNA granules contain various ribosomal subunits, translation factors, decay enzymes, helicases, scaffold proteins, and RNA-binding proteins, and they control the localization, stability, and translation of their RNA cargo. We review the relationshi...

  1. The autocrine role of tryptase in pressure overload-induced mast cell activation, chymase release and cardiac fibrosis

    Directory of Open Access Journals (Sweden)

    Jianping Li

    2016-03-01

    Results and conclusion: The results indicate the presence of PAR-2 on MCs and that tryptase inhibition and nedocromil prevented TAC-induced fibrosis and increases in MC density, activation, and chymase release. Tryptase also significantly increased chymase concentration in ventricular slice culture media, which was prevented by the tryptase inhibitor. Hydroxyproline concentration in culture media was significantly increased with tryptase incubation as compared to the control group and the tryptase group incubated with nafamostat mesilate or chymostatin. We conclude that tryptase contributes to TAC-induced cardiac fibrosis primarily via activation of MCs and the amplified release of chymase.

  2. Immunohistochemical identification of mast cells in formaldehyde-fixed tissue using monoclonal antibodies specific for tryptase.

    Science.gov (United States)

    Walls, A F; Jones, D B; Williams, J H; Church, M K; Holgate, S T

    1990-10-01

    An avidin-biotin enhanced immunoperoxidase procedure using monoclonal antibodies (AA1, AA3, and AA5) prepared against human mast cell tryptase resulted in intense staining of mast cells in paraffin-embedded tissue. The distribution of mast cells observed was similar to that seen when adjacent serial sections were stained using a standard procedure with toluidine blue, though the immunoperoxidase technique permitted the identification of significantly more mast cells. With monoclonal antibody AA1, immunostaining was entirely specific for mast cell granules, and there was negligible background staining in a range of tissues including lung, tonsil, colon, gastric mucosa, skin, and pituitary. There was no staining of antibody on basophils or on any other normal blood leukocyte. The technique was effective with tissue fixed in either Carnoy's or neutral buffered formalin, though the internal mast cell structure was better preserved with formaldehyde fixation. The immunoperoxidase staining procedure with monoclonal antibody AA1 is a highly specific and sensitive means for the detection of mast cells in routinely processed tissues.

  3. Determinants of serum tryptase in a general population

    DEFF Research Database (Denmark)

    Fenger, R V; Linneberg, A; Vidal, C;

    2012-01-01

    Recent studies indicate that mast cells are more abundant in the obese state. Total serum tryptase (ST) is a marker of mast cell numbers or activity. Since obesity and asthma have been consistently linked in epidemiological studies, a possible higher mast cell activity in obesity could be a factor...... between the two conditions. The aim of this study was to investigate determinants of ST and whether a potential association between obesity and allergic respiratory disease would be influenced by levels of ST in obese persons....

  4. Novel, potent, selective, and orally bioavailable human betaII-tryptase inhibitors.

    Science.gov (United States)

    Sperandio, David; Tai, Vincent W-F; Lohman, Julia; Hirschbein, Bernie; Mendonca, Rohan; Lee, Chang-Sun; Spencer, Jeffrey R; Janc, James; Nguyen, Margaret; Beltman, Jerlyn; Sprengeler, Paul; Scheerens, Heleen; Lin, Tong; Liu, Liang; Gadre, Ashwini; Kellogg, Alisha; Green, Michael J; McGrath, Mary E

    2006-08-01

    The synthesis of novel [1,2,4]oxadiazoles and their structure-activity relationship (SAR) for the inhibition of tryptase and related serine proteases is presented. Elaboration of the P'-side afforded potent, selective, and orally bioavailable tryptase inhibitors.

  5. Modulation of enzymatic activity of human mast cell tryptase and chymase by protease inhibitors

    Institute of Scientific and Technical Information of China (English)

    HEShao-Heng; CHENPu; CHENHan-Qiu

    2003-01-01

    AIM: To investigate the actions of protease inhibitors on the enzymatic activities of tryptase and chymase in similarexperimental systems. METHODS: Human lung tryptase and human skin chymase were purified by a similarprocedure involving high salt extraction of tryptase, heparin agarose affinity chromatography, and S-200 Sephacrylgel filtration chromatography. Actions of protease inhibitors on tryptase and chymase activities were examined byenzyme assays. RESULTS: The specific activities of tryptase and chymase were 2.1 kU/g protein and 4.9 kU/g protein, respectively. Both preparations showed a single diffuse band on SDS-PAGE. Among non-native proteaseinhibitors, N-(1-hydroxy-2-naphthoyl)-L- arginyl-L-prolinamide hydrochloride (HNAP), leupeptin, antipain,benzamidine, and protamine inhibited more than 90 % enzymatic activity of tryptase, whereas soy bean trypsininhibitor (SBTI), Z-Ile-Glu-Pro-Phe-CO2Me (ZIGPPM) and chymostatin inhibited more than 95 % enzymaticactivity of chymase. Native protease inhibitors α-antitrypsin and secretory leukocyte protease inhibitor (SLPI)inhibited more than 90 % enzymatic activity of chymase, but lactoferrin appeared to enhance chymase enzymaticactivity. All the 3 inhibitors had weak inhibitory actions on tryptase. CONCLUSION: The protease inhibitorstested had relatively good selectivity to either tryptase or chymase.

  6. Diminished reliability of tryptase as risk indicator of mastocytosis in older overweight subjects

    NARCIS (Netherlands)

    Vos, Byrthe J. P. R.; van der Veer, Eveline; van Voorst Vader, Pieter; Mulder, Andre B.; van der Heide, Sicco; Arends, Suzanne; Kluin-Nelemans, Johanna C.; de Monchy, Jan G. R.; van Doormaal, Jasper J.; Oude Elberink, Joanne

    2015-01-01

    Background: Currently, measurement of serum tryptase level is the most commonly used test to estimate the need for bone marrow biopsy in patients suspected to have indolent systemic mastocytosis (ISM). Yet tryptase levels do not solely reflect the mast cell load and can be elevated by overweight, ol

  7. Genetic factors account for most of the variation in serum tryptase-a twin study

    DEFF Research Database (Denmark)

    Sverrild, A.; van der Sluis, S.; Kyvik, K. O.;

    2013-01-01

    Background: Mast cells are involved in a number of diseases, including inflammatory diseases such as asthma. Tryptase is a known marker of mast cell burden and activity. However, little is known about the genetic influence on serum tryptase variation. Also, only few and conflicting data exist......) in a sample of Danish twins. Methods: A total of 575 twins underwent a skin prick test and had lung function, AHR to methacholine, exhaled nitric oxide and serum tryptase measured. Multiple regression and variance components models (using the statistical package SOLAR) were computed. Results: Serum tryptase...... values were available in 569 subjects. Intraclass correlations of serum tryptase in monozygotic and dizygotic twin pairs were 0.84 and 0.42 (P

  8. 肥大细胞类胰蛋白酶与支气管哮喘%Mast cell tryptase and asthma

    Institute of Scientific and Technical Information of China (English)

    牛青霞; 何韶衡

    2003-01-01

    As an important mediator of allergic inflammation, mast cell tryptase is involved in the in-duction of hypersensitivity, infiltration of inflammatory cells and tissue remodeling in respiratory tract. The ef-fects of tryptase inhibitors on the actions of tryptase show further the potential of tryptase in the pathogenesis of asthma and its inhibitors in the treatment of asthma.

  9. Inhibition of tryptase release from human colon mast cells by histamine receptor antagonists.

    Science.gov (United States)

    He, Shao-Heng; Xie, Hua; Fu, Yi-Ling

    2005-03-01

    The main objective of this study was to investigate the ability of histamine receptor antagonists to modulate tryptase release from human colon mast cells induced by histamine. Enzymatically dispersed cells from human colon were challenged with histamine in the absence or presence of the histamine receptor antagonists, and the tryptase release was determined. It was found that histamine induced tryptase release from colon mast cells was inhibited by up to approximately 61.5% and 24% by the H1 histamine receptor antagonist terfenadine and the H2 histamine receptor antagonist cimetidine, respectively, when histamine and its antagonists were added to cells at the same time. The H3 histamine receptor antagonist clobenpropit had no effect on histamine induced tryptase release from colon mast cells at all concentrations tested. Preincubation of terfenadine, cimetidine or clobenpropit with cells for 20 minutes before challenging with histamine did not enhance the ability of these antihistamines to inhibit histamine induced tryptase release. Apart from terfenadine at 100 microg/ml, the antagonists themselves did not stimulate tryptase release from colon mast cells following both 15 minutes and 35 minutes incubation periods. It was concluded that H1 and H2 histamine receptor antagonists were able to inhibit histamine induced tryptase release from colon mast cells. This not only added some new data to our hypothesis of self-amplification mechanisms of mast cell degranulation, but also suggested that combining these two types of antihistamine drugs could be useful for the treatment of inflammatory bowel disease (IBD).

  10. Modulation of tryptase secretion from human colon mast cells by histamine

    Institute of Scientific and Technical Information of China (English)

    Shao-Heng He; Hua Xie

    2004-01-01

    AIM: To investigate the ability of histamine to modulate tryptase release from human colon mast cells and the potential mechanisms.METHODS: Enzymatically dispersed cells from human colons were challenged with histamine, anti-IgE or calcium ionophore A23187 (CI), and the cell supernatants after challenge were collected. Tryptase release was determined with a sandwich ELISA procedure.able to induce a "bell" shape dose related release of tryptase from colon mast cells. The maximum release of tryptase was approximately 3.5 fold more than spontaneous release. As little as 10 ng/mL histamine showed a similar potency to 10 μg/mL anti-IgE in induction of tryptase release. Histamine induced release of tryptase initiated at 10 s when histamine (100 ng/mL) was added to cells, gradually increased thereafter, and completed at 5 min, Both pertussis toxin or metabolic inhibitors were able to inhibit histamine induced tryptase release. When histamine and anti-IgE were added to colon mast cells at the same time, the quantity of tryptase released was similar to that induced by anti-IgE alone. The similar results were observed with CI. However, when various concentrations of histamine were incubated with cells for 20 min before adding anti-IgE or CI, the quantity of tryptase released was similar to that was induced by histamine alone.CONCLUSION: Histamine is a potent activator of human colon mast cells, which represents a novel and pivotal selfamplification mechanism of mast cell degranulation.

  11. Mast cell tryptase stimulates myoblast proliferation; a mechanism relying on protease-activated receptor-2 and cyclooxygenase-2

    OpenAIRE

    Côté Claude H; Tremblay Marie-Hélène; Duchesne Elise

    2011-01-01

    Abstract Background Mast cells contribute to tissue repair in fibrous tissues by stimulating proliferation of fibroblasts through the release of tryptase which activates protease-activated receptor-2 (PAR-2). The possibility that a tryptase/PAR-2 signaling pathway exists in skeletal muscle cell has never been investigated. The aim of this study was to evaluate whether tryptase can stimulate myoblast proliferation and determine the downstream cascade. Methods Proliferation of L6 rat skeletal m...

  12. Alpha tryptase allele of Tryptase 1 (TPSAB1) gene associated with Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) in Vietnam and Philippines.

    Science.gov (United States)

    Velasquez, Clara Vasquez; Roman, Arthur Dessi; Lan, Nguyen Thi Phuong; Huy, Nguyen Tien; Mercado, Edelwisa Segubre; Espino, Fe Esperanza; Perez, Ma Lucila M; Huong, Vu Thi Que; Thuy, Tran Thi; Tham, Vo Dinh; Nga, Cao Thi Phi; Ha, Tran Thi Ngoc; Bilar, Josie M; Bajaro, Jemimah Dawn P; Baello, Benilda Q; Kikuchi, Mihoko; Yasunami, Michio; Morita, Kouichi; Watanabe, Naohiro; Karbwang, Juntra; Hirayama, Kenji

    2015-05-01

    We previously reported, significantly higher levels of Chymase and Tryptase in early stage plasma of DSS patients prior to the occurrence of shock suggesting a possible role of mast cells in dengue pathogenesis. To further investigate, we analyzed CMA1 promoter SNP (rs1800875) and TPSAB1 gene alleles, which encode the Human Chymase and α- and β- tryptase 1 enzymes respectively, for susceptibility to Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) in patients from hospitals in Vietnam (Ho Chi Minh City and Vinh Long) and the Philippines. While the CMA1 promoter SNP (rs1800875) was not associated with DHF/DSS, the homozygous form of α-tryptase allele was associated with DSS patients in Vinh Long and the Philippines (OR=3.52, pDSS were combined in Vinh Long (OR=1.5, p=0.034) and the Philippines (OR=2.36, p=0.0004); in Ho Chi Minh City when DHF and DSS were combine an association was observed, but it was not statistically significant (OR=1.5, p=0.0505). Therefore, the α-tryptase might have a possible effect on the susceptibility to severe form of Dengue infection.

  13. Tryptase-PAR2 axis in experimental autoimmune prostatitis, a model for chronic pelvic pain syndrome.

    Science.gov (United States)

    Roman, Kenny; Done, Joseph D; Schaeffer, Anthony J; Murphy, Stephen F; Thumbikat, Praveen

    2014-07-01

    Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) affects up to 15% of the male population and is characterized by pelvic pain. Mast cells are implicated in the murine experimental autoimmune prostatitis (EAP) model as key to chronic pelvic pain development. The mast cell mediator tryptase-β and its cognate receptor protease-activated receptor 2 (PAR2) are involved in mediating pain in other visceral disease models. Prostatic secretions and urines from CP/CPPS patients were examined for the presence of mast cell degranulation products. Tryptase-β and PAR2 expression were examined in murine EAP. Pelvic pain and inflammation were assessed in the presence or absence of PAR2 expression and upon PAR2 neutralization. Tryptase-β and carboxypeptidase A3 were elevated in CP/CPPS compared to healthy volunteers. Tryptase-β was capable of inducing pelvic pain and was increased in EAP along with its receptor PAR2. PAR2 was required for the development of chronic pelvic pain in EAP. PAR2 signaling in dorsal root ganglia led to extracellular signal-regulated kinase (ERK)1/2 phosphorylation and calcium influx. PAR2 neutralization using antibodies attenuated chronic pelvic pain in EAP. The tryptase-PAR2 axis is an important mediator of pelvic pain in EAP and may play a role in the pathogenesis of CP/CPPS.

  14. Tryptase - PAR2 axis in Experimental Autoimmune Prostatitis, a model for Chronic Pelvic Pain Syndrome

    Science.gov (United States)

    Roman, Kenny; Done, Joseph D.; Schaeffer, Anthony J.; Murphy, Stephen F.; Thumbikat, Praveen

    2014-01-01

    Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) affects up to 15% of the male population and is characterized by pelvic pain. Mast cells are implicated in the murine experimental autoimmune prostatitis (EAP) model as key to chronic pelvic pain development. The mast cell mediator tryptase-β and its cognate receptor protease-activated receptor 2 (PAR2) are involved in mediating pain in other visceral disease models. Prostatic secretions and urines from CP/CPPS patients were examined for the presence of mast cell degranulation products. Tryptase-β and PAR2 expression were examined in murine experimental autoimmune prostatitis (EAP). Pelvic pain and inflammation were assessed in the presence or absence of PAR2 expression and upon PAR2 neutralization. Tryptase-β and carboxypeptidase A3 were elevated in CP/CPPS compared to healthy volunteers. Tryptase-β was capable of inducing pelvic pain and was increased in EAP along with its receptor PAR2. PAR2 was required for the development of chronic pelvic pain in EAP. PAR2 signaling in dorsal root ganglia lead to ERK1/2 phosphorylation and calcium influx. PAR2 neutralization using antibodies attenuated chronic pelvic pain in EAP. The tryptase-PAR2 axis is an important mediator of pelvic pain in EAP and may play a role in the pathogenesis of CP/CPPS. PMID:24726923

  15. Correlation of IL-18 with Tryptase in Atopic Asthma and Induction of Mast Cell Accumulation by IL-18

    Directory of Open Access Journals (Sweden)

    Junling Wang

    2016-01-01

    Full Text Available Interleukin- (IL- 18 and tryptase were previously reported to relate to asthma, but the correlation between these two potent proinflammatory molecules in asthma and their roles in mast cell accumulation remain uninvestigated. Using flow cytometric analysis technique and ovalbumin- (OVA- sensitized mouse model, it was found that IL-18 and tryptase levels in the plasma of moderate and severe asthma were elevated, and they correlated well with each other. Tryptase and agonist peptides of protease activated receptor- (PAR- 2 induced substantial quantity of IL-18 release. IL-18 and tryptase provoked mast cell accumulation in peritoneum of OVA-sensitized mice. OVA-sensitization increased number of IL-18 receptor (R+ mast cells. IL-18 and tryptase induced dramatic increase in IL-18R+ mast cells and mean fluorescence intensity (MFI of IL-18R on mast cells. Moreover, while IL-18 induced an increase in PAR-2+ mast cells in nonsensitized mice, IL-18 and tryptase provoked increases in IL-4 and thymic stromal lymphopoietin (TSLP in the peritoneum of OVA-sensitized mice. In summary, the correlation between IL-18 and tryptase in plasma of patients with asthma indicates close interactions between them, which should be considered for development of anti-IL-18 and antitryptase therapies. Interactions between IL-18 and tryptase may contribute to mast cell recruitment in asthma.

  16. Induction of Mast Cell Accumulation by Tryptase via a Protease Activated Receptor-2 and ICAM-1 Dependent Mechanism.

    Science.gov (United States)

    Liu, Xin; Wang, Junling; Zhang, Huiyun; Zhan, Mengmeng; Chen, Hanqiu; Fang, Zeman; Xu, Chiyan; Chen, Huifang; He, Shaoheng

    2016-01-01

    Mast cells are primary effector cells of allergy, and recruitment of mast cells in involved tissue is one of the key events in allergic inflammation. Tryptase is the most abundant secretory product of mast cells, but little is known of its influence on mast cell accumulation. Using mouse peritoneal model, cell migration assay, and flow cytometry analysis, we investigated role of tryptase in recruiting mast cells. The results showed that tryptase induced up to 6.7-fold increase in mast cell numbers in mouse peritoneum following injection. Inhibitors of tryptase, an antagonist of PAR-2 FSLLRY-NH2, and pretreatment of mice with anti-ICAM-1, anti-CD11a, and anti-CD18 antibodies dramatically diminished tryptase induced mast cell accumulation. On the other hand, PAR-2 agonist peptides SLIGRL-NH2 and tc-LIGRLO-NH2 provoked mast cell accumulation following injection. These implicate that tryptase induced mast cell accumulation is dependent on its enzymatic activity, activation of PAR-2, and interaction between ICAM-1 and LFA-1. Moreover, induction of trans-endothelium migration of mast cells in vitro indicates that tryptase acts as a chemoattractant. In conclusion, provocation of mast cell accumulation by mast cell tryptase suggests a novel self-amplification mechanism of mast cell accumulation. Mast cell stabilizers as well as PAR-2 antagonist agents may be useful for treatment of allergic reactions.

  17. Design and synthesis of selective keto-1,2,4-oxadiazole-based tryptase inhibitors.

    Science.gov (United States)

    Palmer, James T; Rydzewski, Robert M; Mendonca, Rohan V; Sperandio, David; Spencer, Jeffrey R; Hirschbein, Bernard L; Lohman, Julia; Beltman, Jeri; Nguyen, Margaret; Liu, Liang

    2006-07-01

    Using a scaleable, directed library approach based on orthogonally protected advanced intermediates, we have prepared a series of potent keto-1,2,4-oxadiazoles designed to explore the P(2) binding pocket of human mast cell tryptase, while building in a high degree of selectivity over human trypsin and other serine proteases.

  18. Skin tags: A link between lesional mast cell count/tryptase expression and obesity and dyslipidemia

    Directory of Open Access Journals (Sweden)

    Samar Abdallah M Salem

    2013-01-01

    Full Text Available Background:The etiology of skin tags (STs is not fully understood. A relation to diabetes mellitus and obesity was suggested. Few studies of possible mast cells (MCs involvement were reported. Tyrptase is a mast cell mediator and a potent fibroblast growth factor. It may provide a molecular link between mast cell activation and fibrosis. Aims: The aim was to assess clinical and laboratory findings in patients with STs, and the possible link between obesity, dyslipidemia, and lesional MC count/tryptase expression. Materials and Methods: A total of 20 patients with STs were subjected to clinical examination, estimation of body mass index (BMI, fasting blood glucose (FBG, postprandial blood glucose (PPBG, serum cholesterol and triglycerides, abdominal ultrasound for fatty liver assessment, in addition to study of MCs through staining for MC tryptase in two skin biopsies; lesional and nonlesional (control. Results:All patients showed abnormally high BMI and hypertriglyceridemia, with abnormal sonographic pattern in 15 patients (75%. STs number positively correlated with the age of patients. STs showed significantly higher MC counts and tryptase expression, compared with control skin ( P < 0.001, with no correlation of the STs number or MC count with BMI, FBG, PPBG or serum cholesterol. Obese patients showed a significantly higher MC count than overweight and there was a positive correlation between MC count and serum triglycerides. Axilla and under breast STs showed a higher MC count compared with other sites. Conclusions:STs seem to be related to obesity and hypertriglyceridemia. MCs with their tryptase are possibly involved in pathogenesis of STs. MC count is related to the associated factors; obesity and serum triglycerides. MC tryptase expression is a reliable method for accurate tissue MC counting.

  19. Effect of the house dust mite allergen Der p 1 on tryptase release from human mast cells.

    Science.gov (United States)

    Wang, D Q; Shen, Y Y; Xu, J H; Tang, H

    2016-07-14

    This study aimed to investigate the effects of the house dust mite allergen Der p 1 on the secretion of tryptase from the human mast cell line HMC-1. Flow cytometry was used to determine the expression levels of protease-activated receptor-2 (PAR2) on the surface of HMC-1 cells. HMC-1 cells were treated with Der p 1, SLIGRL-NH2 (PAR2 agonist), LRGILS-NH2 (control peptide for PAR2), or Der p 1 + FSLLRY (PAR2 antagonist), and the tryptase levels were measured using enzyme-linked immunosorbent assay. The biological functions of PAR2 were determined using the calcium green indicator, and intracellular calcium fluorescence intensity in the different groups (Der p 1, SLIGRL-NH2, LRGILS- NH2, Der p 1 + FSLLRY, tryptase, tryptase + FSLLRY, or cell culture medium) was detected by laser scanning confocal microscopy. The mast cells expressed PAR2 receptor on their surfaces. Der p 1 alone induced a significant release of intracellular calcium and tryptase in HMC-1 cells compared with the SLIGRL- NH2 treatment group and the control group. The combination of Der p 1 and FSLLRY partly inhibited intracellular calcium and tryptase release in HMC-1 cells compared with the Der p 1 treatment group. Moreover, tryptase induced a significant release of intracellular calcium in the HMC-1 cells. Der p 1 induced HMC-1 cell degranulation and the release of tryptase by activating the PAR2 receptor on the cell surfaces. Tryptase activated the PAR2 receptor and induced intracellular calcium release from the HMC-1 cells in a positive feedback loop.

  20. Twin screw granulation: steps in granule growth.

    Science.gov (United States)

    Dhenge, Ranjit M; Cartwright, James J; Hounslow, Michael J; Salman, Agba D

    2012-11-15

    The present work focuses on the study of the progression of granules in different compartments along the length of screws in a twin screw granulator (TSG). The effects of varying powder feed rate; liquid to solid ratio and viscosity of granulation liquid on properties of granules was studied. The bigger granules produced at the start of the process were found to change in terms of size, shape and strength along the screw length at all the conditions investigated. The granules became more spherical and their strength increased along the screw length. Tracer granules were also introduced in order to understand the role of kneading and conveying elements in the TSG. The kneading elements promoted consolidation and breakage while the conveying elements led to coalescence, breakage and some consolidation. The results presented here help to provide a qualitative and quantitative understanding of the twin screw granulation process.

  1. Mast cells and acute coronary syndromes: relationship between serum tryptase, clinical outcome and severity of coronary artery disease

    Science.gov (United States)

    Morici, Nuccia; Farioli, Laura; Losappio, Laura Michelina; Colombo, Giulia; Nichelatti, Michele; Preziosi, Donatella; Micarelli, Gianluigi; Oliva, Fabrizio; Giannattasio, Cristina; Klugmann, Silvio; Pastorello, Elide Anna

    2016-01-01

    Objective To assess the relationship between serum tryptase and the occurrence of major cardiovascular and cerebrovascular events (MACCE) at 2-year follow-up in patients admitted with acute coronary syndrome (ACS). To compare serum tryptase to other validated prognostic markers (maximum high-sensitivity troponin (hs-Tn), C reactive protein (CRP) levels at admission, Synergy between percutaneous coronary intervention with Taxus and Cardiac Surgery (SYNTAX) score). Methods We measured serum tryptase at admission in 140 consecutive patients with ACS and in 50 healthy controls. The patients’ follow-up was maintained for 2 years after discharge. The predictive accuracy of serum tryptase for 2-year MACCE was assessed and compared with hs-Tn, CRP and SYNTAX score. Results Serum tryptase levels at admission were significantly higher in patients with ACS compared with the control group (p=0.0351). 2 years after discharge, 28/140 patients (20%) experienced MACCE. Serum tryptase levels, maximum hs-Tn measurements and SYNTAX score were higher in patients who experienced MACCE compared with those without (p<0.0001). Conversely, we found no significant association between MACCE and CRP. The predictive accuracy of serum tryptase for MACCE was set at the cut-off point of 6.7 ng/mL (sensitivity 46%, specificity 84%). Conclusions In patients with ACS, serum tryptase measured during index admission is significantly correlated to the development of MACCE up to 2 years, demonstrating a possible long-term prognostic role of this biomarker. PMID:27752333

  2. Mast cell tryptase stimulates myoblast proliferation; a mechanism relying on protease-activated receptor-2 and cyclooxygenase-2

    Directory of Open Access Journals (Sweden)

    Côté Claude H

    2011-10-01

    Full Text Available Abstract Background Mast cells contribute to tissue repair in fibrous tissues by stimulating proliferation of fibroblasts through the release of tryptase which activates protease-activated receptor-2 (PAR-2. The possibility that a tryptase/PAR-2 signaling pathway exists in skeletal muscle cell has never been investigated. The aim of this study was to evaluate whether tryptase can stimulate myoblast proliferation and determine the downstream cascade. Methods Proliferation of L6 rat skeletal myoblasts stimulated with PAR-2 agonists (tryptase, trypsin and SLIGKV was assessed. The specificity of the tryptase effect was evaluated with a specific inhibitor, APC-366. Western blot analyses were used to evaluate the expression and functionality of PAR-2 receptor and to assess the expression of COX-2. COX-2 activity was evaluated with a commercial activity assay kit and by measurement of PGF2α production. Proliferation assays were also performed in presence of different prostaglandins (PGs. Results Tryptase increased L6 myoblast proliferation by 35% above control group and this effect was completely inhibited by APC-366. We confirmed the expression of PAR-2 receptor in vivo in skeletal muscle cells and in satellite cells and in vitro in L6 cells, where PAR-2 was found to be functional. Trypsin and SLIGKV increased L6 cells proliferation by 76% and 26% above control, respectively. COX-2 activity was increased following stimulation with PAR-2 agonist but its expression remained unchanged. Inhibition of COX-2 activity by NS-398 abolished the stimulation of cell proliferation induced by tryptase and trypsin. Finally, 15-deoxy-Δ-12,14-prostaglandin J2 (15Δ-PGJ2, a product of COX-2-derived prostaglandin D2, stimulated myoblast proliferation, but not PGE2 and PGF2α. Conclusions Taken together, our data show that tryptase can stimulate myoblast proliferation and this effect is part of a signaling cascade dependent on PAR-2 activation and on the downstream

  3. Trypsin, Tryptase, and Thrombin Polarize Macrophages towards a Pro-Fibrotic M2a Phenotype.

    Directory of Open Access Journals (Sweden)

    Michael J V White

    Full Text Available For both wound healing and the formation of a fibrotic lesion, circulating monocytes enter the tissue and differentiate into fibroblast-like cells called fibrocytes and pro-fibrotic M2a macrophages, which together with fibroblasts form scar tissue. Monocytes can also differentiate into classically activated M1 macrophages and alternatively activated M2 macrophages. The proteases thrombin, which is activated during blood clotting, and tryptase, which is released by activated mast cells, potentiate fibroblast proliferation and fibrocyte differentiation, but their effect on macrophages is unknown. Here we report that thrombin, tryptase, and the protease trypsin bias human macrophage differentiation towards a pro-fibrotic M2a phenotype expressing high levels of galectin-3 from unpolarized monocytes, or from M1 and M2 macrophages, and that these effects appear to operate through protease-activated receptors. These results suggest that proteases can initiate scar tissue formation by affecting fibroblasts, fibrocytes, and macrophages.

  4. A short-term model of COPD identifies a role for mast cell tryptase

    Science.gov (United States)

    Beckett, Emma L.; Stevens, Richard L.; Jarnicki, Andrew G.; Kim, Richard Y.; Hanish, Irwan; Hansbro, Nicole G.; Deane, Andrew; Keely, Simon; Horvat, Jay C.; Yang, Ming; Oliver, Brian G.; van Rooijen, Nico; Inman, Mark D.; Adachi, Roberto; Soberman, Roy J.; Hamadi, Sahar; Wark, Peter A.; Foster, Paul S.; Hansbro, Philip M.

    2013-01-01

    Background Cigarette smoke-induced chronic obstructive pulmonary disease (COPD) is a life-threatening inflammatory disorder of the lung. The development of effective therapies for COPD has been hampered by the lack of an animal model that mimics the human disease in a short time-frame. Objectives To create an early onset mouse model of cigarette smoke-induced COPD that develops the hallmark features of the human condition in a short time-frame. To use this model to better understand pathogenesis and the roles of macrophages and mast cells (MCs) in COPD. Methods Tightly controlled amounts of cigarette smoke were delivered to the airways of mice, and the development of the pathological features of COPD was assessed. The roles of macrophages and MC tryptase in pathogenesis were evaluated using depletion and in vitro studies and MC protease-6 deficient mice. Results After just 8 weeks of smoke exposure, wild-type mice developed chronic inflammation, mucus hypersecretion, airway remodeling, emphysema, and reduced lung function. These characteristic features of COPD were glucocorticoid-resistant and did not spontaneously resolve. Systemic effects on skeletal muscle and the heart, and increased susceptibility to respiratory infections also were observed. Macrophages and tryptase-expressing MCs were required for the development of COPD. Recombinant MC tryptase induced pro-inflammatory responses from cultured macrophages. Conclusion A short-term mouse model of cigarette smoke-induced COPD was developed in which the characteristic features of the disease were induced more rapidly than existing models. The model can be used to better understand COPD pathogenesis, and we show a requirement for macrophages and tryptase-expressing MCs. PMID:23380220

  5. Quantitative analysis of tryptase- and chymase-containing mast cells in eosinophilic conditions of cats.

    Science.gov (United States)

    Noli, C; Welle, M; Scarampella, F; Abramo, F

    2003-03-01

    The presence and density of tryptase-positive/chymase-positive mast cells (MCs) (MC(TC)), chymase-positive/tryptase-negative MCs (MCC), and tryptase-positive/chymase-negative MCs (MC(T)) in lesional skin from cats with eosinophilic conditions were investigated. Skin biopsy specimens from eight cats with eosinophilic plaque (three cats), eosinophilic granuloma (two cats), and eosinophilic dermatitis (three cats) were studied. Toluidine blue staining and a double-enzyme-immunohistochemical staining technique were performed to determine MC density and MC subtypes, respectively. MC density varied from 170.3 to 503 cells/mm2 (mean value of 314.9 cells/mm2). In the superficial dermis, 5.9% of the MC belonged to the MC(T), 12.8% to the MC(C), and 81.2% to the MC(TC) subtype. In the deep dermis, 12.8% belonged to the MC(T), 12.8% to the MC(C), and 73.8% to the MC(TC) subtype. It is the first time that MC(C) have been identified. The double-labeling procedure proved to be a reliable tool for identifying simultaneously the presence of MC subtypes in feline skin.

  6. Proliferative action of mast-cell tryptase is mediated by PAR2, COX2, prostaglandins, and PPARγ: Possible relevance to human fibrotic disorders

    OpenAIRE

    Frungieri, Mónica B; Weidinger, Stephan; Meineke, Viktor; Köhn, Frank M; Mayerhofer, Artur

    2002-01-01

    Mast-cell products can stimulate fibroblast proliferation, implying that these cells are key players in fibrosis. One mast-cell product, the serine protease tryptase, is known to activate protease-activated receptor 2 (PAR2) and cause proliferation of fibroblasts. We found that recombinant tryptase, human mast-cell (HMC-1) supernatant, which contains tryptase, and the PAR2-activating peptide SLIGKV exert fibroproliferative actions in human fibroblasts. Here we report insights into this action...

  7. Induction of tryptase and histmine release from human colon mast cells by IgE dependent or independent mechanisms

    Institute of Scientific and Technical Information of China (English)

    Shao-Heng He; Hua Xie; Yong-Song He

    2004-01-01

    AIM: To investigate the tryptase and histamine release ability of human colon mast cells upon IgE dependent or independent activation and the potential mechanisms.METHODS: Enzymatically dispersed cells from human colons were challenged with anti-IgE or calcium ionophore A23187, and the cell supernatants after challenge were collected. Both concentration dependent and time course studies with anti-IgE or calcium ionophore A23187 were performed. Tryptase release was determined with a sandwich ELISA procedure and histamine release was measured usina a glass fibre-based fluorometric assay.RESULTS: Both anti-IgE and calcium ionophore were able to induce dose dependent release of histamine from colon mast cells with up to approximately 60% and 25% net histamine release being achieved with 1 μg/mL calcium ionophore and 10 μg/mL anti-IgE, respectively. Dose dependent release of tryptase was also observed with up to approximately 19 ng/mL and 21 ng/mL release of tryptase being achieved with 10 μg/mL anti-IgE and 1 μg/mL calcium ionophore, respectively. Time course study revealed that both tryptase and histamine release from colon mast cells stimulated by anti-IgE initiated within 10 sec and reached their maximum release at 6 min following challenge. Pretreatment of cells with metabolic inhibitors abolished the actions of anti-IgE as well as calcium ionophore. Tryptase and histamine release, particularly that induced by calcium ionophore was inhibited by pretreatment of cells with pertussis toxin.CONCLUSION: Both anti-IgE and calcium ionophore are able to induce significant release of tryptase and histamine from colon mast cells, indicating that this cell type is likely to contribute to the pathogenesis of colitis and other mast cell associated intestinal diseases.

  8. A brief exposure to tryptase or thrombin potentiates fibrocyte differentiation in the presence of serum or serum amyloid p.

    Science.gov (United States)

    White, Michael J V; Galvis-Carvajal, Elkin; Gomer, Richard H

    2015-01-01

    A key question in both wound healing and fibrosis is the trigger for the initial formation of scar tissue. To help form scar tissue, circulating monocytes enter the tissue and differentiate into fibroblast-like cells called fibrocytes, but fibrocyte differentiation is strongly inhibited by the plasma protein serum amyloid P (SAP), and healthy tissues contain very few fibrocytes. In wounds and fibrotic lesions, mast cells degranulate to release tryptase, and thrombin mediates blood clotting in early wounds. Tryptase and thrombin are upregulated in wound healing and fibrotic lesions, and inhibition of these proteases attenuates fibrosis. We report that tryptase and thrombin potentiate human fibrocyte differentiation at biologically relevant concentrations and exposure times, even in the presence of concentrations of serum and SAP that normally completely inhibit fibrocyte differentiation. Fibrocyte potentiation by thrombin and tryptase is mediated by protease-activated receptors 1 and 2, respectively. Together, these results suggest that tryptase and thrombin may be an initial trigger to override SAP inhibition of fibrocyte differentiation to initiate scar tissue formation.

  9. Elevated Serum Tryptase and Endothelin in Patients with ST Segment Elevation Myocardial Infarction: Preliminary Report

    Directory of Open Access Journals (Sweden)

    Lukasz Lewicki

    2015-01-01

    Full Text Available An inflammatory response plays a crucial role in myocardial damage after an acute myocardial infarction. Objectives. To measure serum concentrations of several mediators in patients with an acute myocardial infarction (STEMI and to assess their potential relationship with a risk of coronary instability. Patients and Methods. The 33 patients with STEMI and 19 healthy volunteers were analyzed. The clinical data were obtained; as well serum concentrations of tryptase, endothelin (ET-1, angiogenin, soluble c-kit, and PDGF were measured. Results. Patients with STEMI had higher serum tryptase and ET-1 than healthy volunteers (2,5 ± 0,4 ng/mL versus 1,1 ± 0,4 ng/mL and 0,7 ± 0,1 ng/mL versus 0,3 ± 0,1 ng/mL, resp.. Subjects with significant lesion in left anterior descending artery (LAD had lower serum ET-1 compared to those with normal LAD (0,6 ± 0,2 pg/mL versus 0,9 ± 0,4 pg/mL. Patients with three-vessel coronary artery disease (CAD had higher level of soluble c-kit compared to those with one- or two-vessel CAD: 19,9 ± 24,1 ng/mL versus 5,6 ± 1,9 ng/mL. Conclusions. Elevated serum tryptase and ET-1 may be markers of increased coronary instability; some cytokines may be related to the extension of CAD.

  10. Granulation of fine powder

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ching-Fong

    2016-08-09

    A mixture of fine powder including thorium oxide was converted to granulated powder by forming a first-green-body and heat treating the first-green-body at a high temperature to strengthen the first-green-body followed by granulation by crushing or milling the heat-treated first-green-body. The granulated powder was achieved by screening through a combination of sieves to achieve the desired granule size distribution. The granulated powder relies on the thermal bonding to maintain its shape and structure. The granulated powder contains no organic binder and can be stored in a radioactive or other extreme environment. The granulated powder was pressed and sintered to form a dense compact with a higher density and more uniform pore size distribution.

  11. Up-regulation of interleukin-8 expressions induced by mast cell tryptase via protease activated receptor-2 in endothelial cell line

    Institute of Scientific and Technical Information of China (English)

    LU Chao; ZHAO Feng-di; LI Xiao-bo; YIN Lian-hua

    2005-01-01

    Background Protease activated receptor-2 is cleaved and activated by trypsin or mast cell tryptase and may play an important role in inflammation. However, it is unknown whetehr PAR-2 can mediate tryptase-induced inflammatory reaction. This study was conduct to investigate wheter PAR-2 could be the activated by mast cell tryptase and medicated the tryptase induced interleukin-8 expression in endothelial cells.Methods Protease activated receptor-2 expression was found in endothelial cell lines ECV304 cell by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Interleukin-8 stimulated by purified human mast cell tryptase was determined by RT-PCR and enzyme linked immunosorbent assay (ELISA). Data were analysed by the S-N-K one-way ANOVA test.Results The present study shows that mRNA and protein of protease activated receptor-2 could be expressed in ECV304 cells, and tryptase upregulated the expression levels of both interleukin-8 mRNA and protein. The increased expression of interleukin-8 was inhibited by an antiprotease activated receptor-2 monoclonal antibody, SAM11. An additional band was observed by Western blotting after the incubation of ECV304 cells with tryptase for 2 hours, which suggested that protease activated receptor-2 was activated. Conclusion Protease activated receptor-2 can mediate the mast cell tryptase stimulated expression of interleukin-8 in ECV304 cell.

  12. ROLE OF SERUM EOSINOPHILIC CATIONIC PROTEIN AND TRYPTASE IN MYELOPROLIFERATIVE AND LYMPHOPROLIFERATIVE DISORDERS

    Directory of Open Access Journals (Sweden)

    L. S. Komarova

    2008-01-01

    Full Text Available Abstract. A role of intracellular proteins of eosinophils and mast cells remains unclear in the patients with hematological neoplasia. There is a substantial evidence that eosinophils possess some common mechanisms of cooperation with mast cells. Therapeutic interventions into key events controlling eosinophil migration may be a leading factor in treatment of hypereosinophylic states in onco-hematological disorders. Due to unknown functions of eosinophils in majority of eosinophilia-associated diseases, it would be useful to establish an algorithm of accurate diagnostics in the patients with eosinophilia, in order to choose more effective treatment in future.We studied serum levels of secretable eosinophil and mast cells proteins in oncohematological patients with increased eosinophil counts. The aim of our study was to test a significance of quantitative assay for tryptase and ECP in the patients with myelo- and lymphoproliferative diseases. The study group included thirty-eight patients with oncohematological diseases, accompanied by a marked eosinophilia (> 0.4 x 109/L. Eighteen patients with bronchial asthma (BA, and eight cases of solid tumors comprised a reference group for polyclonal eosinophilia. The levels of ECP and tryptase were measured in blood serum using a commercial fluoroimmunoenzyme assay («Pharmacia», Uppsala, Sweden. Total ECP levels were markedly increased in general group with hematological malignancies (p < 0.03, , and in cases of chronic GvHD (p < 0.03, and in a sub-group with lymphoproliferative disorders (р = 0.007 as compared to the group of non-hematological diseases.Serum levels of tryptase were significantly increased in the patients with chronic GvHD after allo-HSCT and lymphoproliferative diseases, as compared to the group of patients with solid tumors (р = 0.03, as well in GvHD compared with lymphoproliferative disorders (р < 0.05.A direct correlation was found between serum ECP levels and absolute

  13. Association of Transient Dermal Mastocytosis and Elevated Plasma Tryptase Levels with Development of Adverse Reactions after Treatment of Onchocerciasis with Ivermectin

    National Research Council Canada - National Science Library

    Philip J. Cooper; Lawrence B. Schwartz; Anne-Marie Irani; Kwablah Awadzi; Ronald H. Guderian; Thomas B. Nutman

    2002-01-01

    To investigate the role of mast cells in treatment-associated adverse reactions in patients with onchocerciasis, changes in plasma tryptase levels and skin mast cell counts were examined in 2 groups...

  14. Correlations Between the Density of Tryptase Positive Mast Cells (DMCT and that of New Blood Vessels (CD105+ in Patients with Gastric Cancer

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    Micu Gianina Viorica

    2016-06-01

    Full Text Available Mast cells proteases, tryptase and chymase are directly involved in the growth and progression of solid tumors due to their important role in tumor angiogenesis. We examined the density of tryptase positive mast cells and the mean density of new blood vessels in gastric malignant tumors of patients with and without Helicobacter pylori infection, using immunohistochemical staining for tryptase (for mast cells and CD 105 (for new vessels. Tryptase and CD 105 expression was detected in gastrectomy specimens. In this study, mast cell density correlates with angiogenesis and the growth and progression of gastric cancer. It also shows that the participation of Helicobacter pylori infection in the growth and progress of gastric neoplasia is due to an increase of peritumoral angiogenesis, with subsequent local and distant tumor spread and perivascular growth, but without perineural and nodal involvement.

  15. Mast Cell Tryptase Reduces Junctional Adhesion Molecule-A (JAM-A) Expression in Intestinal Epithelial Cells: Implications for the Mechanisms of Barrier Dysfunction in Irritable Bowel Syndrome.

    LENUS (Irish Health Repository)

    Wilcz-Villega, Ewa M

    2013-07-01

    The objective of this study was to investigate how mast cell tryptase may influence intestinal permeability and tight junction (TJ) proteins in vitro and explore translation to irritable bowel syndrome (IBS).

  16. Mining the granule proteome

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Goetze, Jens P; Johnsen, Anders H

    2015-01-01

    Proteomics of secretory granules is an emerging strategy for identifying secreted proteins, including potentially novel candidate biomarkers and peptide hormones. In addition, proteomics can provide information about the abundance, localization and structure (post-translational modification) of g...

  17. The relation between granule size, granule stickiness, and torque in the high-shear granulation process

    NARCIS (Netherlands)

    Bouwman, A.M.; Henstra, M.J.; Hegge, J.J.M.E.; Zhang, Z.; Ingram, A.; Seville, J.P.K.; Frijlink, H.W.

    2005-01-01

    Purpose. To investigate the background of the observed relationship between measured torque and granule size in high-shear granulation processes. Methods. Torque was measured during the granulation process; the behavior of individual wet granules during compaction was investigated using micromanipul

  18. Altered expression of mast cell chymase and tryptase and of c-Kit in human cutaneous scar tissue.

    Science.gov (United States)

    Hermes, B; Feldmann-Böddeker, I; Welker, P; Algermissen, B; Steckelings, M U; Grabbe, J; Henz, B M

    2000-01-01

    In order to explore a possible involvement of mast cells during human wound healing, we studied sections from scars (4-369-d-old) (N = 20) and normal skin (N = 10) for mast-cell-specific tryptase and chymase by enzyme histochemistry, for the stem cell factor receptor c-Kit and the melanosomal marker TA99 by immunohistochemistry, and for simultaneous c-Kit expression and avidin fluorescence by double staining. Enzyme activities and mRNA expression were also studied in tissue extracts. Chymase-reactive mast cell numbers as well as chymase activity and mRNA expression were reduced in all scars, whereas overall numbers of tryptase-reactive cells did not differ from normal skin, although tryptase activity and mRNA expression were increased in scar extracts. In contrast, numbers of c-Kit positive cells were significantly increased in old scars, and in the mid and lower dermis of all scars. A marked reduction of c-Kit reactivity was noted, however, in avidin-positive dermal mast cells and in epidermal basal cells, despite unchanged numbers of melanosome-positive cells, with an associated overall decrease of c-Kit mRNA in scar extracts. These data thus show that numbers of resident mast cells are very low in human cutaneous scars, suggesting massive mediator release from these cells into fresh wounds. Downregulation of stem cell factor receptors may also prevent these cells from increasing in number even in old scars. Instead, scar tissue is populated by a mast cell subpopulation that is chymase-, avidin-, tryptase +, c-Kit +, reflecting most probably an increased immigration and/or proliferation of immature mast cells and their precursors.

  19. Predomination of IL-17-producing tryptase-positive/chymase-positive mast cells in azoospermic chronic testicular inflammation.

    Science.gov (United States)

    Chen, S-J; Duan, Y-G; Haidl, G; Allam, J-P

    2016-08-01

    Chronic testicular inflammation and infection have been regarded as important factors in the pathogenesis of azoospermia. As key effector cells in innate and adaptive immune system, mast cells (MCs) were observed in inflammation and autoimmune disease. Furthermore, increased expression of tryptase-positive MCs has been reported in testicular disorders associated with male infertility/subfertility. However, little is known about the potential relationship between MCs and chronic testicular inflammation in azoospermic patients. Moreover, the preferential expression of MCs' subtypes in testis of these patients is still far from being understood. Thus, this study aimed to investigate characteristics of testicular MCs as well as their subtypes in azoospermic men with chronic testicular inflammation (AZI, n = 5) by immunohistochemical techniques. Our results showed significant increase of MCs in AZI, and more importantly, considerable numbers of tryptase-positive/chymase-positive MCs could also be demonstrated in AZI, when compared to control groups representing azoospermia without chronic testicular inflammation (AZW, n = 5) and normal spermatogenesis (NT, n = 5) respectively. Most interestingly, immunofluorescence staining revealed autoimmune-associated interleukin (IL)-17-producing MCs in AZI, whereas co-expression of MC markers with tumour necrosis factor (TNF)-α, IL-10 and IL-1β could not be detected. In conclusion, AZI is associated with significant increase of tryptase-positive/chymase-positive MCs expressing IL-17, and these MCs might contribute to the pathogenesis of AZI.

  20. Serum tryptase monitoring in indolent systemic mastocytosis: association with disease features and patient outcome.

    Directory of Open Access Journals (Sweden)

    Almudena Matito

    Full Text Available BACKGROUND: Serum baseline tryptase (sBT is a minor diagnostic criterion for systemic mastocytosis (SM of undetermined prognostic impact. We monitored sBT levels in indolent SM (ISM patients and investigated its utility for predicting disease behaviour and outcome. METHODS: In total 74 adult ISM patients who were followed for ≥48 months and received no cytoreductive therapy were retrospectively studied. Patients were classified according to the pattern of evolution of sBT observed. RESULTS: Overall 16/74 (22% cases had decreasing sBT levels, 48 (65% patients showed increasing sBT levels and 10 (13% patients showed a fluctuating pattern. Patients with significantly increasing sBT (sBT slope ≥0.15 after 48 months of follow-up showed a slightly greater rate of development of diffuse bone sclerosis (13% vs. 2% and hepatomegaly plus splenomegaly (16% vs. 5%, as well as a significantly greater frequency of multilineage vs. mast cells (MC-restricted KIT mutation (p = 0.01 together with a greater frequency of cases with progression of ISM to smouldering and aggressive SM (p = 0.03, and a shorter progression-free survival (p = 0.03. CONCLUSIONS: Monitoring of sBT in ISM patients is closely associated with poor prognosis disease features as well as with disease progression, pointing out the need for a closer follow-up in ISM patients with progressively increasing sBT values.

  1. Effects of RNA interference-induced tryptase down-regulation in P815 cells on IL-6 and TNF-α release of endothelial cells

    Institute of Scientific and Technical Information of China (English)

    Yi-feng JIANG; Feng-di ZHAO; Xiao-bo LI; Yan-xia NING; Xiu-ling ZHI; Rui-zhe QIAN; Lian-hua YIN

    2008-01-01

    Objective:To explore the effects of down-regulated tryptase expression in mast cells on the synthesis and release of interleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α) of vascular endothelial cells.Methods:Tryptase-siRNA (small-interfering RNA)vector was constructed to inhibit tryptase expression in P815 cells.The medium of P815 cells treated by the tryptase-siRNA(RNAi-P815 group)or pure vector(P815 group)was collected and used to culture bEnd.3 cells.The messenger RNAs (mRNAs)of IL-6 and TNF-a in bEnd.3 cells and their protein levels in the medium were measured by reverse transcription polymerase chain reaction(RT-PCR)and enzyme-linked immunosorbent assay(ELISA),respectively.Results:IL-6 and TNF-α mRNAs in bEnd.3 cells cultured in RNAi-P815-conditioned medium decreased significantly compared to those in P815-conditioned medium.Consistently.IL-6 and TNF-α protein levels in the medium of bEnd.3 of RNAi-P815 group were lower than those of P815 group.Conclusion:Reduced tryptase expression significantly inhibited the synthesis and release of IL-6 and TNF-α in vascular endothelial cells.RNA interference targeting tryptasc expression may be a new anti-inflammatory strategy for vascular diseases.

  2. beta-Tryptase up-regulates vascular endothelial growth factor expression via proteinase-activated receptor-2 and mitogen-activated protein kinase pathways in bone marrow stromal cells in acute myeloid leukemia.

    Science.gov (United States)

    Yang, Xiu-Peng; Li, Yan; Wang, Yazhu; Wang, Yue; Wang, Pingping

    2010-08-01

    Tryptases are predominantly mast cell-specific serine proteases with pleiotropic biological activities. Recently, significant amounts of tryptases have been shown to be produced by myeloblasts in certain patients with acute myeloid leukemia (AML), but the function of secreted tryptases in pathological circumstances remains unknown. In this study, we investigated whether beta-tryptase affects the expression of vascular endothelial growth factor (VEGF) in bone marrow stromal cells (BMSCs) in AML. We detected the expression of proteinase-activated receptor-2 (PAR-2) on AML BMSCs and found that beta-tryptase significantly up-regulated VEGF mRNA and protein expression in a dose-dependent manner by real-time PCR, Western blot, and ELISA. Furthermore, beta-tryptase increased ERK1/2 and p38MAPK phosphorylation, and pretreatment with FLLSY-NH(2), PD98059, and SB230580 (PAR-2, ERK1/2, and p38MAPK inhibitors, respectively) inhibited the beta-tryptase-induced production of VEGF. These results suggest that beta-tryptase up-regulates VEGF production in AML BMSCs via the PAR-2, ERK1/2, and p38MAPK signaling pathways.

  3. Molecular Mechanisms of Lymphocyte-Mediated Cytotoxicity

    Institute of Scientific and Technical Information of China (English)

    Zusen Fan; Qixiang Zhang

    2005-01-01

    Granule-mediated cytotoxicity is the major mechanism for lymphocytes to kill viruses, intracellular bacteria and tumors. The cytotoxic granules move to the immunological synapse by exocytosis after recognition of a killer cell.The contents of the granules are delivered into target cells with the help of perforin by endocytosis. A group of serine protease granzymes cleave their critical substrates to initiate DNA damage and cell death. The most abundant granzymes are granzyme A and B. They induce cell death through alternate and nonoverlapping pathways. The substrates and functions of the majority of the orphan granzymes have not yet been identified. It is possible that the diversity of granzymes provides fail-safe mechanisms for killing viruses and tumor cells.

  4. Granulation of increasingly hydrophobic formulations using a twin screw granulator.

    Science.gov (United States)

    Yu, Shen; Reynolds, Gavin K; Huang, Zhenyu; de Matas, Marcel; Salman, Agba D

    2014-11-20

    The application of twin screw granulation in the pharmaceutical industry has generated increasing interest due to its suitability for continuous processing. However, an understanding of the impact of formulation properties such as hydrophobicity on intermediate and finished product quality has not yet been established. Hence, the current work investigated the granulation behaviour of three formulations containing increasing amounts of hydrophobic components using a Consigma™-1 twin screw granulator. Process conditions including powder feed rate, liquid to solid ratio, granulation liquid composition and screw configuration were also evaluated. The size of the wet granules was measured in order to enable exploration of granulation behaviour in isolation without confounding effects from downstream processes such as drying. The experimental observations indicated that the granulation process was not sensitive to the powder feed rate. The hydrophobicity led to heterogeneous liquid distribution and hence a relatively large proportion of un-wetted particles. Increasing numbers of kneading elements led to high shear and prolonged residence time, which acted to enhance the distribution of liquid and feeding materials. The bimodal size distributions considered to be characteristic of twin screw granulation were primarily ascribed to the breakage of relatively large granules by the kneading elements.

  5. Isolation of RNP granules

    DEFF Research Database (Denmark)

    Jønson, Lars; Nielsen, Finn Cilius; Christiansen, Jan

    2011-01-01

    be regarded as a supramolecular assembly of RNA and protein, probably representing several overlapping post-transcriptional operons. The present protocol describes how RNP granules may be isolated by the transgenic expression of a 3X FLAG version of an RNA-binding protein under tetracycline control via...... the tetracycline receptor/operator complex. In this way, inclusion of an appropriate tetracycline concentration ensures expression of the tagged version at the endogenous level, and the 3X FLAG tag is a convenient "handle" for the subsequent immunoprecipitation by immobilized anti-FLAG antibody....

  6. Immunohistochemical quantification of pulmonary mast-cells and post-mortem blood dosages of tryptase and eosinophil cationic protein in 48 heroin-related deaths.

    Science.gov (United States)

    Fineschi, V; Cecchi, R; Centini, F; Reattelli, L P; Turillazzi, E

    2001-09-01

    Recent studies suggest that many fatal heroin overdoses are caused by anaphylactoid reaction. In the present study we measured tryptase and eosinophil cationic protein in post-mortem blood of 48 deaths after heroin injection. We also investigated the presence and pulmonary distribution of mast-cells using specific immunohistochemical antibody for tryptase and morphometric evaluation in those cases of heroin-related deaths. The data were compared with 44 subjects who died following head trauma and to 32 cases of fatal anaphylactic shock. In the heroin-related death cases, the measurements of serum tryptase levels and eosinophil cationic protein dosages resulted in particularly elevated concentrations compared with the trauma cases. Nevertheless, the data that our study supplies by immunohistochemical techniques indicate that when mast-cells count in the lung was determined, no definite pattern was obtained between fatal heroin overdose cases and the control groups. Furthermore, the wide range of morphine concentrations found in post-mortem blood samples suggest that the term 'overdose' is relative and does not sufficiently characterize death associated with heroin addiction. Our study confirms that elevated concentrations of serum tryptase are associated with many heroin-related deaths. At this moment to attribute the cause of these deaths to 'heroin overdose' ignores the likely causal contribution of other possible systemic reactions to the mechanism of death.

  7. Serum Total Tryptase Level Confirms Itself as a More Reliable Marker of Mast Cells Burden in Mast Cell Leukaemia (Aleukaemic Variant

    Directory of Open Access Journals (Sweden)

    P. Savini

    2015-01-01

    Full Text Available Mast cell leukemia (MCL is a very rare form of systemic mastocytosis (SM with a short median survival of 6 months. We describe a case of a 65-year-old woman with aleukaemic variant of MCL with a very high serum total tryptase level of 2255 μg/L at diagnosis, which occurred following an episode of hypotensive shock. She fulfilled the diagnostic criteria of SM, with a bone marrow smear infiltration of 50–60% of atypical mast cells (MCs. She tested negative for the KIT D816V mutation, without any sign of organ damage (no B- or C-findings and only few mediator-related symptoms. She was treated with antihistamine alone and then with imatinib for the appearance of anemia. She maintained stable tryptase level and a very indolent clinical course for twenty-two months; then, she suddenly progressed to acute MCL with a serum tryptase level up to 12960 μg/L. The patient died due to haemorrhagic diathesis twenty-four months after diagnosis. This clinical case maybe represents an example of the chronic form of mast cell leukemia, described as unpredictable disease, in which the serum total tryptase level has confirmed itself as a reliable marker of mast cells burden regardless of the presence of other signs or symptoms.

  8. Granulation techniques and technologies: recent progresses.

    Science.gov (United States)

    Shanmugam, Srinivasan

    2015-01-01

    Granulation, the process of particle enlargement by agglomeration technique, is one of the most significant unit operations in the production of pharmaceutical dosage forms, mostly tablets and capsules. Granulation process transforms fine powders into free-flowing, dust-free granules that are easy to compress. Nevertheless, granulation poses numerous challenges due to high quality requirement of the formed granules in terms of content uniformity and physicochemical properties such as granule size, bulk density, porosity, hardness, moisture, compressibility, etc. together with physical and chemical stability of the drug. Granulation process can be divided into two types: wet granulation that utilize a liquid in the process and dry granulation that requires no liquid. The type of process selection requires thorough knowledge of physicochemical properties of the drug, excipients, required flow and release properties, to name a few. Among currently available technologies, spray drying, roller compaction, high shear mixing, and fluid bed granulation are worth of note. Like any other scientific field, pharmaceutical granulation technology also continues to change, and arrival of novel and innovative technologies are inevitable. This review focuses on the recent progress in the granulation techniques and technologies such as pneumatic dry granulation, reverse wet granulation, steam granulation, moisture-activated dry granulation, thermal adhesion granulation, freeze granulation, and foamed binder or foam granulation. This review gives an overview of these with a short description about each development along with its significance and limitations.

  9. Granule Size Distribution and Porosity of Granule Packing

    Institute of Scientific and Technical Information of China (English)

    DAI Shu-hua; SHEN Feng-man; YU Ai-bing

    2008-01-01

    The granule size distribution and the porosity of the granule packing process were researched.For realizing the optimizing control of the whole sintering production process,researchers must know the factors influencing the granule size distribution and the porosity.Therefore,tests were carried out in the laboratory with regard to the influences of the size and size distribution of raw materials and the total moisture content on the size and size distribution of granule.Moreover,tests for finding out the influences of the moisture content and the granule volume fraction on the porosity were also carried out.The results show that (1) the raw material has little influence on granulation when its size is in the range of 0.51 mm to 1.0 mm;(2) the influence of the material size on granule size plays a dominant role,and in contrast,the moisture content creates a minor effect on granule size;(3) in binary packing system,with the increase in the constituent volume fraction,the porosity initially increases and then decreases,and there is a minimum value on the porosity curve of the binary mixture system;(4) the minimum value of the porosity in binary packing system occurs at different locations for different moisture contents,and this value shifts from right to left on the porosity curve with increasing the moisture content;(5) the addition of small granules to the same size component cannot create a significant influence on the porosity,whereas the addition of large granules to the same system can greatly change the porosity.

  10. Multidimensional modelling of anaerobic granules

    DEFF Research Database (Denmark)

    Picioreanu, C.; Batstone, Damien J.; van Loosdrecht, M.C.M.

    2005-01-01

    . The model uses individual-based representation of biomass particles within the granule (biofilm), and describes spreading by an iterative pushing technique. The overall computational domain consists of one granule, and is divided into a grid with Cartesian coordinates. The number of grid elements does...

  11. Granulated zeolite plant "Alusil", Zvornik

    Directory of Open Access Journals (Sweden)

    Stanković Mirjana S.

    2003-01-01

    Full Text Available The IGPC's Engineering Department designed basic technological and machine projects for a granulated zeolite production plant, on the basis of which a pilot plant with an initial capacity of 5,000 t/y was constructed in 1984, within Birač - Zvornik production complex. The technology in these projects was developed in the laboratories of the IGPC.Several goals were realized by designing a granulated zeolite production plant. This technology is one of the newest state of the art high tech technologies. The product meets all quality demands, as well as environmental regulations, by which granulated zeolite production for various uses was developed. The granulated zeolite production process is fully automatized, and the product has uniform quality. There is no waste material in granulated zeolite production, because all products with unsatisfactory quality are returned to the process. The production process can be controlled manually, which is necessary during start - up, and repairs.

  12. Moluo Yangping Granule (

    Institute of Scientific and Technical Information of China (English)

    LI; En-fu

    2001-01-01

    Peptic ulcer is a common and frequently encountered disease. H2 receptor blocker and several other drugs have been used in treating peptic ulcer (PU) since many years ago, but there still remain a rather large number of intractable ulcer and recurrent ulcer. Recently the discovery of Helicobacter pylori (HP), as well as the relationship between HP and PU relapse was confirmed, but there still lacks of perfect therapeutic program for anti-HP infection(1). From June 1993 to August 1996, we used a pure TCM preparation Moluo Yangping granule (摩罗疡平冲剂, MYG) in treating 64 PU patients, and satisfactory results have been obtained. The report is as follows.

  13. Linking granulation performance with residence time and granulation liquid distributions in twin-screw granulation: An experimental investigation.

    Science.gov (United States)

    Kumar, Ashish; Alakarjula, Maija; Vanhoorne, Valérie; Toiviainen, Maunu; De Leersnyder, Fien; Vercruysse, Jurgen; Juuti, Mikko; Ketolainen, Jarkko; Vervaet, Chris; Remon, Jean Paul; Gernaey, Krist V; De Beer, Thomas; Nopens, Ingmar

    2016-07-30

    Twin-screw granulation is a promising wet granulation technique for the continuous manufacturing of pharmaceutical solid dosage forms. A twin screw granulator displays a short residence time. Thus, the solid-liquid mixing must be achieved quickly by appropriate arrangement of transport and kneading elements in the granulator screw allowing the production of granules with a size distribution appropriate for tableting. The distribution of residence time and granulation liquid is governed by the field conditions (such as location and length of mixing zones) in the twin-screw granulator, thus contain interesting information on granulation time, mixing and resulting sub-processes such as wetting, aggregation and breakage. In this study, the impact of process (feed rate, screw speed and liquid-to-solid ratio) and equipment parameters (number of kneading discs and stagger angle) on the residence time (distribution), the granulation liquid-powder mixing and the resulting granule size distributions during twin-screw granulation were investigated. Residence time and axial mixing data was extracted from tracer maps and the solid-liquid mixing was quantified from moisture maps, obtained by monitoring the granules at the granulator outlet using near infra-red chemical imaging (NIR-CI). The granule size distribution was measured using the sieving method. An increasing screw speed dominantly reduced the mean residence time. Interaction of material throughput with the screw speed and with the number of kneading discs led to most variation in the studied responses including residence time and mixing capacity. At a high screw speed, granulation yield improved due to high axial mixing. However, increasing material throughput quickly lowers the yield due to insufficient mixing of liquid and powder. Moreover, increasing liquid-to-solid ratio resulted in more oversized granules, and the fraction of oversized granules further increased at higher throughput. Although an increasing number

  14. Granulation techniques and technologies: recent progresses

    OpenAIRE

    Srinivasan Shanmugam

    2015-01-01

    Granulation, the process of particle enlargement by agglomeration technique, is one of the most significant unit operations in the production of pharmaceutical dosage forms, mostly tablets and capsules. Granulation process transforms fine powders into free-flowing, dust-free granules that are easy to compress. Nevertheless, granulation poses numerous challenges due to high quality requirement of the formed granules in terms of content uniformity and physicochemical proper...

  15. Added sensitivity of component-resolved diagnosis in hymenoptera venom-allergic patients with elevated serum tryptase and/or mastocytosis

    DEFF Research Database (Denmark)

    Michel, J B; Brockow, K; Darsow, U;

    2016-01-01

    BACKGROUND: Anaphylaxis caused by hymenoptera venom allergy is associated with elevation of baseline serum tryptase (sBT) and/or mastocytosis in about 5% of patients. Up to now, no information has become available on single venom allergen sIgE reactivity and the usefulness of component-resolved a......BACKGROUND: Anaphylaxis caused by hymenoptera venom allergy is associated with elevation of baseline serum tryptase (sBT) and/or mastocytosis in about 5% of patients. Up to now, no information has become available on single venom allergen sIgE reactivity and the usefulness of component......-resolved approaches to diagnose this high-risk patient group. To address the component-resolved sIgE sensitization pattern and diagnostic sensitivity in hymenoptera venom-allergic patients with elevated sBT levels and/or mastocytosis, a panel of yellow jacket and honeybee venom allergens was applied on a widely used...... IgE immunoassay platform. METHODS: Fifty-three patients with mastocytosis and/or elevated sBT tryptase level and systemic reactions to hymenoptera venoms were analyzed for their IgE reactivity to recombinant yellow jacket and honeybee venom allergens by Immulite3 g. RESULTS: sIgE reactivity to Ves v...

  16. Granulopoiesis and granules of human neutrophils

    DEFF Research Database (Denmark)

    Cowland, Jack B; Borregaard, Niels

    2016-01-01

    Granules are essential for the ability of neutrophils to fulfill their role in innate immunity. Granule membranes contain proteins that react to environmental cues directing neutrophils to sites of infection and initiate generation of bactericidal oxygen species. Granules are densely packed...... with proteins that contribute to microbial killing when liberated to the phagosome or extracellularly. Granules are, however, highly heterogeneous and are traditionally subdivided into azurophil granules, specific granules, and gelatinase granules in addition to secretory vesicles. This review will address...... issues pertinent to formation of granules, which is a process intimately connected to maturation of neutrophils from their precursors in the bone marrow. We further discuss possible mechanisms by which decisions are made regarding sorting of proteins to constitutive secretion or storage in granules...

  17. Linking granulation performance with residence time and granulation liquid distributions in twin-screw granulation: An experimental investigation

    DEFF Research Database (Denmark)

    Kumar, Ashish; Alakarjula, Maija; Vanhoorne, Valérie

    2016-01-01

    Twin-screw granulation is a promising wet granulation technique for the continuous manufacturing of pharmaceutical solid dosage forms. A twin screw granulator displays a short residence time. Thus, the solid-liquid mixing must be achieved quickly by appropriate arrangement of transport and kneading...... elements in the granulator screw allowing the production of granules with a size distribution appropriate for tableting. The distribution of residence time and granulation liquid is governed by the field conditions (such as location and length of mixing zones) in the twin-screw granulator, thus contain...... interesting information on granulation time, mixing and resulting sub-processes such as wetting, aggregation and breakage. In this study, the impact of process (feed rate, screw speed and liquid-to-solid ratio) and equipment parameters (number of kneading discs and stagger angle) on the residence time...

  18. Expression and role of a2 vacuolar-ATPase (a2V) in trafficking of human neutrophil granules and exocytosis.

    Science.gov (United States)

    Gilman-Sachs, Alice; Tikoo, Anjali; Akman-Anderson, Leyla; Jaiswal, Mukesh; Ntrivalas, Evangelos; Beaman, Kenneth

    2015-06-01

    Neutrophils kill microorganisms by inducing exocytosis of granules with antibacterial properties. Four isoforms of the "a" subunit of V-ATPase-a1V, a2V, a3V, and a4V-have been identified. a2V is expressed in white blood cells, that is, on the surface of monocytes or activated lymphocytes. Neutrophil associated-a2V was found on membranes of primary (azurophilic) granules and less often on secondary (specific) granules, tertiary (gelatinase granules), and secretory vesicles. However, it was not found on the surface of resting neutrophils. Following stimulation of neutrophils, primary granules containing a2V as well as CD63 translocated to the surface of the cell because of exocytosis. a2V was also found on the cell surface when the neutrophils were incubated in ammonium chloride buffer (pH 7.4) a weak base. The intracellular pH (cytosol) became alkaline within 5 min after stimulation, and the pH increased from 7.2 to 7.8; this pH change correlated with intragranular acidification of the neutrophil granules. Upon translocation and exocytosis, a2V on the membrane of primary granules remained on the cell surface, but myeloperoxidase was secreted. V-ATPase may have a role in the fusion of the granule membrane with the cell surface membrane before exocytosis. These findings suggest that the granule-associated a2V isoform has a role in maintaining a pH gradient within the cell between the cytosol and granules in neutrophils and also in fusion between the surface and the granules before exocytosis. Because a2V is not found on the surface of resting neutrophils, surface a2V may be useful as a biomarker for activated neutrophils.

  19. Variation of granule mass fraction with coordination number in wet granulation process

    Institute of Scientific and Technical Information of China (English)

    Papiya Roy; Manish Vashishtha; Rajesh Khanna; Duwuri Subbarao

    2009-01-01

    In granulation, fine particles combine to form a coarse granule in the form of a particle matrix partially or fully saturated with a binder liquid. The final product of granulation possesses a wide variety of granule size distributions with surface mean diameters which differ with operating conditions. The final granule size depends on the operating conditions, e.g. operating gas velocity, inlet air temperature, initial feed particle size, and viscosity of the binder. The objective of this paper is to find out the uniformity in the relation between the granule mass fraction in the final granule size distribution and the number of feed particles present in the granules. The total number of granules obtained depends on the experimental conditions but the granule mass fraction and the number of feed particles forming a single granule are independent of operating variables, feed material and method of granulation. The paper purports further to compare the uniform nature of mass fraction of the granules in final granule size distribution and the primary particles required to form that particular granule size irrespective of experimental conditions of granulation.

  20. Statistical analysis and comparison of a continuous high shear granulator with a twin screw granulator: Effect of process parameters on critical granule attributes and granulation mechanisms.

    Science.gov (United States)

    Meng, Wei; Kotamarthy, Lalith; Panikar, Savitha; Sen, Maitraye; Pradhan, Shankali; Marc, Michaelis; Litster, James D; Muzzio, Fernando J; Ramachandran, Rohit

    2016-11-20

    This study is concerned with identifying the design space of two different continuous granulators and their respective granulation mechanisms. Performance of a continuous high shear granulator and a twin screw granulator with paracetamol formulations were examined by face-centered cubic design, which focused on investigating key performance metrics, namely, granule size, porosity, flowability and particle morphology of granules as a function of essential input process parameters (liquid content, throughput and rotation speed). Liquid and residence time distribution tests were also performed to gain insights into the liquid-powder mixing and flow behavior. The results indicated that continuous high shear granulation was more sensitive to process variation and produced spherical granules with monomodal size distribution and distinct internal structure and strength variation. Twin screw granulation with such a particular screw configuration showed narrower design space and granules were featured with multimodal size distribution, irregular shape, less detectible porosity difference and tighter range of strength. Granulation mechanisms explored on the basis of nucleation and growth regime maps revealed that for most cases liquid binder was uniformly distributed with fast droplet penetration into the powder bed and that granule consolidation and coalescence mainly took place in the nucleation, steady growth and rapid growth regimes.

  1. Screening for mast cell tryptase and serum IgE antibodies in 18 patients with anaphylactic shock during general anaesthesia.

    Science.gov (United States)

    Dybendal, T; Guttormsen, A B; Elsayed, S; Askeland, B; Harboe, T; Florvaag, E

    2003-11-01

    In the perioperative setting multiple agents can cause anaphylaxis. Often the reactions are dramatic, and due to their lifethreatening potential it is crucial that the responsible agent is identified in order to avoid future adverse reactions. The aim of the present study was to measure the concentration of serum mast cell tryptase (MCT), to investigate the prevalence of serum IgE antibodies against ammonium groups, choline, morphine, suxamethonium, thiopentone and latex and to perform skin prick tests (SPTs) in 18 patients experiencing an anaphylactic reaction during induction of general anaesthesia. Serum samples from 18 patients with an anaphylactic reaction during general anaesthesia were analyzed for MCT and specific IgE against ammonium groups, choline, morphine, suxamethonium, thiopentone and latex. Skin prick tests were performed in 11 out of 18 patients. Ten patients had elevated MCT levels and specific IgE against ammonium ion, morphine and (with the exception of patient nos 3, 9 and 10) suxamethonium. Seven of these patients had positive SPTs to suxamethonium. One of the patients tested positive to latex in addition to suxamethonium. Two patients showed elevated MCT, while specific IgE against the drugs tested was not detected. Three patients tested positive to ammonium ion, morphine and suxamethonium, but negative to MCT. Three patients tested negative to both MCT and specific IgE. Fifteen out of 18 sera tested positive for MCT and/or specific IgE against neuromuscular blocking drugs (NMBDs). Ten of the 18 patients experienced an IgE-mediated anaphylactic reaction to NMBDs during anaesthesia, verified by detection of specific IgE and elevated levels of MCT.

  2. Regulation of secretory granule size by the precise generation and fusion of unit granules.

    Science.gov (United States)

    Hammel, Ilan; Lagunoff, David; Galli, Stephen J

    2010-07-01

    Morphometric evidence derived from studies of mast cells, pancreatic acinar cells and other cell types supports a model in which the post-Golgi processes that generate mature secretory granules can be resolved into three steps: (1) fusion of small, Golgi-derived progranules to produce immature secretory granules which have a highly constrained volume; (2) transformation of such immature granules into mature secretory granules, a process often associated with a reduction in the maturing granule's volume, as well as changes in the appearance of its content and (3) fusion of secretory granules of the smallest size, termed 'unit granules', forming granules whose volumes are multiples of the unit granule's volume. Mutations which perturb this process can cause significant pathology. For example, Chediak-Higashi syndrome / lysosomal trafficking regulator (CHS)/(Lyst) mutations result in giant secretory granules in a number of cell types in human beings with the Chediak-Higashi syndrome and in 'beige' (Lyst(bg)/Lyst(bg)) mice. Analysis of the secretory granules of mast cells and pancreatic acinar cells in Lyst-deficient beige mice suggests that beige mouse secretory granules retain the ability to fuse randomly with other secretory granules no matter what the size of the fusion partners. By contrast, in normal mice, the pattern of granule-granule fusion occurs exclusively by the addition of unit granules, either to each other or to larger granules. The normal pattern of fusion is termed unit addition and the fusion evident in cells with CHS/Lyst mutations is called random addition. The proposed model of secretory granule formation has several implications. For example, in neurosecretory cells, the secretion of small amounts of cargo in granules constrained to a very narrow size increases the precision of the information conveyed by secretion. By contrast, in pancreatic acinar cells and mast cells, large granules composed of multiple unit granules permit the cells to store

  3. Selective sorting of alpha-granule proteins.

    Science.gov (United States)

    Italiano, J E; Battinelli, E M

    2009-07-01

    One of the main functions of blood platelets is to secrete a variety of substances that can modify a developing thrombus, regulate the growth of the vasculature, promote wound repair, and contribute to cell-adhesive events. A majority of this vast array of secreted proteins are stored in alpha-granules. Until recently, it was assumed that platelets contained one homogeneous population of alpha-granules that undergo complete de-granulation during platelet activation. This review focuses on the mechanisms of alpha-granule biogenesis and secretion, with a particular emphasis on recent findings that clearly demonstrate that platelets contain distinct subpopulations of alpha-granules that undergo differential release during activation. We consider the implications of this new paradigm of platelet secretion, discuss mechanisms of alpha-granule biogenesis, and review the molecular basis of transport and delivery of alpha-granules to assembling platelets.

  4. Ofatumumab, Pentostatin, and Cyclophosphamide in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2014-10-30

    Hematopoietic/Lymphoid Cancer; B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  5. The crystal structure of human dipeptidyl peptidase I (cathepsin C) in complex with the inhibitor Gly-Phe-CHN2

    DEFF Research Database (Denmark)

    Mølgaard, Anne; Arnau, Jose; Lauritzen, C.

    2007-01-01

    hDDPI (human dipeptidyl peptidase I) is a lysosomal cysteine protease involved in zymogen activation of granule-associated proteases, including granzymes A and B from cytotoxic T-lymphocytes and natural killer cells, cathepsin G and neutrophil elastase, and mast cell tryptase and chymase...

  6. Bendamustine Plus Alemtuzumab for Refractory Chronic Lymphocytic Leukemia (CLL)

    Science.gov (United States)

    2013-08-20

    Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  7. Twin screw granulation - review of current progress.

    Science.gov (United States)

    Thompson, M R

    2015-01-01

    Twin screw granulation (TSG) is a new process of interest to the pharmaceutical community that can continuously wet granulate powders, doing so at lower liquid concentrations and with better product consistency than found by a high shear batch mixer. A considerable body of research has evolved over the short time since this process was introduced but generally with little comparison of results. A certain degree of confidence has been developed through these studies related to how process variables and many attributes of machinery configuration will affect granulation but some major challenges still lay ahead related to scalability, variations in the processing regimes related to degree of channel fill and the impact of wetting and granulation of complex powder formulations. This review examines the current literature for wet granulation processes studied in twin screw extrusion machinery, summarizing the influences of operational and system parameters affecting granule properties as well as strives to provide some practical observations to newly interested users of the technique.

  8. What Is Chronic Lymphocytic Leukemia?

    Science.gov (United States)

    ... Chronic Lymphocytic Leukemia (CLL) About Chronic Lymphocytic Leukemia What Is Chronic Lymphocytic Leukemia? Cancer starts when cells ... body, including the lymph nodes, liver, and spleen. What is leukemia? Leukemia is a cancer that starts ...

  9. Alvocidib in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2013-07-01

    B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  10. Selective sorting of alpha-granule proteins

    OpenAIRE

    Italiano, J.E.; Battinelli, E. M.

    2009-01-01

    One of the main functions of blood platelets is to secrete a variety of substances that can modify a developing thrombus, regulate the growth of the vasculature, promote wound repair, and contribute to cell-adhesive events. The majority of this vast array of secreted proteins is stored in alpha-granules. Until recently, it was assumed that platelets contained one homogeneous population of alpha-granules that undergo complete de-granulation during platelet activation. This review focuses on th...

  11. The extrusion properties of potato granules

    OpenAIRE

    Kooi, Eng Teong

    1982-01-01

    Potato granules from different sources were found, on extrusion, to produce potato snacks of variable quality. In some instances strip formation was unsatisfactory, in other instances blistering of the snack occurred on frying. In total, about 20-25 batches of potato granules were examined and classified in relation to these two phenomena. The amylose/amylopectin ratios of these samples of potato granules were determined by the semi-micro potentiometric iodine titration technique, but it was ...

  12. Medical image of the week: granulation tissue

    Directory of Open Access Journals (Sweden)

    Ganesh A

    2014-03-01

    Full Text Available A 57 year old woman presented with a tickling sensation in the back of throat and intermittent bleeding from the healing stoma one month after decannulation of her tracheostomy tube. On bronchoscopy a granuloma with surrounding granulation tissue was present in the subglottic space (Figure 1. Argon plasma coagulation (APC was performed to cauterize the granulation tissue (Figure 2. Formation of granulation tissue after tracheostomy is a common complication which can result in tracheal stenosis. APC and electrocautery using flexible bronchoscopy has been shown to safely and effectively remove the granulation tissue.

  13. Mechanism of film formation during granules capsulation in fluidized bed

    OpenAIRE

    Ostroha, Ruslan; Yukhymenko, Mykola

    2013-01-01

    It is proposed to perform granules capsulation process in the device of fluidized bed. Analysis of different approaches to mathematical description of granules growth kinetics was made. Equation of size determination of received granules in the device is proposed including granules growth rate and changes of density of granules distribution according to sizes in film forming process.

  14. Granulation of coal fly ash by using different types of granule agents

    Science.gov (United States)

    Agusta, H.; Nisya, F. N.; Iman, R. N.; Bilad, D. B. C.

    2017-05-01

    The use of coal produces about 5% solid pollutant in the form of ash (fly ash and bottom ash). Of the total ash produced, about 10-20% is bottom ash and 80-90% is fly ash. This study was aimed at obtaining a type of adhesive which could be used as a fly granulation material for soil conditioner. The study was conducted at the pilot plant of Surfactant and Bioenergy Research Center (SBRC) LPPM IPB from April to August 2016. The fly ash used in this study was obtained from Kalimantan. A pan granulator was used in fly ash granule making process. Granule agent materials were diluted in the concentration of 5, 10, and 15%. Different types of granule agents, namely SBRC-M, SBRC-T, and SBRC-SC were used. The formed fly ash granules were then analyzed for their physical properties including particle density, fly ash granule pH, fly ash granule durability, and fly ash granule water holding capacity. Results showed that fly ash granules made from 15% of SBRC-M had the highest particle density (0.75 g/cm3). Fly ash granules made with SBRC-M had higher pH (10) than those made by using SBRC-SC adhesive (9.3) and SBRC-T (9). SBRC-T was found as the granule agent material which produced fly ash granules with the highest durability levels on average. In this study, the use of SBRC-M granule agent resulted in higher water holding capacity (WHC) (40.62%) than did SBRC-SC (38.79%) and SBRC-T (36.85%). As a granule agent, compared to SBRC-SC and SBRC-T, SBRC-M could produce fly ash granules with highest particle density, highest pH, good durability, and best water holding capacity.

  15. MID2 can substitute for MID1 and control exocytosis of lytic granules in cytotoxic T cells

    DEFF Research Database (Denmark)

    Boding, Lasse; Hansen, Ann K; Meroni, Germana;

    2015-01-01

    We have recently shown that the E3 ubiquitin ligase midline 1 (MID1) is upregulated in murine cytotoxic lymphocytes (CTL), where it controls exocytosis of lytic granules and the killing capacity. Accordingly, CTL from MID1 knock-out (MID1(-/-)) mice have a 25-30% reduction in exocytosis of lytic...... granules and cytotoxicity compared to CTL from wild-type (WT) mice. We wondered why the MID1 gene knock-out did not affect exocytosis and cytotoxicity more severely and speculated whether MID2, a close homologue of MID1, might partially compensate for the loss of MID1 in MID1(-/-) CTL. Here, we showed...

  16. Granule exocytosis is required for platelet spreading: differential sorting of α-granules expressing VAMP-7.

    Science.gov (United States)

    Peters, Christian G; Michelson, Alan D; Flaumenhaft, Robert

    2012-07-01

    There has been recent controversy as to whether platelet α-granules represent a single granule population or are composed of different subpopulations that serve discrete functions. To address this question, we evaluated the localization of vesicle-associated membrane proteins (VAMPs) in spread platelets to determine whether platelets actively sort a specific subpopulation of α-granules to the periphery during spreading. Immunofluorescence microscopy demonstrated that granules expressing VAMP-3 and VAMP-8 localized to the central granulomere of spread platelets along with the granule cargos von Willebrand factor and serotonin. In contrast, α-granules expressing VAMP-7 translocated to the periphery of spread platelets along with the granule cargos TIMP2 and VEFG. Time-lapse microscopy demonstrated that α-granules expressing VAMP-7 actively moved from the granulomere to the periphery during spreading. Platelets from a patient with gray platelet syndrome lacked α-granules and demonstrated only minimal spreading. Similarly, spreading was impaired in platelets obtained from Unc13d(Jinx) mice, which are deficient in Munc13-4 and have an exocytosis defect. These studies identify a new α-granule subtype expressing VAMP-7 that moves to the periphery during spreading, supporting the premise that α-granules are heterogeneous and demonstrating that granule exocytosis is required for platelet spreading.

  17. The paradox of high shear granulation : the formation of non-homogeneous granules

    NARCIS (Netherlands)

    Dries, Kaspar van den

    2004-01-01

    Wet granulation is a process used for the particle size enlargement of primary powders. The mixing of a liquid with the powder glues the primary particles together, which results in the formation of the granules. The mixing action can be performed in many ways, like tumbling (drum granulation), flui

  18. Granule fraction inhomogeneity of calcium carbonate/sorbitol in roller compacted granules

    DEFF Research Database (Denmark)

    Bacher, Charlotte; Olsen, P.M.; Bertelsen, P.;

    2008-01-01

    The granule fraction inhomogeneity of roller compacted granules was examined on mixtures of three different morphologic forms of calcium carbonate and three particle sizes of sorbitol. The granule fraction inhomogeneity was determined by the distribution of the calcium carbonate in each of the 10...

  19. Mast Cells Density Positive to Tryptase Correlate with Microvascular Density in both Primary Gastric Cancer Tissue and Loco-Regional Lymph Node Metastases from Patients That Have Undergone Radical Surgery.

    Science.gov (United States)

    Ammendola, Michele; Sacco, Rosario; Zuccalà, Valeria; Luposella, Maria; Patruno, Rosa; Gadaleta, Pietro; Zizzo, Nicola; Gadaleta, Cosmo Damiano; De Sarro, Giovambattista; Sammarco, Giuseppe; Oltean, Mihai; Ranieri, Girolamo

    2016-11-15

    Mast Cells (MCs) play a role in immune responses and more recently MCs have been involved in tumoral angiogenesis. In particular MCs can release tryptase, a potent in vivo and in vitro pro-angiogenic factor via proteinase-activated receptor-2 (PAR-2) activation and mitogen-activated protein kinase (MAPK) phosphorylation. MCs can release tryptase following c-Kit receptor activation. Nevertheless, no data are available concerning the relationship among MCs Density Positive to Tryptase (MCDPT) and Microvascular Density (MVD) in both primary gastric cancer tissue and loco-regional lymph node metastases. A series of 75 GC patients with stage T2-3N2-3M₀ (by AJCC for Gastric Cancer Seventh Edition) undergone to radical surgery were selected for the study. MCDPT and MVD were evaluated by immunohistochemistry and by image analysis system and results were correlated each to other in primary tumor tissue and in metastatic lymph nodes harvested. Furthermore, tissue parameters were correlated with important clinico-pathological features. A significant correlation between MCDPT and MVD was found in primary gastric cancer tissue and lymph node metastases. Pearson t-test analysis (r ranged from 0.74 to 0.79; p-value ranged from 0.001 to 0.003). These preliminary data suggest that MCDPT play a role in angiogenesis in both primary tumor and in lymph node metastases from GC. We suggest that MCs and tryptase could be further evaluated as novel targets for anti-angiogenic therapies.

  20. Regulated protein aggregation: stress granules and neurodegeneration

    Directory of Open Access Journals (Sweden)

    Wolozin Benjamin

    2012-11-01

    Full Text Available Abstract The protein aggregation that occurs in neurodegenerative diseases is classically thought to occur as an undesirable, nonfunctional byproduct of protein misfolding. This model contrasts with the biology of RNA binding proteins, many of which are linked to neurodegenerative diseases. RNA binding proteins use protein aggregation as part of a normal regulated, physiological mechanism controlling protein synthesis. The process of regulated protein aggregation is most evident in formation of stress granules. Stress granules assemble when RNA binding proteins aggregate through their glycine rich domains. Stress granules function to sequester, silence and/or degrade RNA transcripts as part of a mechanism that adapts patterns of local RNA translation to facilitate the stress response. Aggregation of RNA binding proteins is reversible and is tightly regulated through pathways, such as phosphorylation of elongation initiation factor 2α. Microtubule associated protein tau also appears to regulate stress granule formation. Conversely, stress granule formation stimulates pathological changes associated with tau. In this review, I propose that the aggregation of many pathological, intracellular proteins, including TDP-43, FUS or tau, proceeds through the stress granule pathway. Mutations in genes coding for stress granule associated proteins or prolonged physiological stress, lead to enhanced stress granule formation, which accelerates the pathophysiology of protein aggregation in neurodegenerative diseases. Over-active stress granule formation could act to sequester functional RNA binding proteins and/or interfere with mRNA transport and translation, each of which might potentiate neurodegeneration. The reversibility of the stress granule pathway also offers novel opportunities to stimulate endogenous biochemical pathways to disaggregate these pathological stress granules, and perhaps delay the progression of disease.

  1. Twin screw wet granulation: Binder delivery.

    Science.gov (United States)

    Saleh, Mohammed F; Dhenge, Ranjit M; Cartwright, James J; Hounslow, Michael J; Salman, Agba D

    2015-06-20

    The effects of three ways of binder delivery into the twin screw granulator (TSG) on the residence time, torque, properties of granules (size, shape, strength) and binder distribution were studied. The binder distribution was visualised through the transparent barrel using high speed imaging as well as quantified using offline technique. Furthermore, the effect of binder delivery and the change of screw configuration (conveying elements only and conveying elements with kneading elements) on the surface velocity of granules across the screw channel were investigated using particle image velocimetry (PIV). The binder was delivered in three ways; all solid binder incorporated with powder mixture, 50% of solid binder mixed with powder mixture and 50% mixed with water, all the solid binder dissolved in water. Incorporation of all solid binder with powder mixture resulted in the relatively longer residence time and higher torque, narrower granule size distribution, more spherical granules, weaker big-sized granules, stronger small-sized granules and better binder distribution compared to that in other two ways. The surface velocity of granules showed variation from one screw to another as a result of uneven liquid distribution as well as shown a reduction while introducing the kneading elements into the screw configuration.

  2. Autophagy meets FUS-positive Stress Granules

    Science.gov (United States)

    Matus, Soledad; Bosco, Daryl A.; Hetz, Claudio

    2015-01-01

    Mutations in fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS) are linked to familial cases of amyotrophic lateral sclerosis (ALS). Mutant FUS selectively accumulates into discrete cytosolic structures known as stress granules under various stress conditions. In addition, mutant FUS expression can alter the dynamics and morphology of stress granules. Although the link between mutant-FUS and stress granules is well established, the mechanisms modulating stress granule formation and disassembly in the context of ALS are poorly understood. In this issue of Neurobiology of Aging, Ryu and coworkers uncover the impact of autophagy on the potential toxicity of mutant-FUS positive stress granules. The authors provide evidence indicating that enhanced autophagy activity reduces the number of stress granules, which in the case of cells containing mutant-FUS positive stress granules, is neuroprotective. Overall, this study identifies an intersection between the proteostasis network and alterations in RNA metabolism in ALS through the dynamic assembly and disassembly of stress granules. PMID:25444610

  3. Continuous twin screw granulation: influence of process variables on granule and tablet quality.

    Science.gov (United States)

    Vercruysse, J; Córdoba Díaz, D; Peeters, E; Fonteyne, M; Delaet, U; Van Assche, I; De Beer, T; Remon, J P; Vervaet, C

    2012-09-01

    The aim of the current study was to screen theophylline (125 mg) tablets manufactured via twin screw granulation in order to improve process understanding and knowledge of process variables that determine granule and tablet quality. A premix of theophylline anhydrate, α-lactose monohydrate and PVP (ratio: 30/67.5/2.5,w/w) was granulated with demineralized water. Experiments were done using the high-shear wet granulation module (based on twin screw granulation) of the ConsiGma™-25 unit (a continuous tablet manufacturing system) for particle size enlargement. After drying, granules were compressed using a MODUL™ P tablet press (compression force: 10 kN, tablet diameter: 12 mm). Using a D-optimal experimental design, the effect of several process variables (throughput (10-25 kg/h), screw speed (600-950 rpm), screw configuration (number (2, 4, 6 and 12) and angle (30°, 60° and 90°) of kneading elements), barrel temperature (25-40°C) and method of binder addition (dry versus wet)) on the granulation process (torque and temperature increase in barrel wall), granule (particle size distribution, friability and flowability) and tablet (tensile strength, porosity, friability, disintegration time and dissolution) quality was evaluated. The results showed that the quality of granules and tablets can be optimized by adjusting specific process variables (number of kneading elements, barrel temperature and binder addition method) during a granulation process using a continuous twin screw granulator.

  4. Development of granules from phyllanthus niruri spray-dried extract

    OpenAIRE

    Tatiane Pereira de Souza; José Luiz Gómez-Amoza; Ramón Martínez Pacheco; Pedro Ros Petrovick

    2009-01-01

    The aim of this study was to develop granules from Phyllanthus niruri spray-dried extract using dry and wet granulation and to assess techniques to enable the production of granules with improved technological characteristics and yields. Granules were characterized by granulometry, reological parameters, compression and hygroscopic behavior. Independent of the granulation technique, technologically developed granules presented particle diameter, bulk and tapped densities and compressibility i...

  5. Clinical Observation in 102 Cases of Chronic Pelvic Inflammation Treated with Qi Jie Granules

    Institute of Scientific and Technical Information of China (English)

    章勤; 何嘉琳; 何少山; 许萍

    2004-01-01

    Objective: To observe the therapeutic effects of Qi Jie Granule (芪竭颗粒) on chronic pelvic inflammation. Method: The therapeutic effect, T-lymphocytic subgroups and indexes of blood rheology were observed when 102 cases of chronic pelvic inflammation in the treatment group were treated with Qi Jie Granule, and another 70 cases were treated with Qian Jin Pian as the controls. Results: The total effective rate was 96.08% in the treatment group, but 84.29% in the control group with a significant difference between the two groups (P<0.01). Qi Jie Granule was also found effective in improving blood viscosity and regulating T-lymphocytic subgroups, and the difference before and after the treatment was also very significant (P<0.05 or P<0.01). Conclusion: The nature of chronic pelvic inflammation is qi deficiency and blood stasis in accordance with the theory of traditional Chinese medicine (TCM). As a drug that is indicated for chronic pelvic inflammation, its mechanism may be related to the improved blood circulation, accelerated inflammatory absorption and regulated immune function.

  6. Acute Lymphocytic Leukemia

    Science.gov (United States)

    ... for information in your local library and on the Internet. Good sources include the National Cancer Institute, the ... mayoclinic.org/diseases-conditions/acute-lymphocytic-leukemia/basics/definition/CON-20042915 . Mayo Clinic Footer Legal Conditions and ...

  7. Preparation and evaluation of granules with pH-dependent release by melt granulation.

    Science.gov (United States)

    Shiino, Kai; Iwao, Yasunori; Fujinami, Yukari; Itai, Shigeru

    2012-07-15

    This study had two objectives: (1) to prepare, by melt granulation in a high-shear mixer, granules containing acetaminophen (APAP) as a model drug and aminoalkyl methacrylate copolymer E (AMCE) as a pH-sensitive polymer that readily dissolves at pH values lower than 5, and (2) to investigate the effects of AMCE loading (5-15%) on granule properties and the in vitro release profile of drug from the granules. Compared with polymer-free granules, the granules containing 5% and 10% AMCE were found to have higher median diameters and wider particle size distributions. For the formulation containing 15% AMCE, on the other hand, the diameters and distribution were similar to those for polymer-free granules. From compression testing, load-displacement curves revealed that AMCE enhanced particle strength at ambient temperature and induced plastic strain, while suppressing fragmentation of the granules. In addition, from dissolution testing using media with pH 4.0 and pH 6.5, granules containing AMCE, except 15% AMCE loading, exhibited drug release with significant pH dependence. When the pH 4.0 and pH 6.5 dissolution profiles were further compared by calculating the difference factor (f(1)), the 5% AMCE granules showed the strongest pH dependence of drug release among all formulations in this study. Large cracks and breakage were observed on the surface of 10% AMCE granules after they were used in dissolution testing. The obtained results are attributed to the plastic strain properties of AMCE above its glass transition temperature, and to the irregular distribution of AMCE within granules. Hence, this study has demonstrated for the first time that the combination of melt granulation and AMCE incorporation enables the formulation of novel functional granules that exhibit pH-dependent release of the active ingredient. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. THE STUDY OF THE KINETIC OF NATURAL ZEOLITE GRANULES GROWTH AT DIFFERENT WAYS OF GRANULATION

    Directory of Open Access Journals (Sweden)

    Rybachuk VD

    2016-12-01

    Full Text Available Introduction. Active substances and excipients used in the manufacture of medicines in tablet form, in most cases, have poor technological properties. This fact determines the need for prior granulation of mass before compression. Granulators of various sizes and designs, running on different modes, made the formation, growth and consolidation of the powder particles that lead to obtain pellets of different shapes and sizes. From the literature it is known that granulation leads to two forms of granules: isodiametric and nonisodiametric. The first group of particles forms has globular shape with a smooth surface and the proportion in which the length, thickness and height are about the same. They are usually made by fluidized bed granulation, spray drying, pelletizing and granulation in dragee pan. Granules of nonisodiametric form in which length is several times the width and height are made mostly by extrusion and compacting. The geometrical parameters of obtained granules are affected by the properties of raw materials, the granulation modes, type and amount of added humidifier and so on. The shape and size of granules, from a technological point of view, are the key factors that contribute, except organoleptic characteristics of the product, its technological properties such as particle size distribution, bulk volume, the ability of the material to shrinkage, porosity, fluidity, mechanical strength and so on. Properly selected for specific conditions granulation method is able to provide the finished product with the specified technological parameters depending on the needs. The aim of this work was to study the effect of granulation method and its conditions on the kinetics of growth of the natural zeolite granules and some quality characteristics of obtained granules. Material & methods. As objects of study served the natural zeolite pellets produced using 3%, 5%, 7% and 10% potato starch paste and solution of polyvinylpyrrolidone (PVP

  9. Correlative microscopy of detergent granules.

    Science.gov (United States)

    van Dalen, G; Nootenboom, P; Heussen, P C M

    2011-03-01

    The microstructure of detergent products for textile cleaning determines to a large extent the physical properties of these products. Correlative microscopy was used to reveal the microstructure by reconciling images obtained by scanning electron microscopy with energy dispersive X-ray analysis, X-ray microtomography and Fourier transform infrared microscopy. These techniques were applied on the same location of a subsample of a spray-dried detergent base powder embedded in polyacrylate. In this way, the three-dimensional internal and external structure of detergent granules could be investigated from milli to nano scale with detailed spatial information about the components present. This will generate knowledge how to design optimal microstructures for laundry products to obtain product properties demanded by the market. This method is also very useful for other powder systems used in a large variety of industries (e.g. for pharmaceutical, food, ceramic and metal industries).

  10. Serine protease inhibitor 6 protects cytotoxic T cells from self-inflicted injury by ensuring the integrity of cytotoxic granules.

    Science.gov (United States)

    Zhang, Manling; Park, Sun-Mi; Wang, Yue; Shah, Ramila; Liu, Ni; Murmann, Andrea E; Wang, Chyung-Ru; Peter, Marcus E; Ashton-Rickardt, Philip G

    2006-04-01

    How cytotoxic T lymphocytes (CTLs) kill intracellular pathogens without killing themselves has been a recurring question ever since their discovery. By using mice deficient in Serine Protease Inhibitor 6 (Spi6), we show that by inhibiting granzyme B (GrB), Spi6 protects CTLs from self-inflicted injury. Infection with either Lymphocytic Choriomeningitis virus (LCMV) or Listeria monocytogenes (LM) revealed increased apoptosis and diminished survival of Spi6 knockout (KO) CTLs, which was cell autonomous and could be corrected by GrB deficiency. Spi6 KO mice in turn were impaired in their ability to clear LCMV infection. Spi6 KO CTLs revealed a breakdown in the integrity of cytotoxic granules, increased cytoplasmic GrB, and ensuing apoptosis. We conclude that Spi6 protects CTLs from suicide caused by GrB-mediated breakdown of cytotoxic granules.

  11. Impact of screw configuration on the particle size distribution of granules produced by twin screw granulation.

    Science.gov (United States)

    Vercruysse, J; Burggraeve, A; Fonteyne, M; Cappuyns, P; Delaet, U; Van Assche, I; De Beer, T; Remon, J P; Vervaet, C

    2015-02-01

    Twin screw granulation (TSG) has been reported by different research groups as an attractive technology for continuous wet granulation. However, in contrast to fluidized bed granulation, granules produced via this technique typically have a wide and multimodal particle size distribution (PSD), resulting in suboptimal flow properties. The aim of the current study was to evaluate the impact of granulator screw configuration on the PSD of granules produced by TSG. Experiments were performed using a 25 mm co-rotating twin screw granulator, being part of the ConsiGma™-25 system (a fully continuous from-powder-to-tablet manufacturing line from GEA Pharma Systems). Besides the screw elements conventionally used for TSG (conveying and kneading elements), alternative designs of screw elements (tooth-mixing-elements (TME), screw mixing elements (SME) and cutters) were investigated using an α-lactose monohydrate formulation granulated with distilled water. Granulation with only conveying elements resulted in wide and multimodal PSD. Using kneading elements, the width of the PSD could be partially narrowed and the liquid distribution was more homogeneous. However, still a significant fraction of oversized agglomerates was obtained. Implementing additional kneading elements or cutters in the final section of the screw configuration was not beneficial. Furthermore, granulation with only TME or SME had limited impact on the width of the PSD. Promising results were obtained by combining kneading elements with SME, as for these configurations the PSD was narrower and shifted to the size fractions suitable for tableting.

  12. Asymmetric distribution in twin screw granulation.

    Science.gov (United States)

    Chan Seem, Tim; Rowson, Neil A; Gabbott, Ian; de Matas, Marcel; Reynolds, Gavin K; Ingram, Andy

    2016-09-01

    Positron Emission Particle Tracking (PEPT) was successfully employed to validate measured transverse asymmetry in material distribution in the conveying zones of a Twin Screw Granulator (TSG). Flow asymmetry was established to be a property of the granulator geometry and dependent on fill level. The liquid distribution of granules as a function of fill level was determined. High flow asymmetry at low fill level negatively affects granule nucleation leading to high variance in final uniformity. Wetting of material during nucleation was identified as a critical parameter in determining final granule uniformity and fill level is highlighted as a crucial control factor in achieving this. Flow asymmetry of dry material in conveying zones upstream of binder fluid injection leads to poor non-uniform wetting at nucleation and results in heterogeneous final product. The granule formation mechanism of 60°F kneading blocks is suggested to be primarily breakage of agglomerates formed during nucleation. Optimisation of screw configuration would be required to provide secondary growth. This work shows how fill dependent flow regimes affect granulation mechanisms.

  13. Compressibility and compactibility of granules produced by wet and dry granulation.

    Science.gov (United States)

    Bacher, C; Olsen, P M; Bertelsen, P; Sonnergaard, J M

    2008-06-24

    The bulk properties, compactibility and compressibility of granules produced by wet and dry granulation were compared applying a rotary tablet press, three different morphological forms of calcium carbonate and two particle sizes of sorbitol. Granules from both granulation methods possessed acceptable flow properties; however, the ground (Mikhart) and cubic (Scoralite) calcium carbonate demonstrated better die-filling abilities in the tablet press than the scalenhedral calcium carbonate (Sturcal). The wet processed granules showed in general larger compression properties. This was explained as these granules were mechanical stronger and had a higher initial porosity. In some cases, a large particle surface area of calcium carbonate and sorbitol resulted in a small, insignificant improvement of the consolidation characteristics. A correlation between the compression and compaction characteristics was demonstrated.

  14. A TECHNICAL NOTE ON GRANULATION TECHNOLOGY: A WAY TO OPTIMISE GRANULES

    Directory of Open Access Journals (Sweden)

    Mahammed Athar A. Saikh

    2013-01-01

    Full Text Available To provide an updated technical note on granulation technology (GT, mostly on novel GT, that will help researcher working/engaged in designing an efficient GT for getting granules with desired features. Granules were most widely used in the production of pharmaceutical oral dosage forms. Advancement in GT had revolutionized the sphere and resulted in development of several processes. Each and every process had advantages and disadvantages, and limitations. Depth knowledge in GT was a prerequisite to process product for obtaining targeted granulation with desired product parameters. In this regards updated literatures were collected from data bases, studied and was presented for easy reference of scientists engaged in granule production, so that they can adopt appropriate and suitable GT. Presented handy note will help researchers in designing a robust GT for getting optimised granule.

  15. Distribution of binder in granules produced by means of twin screw granulation.

    Science.gov (United States)

    Fonteyne, Margot; Fussell, Andrew Luke; Vercruysse, Jurgen; Vervaet, Chris; Remon, Jean Paul; Strachan, Clare; Rades, Thomas; De Beer, Thomas

    2014-02-28

    According to the quality by design principle processes may not remain black-boxes and full process understanding is required. The granule size distribution of granules produced via twin screw granulation is often found to be bimodal. The aim of this study was to gain a better understanding of binder distribution within granules produced via twin screw granulation in order to investigate if an inhomogeneous spread of binder is causing this bimodal size distribution. Theophylline-lactose-polyvinylpyrrolidone K30 (PVP) (30-67.5-2.5%, w/w) was used as a model formulation. The intra-granular distribution of PVP was evaluated by means of hyperspectral coherent anti-Stokes Raman scattering (CARS) microscopy. For the evaluated formulation, no PVP rich zones were detected when applying a lateral spatial resolution of 0.5 μm, indicating that PVP is homogenously distributed within the granules.

  16. THE STUDY OF THE KINETIC OF NATURAL ZEOLITE GRANULES GROWTH AT DIFFERENT WAYS OF GRANULATION

    OpenAIRE

    Rybachuk VD

    2016-01-01

    Introduction. Active substances and excipients used in the manufacture of medicines in tablet form, in most cases, have poor technological properties. This fact determines the need for prior granulation of mass before compression. Granulators of various sizes and designs, running on different modes, made the formation, growth and consolidation of the powder particles that lead to obtain pellets of different shapes and sizes. From the literature it is known that granulation leads to two forms ...

  17. Cohesive strength of iron ore granules

    Directory of Open Access Journals (Sweden)

    Contreras Rafael Jaimes

    2017-01-01

    Full Text Available We present an experimental and numerical investigation of the mechanical strength of crude iron ore (Hematite granules in which capillary bonds between primary particles are the source of internal cohesion. The strength is measured by subjecting the granules to vertical compression between two plates. We show that the behavior of the granules is ductile with a well-defined plastic threshold which increases with the amount of water. It is found that the compressive strength scales with capillary cohesion with a pre-factor that is nearly independent of size polydispersity for the investigated range of parameters but increases with friction coefficient between primary particles. This weak dependence may be attributed to the class of fine particles which, due to their large number, behaves as a cohesive matrix that controls the strength of the granule.

  18. Cohesive strength of iron ore granules

    Science.gov (United States)

    Contreras, Rafael Jaimes; Berger, Nicolas; Izard, Edouard; Douce, Jean-François; Koltsov, Alexey; Delenne, Jean-Yves; Azema, Emilien; Nezamabadi, Saeid; van Loo, Frédéric; Pellenq, Roland; Radjai, Farhang

    2017-06-01

    We present an experimental and numerical investigation of the mechanical strength of crude iron ore (Hematite) granules in which capillary bonds between primary particles are the source of internal cohesion. The strength is measured by subjecting the granules to vertical compression between two plates. We show that the behavior of the granules is ductile with a well-defined plastic threshold which increases with the amount of water. It is found that the compressive strength scales with capillary cohesion with a pre-factor that is nearly independent of size polydispersity for the investigated range of parameters but increases with friction coefficient between primary particles. This weak dependence may be attributed to the class of fine particles which, due to their large number, behaves as a cohesive matrix that controls the strength of the granule.

  19. Atrial natriuretic peptide (ANP)-granules: ultrastructure ...

    African Journals Online (AJOL)

    AJB SERVER

    2006-12-29

    Dec 29, 2006 ... physiological conditions: temperature, dehydration and nutritional condition. The main ... Granule content is released into the extra-cellular space (extrusion). The ANP causes .... Studies carried out in humans (Tanaka et al.,.

  20. Measuring stellar granulation during planet transits

    CERN Document Server

    Chiavassa, A; Selsis, F; Leconte, J; Von Paris, P; Bordé, P; Magic, Z; Collet, R; Asplund, M

    2016-01-01

    Stellar activity and convection-related surface structures might cause bias in planet detection and characterization that use these transits. Surface convection simulations help to quantify the granulation signal. We used realistic three-dimensional radiative hydrodynamical simulations from the Stagger grid and synthetic images computed with the radiative transfer code Optim3D to model the transits of three prototype planets: a hot Jupiter, a hot Neptune, and a terrestrial planet. We computed intensity maps from RHD simulations of the Sun and a K-dwarf star at different wavelength bands from optical to far-infrared. We modeled the transit using synthetic stellar-disk images and emulated the temporal variation of the granulation intensity. We identified two types of granulation noise that act simultaneously during the planet transit: (i) the intrinsic change in the granulation pattern with timescales smaller than the usual planet transit, and (ii) the fact that the transiting planet occults isolated regions of...

  1. Chemokines, lymphocytes, and HIV

    Directory of Open Access Journals (Sweden)

    Farber J.M.

    1998-01-01

    Full Text Available Chemokines are members of a family of more than 30 human cytokines whose best-described activities are as chemotactic factors for leukocytes and that are presumed to be important in leukocyte recruitment and trafficking. While many chemokines can act on lymphocytes, the roles of chemokines and their receptors in lymphocyte biology are poorly understood. The recent discoveries that chemokines can suppress infection by HIV-1 and that chemokine receptors serve, along with CD4, as obligate co-receptors for HIV-1 entry have lent urgency to studies on the relationships between chemokines and lymphocytes. My laboratory has characterized Mig and Crg-2/IP-10, chemokines that are induced by IFN-g and that specifically target lymphocytes, particularly activated T cells. We have demonstrated that the genes for these chemokines are widely expressed during experimental infections in mice with protozoan and viral pathogens, but that the patterns of mig and crg-2 expression differed, suggesting non-redundant roles in vivo. Our related studies to identify new chemokine receptors from activated lymphocytes resulted in the cloning of STRL22 and STRL33. We and others have shown that STRL22 is a receptor for the CC chemokine MIP-3a, and STRL22 has been re-named CCR6. Although STRL33 remains an orphan receptor, we have shown that it can function as a co-receptor for HIV-1 envelope glycoproteins, and that it is active with a broader range of HIV-1 envelope glycoproteins than the major co-receptors described to date. The ability of STRL33 to function with a wide variety of envelope glycoproteins may become particularly important if therapies are instituted to block other specific co-receptors. We presume that investigations into the roles of chemokines and their receptors in lymphocyte biology will provide information important for understanding the pathogenesis of AIDS and for manipulating immune and inflammatory responses for clinical benefit

  2. Acid resistance of starch granules

    Energy Technology Data Exchange (ETDEWEB)

    Nara, S.; Sakakura, M.; Komiya, T.

    1983-08-01

    When potato starch was hydrolyzed to form Naegeli amylodextrin by 16% sulfuric acid at 30/sup 0/C, only the amorphous portion of the starch granules was deteriorated. The crystallinity of Naegeli amylodextrin showing the hydrolysis ratio of 0.22 was 1.28 times as large as that of original starch. The hydrolysis process at above 45/sup 0/C was given by two exponential equations. The value of acid resistance portion (C/sub 0/) at 30 and 38/sup 0/C was 100%, while the values at 45, 50 and 55/sup 0/C were 67, 38 and 18%, respectively. The high value of C/sub 0/ generally showed the high acid resistance in the various starches. Sweet potato and waxy rice starches were more easily hydrolysed than other starches, although they gave the relatively high value of C/sub 0/. Thus, it was slightly more difficult for low acid resistance portion of potato starch to be hydrolyzed than for that of other starches. Moreover, that of waxy rice was easily hydrolyzed.

  3. Hippocampal granule cells opt for early retirement.

    Science.gov (United States)

    Alme, C B; Buzzetti, R A; Marrone, D F; Leutgeb, J K; Chawla, M K; Schaner, M J; Bohanick, J D; Khoboko, T; Leutgeb, S; Moser, E I; Moser, M-B; McNaughton, B L; Barnes, C A

    2010-10-01

    Increased excitability and plasticity of adult-generated hippocampal granule cells during a critical period suggests that they may "orthogonalize" memories according to time. One version of this "temporal tag" hypothesis suggests that young granule cells are particularly responsive during a specific time period after their genesis, allowing them to play a significant role in sculpting CA3 representations, after which they become much less responsive to any input. An alternative possibility is that the granule cells active during their window of increased plasticity, and excitability become selectively tuned to events that occurred during that time and participate in later reinstatement of those experiences, to the exclusion of other cells. To discriminate between these possibilities, rats were exposed to different environments at different times over many weeks, and cell activation was subsequently assessed during a single session in which all environments were revisited. Dispersing the initial experiences in time did not lead to the increase in total recruitment at reinstatement time predicted by the selective tuning hypothesis. The data indicate that, during a given time frame, only a very small number of granule cells participate in many experiences, with most not participating significantly in any. Based on these and previous data, the small excitable population of granule cells probably correspond to the most recently generated cells. It appears that, rather than contributing to the recollection of long past events, most granule cells, possibly 90-95%, are effectively "retired." If granule cells indeed sculpt CA3 representations (which remains to be shown), then a possible consequence of having a new set of granule cells participate when old memories are reinstated is that new representations of these experiences might be generated in CA3. Whatever the case, the present data may be interpreted to undermine the standard "orthogonalizer" theory of the role of

  4. Effect of Drug Sera from per os Da Cheng Qi(大承气) Granule on Production/Secretion of IL-2 by Intestinal Intraepithelial Lymphocytes of Mice%大承气颗粒药物血清对小鼠肠上皮内淋巴细胞产生/分泌IL-2的作用

    Institute of Scientific and Technical Information of China (English)

    方步武; 吴咸中; 来丽娜; 陈菲; 刘俊红; 李继坤; 王民宪; 崔志清; 林秀珍

    2005-01-01

    目的:探讨大承气颗粒药物血清对小鼠肠上皮内淋巴细胞产生/分泌白细胞介素-2(interleukin-2,IL-2)的作用.方法:以不同浓度的大承气颗粒剂灌胃大鼠后不同时间点于无菌条件下采取腹腔静脉血,制备药物血清;分离培养肠上皮内淋巴细胞(intestinal intraepithelial lymphocytes,IELs),以药物血清作用于IELs,设培养液对照、IEL对照、正常血清对照,采用放射免疫分析法测定IL-2.结果:不同浓度大承气颗粒的药物血清在多数时间点的作用明显强于培养液对照、IEL对照及正常大鼠血清对照.正常大鼠血清对照组与IEL对照组的IL-2水平很接近.同时间点的药物血清比较,在30 min和12 h时,4%大承气颗粒的药物血清作用强;在3 h时,40%大承气颗粒的作用最强.4%、20%大承气颗粒的药物血清使小鼠分泌IL-2的作用在1.5 h达峰值,在24 h出现第二个峰值;40%大承气颗粒药物血清使IEL分泌IL-2的峰值在3 h.结论:不同浓度的大承气颗粒制备的药物血清具有使IEL产生/分泌IL-2的作用;该作用涉及到药物本身和药物在体内的活性代谢物和/或其诱导的内源性活性物质的作用.

  5. Intracranial localization of arachnoid granulations in rats

    Institute of Scientific and Technical Information of China (English)

    Yanan Dong; Min Yu; Lei Meng; Yong Jiang; Jun Gao; Honghai Peng; Jianguo Shi

    2008-01-01

    BACKGROUND: This paper describes histomorphologic studies on arachnoid granulations in rats, which have not been investigated in China to our knowledge.OBJECTIVE: To observe the distribution of intracranial arachnoid granulations in rats. DESIGN, TIME AND SETTING: The observational experiment was performed in the Academy of Life Sciences of Shandong Taishan Medical College from May to August 2004.MATERIALS: Thirty healthy adult Wistar rats (3-4 months old) of SPF grade, equal numbers of each sex, were selected for this study. Methylene blue parenteral solution was provided by Jiangsu Jichuan Pharmaceutical Company (China), and an optical microscope (Type: CH20; Olympus Co. Ltd., Japan) was used for observation of the histomorphology of the arachnoid granulations.METHOD: Injection of methylene blue parenteral solution into the cerebellomedullary cistern of rats.MAIN OUTCOME MEASURE: The blue stained parts of the lateral sinus were sectioned, stained by hematoxylin and eosin, and then observed under the microscope.RESULTS: The cavitas subarachnoidealis had extensive blue staining after methylene blue injection, while the arachnoid and dura were without dye accumulation. The blue dye indicated the location of the arachnoid granulations. The location of these granulations was fixed, mainly in the lateral sinus at both sides of confluence within 4 mm of the internal jugular vein.CONCLUSION: The arachnoid granulations of the rat were located mainly in the lateral sinuses of the dura mater.

  6. Cyclophosphamide, Alvocidib, and Rituximab in Treating Patients With High Risk B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2015-11-10

    Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Small Lymphocytic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  7. LYMPHOCYTE APOPTOSIS IN PSORIASIS

    Directory of Open Access Journals (Sweden)

    О. M. Kapuler

    2006-01-01

    Full Text Available Abstract. Forty-two patients with progressive vulgar psoriasis (PASI = 19.7 ± 1.5 and 40 healthy volunteers were under investigation. Psoriatic patients were characterized by increased number of CD4+ CD95+ peripheral blood T lymphocytes, which correlates with clinical psoriatic score, and by increased levels of soluble Fas (sFas in serum, as compared to controls (resp., 1868.1 ± 186.8 pg/ml vs. 1281.4 ± 142.5 pg/ml, PLSD = 0.019. The levels of spontaneous lymphocyte apoptosis and anti-Fas (Mab-induced apoptosis in psoriatic patients did not differ from the controls. However, apoptosis induced by “oxidative stress” (50 M Н202, 4 hrs was depressed in the patients. Moreover, a simultaneous assessment of cell cycle structure (metachromatic staining with Acridine Orange, apoptosis and Fas receptor expression (AnnV-FITC/antiFas mAbs-PE staining following a short-term mitogenic stimulation (PHA-P, 5 µg/ml, 24 hrs were performed. We found no marked differences in mitogenic reactivity, activation-induced apoptosis, and activation-induced Fas receptor expression when studying lymphocytes from healthy donors and psoriatic patients. However, PHA-activated lymphocytes from psoriatic patients displayed a significantly decreased ratio of AnnV+CD95+ to the total AnnV+ subpopulation, thus suggesting a decreased role of Fas-dependent mechanisms of apoptosis during the cell activation. The data obtained confirm a view, that an abnormal lymphocyte “apoptotic reactivity”, which plays a crucial role in the mechanisms of autoimmunity, may also of importance in the pathogenesis of psoriasis.

  8. Study of light scattering by a granulated coated sphere - a model of granulated blood cells

    NARCIS (Netherlands)

    M.A. Yurkin; D. de Kanter; A.G. Hoekstra

    2008-01-01

    We performed extensive simulations of light scattering by granulated coated sphere model using the discrete dipole approximation and varying model parameters in the ranges of sizes and refractive indices of granulated blood cells. We compared these results with predictions of Maxwell-Garnett effecti

  9. Granule size control and targeting in pulsed spray fluid bed granulation.

    Science.gov (United States)

    Ehlers, Henrik; Liu, Anchang; Räikkönen, Heikki; Hatara, Juha; Antikainen, Osmo; Airaksinen, Sari; Heinämäki, Jyrki; Lou, Honxiang; Yliruusi, Jouko

    2009-07-30

    The primary aim of the study was to investigate the effects of pulsed liquid feed on granule size. The secondary aim was to increase knowledge of this technique in granule size targeting. Pulsed liquid feed refers to the pump changing between on- and off-positions in sequences, called duty cycles. One duty cycle consists of one on- and off-period. The study was performed with a laboratory-scale top-spray fluid bed granulator with duty cycle length and atomization pressure as studied variables. The liquid feed rate, amount and inlet air temperature were constant. The granules were small, indicating that the powder has only undergone ordered mixing, nucleation and early growth. The effect of atomizing pressure on granule size depends on inlet air relative humidity, with premature binder evaporation as a reason. The duty cycle length was of critical importance to the end product attributes, by defining the extent of intermittent drying and rewetting. By varying only the duty cycle length, it was possible to control granule nucleation and growth, with a wider granule size target range in increased relative humidity. The present study confirms that pulsed liquid feed in fluid bed granulation is a useful tool in end product particle size targeting.

  10. Investigation of Physicochemical Drug Properties to Prepare Fine Globular Granules Composed of Only Drug Substance in Fluidized Bed Rotor Granulation.

    Science.gov (United States)

    Mise, Ryohei; Iwao, Yasunori; Kimura, Shin-Ichiro; Osugi, Yukiko; Noguchi, Shuji; Itai, Shigeru

    2015-01-01

    The effect of some drug properties (wettability and particle size distribution) on granule properties (mean particle size, particle size distribution, sphericity, and granule strength) were investigated in a high (>97%) drug-loading formulation using fluidized bed rotor granulation. Three drugs: acetaminophen (APAP); ibuprofen (IBU); and ethenzamide (ETZ) were used as model drugs based on their differences in wettability and particle size distribution. Granules with mean particle sizes of 100-200 µm and a narrow particle size distribution (PSD) could be prepared regardless of the drug used. IBU and ETZ granules showed a higher sphericity than APAP granules, while APAP and ETZ granules exhibited higher granule strength than IBU. The relationship between drug and granule properties suggested that the wettability and the PSD of the drugs were critical parameters affecting sphericity and granule strength, respectively. Furthermore, the dissolution profiles of granules prepared with poorly water-soluble drugs (IBU and ETZ) showed a rapid release (80% release in 20 min) because of the improved wettability with granulation. The present study demonstrated for the first time that fluidized bed rotor granulation can prepare high drug-loaded (>97%) globular granules with a mean particle size of less than 200 µm and the relationship between physicochemical drug properties and the properties of the granules obtained could be readily determined, indicating the potential for further application of this methodology to various drugs.

  11. Eosinophil secretion of granule-derived cytokines

    Directory of Open Access Journals (Sweden)

    Lisa A Spencer

    2014-10-01

    Full Text Available Eosinophils are tissue-dwelling leukocytes, present in the thymus, and gastrointestinal and genitourinary tracts of healthy individuals at baseline, and recruited, often in large numbers, to allergic inflammatory foci and sites of active tissue repair. The biological significance of eosinophils is vast and varied. In health, eosinophils support uterine and mammary gland development, and maintain bone marrow plasma cells and adipose tissue alternatively activated macrophages, while in response to tissue insult eosinophils function as inflammatory effector cells, and, in the wake of an inflammatory response, promote tissue regeneration and wound healing. One common mechanism driving many of the diverse eosinophil functions is the regulated and differential secretion of a vast array of eosinophil-derived cytokines. Eosinophils are distinguished from most other leukocytes in that many, if not all, of the over three dozen eosinophil-derived cytokines are pre-synthesized and stored within intracellular granules, poised for very rapid, stimulus-induced secretion. Eosinophils engaged in cytokine secretion in situ utilize distinct pathways of cytokine release that include: classical exocytosis, whereby granules themselves fuse with the plasma membrane and release their entire contents extracellularly; piecemeal degranulation, whereby granule-derived cytokines are selectively mobilized into vesicles that emerge from granules, traverse the cytoplasm and fuse with the plasma membrane to release discrete packets of cytokines; and eosinophil cytolysis, whereby intact granules are extruded from eosinophils, and deposited within tissues. In this latter scenario, extracellular granules can themselves function as stimulus-responsive secretory-competent organelles within the tissue. Here we review the distinctive processes of differential secretion of eosinophil granule-derived cytokines.

  12. Aerobic granulation of protein-rich granules from nitrogen-lean wastewaters.

    Science.gov (United States)

    Chen, Yu-You; Ju, Sheau-Pyng; Lee, Duu-Jong

    2016-10-01

    Proteins (PN)-rich granules are stable in structure in long-term reactor operations. This study proposed to cultivate PN-rich granules with PN/polysaccharides (PS) >20 from nitrogen lean wastewater, with ammonia-nitrogen as sole nitrogen source at chemical oxygen demand (COD)/N of 153.8. The yielded granules can sustain their structural stability in sequencing batch reactor mode for sufficient treatment of wastewaters up to 7000mg/L COD and with COD/Nnitrogen fed in the nitrogen-lean wastewater is converted to the PN in the granules. The replacement of ammonia by nitrate as sole nitrogen source led to granules enriched with γ-proteobacteria which are easily deteriorated at low OLR.

  13. Formation of volutin granules in Corynebacterium glutamicum.

    Science.gov (United States)

    Pallerla, Srinivas Reddy; Knebel, Sandra; Polen, Tino; Klauth, Peter; Hollender, Juliane; Wendisch, Volker F; Schoberth, Siegfried M

    2005-02-01

    Volutin granules are intracellular storages of complexed inorganic polyphosphate (poly P). Histochemical staining procedures differentiate between pathogenic corynebacteria such as Corynebacterum diphtheriae (containing volutin) and non-pathogenic species, such as C. glutamicum. Here we report that strains ATCC13032 and MH20-22B of the non-pathogenic C. glutamicum also formed subcellular entities (18-37% of the total cell volume) that had the typical characteristics of volutin granules: (i) volutin staining, (ii) green UV fluorescence when stained with 4',6-diamidino-2-phenylindole, (iii) electron-dense and rich in phosphorus when determined with transmission electron microscopy and X-ray microanalysis, and (iv) 31P NMR poly P resonances of isolated granules dissolved in EDTA. MgCl2 addition to the growth medium stimulated granule formation but did not effect expression of genes involved in poly P metabolism. Granular volutin fractions from lysed cells contained polyphosphate glucokinase as detected by SDS-PAGE/MALDI-TOF, indicating that this poly P metabolizing enzyme is present also in intact poly P granules. The results suggest that formation of volutin is a more widespread phenomenon than generally accepted.

  14. Amylase activity in substrate deficiency aerobic granules.

    Science.gov (United States)

    Lee, Chuen-Chi; Lee, Duu-Jong; Lai, Juin-Yih

    2009-01-01

    Immunohistochemical staining was applied together with the multicolor fluorescent scheme to demonstrate the amylase activity for polysaccharide hydrolysis in stored or starved aerobic granules that are in substrate deficiency. If sufficient nutrients were present, alpha-amylase and beta-amylase were found close to the surface layer of the original granules. Following storage or starvation during which most external nutrients were depleted, the alpha-amylase and beta-amylase were distributed over the entire granule interior, suggesting endogenous respiration at the core of the granule. In particular, the fluorescent intensities of alpha-amylase and beta-amylase were enriched 5-20 microm from the edge of the internal cavity, suggesting the strong correlation between polysaccharide hydrolysis and the formation of interior cavities. The secreted amylase was located near the living cells, suggesting that the polysaccharide hydrolysis is restricted to local environment that occurs near the functional strains. Internal hydrolysis within the core, for the case of both proteins and polysaccharides should correspond in principle to the loss of granule stability.

  15. 类胰蛋白酶在冠心病患者尸检心脏组织中的表达%Expression of tryptase in patiens with coronary heart disease autopsy heart tissue

    Institute of Scientific and Technical Information of China (English)

    付立平; 张付瑶; 王涛; 王慧君

    2012-01-01

    Objective To investigate the relationship between tryptase expression in patients with coronary heart disease and severity of the coronary artery disease. Methods Autopsy heart samples (n =70) collected during 2008-2011 were divided into 4 groups..Group A (20 cases) died of sudden death with coronary heart disease (SCD) ;group B (20 cases) , non-sudden death with coronary heart disease; group C (10 cases) died of anaphylaxis sudden death;group D (20 cases) ,died of any cause without atherosclerosis. Tryptase was detected by immunohistochemistry ( SP method) and image analysis system. Results OD in ischemic myocardium were significantly higher in SCD, CHD, sudden death of hypersensi-tivity up than that in the control group, and comparison among the groups showed statistically significantly differences (P<0.05). Conclusions Tryptase expression is increased in ischemic myocardium of SCD patients. Increased expression of tryptase in ischemic myocardium is closely related to the occurrence of SCD, providing new ways for SCD diagnosis and clinical research of prevention and treatment of coronary heart disease.%目的 探讨类胰蛋白酶(tryptase)与冠心病病情及与冠状动脉病变程度的关系.方法 从本教研室2008~2011年尸检档案中挑选病例及心脏标本共70例.分为四组:A组:冠心病猝死(SCD,20例);B组:冠心病非猝死者(CHD,20例);C组:过敏性猝死(10例);D组:阴性对照(无明显动脉粥样硬化病变的死者,20例).应用免疫组化染色(SP法)和图像定量分析法,观察每例左心室缺血心肌的类胰蛋白酶染色情况和光密度.结果 SCD组、CHD组、过敏性猝死组光密度值均高于阴性对照组,各组间比较均有显著差异(P<0.01).结论 缺血心肌中类胰蛋白酶的表达增加与SCD的发生密切相关,为SCD的诊断和临床对冠心病防治的研究提供新的途径.

  16. Amniotic Fluid Embolism Pathophysiology Suggests the New Diagnostic Armamentarium: β-Tryptase and Complement Fractions C3-C4 Are the Indispensable Working Tools

    Directory of Open Access Journals (Sweden)

    Francesco Paolo Busardò

    2015-03-01

    Full Text Available Amniotic fluid embolism (AFE is an uncommon obstetric condition involving pregnant women during labor or in the initial stages after delivery. Its incidence is estimated to be around 5.5 cases per 100,000 deliveries. Therefore, this paper investigated the pathophysiological mechanism, which underlies AFE, in order to evaluate the role of immune response in the development of this still enigmatic clinical entity. The following databases (from 1956 to September 2014 Medline, Cochrane Central, Scopus, Web of Science and Science Direct were used, searching the following key words: AFE, pathophysiology, immune/inflammatory response, complement and anaphylaxis. The main key word “AFE” was searched singularly and associated individually to each of the other keywords. Of the 146 sources found, only 19 were considered appropriate for the purpose of this paper. The clinical course is characterized by a rapid onset of symptoms, which include: acute hypotension and/or cardiac arrest, acute hypoxia (with dyspnoea, cyanosis and/or respiratory arrest, coagulopathies (disseminated intravascular coagulation and/or severe hemorrhage, coma and seizures. The pathology still determines a significant morbidity and mortality and potential permanent neurological sequelae for surviving patients. At this moment, numerous aspects involving the pathophysiology and clinical development are still not understood and several hypotheses have been formulated, in particular the possible role of anaphylaxis and complement. Moreover, the detection of serum tryptase and complement components and the evaluation of fetal antigens can explain several aspects of immune response.

  17. Measuring stellar granulation during planet transits

    Science.gov (United States)

    Chiavassa, A.; Caldas, A.; Selsis, F.; Leconte, J.; Von Paris, P.; Bordé, P.; Magic, Z.; Collet, R.; Asplund, M.

    2017-01-01

    Context. Stellar activity and convection-related surface structures might cause bias in planet detection and characterization that use these transits. Surface convection simulations help to quantify the granulation signal. Aims: We used realistic three-dimensional (3D) radiative hydrodynamical (RHD) simulations from the Stagger grid and synthetic images computed with the radiative transfer code Optim3D to model the transits of three prototype planets: a hot Jupiter, a hot Neptune, and a terrestrial planet. Methods: We computed intensity maps from RHD simulations of the Sun and a K-dwarf star at different wavelength bands from optical to far-infrared that cover the range of several ground- and space-based telescopes which observe exoplanet transits. We modeled the transit using synthetic stellar-disk images obtained with a spherical-tile imaging method and emulated the temporal variation of the granulation intensity generating random images covering a granulation time-series of 13.3 h. We measured the contribution of the stellar granulation on the light curves during the planet transit. Results: We identified two types of granulation noise that act simultaneously during the planet transit: (i) the intrinsic change in the granulation pattern with timescale (e.g., 10 min for solar-type stars assumed in this work) is smaller than the usual planet transit ( hours as in our prototype cases); and (ii) the fact that the transiting planet occults isolated regions of the photosphere that differ in local surface brightness as a result of convective-related surface structures. First, we showed that our modeling approach returns granulation timescale fluctuations that are comparable with what has been observed for the Sun. Then, our statistical approach shows that the granulation pattern of solar and K-dwarf-type stars have a non-negligible effect of the light curve depth during the transit, and, consequentially on the determination of the planet transit parameters such as the

  18. Antimicrobial-Coated Granules for Disinfecting Water

    Science.gov (United States)

    Akse, James R.; Holtsnider, John T.; Kliestik, Helen

    2011-01-01

    Methods of preparing antimicrobialcoated granules for disinfecting flowing potable water have been developed. Like the methods reported in the immediately preceding article, these methods involve chemical preparation of substrate surfaces (in this case, the surfaces of granules) to enable attachment of antimicrobial molecules to the surfaces via covalent bonds. A variety of granular materials have been coated with a variety of antimicrobial agents that include antibiotics, bacteriocins, enzymes, bactericides, and fungicides. When employed in packed beds in flowing water, these antimicrobial-coated granules have been proven effective against gram-positive bacteria, gram-negative bacteria, fungi, and viruses. Composite beds, consisting of multiple layers containing different granular antimicrobial media, have proven particularly effective against a broad spectrum of microorganisms. These media have also proven effective in enhancing or potentiating the biocidal effects of in-line iodinated resins and of very low levels of dissolved elemental iodine.

  19. MEMBRANE-COATING GRANULES OF KERATINIZING EPITHELIA.

    Science.gov (United States)

    MATOLTSY, A G; PARAKKAL, P F

    1965-02-01

    The purpose of this study has been to obtain information on the development of the envelop of horny cells that resists the action of keratinolytic agents. Toward this end the epidermis, oral mucosa, and tongue epithelium of various vertebrates, as well as the isolated envelopes of horny cells, were examined by electron microscopy. It was found that small cytoplasmic granules (1,000 to 5,000 A) that develop within differentiating epithelial cells move toward the cell periphery, and after fusion with the plasma membrane, empty their contents into the intercellular spaces. The content of the granules spreads over the cell surfaces, and subsequently a thickened and coated cell envelope is formed that resists the action of keratinolytic agent. The membrane-coating granule is regarded as a specific differentiation product of the keratinizing epithelium. It contains numerous inner membranes and is assumed to engage in synthetic activities such as, perhaps, the formation of polysaccharides.

  20. Arachnoid granulation affected by subarachnoid hemorrhage

    Directory of Open Access Journals (Sweden)

    R.P. Chopard

    1993-11-01

    Full Text Available The purpose of this study was to investigate using light microscopy the fibro-cellular components of arachnoid granulations affected by mild and severe subarachnoid hemorrage. The erythrocytes were in the channels delimitated by collagenous and elastic bundles and arachnoid cells, showing their tortuous and intercommunicating row from the pedicle to the fibrous capsule. The core portion of the pedicle and the center represented a principal route to the bulk outflow of cerebrospinal fluid and erythrocytes. In the severe hemorrhage, the fibrocellular components are desorganized, increasing the extracellular channels. We could see arachnoid granulations without erythrocytes, which cells showed big round nucleous suggesting their transformation into phagocytic cells.

  1. Molecular composition of IMP1 ribonucleoprotein granules

    DEFF Research Database (Denmark)

    Jønson, Lars; Vikesaa, Jonas; Krogh, Anders

    2007-01-01

    Localized mRNAs are transported to sites of local protein synthesis in large ribonucleoprotein (RNP) granules, but their molecular composition is incompletely understood. Insulin-like growth factor II mRNA-binding protein (IMP) zip code-binding proteins participate in mRNA localization, and in mo......Localized mRNAs are transported to sites of local protein synthesis in large ribonucleoprotein (RNP) granules, but their molecular composition is incompletely understood. Insulin-like growth factor II mRNA-binding protein (IMP) zip code-binding proteins participate in mRNA localization...

  2. Neutrophil granules in health and disease

    DEFF Research Database (Denmark)

    Häger, M; Cowland, J B; Borregaard, N

    2010-01-01

    Neutrophil granules store proteins that are critically important for the neutrophil to move from the vascular bed to tissues and to kill microorganisms. This is illustrated in nature when individual proteins are deleted due to inherited mutations of their cognate genes, and such deficiencies result...... in the conditions leucocyte adhesion deficiency and chronic granulomatous disease. The granules of the neutrophil have traditionally been divided into two or three major types but are instead a continuum where several subtypes can be identified with differences in protein content and propensity for mobilization...

  3. Continuous melt granulation: Influence of process and formulation parameters upon granule and tablet properties.

    Science.gov (United States)

    Monteyne, Tinne; Vancoillie, Jochem; Remon, Jean-Paul; Vervaet, Chris; De Beer, Thomas

    2016-10-01

    The pharmaceutical industry has a growing interest in alternative manufacturing models allowing automation and continuous production in order to improve process efficiency and reduce costs. Implementing a switch from batch to continuous processing requires fundamental process understanding and the implementation of quality-by-design (QbD) principles. The aim of this study was to examine the relationship between formulation-parameters (type binder, binder concentration, drug-binder miscibility), process-parameters (screw speed, powder feed rate and granulation temperature), granule properties (size, size distribution, shape, friability, true density, flowability) and tablet properties (tensile strength, friability, dissolution rate) of four different drug-binder formulations using Design of experiments (DOE). Two binders (polyethylene glycol (PEG) and Soluplus®) with a different solid state, semi-crystalline vs amorphous respectively, were combined with two model-drugs, metoprolol tartrate (MPT) and caffeine anhydrous (CAF), both having a contrasting miscibility with the binders. This research revealed that the granule properties of miscible drug-binder systems depended on the powder feed rate and barrel filling degree of the granulator whereas the granule properties of immiscible systems were mainly influenced by binder concentration. Using an amorphous binder, the tablet tensile strength depended on the granule size. In contrast, granule friability was more important for tablet quality using a brittle binder. However, this was not the case for caffeine-containing blends, since these phenomena were dominated by the enhanced compression properties of caffeine Form I, which was formed during granulation. Hence, it is important to gain knowledge about formulation behavior during processing since this influences the effect of process parameters onto the granule and tablet properties.

  4. Granule size distributions after twin-screw granulation - Do not forget the feeding systems.

    Science.gov (United States)

    Meier, R; Thommes, M; Rasenack, N; Moll, K-P; Krumme, M; Kleinebudde, P

    2016-09-01

    The aim of this study was to investigate the influence of qualitatively different powder feeder performances on resulting granule size distributions after twin-screw granulation of a highly drug loaded, hydrophobic mixture and a mannitol powder. It was shown that powder feeder related problems usually cannot be identified by trusting in the values given by the feeder. Therefore, a newly developed model for the evaluation of the performance of powder feeders was introduced and it was tried to connect this model to residence time distributions in twin-screw granulation processes. The influence of feeder performances on resulting granule size distributions varied, depending on the applied screw configuration and the used powder. Regarding the hydrophobic and highly drug loaded formulation, which was granulated at an L/S-ratio of 0.5, a pure conveying screw and a medium kneading configuration, consisting of 60° kneading blocks were negatively influenced by poor feeder settings. For optimal settings more narrow distributions could be obtained. For an extensive kneading configuration good and poor settings resulted in mono-modal granule size distributions but were differing in the overall size. Mannitol, a model substance for a liquid sensitive formulation was granulated at an L/S-ratio of 0.075. It was even more important to maintain optimal feeding as mannitol was highly affected by poor feeder performances. Even an extensive kneading configuration could not level the errors in powder feeder performance, resulting in qualitatively different granule size distributions. The results of this study demonstrate the importance of detailed knowledge about applied feeding systems to gain optimal performance in twin-screw granulation.

  5. Rock mechanics modeling based on soft granulation theory

    CERN Document Server

    Owladeghaffari, H

    2008-01-01

    This paper describes application of information granulation theory, on the design of rock engineering flowcharts. Firstly, an overall flowchart, based on information granulation theory has been highlighted. Information granulation theory, in crisp (non-fuzzy) or fuzzy format, can take into account engineering experiences (especially in fuzzy shape-incomplete information or superfluous), or engineering judgments, in each step of designing procedure, while the suitable instruments modeling are employed. In this manner and to extension of soft modeling instruments, using three combinations of Self Organizing Map (SOM), Neuro-Fuzzy Inference System (NFIS), and Rough Set Theory (RST) crisp and fuzzy granules, from monitored data sets are obtained. The main underlined core of our algorithms are balancing of crisp(rough or non-fuzzy) granules and sub fuzzy granules, within non fuzzy information (initial granulation) upon the open-close iterations. Using different criteria on balancing best granules (information pock...

  6. Curcumin and Cholecalciferol in Treating Patients With Previously Untreated Stage 0-II Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2016-10-04

    Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia

  7. Granulate of stainless steel as compensator material

    NARCIS (Netherlands)

    J.P.C. van Santvoort (J. P C)

    1995-01-01

    textabstractCompensators produced with computer controlled milling devices usually consist of a styrofoam mould, filled with an appropriate material. We investigated granulate of stainless steel as filling material. This cheap, easy to use, clean and re-usable material can be obtained with an averag

  8. Structural studies on methylated starch granules

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Burgt, Y.E.M. van der; Bergsma, J.; Bleeker, I.P.; Mijland, P.J.H.C.; Kamerling, J.P.

    2000-01-01

    Granules of potato starch and amylopectin potato starch were methylated in aqueous alkaline suspension. Here, an overview is given of all structural aspects that have been studied with respect to the determination of the location of the substituents. Methods, which are generally applicable, were

  9. Starch Granule Variability in Wild Solanum Species

    Science.gov (United States)

    Because most of the dry matter of potato tubers is starch, an understanding of starch properties is important in potato improvement programs. Starch granule size is considered to influence tuber processing quality parameters such as gelatinization temperature, viscosity, and water holding capacity. ...

  10. Neutrophil granules in health and disease

    DEFF Research Database (Denmark)

    Häger, M; Cowland, J B; Borregaard, N

    2010-01-01

    Neutrophil granules store proteins that are critically important for the neutrophil to move from the vascular bed to tissues and to kill microorganisms. This is illustrated in nature when individual proteins are deleted due to inherited mutations of their cognate genes, and such deficiencies resu...

  11. Creep of granulated loose-fill insulation

    DEFF Research Database (Denmark)

    Rasmussen, Torben Valdbjørn

    with SP-Building Physics in Sweden and VTT Building Technology in Finland. For the round robin test a cellulosic fibre insulation material was used. The proposed standardised method for creep tests and theories are limited to cases when the granulated loose-fill material is exposed to a constant...

  12. High-shear granulation as a manufacturing method for cocrystal granules

    DEFF Research Database (Denmark)

    Rehder, Sönke; Christensen, Niels Peter Aae; Rantanen, Jukka

    2013-01-01

    influenced by the excipients, since in presence of calcium hydrogenphosphate, the poorly water-soluble salt calcium tartrate monohydrate was formed at high relative humidity. Interestingly, compactability was increased by cocrystal formation compared to that of the reference granules (piracetam...

  13. Apatite accumulation enhances the mechanical property of anammox granules

    NARCIS (Netherlands)

    Lin, Y. M.; Lotti, T.; Sharma, P. K.; van Loosdrecht, M. C. M.

    2013-01-01

    The strength of granular sludge is essential for the mechanical stability of the granules. Inorganic precipitants form a major factor influencing the strength of the granules. To check the possibility of apatite accumulation in anammox granules, and study its contribution to the mechanical strength

  14. Lymphocyte 'homing' and chronic inflammation.

    Science.gov (United States)

    Sakai, Yasuhiro; Kobayashi, Motohiro

    2015-07-01

    Chronic inflammation is a response to prolonged exposure to injurious stimuli that harm and destroy tissues and promote lymphocyte infiltration into inflamed sites. Following progressive accumulation of lymphocytes, the histology of inflamed tissue begins to resemble that of peripheral lymphoid organs, which can be referred to as lymphoid neogenesis or formation of tertiary lymphoid tissues. Lymphocyte recruitment to inflamed tissues is also reminiscent of lymphocyte homing to peripheral lymphoid organs. In the latter, under physiological conditions, homing receptors expressed on lymphocytes adhere to vascular addressin expressed on high endothelial venules (HEVs), initiating a lymphocyte migration process composed of sequential adhesive interactions. Intriguingly, in chronic inflammation, HEV-like vessels are induced de novo, despite the fact that the inflamed site is not originally lymphoid tissue, and these vessels contribute to lymphocyte recruitment in a manner similar to physiological lymphocyte homing. In this review, we first describe physiological lymphocyte homing mechanisms focusing on vascular addressins. We then describe HEV-like vessel-mediated pathogenesis seen in various chronic inflammatory disorders such as Helicobacter pylori gastritis, inflammatory bowel disease (IBD), autoimmune pancreatitis and sclerosing sialadenitis, as well as chronic inflammatory cell neoplasm MALT lymphoma, with reference to our work and that of others.

  15. Lymphocyte Trafficking to Mucosal Tissues

    DEFF Research Database (Denmark)

    Mikhak, Zamaneh; Agace, William Winston; Luster, Andrew D.

    2015-01-01

    Lymphocytes are the key cells of the adaptive immune system that provide antigen-specific responses tailored to the context of antigen exposure. Through cytokine release and antibody production, lymphocytes orchestrate and amplify the recruitment and function of other immune cells and contribute...... to host defense against invading pathogens and the pathogenesis of many inflammatory diseases. Lymphocyte function is critically dependent on their ability to traffic into the correct anatomic locations at the appropriate times. This process is highly regulated and requires that lymphocytes interact...

  16. Lymphocytic Interstitial Pneumonia.

    Science.gov (United States)

    Panchabhai, Tanmay S; Farver, Carol; Highland, Kristin B

    2016-09-01

    Lymphocytic interstitial pneumonia (LIP) is a rare lung disease on the spectrum of benign pulmonary lymphoproliferative disorders. LIP is frequently associated with connective tissue diseases or infections. Idiopathic LIP is rare; every attempt must be made to diagnose underlying conditions when LIP is diagnosed. Computed tomography of the chest in patients with LIP may reveal ground-glass opacities, centrilobular and subpleural nodules, and randomly distributed thin-walled cysts. Demonstrating polyclonality with immunohistochemistry is the key to differentiating LIP from lymphoma. The 5-year mortality remains between 33% and 50% and is likely to vary based on the underlying disease process.

  17. Reduced responses of submucous neurons from irritable bowel syndrome patients to a cocktail containing histamine, serotonin, TNFα and tryptase (IBS-cocktail

    Directory of Open Access Journals (Sweden)

    Daniela eOstertag

    2015-12-01

    Full Text Available Background & Aims:Malfunctions of enteric neurons are believed to play an important role in the pathophysiology of irritable bowel syndrome (IBS. Our aim was to investigate whether neuronal activity in biopsies from IBS patients is altered in comparison to healthy controls (HC.Methods:Activity of human submucous neurons in response to electrical nerve stimulation and local application of nicotine or a mixture of histamine, serotonin, tryptase and TNF-α (IBS-cocktail was recorded in biopsies from 17 HC and 35 IBS patients with the calcium-sensitive-dye Fluo-4 AM. The concentrations of the mediators resembeled those found in biopsy supernatants or blood. Neuronal activity in guinea-pig submucous neurons was studied with the voltage-sensitive-dye di-8-ANEPPS. Results:Activity in submucous ganglia in response to nicotine or electrical nerve stimulation was not different between HC and IBS patients (P=0.097 or P=0.448. However, the neuronal response after application of the IBS-cocktail was significantly decreased (P=0.039 independent of whether diarrhea (n=12, constipation (n=5 or bloating (n=5 was the predominant symptom. In agreement with this we found that responses of submucous ganglia conditioned by overnight incubation with IBS mucosal biopsy supernatant to spritz application of this supernatant was significantly reduced (P=0.019 when compared to incubation with HC supernatant.Conclusion:We demonstrated for the first time reduced neuronal responses in mucosal IBS biopsies to an IBS mediator cocktail. While excitability to classical stimuli of enteric neurons was comparable to HC, the activation by the IBS-cocktail was decreased. This was very likely due to desensitization to mediators constantly released by mucosal and immune cells in the gut wall of IBS patients.

  18. Polyamines are present in mast cell secretory granules and are important for granule homeostasis.

    Directory of Open Access Journals (Sweden)

    Gianni García-Faroldi

    Full Text Available BACKGROUND: Mast cell secretory granules accommodate a large number of components, many of which interact with highly sulfated serglycin proteoglycan (PG present within the granules. Polyamines (putrescine, spermidine and spermine are absolutely required for the survival of the vast majority of living cells. Given the reported ability of polyamines to interact with PGs, we investigated the possibility that polyamines may be components of mast cell secretory granules. METHODOLOGY/PRINCIPAL FINDINGS: Spermidine was released by mouse bone marrow derived mast cells (BMMCs after degranulation induced by IgE/anti-IgE or calcium ionophore A23187. Additionally, both spermidine and spermine were detected in isolated mouse mast cell granules. Further, depletion of polyamines by culturing BMMCs with α-difluoromethylornithine (DFMO caused aberrant secretory granule ultrastructure, impaired histamine storage, reduced serotonin levels and increased β-hexosaminidase content. A proteomic approach revealed that DFMO-induced polyamine depletion caused an alteration in the levels of a number of proteins, many of which are connected either with the regulated exocytosis or with the endocytic system. CONCLUSIONS/SIGNIFICANCE: Taken together, our results show evidence that polyamines are present in mast cell secretory granules and, furthermore, indicate an essential role of these polycations during the biogenesis and homeostasis of these organelles.

  19. Experimental investigation of granule size and shape dynamics in twin-screw granulation.

    Science.gov (United States)

    Kumar, Ashish; Vercruysse, Jurgen; Bellandi, Giacomo; Gernaey, Krist V; Vervaet, Chris; Remon, Jean Paul; De Beer, Thomas; Nopens, Ingmar

    2014-11-20

    A twin-screw granulator (TSG), a promising equipment for continuous high shear wet granulation (HSWG), achieves the desired level of mixing by a combination of the appropriate screw configuration and a suitable set of process settings (e.g. feed rate, screw speed, etc.), thus producing a certain granule size and shape distribution (GSSD). However, the primary sizing and shaping mechanism behind the resulting distribution is not well understood due to the opacity of the multiphase system in the granulator. This study experimentally characterised the GSSD dynamics along the TSG barrel length in order to understand the function of individual screw modules and process settings, as well as their interaction. Particle size analysis of granules collected at the outlet of the TSG suggested significant interaction between the process and screw configuration parameters influencing the heterogeneity in the GSSD. By characterising the samples collected along the screw length, a variable influence of the screw modules at different process conditions was observed. At low liquid-to-solid ratio (L/S), the first kneading module seemed to play a significant role in mixing, whereas the second kneading module was found to be more involved in reshaping the granules. At high L/S and high throughput, aggregation mainly took place in the second kneading module changing the GSSD. The results obtained from this study will be further used for the calibration and validation of a mechanistic model and, hence, support future development of a more detailed understanding of the HSWG process in a TSG.

  20. Microbial starch binding domains are superior to granule bound starch synthase 1 for anchoring luciferase to potato starch granules

    NARCIS (Netherlands)

    Ji, Q.; Vincken, J.P.; Suurs, L.C.J.M.; Visser, R.G.F.

    2006-01-01

    Microbial starch-binding domains (SBD) and granule-bound starch synthase I (GBSSI) are proteins which are accumulated in potato starch granules. The efficiency of SBD and GBSSI for targeting active luciferase reporter proteins to granules during starch biosynthesis was compared. GBSSI or SBD sequenc

  1. Chronic lymphocytic leukaemia

    Science.gov (United States)

    Kipps, Thomas J.; Stevenson, Freda K.; Wu, Catherine J.; Croce, Carlo M.; Packham, Graham; Wierda, William G.; O’Brien, Susan; Gribben, John; Rai, Kanti

    2017-01-01

    Chronic lymphocytic leukaemia (CLL) is a malignancy of CD5+ B cells that is characterized by the accumulation of small, mature-appearing lymphocytes in the blood, marrow and lymphoid tissues. Signalling via surface immunoglobulin, which constitutes the major part of the B cell receptor, and several genetic alterations play a part in CLL pathogenesis, in addition to interactions between CLL cells and other cell types, such as stromal cells, T cells and nurse-like cells in the lymph nodes. The clinical progression of CLL is heterogeneous and ranges from patients who require treatment soon after diagnosis to others who do not require therapy for many years, if at all. Several factors, including the immunoglobulin heavy-chain variable region gene (IGHV) mutational status, genomic changes, patient age and the presence of comorbidities, should be considered when defining the optimal management strategies, which include chemotherapy, chemoimmunotherapy and/or drugs targeting B cell receptor signalling or inhibitors of apoptosis, such as BCL-2. Research on the biology of CLL has profoundly enhanced our ability to identify patients who are at higher risk for disease progression and our capacity to treat patients with drugs that selectively target distinctive phenotypic or physiological features of CLL. How these and other advances have shaped our current understanding and treatment of patients with CLL is the subject of this Primer. PMID:28102226

  2. Decreased deformability of lymphocytes in chronic lymphocytic leukemia

    Science.gov (United States)

    Zheng, Yi; Wen, Jun; Nguyen, John; Cachia, Mark A.; Wang, Chen; Sun, Yu

    2015-01-01

    This paper reports the first study of stiffness/deformability changes of lymphocytes in chronic lymphocytic leukemia (CLL) patients, demonstrating that at the single cell level, leukemic metastasis progresses are accompanied by biophysical property alterations. A microfluidic device was utilized to electrically measure cell volume and transit time of single lymphocytes from healthy and CLL patients. The results from testing thousands of cells reveal that lymphocytes from CLL patients have higher stiffness (i.e., lower deformability), as compared to lymphocytes in healthy samples, which was also confirmed by AFM indentation tests. This observation is in sharp contrast to the known knowledge on other types of metastatic cells (e.g., breast and lung cancer cells) whose stiffness becomes lower as metastasis progresses.

  3. Form, formation, and deformation : the influence of material properties and process conditions on the shape of granules produced by high shear granulation

    NARCIS (Netherlands)

    Bouwman, Anneke Margriet

    2005-01-01

    High shear granulation The introduction of this thesis describes the high shear granulation process. High shear granulation is a commonly used unit operation to produce larger granules of primary particles. The granulation process has been described to consist of different stages. The initial growth

  4. Obinutuzumab in chronic lymphocytic leukemia.

    Science.gov (United States)

    Dupuis, Jehan

    2015-09-01

    Obinutuzumab is the second next-generation monoclonal anti-CD20 antibody (after ofatumumab) to enter clinical practice in chronic lymphocytic leukemia. Its superiority in association with chlorambucil as compared with chlorambucil alone has led to its approval as a first-line treatment for chronic lymphocytic leukemia, for patients who are not candidates for a more intensive treatment.

  5. Protein Methylation and Stress Granules: Posttranslational Remodeler or Innocent Bystander?

    Directory of Open Access Journals (Sweden)

    Wen Xie

    2011-01-01

    Full Text Available Stress granules contain a large number of post-translationally modified proteins, and studies have shown that these modifications serve as recruitment tags for specific proteins and even control the assembly and disassembly of the granules themselves. Work originating from our laboratory has focused on the role protein methylation plays in stress granule composition and function. We have demonstrated that both asymmetrically and symmetrically dimethylated proteins are core constituents of stress granules, and we have endeavored to understand when and how this occurs. Here we seek to integrate this data into a framework consisting of the currently known post-translational modifications affecting stress granules to produce a model of stress granule dynamics that, in turn, may serve as a benchmark for understanding and predicting how post-translational modifications regulate other granule types.

  6. Enhanced aerobic nitrifying granulation by static magnetic field.

    Science.gov (United States)

    Wang, Xin-Hua; Diao, Mu-He; Yang, Ying; Shi, Yi-Jing; Gao, Ming-Ming; Wang, Shu-Guang

    2012-04-01

    One of the main challenging issues for aerobic nitrifying granules in treating high strength ammonia wastewater is the long granulation time required for activated sludge to transform into aerobic granules. The present study provides a novel strategy for enhancing aerobic nitrifying granulation by applying an intensity of 48.0mT static magnetic field. The element analysis showed that the applied magnetic field could promote the accumulation of iron compounds in the sludge. And then the aggregation of iron decreased the full granulation time from 41 to 25days by enhancing the setting properties of granules and stimulating the secretion of extracellular polymeric substances (EPS). Long-term, cycle experiments and fluorescence in-situ hybridization (FISH) analysis proved that an intensity of 48.0mT magnetic field could enhance the activities and growth of nitrite-oxidizing bacteria (NOB). These findings suggest that magnetic field is helpful and reliable for accelerating the aerobic nitrifying granulation.

  7. Hemoglobin expression in rat experimental granulation tissue

    Institute of Scientific and Technical Information of China (English)

    Miretta Tommila; Christoffer Stark; Anne Jokilammi; Ville Peltonen; Risto Penttinen; Erika Ekholm

    2011-01-01

    The general opinion that hemoglobin is only a carrier protein for oxygen and carbon dioxide has been challenged by several recent studies showing hemoglobin expression in other cells than those of the erythroid series, for example, in macrophages. We discovered β-globin expression in rat experimental granulation tissue induced by subcutaneously implanted cellulose sponges. Closer investigation revealed also α-globin expression. The first peak of the biphasic globin expression noticed during granulation tissue formation correlated with the invasion of monocytes/macrophages, whereas the second one seemed to be connected to the appearance of hematopoietic progenitors. Data presented in this study indicate globin expression both in macrophages and in immature erythroid cells as validated by erythroid-specific markers.

  8. The morphological details of globular keratohyalin granules.

    Science.gov (United States)

    Westerhof, W; Dingemans, K P

    1986-10-01

    In quickly dividing epithelia such as that of the tongue, keratohyalin formation takes place in globular keratohyalin granules (KHG). This is in contrast with the irregular KHG as seen in normal, slowly dividing epidermis. The morphogenesis of the globular KHG is explained in this study. In small KHG, dense aggregates of ribosomes can be seen at the site of blebs. It is suggested that these blebs framed with ribosomes are internalized giving rise to "dense homogeneous deposits" or "single granules". Lipid droplets occur in the upper spinous and horny layer. Globular KHG also contain variable amounts of lipids, and the lipid content seems to be inversely related to the protein content, dependent on the degree of cell differentiation or on the rate of cell turnover. It is suggested that in epithelia with a high cell turnover few rigid keratohyalin components are dispersed in lipids, which maintain a globular shape due to the surface tension.

  9. Zymophagy: Selective Autophagy of Secretory Granules

    Directory of Open Access Journals (Sweden)

    Maria I. Vaccaro

    2012-01-01

    Full Text Available Timing is everything. That's especially true when it comes to the activation of enzymes created by the pancreas to break down food. Pancreatic enzymes are packed in secretory granules as precursor molecules called zymogens. In physiological conditions, those zymogens are activated only when they reach the gut, where they get to work releasing and distributing nutrients that we need to survive. If this process fails and the enzymes are prematurely activated within the pancreatic cell, before they are released from the gland, they break down the pancreas itself causing acute pancreatitis. This is a painful disease that ranges from a mild and autolimited process to a severe and lethal condition. Recently, we demonstrated that the pancreatic acinar cell is able to switch on a refined mechanism that could explain the autolimited form of the disease. This is a novel selective form of autophagy named zymophagy, a cellular process to specifically detect and degrade secretory granules containing activated enzymes before they can digest the organ. In this work, we revise the molecules and mechanisms that mediate zymophagy, a selective autophagy of secretory granules.

  10. Influence of binder droplet dimension on granulation rate during fluidized bed granulation.

    Science.gov (United States)

    Fujiwara, Maya; Dohi, Masafumi; Otsuka, Tomoko; Yamashita, Kazunari; Sako, Kazuhiro

    2013-01-01

    Here, we statistically identified the critical factor of the granulation rate during the fluidized bed granulation process. Lactose was selected as the excipient and was granulated with several binders, including hydroxypropyl cellulose, hydroxypropyl methyl cellulose, and polyvinylpyrrolidone. The viscosity, density, and surface tension of the binder solution, contact angle, and the work done during adhesion and cohesion between the binder and lactose, mist diameter, Stokes number, and the dimension of the droplet were considered. The Stokes number was defined as the ratio of the inertial force to the viscous-damping force of a particle. We confirmed that droplet diameter after adhesion had the highest correlation coefficient with the granulation rate constant in our investigated parameters. Partial least squares regression revealed two critical principal components of the granulation rate: one relating to the droplet dimension, which is composed of mist diameter and diameter and thickness of the droplet after adhesion of the binder to the lactose surface; and the other relating to wettability, which involves the work done during adhesion and cohesion, surface tension, and the thickness of the droplet after adhesion of the binder to the lactose surface.

  11. Laboratorial diagnosis of lymphocytic meningitis

    Directory of Open Access Journals (Sweden)

    Sérgio Monteiro de Almeida

    Full Text Available Meningitis is the main infectious central nervous system (CNS syndrome. Viruses or bacteria can cause acute meningitis of infectious etiology. The term "Aseptic Meningitis" denotes a clinical syndrome with a predominance of lymphocytes in the cerebrospinal fluid (CSF, with no common bacterial agents identified in the CSF. Viral meningitis is considered the main cause of lymphocyte meningitis. There are other etiologies of an infectious nature. CSF examination is essential to establish the diagnosis and to identify the etiological agent of lymphocytic meningitis. We examined CSF characteristics and the differential diagnosis of the main types of meningitis.

  12. Laboratorial diagnosis of lymphocytic meningitis

    Directory of Open Access Journals (Sweden)

    Sérgio Monteiro de Almeida

    2007-10-01

    Full Text Available Meningitis is the main infectious central nervous system (CNS syndrome. Viruses or bacteria can cause acute meningitis of infectious etiology. The term "Aseptic Meningitis" denotes a clinical syndrome with a predominance of lymphocytes in the cerebrospinal fluid (CSF, with no common bacterial agents identified in the CSF. Viral meningitis is considered the main cause of lymphocyte meningitis. There are other etiologies of an infectious nature. CSF examination is essential to establish the diagnosis and to identify the etiological agent of lymphocytic meningitis. We examined CSF characteristics and the differential diagnosis of the main types of meningitis.

  13. A second look at intraepithelial Langerhans cells in mycosis fungoides and related disorders. Ultrastructural study with special reference to Langerhans granules and virus-like particles.

    Science.gov (United States)

    Füllbrandt, U; Meissner, K; Löning, T; Jänner, M

    1983-01-01

    Skin biopsies of patients with small and large plaque parapsoriasis, premycotic lesions and mycosis fungoides in different stages were examined. Special attention was paid to the relationships between Langerhans cells (LC) and the neighbouring keratinocytes and lymphocytes. At the contact areas of LC and keratinocytes as well as LC and lymphocytes, particular cell membrane phenomena were observed. Aggregations of Langerhans granules and fusions of granules with LC plasma membranes were found exclusively at LC-keratinocyte interfaces. At LC-lymphocyte contact zones cell membrane appositions were seen. In all cases investigated, virus-like particles were mainly found in LC and indeterminate cells (IDC). In 3 cases lymphocytes also contained these particles. It was of particular interest that virus-like particles were observed in skin specimens of all diseases investigated. Discrimination of these particles from other cellular organelles - especially lysosomes - was difficult, however. The significance of our findings, particularly regarding to the supposed virus aetiology of cutaneous T cell lymphomas, is discussed.

  14. WET-GRANULATION RESEARCH WITH APPLICATION TO SCALE-UP

    Institute of Scientific and Technical Information of China (English)

    Gabriel I.Tardos

    2005-01-01

    Granulation is a unit operation by which larger granules are produced from fine, powdery particles to improve appearance, flow properties and mixedness, reduce dustiness and, in general, produce engineered particles with superior attributes. Agglomeration in wet granulation is achieved by introducing a "binder" fluid onto a shearing mass of fine powders. This paper gives a general overview of the process with emphasis on a simplified granulation model based on a dimensionless parameter containing inertia and viscous dissipation energies between colliding particles: the so-called Stokes number. The model incorporates most common features of all granulation devices (mixers) used in the pharmaceutical industry.Also described in the paper is a computer simulation that captures the movement of flowing powder in an ideal mixer-granulator with constant shear rate. A fraction of the total number of particles is wet (covered by binder and therefore "sticky") while the rest of the particles are dry. The numerical simulation depicts two distinct regimes of agglomeration found in a typical granulator: granule growth and subsequent breakup. During granule growth-simulations, final granule size and shape distributions are obtained by analyzing the size and shape of formed granules using a pattern-recognition technique. A second kind of simulation, also using rapid granular flow modeling, follows the rotation and deformation of an "agglomerate" held together by a liquid binder. Results from these simulations yield critical values of the Stokes number. Below the critical value, the agglomerates are stable and only rotate in response to shear while above the critical value they break into two or more pieces. At the critical value, they attain a steady elongated shape. Using values of the critical Stokes number, the model predicts the size of formed granules.The existence of the critical state in which granules attain a characteristic elongated shape is used to measure shear forces

  15. Formation of artificial granules for proving gelation as the main mechanism of aerobic granulation in biological wastewater treatment.

    Science.gov (United States)

    Li, Yun; Yang, Shu-Fang; Zhang, Jian-Jun; Li, Xiao-Yan

    2014-01-01

    In this study, gelation-facilitated biofilm formation as a new mechanism is proposed for the phenomenon of aerobic granulation in biological wastewater treatment. To obtain an experimental proof for the gelation-based theory, the granulation process was simulated in a chemical system using latex particles for bacterial cells and organic polymers (alginate and peptone) for extracellular polymeric substances (EPS) in a solution with the addition of cations (Ca²⁺, Mg²⁺ and Fe³⁺). The results showed that at a low alginate content (70 mg g⁻¹ mixed liquid suspended solids (MLSS)) flocculation was observed in the suspension with loose flocs. At a higher alginate content (180 mg g⁻¹ MLSS), together with discharge of small flocs, formation of artificial gel granules was successfully achieved leading to granulation. The artificial granules show a morphological property similar to that of actual microbial granules. However, if the protein content increased, granulation became difficult with little gel formation. The experimental work demonstrates the importance of the bonding interactions between EPS functional groups and cations in gel formation and granulation. The laboratory results on the formation of artificial granules provide a sound proof for the theory of gelation-facilitated biofilm formation as the main mechanism for aerobic granulation in sludge suspensions.

  16. Visualization and understanding of the granulation liquid mixing and distribution during continuous twin screw granulation using NIR chemical imaging.

    Science.gov (United States)

    Vercruysse, Jurgen; Toiviainen, Maunu; Fonteyne, Margot; Helkimo, Niko; Ketolainen, Jarkko; Juuti, Mikko; Delaet, Urbain; Van Assche, Ivo; Remon, Jean Paul; Vervaet, Chris; De Beer, Thomas

    2014-04-01

    Over the last decade, there has been increased interest in the application of twin screw granulation as a continuous wet granulation technique for pharmaceutical drug formulations. However, the mixing of granulation liquid and powder material during the short residence time inside the screw chamber and the atypical particle size distribution (PSD) of granules produced by twin screw granulation is not yet fully understood. Therefore, this study aims at visualizing the granulation liquid mixing and distribution during continuous twin screw granulation using NIR chemical imaging. In first instance, the residence time of material inside the barrel was investigated as function of screw speed and moisture content followed by the visualization of the granulation liquid distribution as function of different formulation and process parameters (liquid feed rate, liquid addition method, screw configuration, moisture content and barrel filling degree). The link between moisture uniformity and granule size distributions was also studied. For residence time analysis, increased screw speed and lower moisture content resulted to a shorter mean residence time and narrower residence time distribution. Besides, the distribution of granulation liquid was more homogenous at higher moisture content and with more kneading zones on the granulator screws. After optimization of the screw configuration, a two-level full factorial experimental design was performed to evaluate the influence of moisture content, screw speed and powder feed rate on the mixing efficiency of the powder and liquid phase. From these results, it was concluded that only increasing the moisture content significantly improved the granulation liquid distribution. This study demonstrates that NIR chemical imaging is a fast and adequate measurement tool for allowing process visualization and hence for providing better process understanding of a continuous twin screw granulation system.

  17. Bone regeneration in rabbit calvaria with novel monetite granules.

    Science.gov (United States)

    Tamimi, Faleh; Torres, Jesús; Kathan, Carlos; Baca, Rafael; Clemente, Celia; Blanco, Luis; Lopez Cabarcos, Enrique

    2008-12-15

    The aim of this study was to evaluate whether local application of monetite granules would induce bone regeneration in critical size defects on rabbits calvaria. Novel monetite granules were synthesized by thermal conversion of preset brushite cement. Twelve female New Zealand rabbits were used for this study. Two identical 10-mm-diameter bicortical cranial defects were created in each animal. One of the defects was grafted with monetite granules while the contralateral was left unfilled as negative control. Animals were sacrificed at 4 and 8 weeks after surgery, and biopsies were taken for histological and histomorphometrical evaluation under light microscopy. Wilcoxon test was used for statistical analysis. The histological observations showed signs of graft resorption as newly formed bone tissue grew surrounding and penetrating the monetite granules. Histomorphometric evaluation showed that the augmented bone volume as well as the augmented mineral tissue was higher in the defects treated with monetite granules (p monetite granules in bone defects enhances bone healing significantly.

  18. Flow of formulation granules through a conical hopper

    Directory of Open Access Journals (Sweden)

    Mazumder B

    2008-01-01

    Full Text Available Gravity flow characteristics of various pharmaceutical granules through static conical hoppers of different cone angles were studied. Mass flow rate depends on properties of granules and cone angles when environmental conditions such as temperature and relative humidity are kept within a fixed range. The granules were made with active pharmaceutical ingredients as per Indian pharmacopoeia with other additives like binders and diluents. Lubricants were added with the granules to observe their effects on mass flow rate. Magnesium stearate and colloidal silicon dioxide of different proportions were used as lubricants after granulation. A new dimensionally analyzed equation was developed to predict flow rate of the granules. The developed equation agreed well with the experimental data with a percentage deviation of ±10%.

  19. Information granules and entropy theory in information systems

    Institute of Scientific and Technical Information of China (English)

    LIANG JiYe; QIAN YuHua

    2008-01-01

    Information granulation and entropy theory are two main approaches to research uncertainty of an information system,which have been widely applied in many practical issues.In this paper,the characterizations and representations of information granules under various binary relations are investigated in information systems,an axiom definition of information granulation is presented,and some existing definitions of information granulation become its special forms.Entropy theory in information systems is further developed and the granulation monotonicity of each of them is proved.Moreover,the complement relationship between information granulation and entropy is established.This investigation unifies the results of measures for uncertainties in complete information systems and incomplete information systems.

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

    Science.gov (United States)

    Ruszczak, Z; Ciborska, L; Kaszuba, A

    1988-12-01

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

  1. Giant arachnoid granulation in a patient with benign intracranial hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Kiroglu, Yilmaz; Yaqci, Baki; Cirak, Bayram; Karabulut, Nevzat [Pamukkale University, Department of Radiology, School of Medicine, Denizli (Turkey)

    2008-10-15

    We report magnetic resonance (MR), computed tomography (CT) and angiographic imaging of an unusual giant arachnoid granulation in the superior sagittal sinus in a man with headache and vertigo. Intrasinus pressure measurements revealed a significant pressure gradient across the lesion. MR imaging is useful to identify giant arachnoid granulation and dural sinus thrombosis, whereas dural sinus pressure measurement in certain cases of giant arachnoid granulations can be used to evaluate the lesion as the cause of the patient's symptoms. (orig.)

  2. Comparison of low shear, high shear, and fluid bed granulation during low dose tablet process development.

    Science.gov (United States)

    Hausman, Debra S

    2004-03-01

    Three processing methods were compared to develop a low dose (0.1%) immediate release tablet. Similar formulations were used to evaluate low shear, high shear, and fluid bed granulation methods. For each granulation process, the drug was dissolved or suspended in the granulating fluid and sprayed into the granulator. Both water and methanol were evaluated as granulating fluids. The low shear granulation was performed in a Patterson-Kelley V-Blender with I-bar. The high shear granulation was performed in a GRAL (top entry impeller) and a Diosna (bottom mounted impeller). Fluid bed granulation was also performed using top-spray. Acceptable content uniformity was obtained using each technology. The type of granulator and granulating solvent affected the granulation particle size distributions and bulk/tap densities. However, the addition of extragranular microcrystalline cellulose minimized the effect of variable granulation properties and allowed similar tablets to be produced from each granulation process.

  3. Initiation of lymphocyte DNA synthesis.

    Science.gov (United States)

    Coffman, F D; Fresa, K L; Cohen, S

    1991-01-01

    The initiation of DNA replication in T lymphocytes appears to be regulated by two distinct activities: one associated with proliferation which mediates initiation, and another associated with quiescence which blocks initiation. Activated lymphocytes and proliferating lymphoid cell lines produce an activity, termed ADR, which can initiate DNA replication in isolated, quiescent nuclei. ADR is heat-labile, has protease activity or interacts closely with a protease, and is distinct from the DNA polymerases. ADR activity is absent in quiescent lymphocytes and appears in mitogen-stimulated lymphocytes after IL-2 binding. The generation of active ADR appears to be mediated by phosphorylation of a precursor which is present in resting cells. Nuclei from mitogen-unresponsive lymphocytes fail to initiate DNA replication in response to ADR, of potential importance in the age-related decline of immunity. Quiescent lymphocytes lack ADR and synthesize an ADR-inhibitory activity. The ADR inhibitor is a heat-stable protein which suppresses the initiation of DNA synthesis, but is ineffective at suppressing elongation once DNA strand replication has begun. Nuclei from several neoplastic cell lines fail to respond to the ADR inhibitor, which may play a role in the continuous proliferation of these cells. At least one of these neoplastic cell lines produces both ADR and an inhibitory factor. These findings suggest that the regulation of proliferation is dependent on the balance between activating and inhibitory pathways.

  4. Freeze granulation for the processing of silicon nitride ceramics

    Energy Technology Data Exchange (ETDEWEB)

    Lyckfeldt, O. [Swedish Ceramic Inst., Goeteborg (Sweden); Rundgren, K. [Permascand AB, Ljungaverk (Sweden); Sjoestedt, M. [PowderPro HB, Hisings Backa (Sweden)

    2004-07-01

    Freeze granulation (LS-2, PowderPro HB, Sweden) has been demonstrated as a favourable alternative to conventional granulation methods (spray drying, sieve granulation etc) in the production of granules for the pressing of high-performance ceramic powders. Freeze granulation/freeze drying prevents the migration of pressing aids or particle fines to the granule surface, as is the case in spray drying. This ensures granule homogeneity and an easy breakdown of granules during pressing. This, in turn, results in defect minimisation and optimal conditions for the sintering and the development of the desired material properties. In this study silicon nitride materials have been produced using freeze granulation, pressing and sintering to validate the performance. Materials with competitive properties were manufactured based on medium-cost, direct-nitrided powders (SicoNide P95, Permascand AB, Sweden), various pressing and sintering aid compositions as well as various pressing and sintering schedules. MgO vs Fe{sub 2}O{sub 3} as sintering aid, PEG vs PVA as binder and higher pressure at the initial uniaxial pressing were found to promote the sintering performance. (orig.)

  5. Application of the Molecular Combing Technique to Starch Granules

    Directory of Open Access Journals (Sweden)

    Zhong-Dong Liu

    2009-10-01

    Full Text Available The molecular combing technique was used to dissociate the nanostructural units of starch granules from the starch fragments after a gelatinization process. With the help of atomic force microscopy (AFM, we observed that some nanostructural chains were just flowing out of the granules. It proves that there are substantive nanostructural units in the starch granules, a phenomenon not previously observed, so these nanostructural units were defined as suspected intermediates. Furthermore, we conclude that blocklets of starch granules are formed through twisting or distortion of nanochains.

  6. CHARACTERIZATION AND ADSORPTION PROPERTIES OF POROUS CARBON NANOFIBER GRANULES

    Institute of Scientific and Technical Information of China (English)

    Jiuling Chen; Qinghai Chen; Yongdan Li

    2006-01-01

    The properties of the porous granules produced by agglomeration of catalytically grown carbon nanofibers were investigated in this work. The single pellet crushing strength of the granules is high, e.g., 1.6-2.5 MPa. They have adsorption at 298 K of benzene or phenol on the granules is much lower than that on activated carbon and depends not only on the specific surface area of the carbon material but also on the sewing structure of the granules and the morphology of the carbon nanofibers. Treatment in dilute nitric acid appreciably reduces such adsorption.

  7. Aerobic granulation of pure bacterial strain Bacillus thuringiensis

    Institute of Scientific and Technical Information of China (English)

    Sunil S ADAV; Duu-Jong LEE

    2008-01-01

    The objective of this study is to cultivate aer-obic granules by pure bacterial strain, Bacillus thuringien-sis, in a sequencing batch reactor. Stable granules sized 2.0-2.2 mm were formed in the reactor after a five-week cultivation. These granules exhibited excellent settling attributes, and degraded phenol at rates of 1.49 and concentration, respectively. Confocal laser scanning microscopic test results show that Bacillus thuringiensis was distributed over the initial small aggregates, and the outer edge of the granule was away from the core regime in the following stage.

  8. Osseointegration of alumina bioceramic granules: A comparative experimental study

    Science.gov (United States)

    Rerikh, V. V.; Avetisyan, A. R.; Zaydman, A. M.; Anikin, K. A.; Bataev, V. A.; Nikulina, A. A.; Sadovoy, M. A.; Aronov, A. M.; Semantsova, E. S.

    2016-08-01

    To perform a comparative analysis of osseointegration of bioceramic alumina-based granules, hydroxyapatite-based granules, and deproteinized bone granules. The experiment was conducted on 52 adult male Kyoto-Wistar rats weighing 350 to 520 g. The animals were divided into five matched groups that differed only in the type of an implanted material. The granules were implanted in the lumbar vertebral bodies and in the distal right femur of each laboratory animal. Two months after surgery, the animals were euthanized, followed by tissue sampling for morphological studies. An examination of specimens from the groups with implanted alumina granules revealed the newly formed trabecular bone with remodeling signs. The bone tissue filled the intragranular space, tightly adhering to the granule surface. There was no connective tissue capsule on the border between bone tissue and alumina granules. Cylindrical bioceramic alumina-based granules with an open internal channel have a higher strength surpassing than that of analogs and the osseointegration ability close to that of hydroxyapatite and deproteinized bone granules.

  9. Microbial granulation for lactic acid production.

    Science.gov (United States)

    Kim, Dong-Hoon; Lee, Mo-Kwon; Hwang, Yuhoon; Im, Wan-Taek; Yun, Yeo-Myeong; Park, Chul; Kim, Mi-Sun

    2016-01-01

    This work investigated the formation of microbial granules to boost the productivity of lactic acid (LA). The flocculated form of LA-producing microbial consortium, dominated by Lactobacillus sp. (91.5% of total sequence), was initially obtained in a continuous stirred-tank reactor (CSTR), which was fed with 2% glucose and operated at a hydraulic retention time (HRT) of 12 h and pH 5.0 ± 0.1 under a thermophilic condition (50°C). The mixed liquor in the CSTR was then transferred to an up-flow anaerobic sludge blanket reactor (UASB). The fermentation performance and granulation process were monitored with a gradual decrease of HRT from 8.0 to 0.17 h, corresponding to an increase in the substrate loading from 60 to 2,880 g glucose L(-1) d(-1) . As the operation continued, the accumulation of biomass in the UASB was clearly observed, which changed from flocculent to granular form with decrease in HRT. Up to the HRT decrease to 0.5 h, the LA concentration was maintained at 19-20 g L(-1) with over 90% of substrate removal efficiency. However, further decrease of HRT resulted in a decrease of LA concentration with increase in residual glucose. Nevertheless, the volumetric LA productivity continuously increased, reaching 67 g L-fermenter (-1) h(-1) at HRT 0.17 h. The size of LA-producing granules and hydrophobicity gradually increased with decrease in HRT, reaching 6.0 mm and 60%, respectively. These biogranules were also found to have high settling velocities and low porosities, ranging 2.69-4.73 cm s(-1) and 0.39-0.92, respectively. © 2015 Wiley Periodicals, Inc.

  10. Observation of polyphosphate granules in cable bacteria

    Science.gov (United States)

    Yang, T.; Nielsen, L. P.; Risgaard-Petersen, N.

    2015-12-01

    Cable bacteria are long filamentous bacteria that capable for long distance electron transport: transporting electrons derived from oxidizing sulfide in anoxic layers, to oxygen at the sediment surface, over a distance of centimeters. Cable bacteria are found in many types of freshwater and marine sediment all over the world, with density of approximately thousands of kilometers per square meter. These long filaments are composed by individual cells closely related to Desulfobulbaceae, connected with a shared outer membrane inside which the strings structure are presumed to be highly conductive. The observed doubling time of cells within the filament is about 20 min, which is among the shortest compare to other bacteria. In these cable cells, we constantly observed polyphosphate granules (poly-P), regardless of cell dimension and shape. This is very interesting since it has long been recognized that the microbial polyP content is low during rapid growth and increases under unfavorable conditions, for example, increasing sulfide concentration and anoxia resulted in a decomposition of poly-P in Beggiatoa. Here, we investigated marine cable bacteria from Netherland and Aarhus Bay, focusing on the poly-P dynamics under various redox conditions. In poly-P stained cells, typically there are two big poly-P granules locate at each polar. In dividing cells, however, the morphology of poly-P changed to six small granules precisely arranged to two row. Moreover, the cells seem be able to continuously divide more than one time without elongation step. These varied poly-P morphologies demonstrate that poly-P is closely related to the cell growth and cell division, by an unknown mechanism. Individual cable filaments were picked up and were exposed to different redox conditions; our primary data indicated the cable cells could suffer anoxic condition better than oxic condition. We also detected decomposition of poly-P under anoxia. These results call for an in-depth examination

  11. Distribution of binder in granules produced by means of twin screw granulation

    DEFF Research Database (Denmark)

    Fonteyne, Margot; Fussell, Andrew Luke; Vercruysse, Jurgen

    2014-01-01

    -granular distribution of PVP was evaluated by means of hyperspectral coherent anti-Stokes Raman scattering (CARS) microscopy. For the evaluated formulation, no PVP rich zones were detected when applying a lateral spatial resolution of 0.5 μm, indicating that PVP is homogenously distributed within the granules....

  12. In planta modification of potato starch granule biogenesis by different granule-bound fusion proteins

    NARCIS (Netherlands)

    Nazarian, F.

    2007-01-01

    Starch is composed of amylose and amylopectin and it is deposited in amyloplasts/choloroplasts as semi-crystalline granules. Many biosynthetic enzymes are involved in starch degradation and biosynthesis. Some microbial starch degrading enzymes have a Starch Binding Domain (SBD) which has affinity fo

  13. Interleukin-1 mediates long-term hippocampal dentate granule cell loss following postnatal viral infection.

    Science.gov (United States)

    Orr, Anna G; Sharma, Anup; Binder, Nikolaus B; Miller, Andrew H; Pearce, Bradley D

    2010-05-01

    Viral infections of the developing CNS can cause long-term neuropathological sequela through undefined mechanisms. Proinflammatory cytokines such as IL-1beta have gained attention in mediating neurodegeneration in corticohippocampal structures due to a variety of insults in adults, though there is less information on the developing brain. Little is known concerning the spatial-temporal pattern of IL-1beta induction in the developing hippocampus following live virus infection, and there are few studies addressing the long-term consequences of this cytokine induction. We report that infection of rats with lymphocytic choriomeningitis virus on postnatal day 4 induces IL-1beta protein in select regions of the hippocampus on 6, 15, 21, and 45 days after infection. This infection resulted in a 71% reduction of dentate granule cell neurons by the time the rats reached mid-adulthood. We further investigated the causative role of IL-1 in this dentate granule cell loss by blocking IL-1 activity using an IL-1ra-expressing adenoviral vector administered at the time of infection. Blockade of IL-1 abrogated the infection-associated neuron loss in this vivo model. Considering that IL-1 can be triggered by multiple perinatal insults, our findings suggest that early therapy with anti-inflammatory agents that block IL-1 may be effective for reducing adulthood neuropathology.

  14. Evaluation of granulated lactose as a carrier for DPI formulations 1: effect of granule size.

    Science.gov (United States)

    Du, Ping; Du, Ju; Smyth, Hugh D C

    2014-12-01

    The objective of this study was to investigate the effect of large granulated lactose carrier particle systems on aerosol performance of dry powder inhaler formulations. Granulated lactose carriers with average sizes ranging from 200 to 1,000 μm were prepared and subsequently fractionated into separate narrow size powders. The fractionated granulated lactose (GL) samples were characterized in terms of size, specific surface area, surface roughness, morphology, density, flowability, and solid-state. The in vitro aerosolization performance was performed on the different size fractions of GL samples from a commercial inhaler device (Aerolizer®) with a model formulation (2% w/w salbutamol sulfate). The cascade impaction parameters employed were 60 or 90 L/min with standard (aperture size, 0.6 mm) or modified piercing holes (aperture size, 1.2 mm) of the inhaler loaded capsules. It was shown that the largest size fraction formulation (850-1000 μm) had a slight improvement in the fine particle fraction (FPF) compared to immediately preceding size fractions, explained by a smaller adhesive force between drug and carrier. Compared to commercial piercing holes, enlarged piercing holes generated a slight decreasing trend of FPF as the lactose powder sizes increased from 200-250 μm to 600-850 μm, perhaps due to the reduced detachment force by flow forces. The size, surface roughness, density, and flowability of lactose carrier as well as device design all contributed to the aerosol dispersion performance of granulated lactose-based adhesive mixtures. It was concluded that poorer or enhanced redispersion performance is not an inherent property to the significantly large size of granulated lactose carriers as previously contended.

  15. Influence of process variable and physicochemical properties on the granulation mechanism of mannitol in a fluid bed top spray granulator.

    Science.gov (United States)

    Bouffard, Jonathan; Kaster, Meagan; Dumont, Hubert

    2005-10-01

    This study investigated the influence of specific process variables, including the hydroxypropyl cellulose (HPC) binder solution atomization, on the fluidized bed top spray granulation of mannitol. Special attention was given to the relationship between wetting and the granule growth profile. The atomization of the HPC binder solution using a binary nozzle arrangement produced droplets of decreasing size as the atomization pressure was increased, while changes in the spray rate had little effect on the mean droplet size. Increasing the HPC binder concentration from 2 to 8% w/w increased the binder droplet size and was most likely attributed to higher solution viscosity. The top spray granulation of mannitol showed induction type growth behavior. Process conditions like high spray rate, low fluidizing air velocity and binder solution concentration that promote the availability of HPC binder solution at the surface of the particles appeared to be key in enhancing nucleation and growth of the granules. Increasing the bed moisture level, up to a certain value, reduced the contribution of attrition to the overall growth profile of the granule and, more significantly, produced less granule breakage on drying. It was observed that the mean granule size could be reduced as much as 40% between the end of granulation and the end of drying for lower initial bed moisture level despite a shorter drying phase. High atomization pressure, especially when maintained during the drying phase, contributed substantially to granule breakage.

  16. Conditional knockout of tumor overexpressed gene in mouse neurons affects RNA granule assembly, granule translation, LTP and short term habituation.

    Directory of Open Access Journals (Sweden)

    Elisa Barbarese

    Full Text Available In neurons, specific RNAs are assembled into granules, which are translated in dendrites, however the functional consequences of granule assembly are not known. Tumor overexpressed gene (TOG is a granule-associated protein containing multiple binding sites for heterogeneous nuclear ribonucleoprotein (hnRNP A2, another granule component that recognizes cis-acting sequences called hnRNP A2 response elements (A2REs present in several granule RNAs. Translation in granules is sporadic, which is believed to reflect monosomal translation, with occasional bursts, which are believed to reflect polysomal translation. In this study, TOG expression was conditionally knocked out (TOG cKO in mouse hippocampal neurons using cre/lox technology. In TOG cKO cultured neurons granule assembly and bursty translation of activity-regulated cytoskeletal associated (ARC mRNA, an A2RE RNA, are disrupted. In TOG cKO brain slices synaptic sensitivity and long term potentiation (LTP are reduced. TOG cKO mice exhibit hyperactivity, perseveration and impaired short term habituation. These results suggest that in hippocampal neurons TOG is required for granule assembly, granule translation and synaptic plasticity, and affects behavior.

  17. Drug distribution in wet granulation: foam versus spray.

    Science.gov (United States)

    Tan, Melvin X L; Nguyen, Thanh H; Hapgood, Karen P

    2013-09-01

    Foam granulation technology is a new wet granulation approach for pharmaceutical formulations. This study evaluates the performance of foam and spray granulation in achieving uniform drug distribution using a model formulation. To observe wetting and nuclei formation, single drop/foam penetration experiments were performed on a static powder bed comprised of varying compositions of hydrophilic/hydrophobic glass ballotini, and hydrophilic lactose/hydrophobic salicylic acid respectively. High shear granulation experiments were performed in a 5L mixer using varying compositions of hydrophilic lactose and hydrophobic salicylic acid. Four percent hydroxylpropyl methylcellulose (HPMC) solution was delivered at 90 g/min as either a foam (92% FQ) or an atomized spray whilst recording impeller power consumption. After drying, the granule size distribution was measured and the granule composition was estimated using gravimetric filtration in methanol. Foam penetration was less dependent on the powder hydrophobicity compared to drop penetration. For glass ballotini powder mixtures, foam induced nucleation created nuclei with relatively uniform structure and size regardless of the powder hydrophobicity. For salicylic acid and lactose mixtures, increasing the proportion of salicylic acid reduced the nuclei granule size for both foam and drop binder addition. The granule drug distribution was not significantly affected by the binder addition method. Processing conditions, including liquid binder amount, impeller speed, wet massing, and the wettability properties of the formulation were the dominant factors for delivering homogeneous granules. The study reveals that foam and spray granulation involve different nucleation mechanisms - spray tends to incur early liquid penetration whereas foam granulation operates well in mechanical dispersion.

  18. Rheological and fractal hydrodynamics of aerobic granules.

    Science.gov (United States)

    Tijani, H I; Abdullah, N; Yuzir, A; Ujang, Zaini

    2015-06-01

    The structural and hydrodynamic features for granules were characterized using settling experiments, predefined mathematical simulations and ImageJ-particle analyses. This study describes the rheological characterization of these biologically immobilized aggregates under non-Newtonian flows. The second order dimensional analysis defined as D2=1.795 for native clusters and D2=1.099 for dewatered clusters and a characteristic three-dimensional fractal dimension of 2.46 depicts that these relatively porous and differentially permeable fractals had a structural configuration in close proximity with that described for a compact sphere formed via cluster-cluster aggregation. The three-dimensional fractal dimension calculated via settling-fractal correlation, U∝l(D) to characterize immobilized granules validates the quantitative measurements used for describing its structural integrity and aggregate complexity. These results suggest that scaling relationships based on fractal geometry are vital for quantifying the effects of different laminar conditions on the aggregates' morphology and characteristics such as density, porosity, and projected surface area.

  19. Microbial granulation for lactic acid production

    DEFF Research Database (Denmark)

    Kim, Dong-Hoon; Lee, Mo-Kwon; Hwang, Yuhoon

    2016-01-01

    was fed with 2% glucose and operated at a hydraulic retention time (HRT) of 12 h and pH 5.0 ± 0.1 under a thermophilic condition (50°C). The mixed liquor in the CSTR was then transferred to an up-flow anaerobic sludge blanket reactor (UASB). The fermentation performance and granulation process were......This work investigated the formation of microbial granules to boost the productivity of lactic acid (LA). The flocculated form of LA-producing microbial consortium, dominated by Lactobacillus sp. (91.5% of total sequence), was initially obtained in a continuous stirred-tank reactor (CSTR), which...... monitored with a gradual decrease of HRT from 8.0 to 0.17 h, corresponding to an increase in the substrate loading from 60 to 2,880 g glucose L−1d−1. As the operation continued, the accumulation of biomass in the UASB was clearly observed, which changed from flocculent to granular form with decrease in HRT...

  20. 21 CFR 520.970a - Flunixin meglumine granules.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Flunixin meglumine granules. 520.970a Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.970a Flunixin meglumine granules. (a) Specifications. Each 10-gram packet contains flunixin meglumine equivalent to 250...

  1. Application of granulating of tires; Aplicaciones de granulado de NFUs

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez Justicia, A.

    2001-07-01

    At present, used tires are mainly used as fuel, retreading and granulating of tires. In this article. I will focus on the last option, talking about some of the multiple applications and going into detail of the making process of the granulation of used tires in a recycling plant. (Author)

  2. Cerebellar Granule Cells: Dense, Rich and Evolving Representations

    NARCIS (Netherlands)

    Badura, Aleksandra; De Zeeuw, Chris I

    2017-01-01

    For half a century it was assumed that granule cells use ultra-sparse encoding, but now in vivo calcium-imaging studies have shown that large ensembles of granule cells provide dense signals, which themselves evolve and adapt during training.

  3. Osseous drill holes to promote granulation tissue: Radiologic appearance

    Energy Technology Data Exchange (ETDEWEB)

    Resnik, C.S.; Reiner, B.I.; Diaconis, J.N. (Maryland Univ. Medical System/Hospital, Baltimore, MD (USA). Dept. of Radiology); Goldberg, N.H. (Maryland Univ. Medical System/Hospital, Baltimore, MD (USA). Div. of Plastic Surgery)

    1991-04-01

    Skin grafting following extensive soft-tissue loss is often delayed until adequate granulation tissue can be generated. Surgical drill holes into the marrow cavity promote development of granulation tissue. This article illustrates the radiology appearance of these drill holes in four patients. (orig.).

  4. Investigation of Compost Fertilizer Granulation Parameters Using Response Surface Methodology

    Directory of Open Access Journals (Sweden)

    Y Ghasemi

    2015-03-01

    Full Text Available Nowadays compost fertilizers are suitable alternative to chemical fertilizers, due to the threats for human health and agriculture products. The most important problems for applying the compost fertilizer in the farm are: transportation (high volume, high moisture content, spreading problem, impurity such as dust and storage. To solve the problems mentioned, pressing process such as converting the compost to pellets and granules are suggested. In this research the effects of some granulation parameters on the percent of useful granules in a laboratory scale rotating drum was evaluated. The percentage of useful granules decreased by increasing the granulation time and increased by increasing the percentage of drum filling. The optimal conditions for granules production was achieved at drum rotational speed of 40.38 rpm, granulation time of 15 min, drum filling of 10% and molasse percentage of 40.97. According to these conditions, the response for useful granule was estimated as 81.6% with R2 of 0.924.

  5. Proteoglycans support proper granule formation in pancreatic acinar cells.

    Science.gov (United States)

    Aroso, Miguel; Agricola, Brigitte; Hacker, Christian; Schrader, Michael

    2015-10-01

    Zymogen granules (ZG) are specialized organelles in the exocrine pancreas which allow digestive enzyme storage and regulated secretion. The molecular mechanisms of their biogenesis and the sorting of zymogens are still incompletely understood. Here, we investigated the role of proteoglycans in granule formation and secretion of zymogens in pancreatic AR42J cells, an acinar model system. Cupromeronic Blue cytochemistry and biochemical studies revealed an association of proteoglycans primarily with the granule membrane. Removal of proteoglycans by carbonate treatment led to a loss of membrane curvature indicating a supportive role in the maintenance of membrane shape and stability. Chemical inhibition of proteoglycan synthesis impaired the formation of normal electron-dense granules in AR42J cells and resulted in the formation of unusually small granule structures. These structures still contained the zymogen carboxypeptidase, a cargo molecule of secretory granules, but migrated to lighter fractions after density gradient centrifugation. Furthermore, the basal secretion of amylase was increased in AR42J cells after inhibitor treatment. In addition, irregular-shaped granules appeared in pancreatic lobules. We conclude that the assembly of a proteoglycan scaffold at the ZG membrane is supporting efficient packaging of zymogens and the proper formation of stimulus-competent storage granules in acinar cells of the pancreas.

  6. Monetite granules versus particulate autologous bone in bone regeneration.

    Science.gov (United States)

    Torres, Jesús; Tamimi, Iskandar; Cabrejos-Azama, Jatsue; Tresguerres, Isabel; Alkhraisat, Mohammad; López-Cabarcos, Enrique; Hernández, Gonzalo; Tamimi, Faleh

    2015-07-01

    The aim of this study was to test bone tissue response to monetite granules in comparison with intramembranous autologous bone graft in a rabbit calvaria critical size defect model. Novel monetite granules were synthesized by thermal conversion of set brushite cement. Eight female New Zealand rabbits were used for this study. Two identical 10mm diameter bicortical cranial defects were created in each animal. One of the defects was grafted with monetite granules while the contralateral was grafted with granules of intramembranous autologous bone as control. Animals were sacrificed 8 weeks after surgery and biopsies were taken for histological and histomorphometrical evaluation under light microscopy. Wilcoxon test was used for statistical analysis. The bone defects treated with either autologous bone or monetite granules were able to heal within the study period. Upon histological observation the defects treated with autologous bone granules resembled the adjacent intact calvaria, whereas the defects treated with monetite showed a high infiltration of new bone and only 13.4±8.4% of remaining granules. The percentage of bone volume in the defects of the control group (71±9%) was 16% higher than in the study group (55±10%) (p0.05). The amount of augmented mineralized tissue in the bone defects obtained with monetite granules was not significantly different from that obtained with autologous bone. This study confirms the potential of monetite based biomaterials as an alternative to autologous bone graft. Copyright © 2015 Elsevier GmbH. All rights reserved.

  7. The Color of Lactotroph Secretory Granules Stained with FM1-43 Depends on Dye Concentration

    OpenAIRE

    Johnson, Joseph M.; Betz, William J.

    2007-01-01

    When pituitary lactotroph granules undergo exocytosis in the presence of FM1-43, their cores absorb dye and fluoresce brightly. We report that different granules fluoresce with different colors, despite being stained with a single fluorescent dye; emission spectra from individual granules show up to a 25 nm difference between the greenest and reddest granules. We found a correlation between granule color and average fluorescence intensity, suggesting that granule color depends upon dye concen...

  8. Understanding and predicting bed humidity in fluidized bed granulation.

    Science.gov (United States)

    Hu, Xinhui; Cunningham, John; Winstead, Denita

    2008-04-01

    Bed humidity is a critical parameter that needs to be controlled in a fluidized bed granulation to ensure reliability. To predict and control the bed humidity during the fluidized bed granulation process, a simple model based on the mass conservation of moisture was developed. The moisture mass balance model quantitatively simulates the effects of spray rate, binder solution concentration, airflow rate, inlet air temperature, and dew point on the bed humidity. The model was validated by a series of granulations performed in different scale granulators including Glatt GPCG-1, GPCG-15, and GPCG-60. Good agreement was observed between the theoretical prediction and the measured loss on drying (LOD). The model developed in the current work enables us to choose the appropriate parameters for the fluidized bed granulation and can be used as a valuable tool in process scaling-up.

  9. A Calculus on Granules from Rough Inclusions in Information Systems

    Institute of Scientific and Technical Information of China (English)

    Lech Polkowski

    2006-01-01

    Indiscernibility relations induced in information systems in the sense of Pawlak,define granules of knowledge as unions of their equivalence classes,leading to regular structures like Boolean algebras. Apart from Boolean operations on granules, under afixed set of attributes,that induce the partition topology on their collection, one may search for more flexible schemes that would induce in collections of granules some non-trivial topologies and in particular quasi-metrics on granules, allowing for richer structures. A way of realization of this program has been proposed as the paradigm of rough mereology; although abstract, stemming from an alternative set theory, yet it offers a calculus based on kind of quasi-metrics that allows for discussing granules from the point of view of their closeness. In thiswork, we would liketopresent theideas of this approach and basic results with short discussion of applications.

  10. Hilar mossy cell circuitry controlling dentate granule cell excitability

    Directory of Open Access Journals (Sweden)

    Seiichiro eJinde

    2013-02-01

    Full Text Available Glutamatergic hilar mossy cells of the dentate gyrus can either excite or inhibit distant granule cells, depending on whether their direct excitatory projections to granule cells or their projections to local inhibitory interneurons dominate. However, it remains controversial whether the net effect of mossy cell loss is granule cell excitation or inhibition. Clarifying this controversy has particular relevance to temporal lobe epilepsy, which is marked by dentate granule cell hyperexcitability and extensive loss of dentate hilar mossy cells. Two diametrically opposed hypotheses have been advanced to explain this granule cell hyperexcitability – the dormant basket cell and the irritable mossy cell hypotheses. The dormant basket cell hypothesis proposes that mossy cells normally exert a net inhibitory effect on granule cells and therefore their loss causes dentate granule cell hyperexcitability. The irritable mossy cell hypothesis takes the opposite view that mossy cells normally excite granule cells and that the surviving mossy cells in epilepsy increase their activity, causing granule cell excitation. The inability to eliminate mossy cells selectively has made it difficult to test these two opposing hypotheses. To this end, we developed a transgenic toxin-mediated, mossy cell-ablation mouse line. Using these mutants, we demonstrated that the extensive elimination of hilar mossy cells causes granule cell hyperexcitability, although the mossy cell loss observed appeared insufficient to cause clinical epilepsy. In this review, we focus on this topic and also suggest that different interneuron populations may mediate mossy cell-induced translamellar lateral inhibition and intralamellar recurrent inhibition. These unique local circuits in the dentate hilar region may be centrally involved in the functional organization of the dentate gyrus.

  11. A highly sustainable and versatile granulation method of nanodrugs via their electrostatic adsorption onto chitosan microparticles as the granulation substrates.

    Science.gov (United States)

    Yang, Yue; Hadinoto, Kunn

    2013-08-16

    Nanodrugs play important roles in enhancing the sustainability of pharmaceutical manufacturing via their ability to enhance the bioavailability of poorly soluble drugs, resulting in less drug wastage and less mass/energy consumed in their manufacturing. Despite their sustainability enhancement capability, solid dosage form manufacturing of nanodrugs remains lacking from the sustainability perspective. One example is the granulation of nanodrugs prior to tablet preparation, where existing methods (e.g. wet granulation, spray granulation, spray drying) require high energy and time expenses, or are highly intricate often leading to product inconsistencies. Herein we present an alternative nanodrug granulation method via electrostatic adsorption of the nanodrugs onto chitosan microparticles acting as granulation substrates. The method is sustainable involving only mixing of aqueous suspensions of the nanodrugs and substrates under ambient conditions, followed by washing and drying. We investigate the effects of substrate's physical characteristics and nanodrug to substrate ratio on the nanodrug loading in the granules, content uniformity, nanodrug recovery, and granule flowability. Ciprofloxacin and curcumin nanoplexes prepared by drug-polyelectrolyte complexation are used as the model nanodrugs with neutrally, positively, and negatively charged chitosan microparticles as the substrates. Granules having 25% (w/w) nanodrug loading at 50% (w/w) recovery with good flowability have been successfully prepared. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Fluidization of Wet Granulates under Hydrodynamic Shear

    CERN Document Server

    Battiato, I

    2012-01-01

    We investigate the fluidization threshold of three-dimensional cohesive granulates under hydrodynamic shear forces exerted by a creeping ow. A continuum model of flow through porous media provides an analytical expression for the average drag force on a single grain. The balance equation for the forces and a force propagation model are then used to investigate the effects of porosity and packing structure on the stability of the pile. We obtain a closed-form expression for the fluidization threshold of a regular packing of mono-disperse frictionless cohesive spherical grains in a planar fracture. The compound effect of structural (packing orientation and porosity) and dynamical properties of the system on its stability is quantified.

  13. Cerebellar granule cells are predominantly generated by terminal symmetric divisions of granule cell precursors.

    Science.gov (United States)

    Nakashima, Kie; Umeshima, Hiroki; Kengaku, Mineko

    2015-06-01

    Neurons in the central nervous system (CNS) are generated by symmetric and asymmetric cell division of neural stem cells and their derivative progenitor cells. Cerebellar granule cells are the most abundant neurons in the CNS, and are generated by intensive cell division of granule cell precursors (GCPs) during postnatal development. Dysregulation of GCP cell cycle is causal for some subtypes of medulloblastoma. However, the details and mechanisms underlying neurogenesis from GCPs are not well understood. Using long-term live-cell imaging of proliferating GCPs transfected with a fluorescent newborn-granule cell marker, we found that GCPs underwent predominantly symmetric divisions, generating two GCPs or two neurons, while asymmetric divisions generating a GCP and a neuron were only occasionally observed, in both dissociated culture and within tissues of isolated cerebellar lobules. We found no significant difference in cell cycle length between proliferative and neurogenic divisions, or any consistent changes in cell cycle length during repeated proliferative division. Unlike neural stem cells in the cerebral cortex and spinal cord, which generate many neurons by repeated asymmetric division, cerebellar GCPs produce neurons predominantly by terminal symmetric division. These results indicate diverse mechanisms of neurogenesis in the mammalian brain. © 2015 Wiley Periodicals, Inc.

  14. Studies on rabbit lymphocytes in vitro

    Science.gov (United States)

    Sell, S.; Gell, P. G. H.

    1969-01-01

    Anti-allotypic sera that have no known allotypic determinants other than those also present in the genotype of the lymphocyte donor are as able to induce lymphocyte `blast' transformation in vitro as are anti-allotypic sera that do have allotypic determinants that are not present in the lymphocyte donor. Therefore, anti-allotypic sera do not appear to function in the stimulation of blast transformation by providing access for any of the known allotypic determinants into lymphocytes. PMID:5769980

  15. A Granule Model for Evaluating Adhesion of Pharmaceutical Binders

    Directory of Open Access Journals (Sweden)

    Hossein Orafai

    2003-10-01

    Full Text Available Granule capability is defined in terms of the strength of individual granule and friability of granulation batch to withstand breaking, abrasion and compactibility. Binder(s are added to perform the above properties .The common methods to asses their capability are to test crushing strength of the granules directly and to make statistical analysis and /or testing the friability of bulk granulation. In this work four substrate models including polymethylmetacrylate beads(PMMA,glass powder, acetaminophen, and para-aminobebzoic acid were chosen. The binder models were corn starch, gelatin, methylcellulose (MC and hydroxypropylmethylcellulose (HPMC. After massing the substrates with the binder solutions, discs were produced by the mean of the mold technique. The discs were dried and conditioned and then tested for tensile strength while the failed areas were scanned by SEM. Various granulations were made and the results of friability and crush strength were compared with the discs strength .The bond areas in the SEM showed the trend with the binder concentration .A comparison of the standard deviation shows that discs have much lower level of the strength than granules. The resulting discs showed a higher performance which is related to the stems for the discs shape .In conclusion, this method is a simple and is applicable to differentiate efficacy of binder under studies.

  16. Optimization for blast furnace slag dry cooling granulation device

    Science.gov (United States)

    Dazhan, Sheng; Yali, Wang; Ruiyun, Wang; Suping, Cui; Xiaoyu, Ma

    2017-03-01

    Since the large accumulation amount of blast furnace slag (BFS) with recycling value, it has become a hot topic for recovery utilization. Compared with the existing various BFS granulation process, the dry granulation process can promote the use of blast furnace granulated slag as cement substitute and concrete admixtures. Our research group developed a novel dry cooling granulation experiment device to treat BFS. However, there are still some problems to be solved. The purpose of this research is to improve the cooling and granulation efficiency of the existing dry type cooling equipment. This topic uses the FLUENT simulation software to study the impact of the number of air inlet on the cooling effect of the device. The simulation result is that the device possessing eight air inlets can increase the number of hot and cold gas exchanged, resulting in a better cooling effect. According to the power consumption, LCA analysis was carried out on the cooling granulation process. The results show that the device equipped eight air inlets not only improved the original equipment cooling granulation effect, but also increased resource utilization ratio, realized energy-saving and emission reduction.

  17. UNCERTAINTY HANDLING IN DISASTER MANAGEMENT USING HIERARCHICAL ROUGH SET GRANULATION

    Directory of Open Access Journals (Sweden)

    H. Sheikhian

    2015-08-01

    Full Text Available Uncertainty is one of the main concerns in geospatial data analysis. It affects different parts of decision making based on such data. In this paper, a new methodology to handle uncertainty for multi-criteria decision making problems is proposed. It integrates hierarchical rough granulation and rule extraction to build an accurate classifier. Rough granulation provides information granules with a detailed quality assessment. The granules are the basis for the rule extraction in granular computing, which applies quality measures on the rules to obtain the best set of classification rules. The proposed methodology is applied to assess seismic physical vulnerability in Tehran. Six effective criteria reflecting building age, height and material, topographic slope and earthquake intensity of the North Tehran fault have been tested. The criteria were discretized and the data set was granulated using a hierarchical rough method, where the best describing granules are determined according to the quality measures. The granules are fed into the granular computing algorithm resulting in classification rules that provide the highest prediction quality. This detailed uncertainty management resulted in 84% accuracy in prediction in a training data set. It was applied next to the whole study area to obtain the seismic vulnerability map of Tehran. A sensitivity analysis proved that earthquake intensity is the most effective criterion in the seismic vulnerability assessment of Tehran.

  18. Scanning electron microscopy of interaction of peripheral blood lymphocytes from colonic cancer patients with human colonic cancer-derived cells; P-4788.

    Directory of Open Access Journals (Sweden)

    Sugihara,Mutsuto

    1979-12-01

    Full Text Available Peripheral blood lymphocytes and the various lymphocyte fractions from patients with cancer of the colon were cultivated with target cells (P-4788 derived from the colon cancer. Changes in the surface ultrastructure during tumor cell destruction were studied by scanning electron microscopy (SEM. P-4788 cells adhering to the coverslip showed various surface activity. The surfaces of some cells were relatively flat; others were smooth or had fine granules. Still other cells were villous, round or had marked blebs. When host lymphocytes were added to the target cells, adhesion of the two cell groups began by many fine projections. After incubation for 6 h, some lymphocytes had adhered to the target cells. Many lymphocytes had adhered to the target tumor cells by 24--48 h incubation. Ultimately the tumor cells became swollen and disrupted. Most lymphocytes adherent to the target cells had few microvilli. Lymphocytes after elimination of phagocytes by carbonyl iron treatment also adhered readily. Some target cells showed adhesion with lymphocytes passed through nylon-wool columns, although the number of lymphocytes adhering was fewer than in the case of lymphocytes not passed through nylon-wool columns. T cells were collected from lymphocytes that form rosettes with SRBC by isolation with NH4Cl. They had markedly elongated microvilli which in places were sparsely scattered and tended to be localized on the side, a finding which suggests loss of cell activity by the time of SEM. Only a few T cells adhered to target cells and they seemed to be T cells without activity. It was thought that there are cytotoxic cells among T cells and that the co-existence of T cells, non-T cells and monocytes caused target cell destruction.

  19. Rapid exacerbation of lymphocytic infundibuloneurohypophysitis

    Science.gov (United States)

    Shibue, Kimitaka; Fujii, Toshihito; Goto, Hisanori; Yamashita, Yui; Sugimura, Yoshihisa; Tanji, Masahiro; Yasoda, Akihiro; Inagaki, Nobuya

    2017-01-01

    Abstract Rationale: Lymphocytic hypophysitis is a relatively rare autoimmune disease defined by lymphocytic infiltration to the pituitary. Its rarity and wide spectrum of clinical manifestations make clarification of the pathology difficult. Here, we describe a case we examined from the primary diagnosis to final discharge, showing the serial progression of lymphocytic infundibuloneurohypophysitis (LINH) to panhypopituitarism with extrapituitary inflammatory invasion in a short period, and responding favorably to high-dose glucocorticoid treatment. Patient concerns: Polyuria, General fatigue and Nausea/Vomiting. Diagnoses: Central diabetes insipidus (CDI), Lymphocytic infundibuloneurohypophysitis (LINH). Interventions: Desmopressin acetate, High-dose glucocorticoid (GC) treatment. Outcomes: He was prescribed desmopressin acetate and subsequently discharged. A month later, he revisited our hospital with general fatigue and nausea/vomiting. A screening test disclosed hypopituitarism with adrenal insufficiency. MRI revealed expanded contrast enhancement to the peripheral extrapituitary lesion. He received high-dose GC treatment and the affected lesion exhibited marked improvement on MRI, along with the recovery of the anterior pituitary function. Lessons: This case demonstrates the potential for classical LINH to develop into panhypopituitarsim. We consider this is the first documentation of approaching the cause of atypical LINH with progressive clinical course from the pathological viewpoint. PMID:28248860

  20. Treatment of chronic lymphocytic leukemia.

    Science.gov (United States)

    Ferrajoli, Alessandra; O'Brien, Susan M

    2004-04-01

    Treatment options for patients with chronic lymphocytic leukemia have changed over the past two decades. This article reviews the experience accumulated with the use of alkylating agents alone and in combination; purine analogues alone and in combination and monoclonal antibodies such as rituximab, and alemtuzumab alone and in combination. The results obtained with different treatment strategies are summarized, compared, and reviewed.

  1. The Leader Protein of Cardioviruses Inhibits Stress Granule Assembly ▿

    Science.gov (United States)

    Borghese, Fabian; Michiels, Thomas

    2011-01-01

    Stress granules (SG) are cytoplasmic aggregates of stalled translation preinitiation complexes that form in cells exposed to various environmental stresses. Here, we show that stress granules assemble in cells infected with Theiler's murine encephalomyelitis virus (TMEV) mutants carrying alterations in the leader (L) protein, but not in cells infected with wild-type TMEV. Stress granules also formed in STAT1-deficient cells, suggesting that SG formation was not a consequence of increased type I interferon (IFN) production when cells were infected with the mutant virus. Ectopic expression of the wild-type L protein was sufficient to inhibit stress granule formation induced by sodium arsenite or thapsigargin treatment. In conclusion, TMEV infection induces stress granule assembly, but this process is inhibited by the L protein. Unlike poliovirus-induced stress granules, TMEV-induced stress granules did not contain the nuclear protein Sam68 but contained polypyrimidine tract binding protein (PTB), an internal ribosome entry site (IRES)-interacting protein. Moreover, G3BP was not degraded and was found in SG after TMEV infection, suggesting that SG content could be virus specific. Despite the colocalization of PTB with SG and the known interaction of PTB with viral RNA, in situ hybridization and immunofluorescence assays failed to detect viral RNA trapped in infection-induced SG. Recombinant Theiler's viruses expressing the L protein of Saffold virus 2 (SAFV-2), a closely related human theilovirus, or the L protein of mengovirus, an encephalomyocarditis virus (EMCV) strain, also inhibited infection-induced stress granule assembly, suggesting that stress granule antagonism is a common feature of cardiovirus L proteins. PMID:21752908

  2. The leader protein of cardioviruses inhibits stress granule assembly.

    Science.gov (United States)

    Borghese, Fabian; Michiels, Thomas

    2011-09-01

    Stress granules (SG) are cytoplasmic aggregates of stalled translation preinitiation complexes that form in cells exposed to various environmental stresses. Here, we show that stress granules assemble in cells infected with Theiler's murine encephalomyelitis virus (TMEV) mutants carrying alterations in the leader (L) protein, but not in cells infected with wild-type TMEV. Stress granules also formed in STAT1-deficient cells, suggesting that SG formation was not a consequence of increased type I interferon (IFN) production when cells were infected with the mutant virus. Ectopic expression of the wild-type L protein was sufficient to inhibit stress granule formation induced by sodium arsenite or thapsigargin treatment. In conclusion, TMEV infection induces stress granule assembly, but this process is inhibited by the L protein. Unlike poliovirus-induced stress granules, TMEV-induced stress granules did not contain the nuclear protein Sam68 but contained polypyrimidine tract binding protein (PTB), an internal ribosome entry site (IRES)-interacting protein. Moreover, G3BP was not degraded and was found in SG after TMEV infection, suggesting that SG content could be virus specific. Despite the colocalization of PTB with SG and the known interaction of PTB with viral RNA, in situ hybridization and immunofluorescence assays failed to detect viral RNA trapped in infection-induced SG. Recombinant Theiler's viruses expressing the L protein of Saffold virus 2 (SAFV-2), a closely related human theilovirus, or the L protein of mengovirus, an encephalomyocarditis virus (EMCV) strain, also inhibited infection-induced stress granule assembly, suggesting that stress granule antagonism is a common feature of cardiovirus L proteins.

  3. Zinc sulfide in intestinal cell granules of Ancylostoma caninum adults

    Energy Technology Data Exchange (ETDEWEB)

    Gianotti, A.J.; Clark, D.T.; Dash, J. (Portland State Univ., OR (USA))

    1991-04-01

    A source of confusion has existed since the turn of the century about the reddish brown, weakly birefringent 'sphaerocrystals' located in the intestines of strongyle nematodes, Strongylus and Ancylostoma. X-ray diffraction and energy dispersive spectrometric analyses were used for accurate determination of the crystalline order and elemental composition of the granules in the canine hookworm Ancylostoma caninum. The composition of the intestinal pigmented granules was identified unequivocally as zinc sulfide. It seems most probable that the granules serve to detoxify high levels of metallic ions (specifically zinc) present due to the large intake of host blood.

  4. Fludarabine Phosphate, Radiation Therapy, and Rituximab in Treating Patients Who Are Undergoing Donor Stem Cell Transplant Followed by Rituximab for High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2017-03-27

    Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma; T-Cell Large Granular Lymphocyte Leukemia

  5. Fludarabine Phosphate and Total-Body Irradiation Before Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia

    Science.gov (United States)

    2016-07-18

    B-Cell Prolymphocytic Leukemia; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

  6. Human yeast-specific CD8 T lymphocytes show a nonclassical effector molecule profile.

    Science.gov (United States)

    Breinig, Tanja; Scheller, Nicoletta; Glombitza, Birgit; Breinig, Frank; Meyerhans, Andreas

    2012-05-01

    Pathogenic yeast and fungi represent a major group of human pathogens. The consequences of infections are diverse and range from local, clinically uncomplicated mycosis of the skin to systemic, life-threatening sepsis. Despite extensive MHC class I-restricted frequencies of yeast-specific CD8 T lymphocytes in healthy individuals and the essential role of the cell-mediated immunity in controlling infections, the characteristics and defense mechanisms of antifungal effector cells are still unclear. Here, we describe the direct analysis of yeast-specific CD8 T lymphocytes in whole blood from healthy individuals. They show a unique, nonclassical phenotype expressing granulysin and granzyme K in lytic granules instead of the major effector molecules perforin and granzyme B. After stimulation in whole blood, yeast-specific CD8 T cells degranulated and, upon cultivation in the presence of IL-2, their granula were refilled with granulysin rather than with perforin and granzyme B. Moreover, yeast-specific stimulation through dendritic cells but not by yeast cells alone led to degranulation of the effector cells. As granulysin is the only effector molecule in lytic granules known to have antifungal properties, our data suggest yeast-specific CD8 T cells to be a nonclassical effector population whose antimicrobial effector machinery seems to be tailor-made for the efficient elimination of fungi as pathogens.

  7. Correlation between microbial community and granule conductivity in anaerobic bioreactors for brewery wastewater treatment

    DEFF Research Database (Denmark)

    Shrestha, Pravin; Malvankar, Nikhil S.; Werner, Jeffrey

    2014-01-01

    granules from an aerobic bioreactor designed for phosphate removal were not. There was a moderate correlation (r = 0.67) between the abundance of Geobacter species in the UASB granules and granule conductivity, suggesting that Geobacter contributed to granule conductivity. These results, coupled...

  8. Phase transition time delays in irradiated superheated superconducting granules

    CERN Document Server

    Abplanalp, M; Czapek, G; Diggelmann, U; Furlan, M; Gabutti, A; Janos, S; Moser, U; Pozzi, R; Pretzl, Klaus P; Schmiemann, K; Perret-Gallix, D; Van den Brandt, B; Konter, J A; Mango, S

    1994-01-01

    The time difference between a particle interaction in a Superheated Superconducting Granule (SSG) and the resulting phase transition signal has been explored. Detectors containing Zn and Sn SSG were irradiated with neutrons and protons to study the heating mechanism taking place in nuclear recoil and ionizing events. Scattered neutrons have been detected by a scintillator hodoscope behind the SSG with a recoil energy measurement resolution of 10\\% and an interaction time resolution of 1ns. The fast transition of the metastable granules allowed to determine the elapsed time between an energy deposition and the phase transition signal. In the case of Sn granules, the results show that the time distributions are narrow and independent of the deposited energy in nuclear recoil and ionizing events. In Zn, however, the time distributions are much broader and depend on the energy deposition in the granule.

  9. Treatment of hyper-granulated limb wounds in horses

    Directory of Open Access Journals (Sweden)

    O. A. Bader

    2011-01-01

    Full Text Available This study was performed to investigate the different methods of treating hyper granulation tissue on experimentally induced wounds in equine limbs. Wounds were induced by removal of a skin patch and subcutaneous tissue for about 5-7 cm width and 6-8 cm in length from the dorsal and lateral aspect of the fore and hind limbs below the carpal and tarsal joints. The wounds were left open without treatment and the animals were trained 2-2.5 hours every day for about 3-5 weeks until hyper granulation tissue was developed. The schedule for the treatment of hyper granulation was divided into five groups each contained eight wounds of hyper granulation tissue; each main group was divided into two subgroups. The subgroups of first, second, third, fourth and fifth groups were treated by the following schedules: bandage alone; copper sulphate ointment 10%; silver nitrate ointment 2%; red mercury ointment 11%; and laser therapy (at a total dose of 9.72 Joule / cm2 respectively. While the second subgroups were treated by surgical resection of the hyper granulation tissue, followed by the same treatments applied on the first subgroup. The bandage for all experimental groups was changed every 48 hours until healing was occurred. The clinical and histological observation of the first group revealed that the healing take long period comparing with other groups. The mean of wound healing were 65 days in non surgical removal of hyper granulation tissue subgroup, while 57 days in surgical removed of hyper granulation tissue subgroup. The results of the second, third, fourth groups revealed that the caustic material especially red mercury has a role in healing processes through depressing the hyper granulation tissue. The mean of wound healing of the second group was 42.25 days in non surgical removal of hyper granulation tissue subgroup while 37.25 days in surgically removed hyper granulation tissue subgroup. In the third group the mean of wound healing was 45

  10. Heterogeneity of secretory granules of silent pituitary adenomas

    DEFF Research Database (Denmark)

    Holck, S; Wewer, U M; Albrechtsen, R

    1988-01-01

    Silent pituitary adenomas were compared with hormonally active tumors taking into account the size, number, and ultrastructural characteristics of secretory granules (SG). The study group (a total of 79 primary pituitary adenomas) comprised 27 silent, 21 growth hormone (GH)-producing-, 16 prolactin...... (PRL)-producing-, 5 GH-PRL-producing- and 10 adrenocorticotropic hormone (ACTH)-producing adenomas. The SG of silent adenomas were significantly smaller than SG in endocrine active adenomas. All hormonally inactive tumors also contained small (mean, 94 nm) specific cytoplasmic granules, designated...... approximately 10 to 50% of the granules in each cell. These granules were not seen in hormonally active tumors and considered therefore diagnostic of silent pituitary adenomas....

  11. In vitro binding of puroindolines to wheat starch granules

    DEFF Research Database (Denmark)

    Sørensen, Helle Aagaard; Darlington, H.F.; Shewry, P.R.

    2001-01-01

    Puroindoline (pin) preparations made from flours of hard and soft wheats contained a mixture of pin-a, 0.19/0.53 alpha -amylase inhibitor, and purothionins. Starch granule preparations from the same cultivars were treated with proteinase to remove surface proteins and incubated with solutions...... of the pin preparations. Binding of pin-a and purothionins but not the 0.19/0.53 inhibitor was observed with no apparent differences between the behavior of the pin preparations or starch granule preparations from hard or soft types. No binding was observed when several other proteins (bovine serum albumin......, total albumins, a commercial preparation of wheat alpha -amylase inhibitors, and barley beta -amylase) were incubated with the starch granules under the same conditions, indicating that in vitro binding can be used to study specific starch granule and protein interactions....

  12. Development of granules from Phyllanthus niruri spray-dried extract

    Directory of Open Access Journals (Sweden)

    Tatiane Pereira de Souza

    2009-12-01

    Full Text Available The aim of this study was to develop granules from Phyllanthus niruri spray-dried extract using dry and wet granulation and to assess techniques to enable the production of granules with improved technological characteristics and yields. Granules were characterized by granulometry, reological parameters, compression and hygroscopic behavior. Independent of the granulation technique, technologically developed granules presented particle diameter, bulk and tapped densities and compressibility indexes suitable for a solid dosage form. The compression behavior showed plastic and fragmentary deformation for granules produced by the dry granulation technique and predominantly plastic deformation for wet granulation. Concerning the humidity sorption, the study showed that granules absorb less humidity than the spray-dried extract. However, granules with Eudragit® E 100 were the least hygroscopic.O objetivo deste estudo foi desenvolver grânulos de extrato Phyllantus niruri seco por aspersão e por granulação úmida e avaliar técnicas que possibilitem a produção de grânulos com características tecnológicas e rendimentos aperfeiçoados. Os grânulos foram caracterizados por granulometria, parâmetros reológicos, compressão e comportamento higroscópico. Independentemente da técnica de granulação, os grânulos tecnologicamente desenvolvidos apresentaram diâmetro de partículas, densidades aparente e compactada e índices de compressibilidade adequados para a formulação sólida. O comportamento de compressão mostrou deformação plástica e elástica para os grânulos produzidos por técnicas de granulação seca e, predominantemente, deformação plástica para a granulação úmida. Com relação à absorção da umidade, o estudo mostrou que os grânulos absorvem menos umidade do que o extrato seco por aspersão. Entretanto, os grânulos com Eudragit E 100 foram os menos higroscópicos.

  13. Fluidization of wet granulates under shear.

    Science.gov (United States)

    Rahbari, S H Ebrahimnazhad; Vollmer, J; Herminghaus, S; Brinkmann, M

    2010-12-01

    Small amounts of a wetting liquid render sand a stiff and moldable material. The cohesive forces between the sand grains are caused by capillary bridges at the points of contact. Due to the finite strength of these bridges wet sand undergoes a transition from an arrested (i.e., solidified) to a fluidized state under an externally applied shear force. The transition between these two dynamic states is studied in a MD-type simulation of a two-dimensional assembly of bidisperse frictionless disks under the action of a cosine force profile. In addition to soft core repulsion the disks interact through a hysteretic and short ranged attractive force modeling the effect of the capillary bridges. In this model the transition between the fluidized and the arrested state is discontinuous and hysteretic. The parameter dependence of the critical force for solidification is modeled by combining theoretical arguments with a detailed numerical exploration of the transition. We address a range of densities from slightly below close packing until slightly above densities where the system approaches a shear-banded state. Differences and similarities of the transition in wet granulates to the jamming transition are also addressed.

  14. Giant arachnoid granulation mimicking dural sinus thrombosis.

    Science.gov (United States)

    Ayaz, Ercan; Atalay, Basak; Baysal, Begumhan; Senturk, Senem; Aslan, Ahmet

    2017-01-01

    Arachnoid granulations (AG) are composed of dense, collagenous connective tissue that includes clusters of arachnoid cells. They tend to invaginate into the dural sinuses, through which cerebrospinal fluid enters the venous system. AG are most commonly seen at the junction between the middle and lateral thirds of the transverse sinuses near the entry sites of the superficial veins. Presently described is the case of a 21-year-old female who presented at the clinic with recurrent headaches. Magnetic resonance (MR) imaging revealed a 3.5-cm lesion, which extended from confluens sinuum through the superior sagittal sinus. The lesion had created a scallop-shaped area of erosion in the neighboring occipital bone. To exclude sinus thrombosis, MR venography was performed, which displayed a maintained venous flow around the lesion. Headaches were treated symptomatically with medical therapy. Giant AG can be misdiagnosed as dural sinus thrombosis. MR imaging combined with MR venography is the most useful diagnostic tool to differentiate giant AG from dural sinus thrombosis.

  15. Brain Herniation into Giant Arachnoid Granulation: An Unusual Case

    Science.gov (United States)

    Santos, Gonçalo Roque

    2017-01-01

    Arachnoid granulations are structures filled with cerebrospinal fluid (CSF) that extend into the venous sinuses through openings in the dura mater and allow the drainage of CSF from subarachnoid space into venous system. Usually they are asymptomatic but can be symptomatic when large enough to cause sinus occlusion. We report a rare case of a brain herniation into a giant arachnoid granulation in an asymptomatic elderly male patient, which was discovered incidentally. PMID:28392955

  16. Preparation of Glass Ceramic Based on Granulated Slag and Cullet

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The glass-ceramic was prepared on the basis of materials of granulated slag containing high-calcium oxide and cullet.The content of granulated slag ranges from 50%-60%wt in the glass compositions. The samples were analyzed by DTA, SEM and XRD.The results show that the main crystal phase of the glass-ceramic is β-CaSiO3,Which is in scattering fiber or column form.The applying properties have also been measured.

  17. Asymmetric cell division of granule neuron progenitors in the external granule layer of the mouse cerebellum

    OpenAIRE

    Parthiv Haldipur; Iswariya Sivaprakasam; Vinod Periasamy; Subashika Govindan; Shyamala Mani

    2015-01-01

    ABSTRACT The plane of division of granule neuron progenitors (GNPs) was analysed with respect to the pial surface in P0 to P14 cerebellum and the results showed that there was a significant bias towards the plane of cell division being parallel to pial surface across this developmental window. In addition, the distribution of β-Catenin in anaphase cells was analysed, which showed that there was a significant asymmetry in the distribution of β-Catenin in dividing GNPs. Further, inhibition of S...

  18. Asymmetric cell division of granule neuron progenitors in the external granule layer of the mouse cerebellum.

    Science.gov (United States)

    Haldipur, Parthiv; Sivaprakasam, Iswariya; Periasamy, Vinod; Govindan, Subashika; Mani, Shyamala

    2015-05-15

    The plane of division of granule neuron progenitors (GNPs) was analysed with respect to the pial surface in P0 to P14 cerebellum and the results showed that there was a significant bias towards the plane of cell division being parallel to pial surface across this developmental window. In addition, the distribution of β-Catenin in anaphase cells was analysed, which showed that there was a significant asymmetry in the distribution of β-Catenin in dividing GNPs. Further, inhibition of Sonic Hedgehog (Shh) signalling had an effect on plane of cell division. Asymmetric distribution of β-Catenin was shown to occur towards the source of a localized extracellular cue.

  19. Preventive effect of Ganfujian granule on experimental hepatocarcinoma in rats

    Institute of Scientific and Technical Information of China (English)

    Yan Qian; Chang-Quan Ling

    2004-01-01

    AIM: To investigate the inhibitory effect of dietary and medicinal formula Ganfujian granule on diethylnitrosamine (DEN)-induced hepatocarcinoma in rats.METHODS: Male SD rats had free access to water containing 0.1 g/L DEN for 16 weeks, during which the rats fed with standard diet or administration of Ganfujian granule (30.4 g/Kg in diet). At weeks 4, 8, 12 and 16 of hepatocarcinogenesis 5 rats of each group were sacrificed, and at week 20 another 30 rats were sacrificed from each group. The end point for survival observation was at week 28.Immunochemistry methods were used to examine the effect of Ganfujian granule on the process of hepatocarcinogenesis including proliferation of hepatocytes and cell cycle modulation.RESULTS: Ganfujian granule could reduce and delay the incidence of hepatocarcinoma in rats and prolong the survival of animals. In addition, Ganfujian granule had a marked inhibitory effect on high expression of cyclin dependent kinase (CDK4) during the whole process of hepatocarcinogenesis and cyclin D1 at week 16 and the number of proliferating cell nuclear antigen (PCNA) positive cells in different stages of hepatocarcinogenesis.CONCLUSION: Ganfujian granule can reduce and delay the incidence of hepatocarcinoma in rats by exerting direct or indirect effects on cell cycle and inhibiting uncontrolled proliferation of hepatocytes.

  20. Investigation of Physicochemical Drug Properties to Prepare Fine Globular Granules Composed of Only Drug Substance in Fluidized Bed Rotor Granulation

    National Research Council Canada - National Science Library

    Mise, Ryohei; Iwao, Yasunori; Kimura, Shin-ichiro; Osugi, Yukiko; Noguchi, Shuji; Itai, Shigeru

    2015-01-01

    ...%) drug-loading formulation using fluidized bed rotor granulation. Three drugs: acetaminophen (APAP); ibuprofen (IBU); and ethenzamide (ETZ) were used as model drugs based on their differences in wettability and particle size distribution...

  1. Twin screw wet granulation: the study of a continuous twin screw granulator using Positron Emission Particle Tracking (PEPT) technique.

    Science.gov (United States)

    Lee, Kai T; Ingram, Andy; Rowson, Neil A

    2012-08-01

    In this paper, Positron Emission Particle Tracking (PEPT) techniques are utilised to track the trajectory of single particles through the mixing and conveying zones of a Twin Screw Granulator (TSG). A TSG consisting of conveying zones and mixing zones is used in this study. The mixing zones are arranged with kneading discs at an angle of 30°, 60° or 90°. Experiments were carried out using different mixing configurations with various screw speed and total mass flow rate. The PEPT data obtained were then utilised to obtain the residence time distribution (RTD) and the Peclet number in an attempt to gain some insight into the mixing of the process. The fill level of the granulator was also estimated to study the mechanism of granulation. As might be expected, it was shown that the residence time of the granulation process increases with decreasing screw speed. It also increases with increasing angle of the arrangement of kneading blocks in the mixing zones, but will decreases when powder feed rate is increased. The fill level of the mixing zone in particular increases when the screw speed decreases or when powder feed rate increases. Furthermore, the fill level of the granulator will increase when the mixing zone configuration changes from 30° to 90°. It is shown that the granulator is never fully filled, even using 90° mixer elements implying limited compaction which may explain why the granules produced are porous compared with those from a high shear mixer. Interestingly, the RTD analysis reveals that the extent of axial mixing in the mixing zone of the granulator does not change significantly for different configurations and process conditions. There is evidence of a tail in the RTD which implies some material hold up and channelling.

  2. Impact of screw elements on continuous granulation with a twin-screw extruder.

    Science.gov (United States)

    Djuric, Dejan; Kleinebudde, Peter

    2008-11-01

    The influence of different screw element types on wet granulation process with a twin-screw extruder was investigated. Lactose granules were prepared with different screw configurations such as conveying, combing mixer and kneading elements. The use of kneading blocks led to an almost complete agglomeration of lactose, whereas kneading and combing mixer elements resulted in smaller granules in comparison. Granule porosity varied between 17.4% and 50.6%. Granule friability values ranged from 1.2% to 38.5%. Conveying elements led to the most porous and friable granules, whereas kneading blocks produced the densest and least friable granules. Combing mixer elements produced granules with median properties. A linear correlation between granule porosity and the natural logarithm of granule friability was detected. Flowability of granules was also influenced by the element type. Compressed granules with higher granule porosities resulted in tablets with higher tensile strength values and vice versa. Twin-screw extruders proved to be a versatile tool for wet granulation. By the choice of a suitable screw element granule and tablet characteristics were influenced.

  3. Fuzheng Kangbai Granule (扶正抗白冲剂) on Immune Function and Survival Time in Minimal Residual Leukemia Model Mice

    Institute of Scientific and Technical Information of China (English)

    许勇钢; 麻柔; 胡乃平; 刘锋; 杨经敏; 马玲; 胡晓梅

    2001-01-01

    To observe the effects of Fuzheng Kangbai Granule (FZKBG) on immune function and survival time in minimal residual leukemia (MRL) model mice and explore its mechanism. Methods: MRL model mice were established by hypodermic inoculation with L7212 cells 1×106 following intraperitoneal injection of cytoxan (CTX) 250 mg/kg 3 days later, and divided into the control group and FZKBG treated group. The changes of T-lymphocyte subsets, including CD3+, CD4+ and CD8+, and the survival time in model mice were observed. Results: Compared with the control, FZKBG could obviously increase both the percentage and absolute value of CD3+ and CD4+ lymphocytes and prolong the survival time of model mice, the prolongation rate being 29.6% - 60.4%. Conclusion: FZKBG could markedly prolong the survival time of MRL mice, and its mechanism might be through elevating the immunologic function and inhibiting the leukemia cells in model mice.

  4. Gamma/delta intraepithelial lymphocytes in the mouse small intestine.

    Science.gov (United States)

    Ogata, Masaki; Itoh, Tsunetoshi

    2016-09-01

    Although many studies of intraepithelial lymphocytes (IELs) have been reported, most of them have focused on αβ-IELs; little attention has been paid to γδ-IELs. The function of γδ-IELs remains largely unclear. In this article, we briefly review a number of reports on γδ-IELs, especially those in the small intestine, along with our recent studies. We found that γδ-IELs are the most abundant (comprising >70 % of the) IELs in the duodenum and the jejunum, implying that it is absolutely necessary to investigate the function(s) of γδ-IELs when attempting to delineate the in vivo defense system of the small intestine. Intraperitoneal injection of anti-CD3 mAb stimulated the γδ-IELs and caused rapid degranulation of them. Granzyme B released from their granules induced DNA fragmentation of duodenal and jejunal epithelial cells (paracrine) and of the IELs themselves (autocrine). However, perforin (Pfn) was not detected, and DNA fragmentation was induced even in Pfn-knockout mice; our system was therefore found to present a novel type of in vivo Pfn-independent DNA fragmentation. We can therefore consider γδ-IELs to be a novel type of large granular lymphocyte without Pfn. Fragmented DNA was repaired in the cells, indicating that DNA fragmentation alone cannot be regarded as an unambiguous marker of cell death or apoptosis. Finally, since the response was so rapid and achieved without the need for accessory cells, it seems that γδ-IELs respond readily to various stimuli, are activated only once, and die 2-3 days after activation in situ without leaving their site. Taken together, these results suggest that γδ-IELs are not involved in the recognition of specific antigen(s) and are not involved in the resulting specific killing or exclusion of the relevant antigen(s).

  5. Opinion: Interactions of innate and adaptive lymphocytes

    Science.gov (United States)

    Gasteiger, Georg; Rudensky, Alexander Y.

    2015-01-01

    Innate lymphocytes, including natural killer (NK) cells and the recently discovered innate lymphoid cells (ILCs) have crucial roles during infection, tissue injury and inflammation. Innate signals regulate the activation and homeostasis of innate lymphocytes. Less well understood is the contribution of the adaptive immune system to the orchestration of innate lymphocyte responses. We review our current understanding of the interactions between adaptive and innate lymphocytes, and propose a model in which adaptive T cells function as antigen-specific sensors for the activation of innate lymphocytes to amplify and instruct local immune responses. We highlight the potential role of regulatory and helper T cells in these processes and discuss major questions in the emerging area of crosstalk between adaptive and innate lymphocytes. PMID:25132095

  6. Identification of a major QTL controlling the content of B-type starch granules in Aegilops

    Science.gov (United States)

    Howard, Thomas; Rejab, Nur Ardiyana; Griffiths, Simon; Leigh, Fiona; Leverington-Waite, Michelle; Simmonds, James; Uauy, Cristobal; Trafford, Kay

    2011-01-01

    Starch within the endosperm of most species of the Triticeae has a unique bimodal granule morphology comprising large lenticular A-type granules and smaller near-spherical B-type granules. However, a few wild wheat species (Aegilops) are known to lack B-granules. Ae. peregrina and a synthetic tetraploid Aegilops with the same genome composition (SU) were found to differ in B-granule number. The synthetic tetraploid had normal A- and B-type starch granules whilst Ae. peregrina had only A-granules because the B-granules failed to initiate. A population segregating for B-granule number was generated by crossing these two accessions and was used to study the genetic basis of B-granule initiation. A combination of Bulked Segregant Analysis and QTL mapping identified a major QTL located on the short arm of chromosome 4S that accounted for 44.4% of the phenotypic variation. The lack of B-granules in polyploid Aegilops with diverse genomes suggests that the B-granule locus has been lost several times independently during the evolution of the Triticeae. It is proposed that the B-granule locus is susceptible to silencing during polyploidization and a model is presented to explain the observed data based on the assumption that the initiation of B-granules is controlled by a single major locus per haploid genome. PMID:21227932

  7. Microbial community variation in cryoconite granules on Qaanaaq Glacier, NW Greenland.

    Science.gov (United States)

    Uetake, Jun; Tanaka, Sota; Segawa, Takahiro; Takeuchi, Nozomu; Nagatsuka, Naoko; Motoyama, Hideaki; Aoki, Teruo

    2016-09-01

    Cryoconite granules are aggregations of microorganisms with mineral particles that form on glacier surfaces. To understand the processes by which the granules develop, this study focused on the altitudinal distribution of the granules and photosynthetic microorganisms on the glacier, bacterial community variation with granules size and environmental factors affecting the growth of the granules. Size-sorted cryoconite granules collected from five different sites on Qaanaaq Glacier were analyzed. C and N contents were significantly higher in large (diameter greater than 250 μm) granules than in smaller (diameter 30-249 μm) granules. Bacterial community structures, based on 16S rRNA gene amplicon sequencing, were different between the smaller and larger granules. The filamentous cyanobacterium Phormidesmis priestleyi was the dominant bacterial species in larger granules. Multivariate analysis suggests that the abundance of mineral particles on the glacier surface is the main factor controlling growth of these cyanobacteria. These results show that the supply of mineral particles on the glacier enhances granule development, that P. priestleyi is likely the key species for primary production and the formation of the granules and that the bacterial community in the granules changes over the course of the granule development.

  8. [Adoptive transfer of T lymphocytes].

    Science.gov (United States)

    Vié, H; Clémenceau, B

    2017-09-01

    Within a few years, the success of treatments based on the use of T-cells armed with a chimeric T-receptor for the CD19 molecule (CAR-T CD19) has revolutionized the perception of adoptive transfer approaches. The levels of responses observed in acute leukemias, of the order of 70-90 % are indeed unprecedented. The medical and financial enthusiasm aroused by these results has led to the current situation where more than 300 clinical trials are under way, against some thirty different antigens. This enthusiasm, well justified by the first successes, must however be tempered by the difficulties associated with the use of these cells. Indeed, the management of patients is made very complex both for medical reasons, because the toxicities associated with these treatments are important, and for technical reasons, because the preparation of T lymphocytes for therapeutic use requires dedicated structures. During this same period, knowledge of the mechanisms of regulation of T lymphocytes and the possibilities offered by synthetic biology and techniques of genome engineering have progressed considerably. Combined, they allow envisaging a true "programming" of the T lymphocytes, intended to improve the efficiency of the treatments and the safety of the patients. Medical and industrial perspectives and the role of these approaches in the arsenal of cancer therapies will depend largely on two conditions: the emergence of a robust demonstration of their effectiveness in solid tumors, and the establishment of an acceptable production and distribution model 1. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Lymphocyte subpopulations in Sheehan's syndrome.

    Science.gov (United States)

    Atmaca, Hulusi; Araslı, Mehmet; Yazıcı, Zihni Acar; Armutçu, Ferah; Tekin, Ishak Özel

    2013-06-01

    The role of autoimmunity in the development of Sheehan's syndrome is obscure. There are a limited number of studies investigating the immunological alterations accompanying Sheehan's Syndrome. Our objective was to evaluate lymphocyte subsets in these patients. We conducted a cross-sectional clinical study. Cytofluorometry was used for the immunophenotyping of peripheral blood leukocytes from patients with Sheehan's syndrome followed up in the endocrine clinic during 2005-2009. Fifteen consecutive patients (mean age 61.6 ± 11.3, range 34-75 years) and 25 healthy controls (mean age 56.7 ± 10.6, range 34-80 years) were included. There was no statistically significant difference between the groups in terms of mean age. The percentages of CD19(+), CD16(+)/56(+), CD8(+)28(-), γδTCR(+), CD8(+); the total lymphocyte counts; and the ratio of CD8(+)28(-)/CD8(+)28(+) were similar (p > 0.05) between patients and controls. Whereas the leucocyte counts (p = 0.003), the percentage of CD3 (+) DR (+) (p Sheehan's syndrome compared to healthy controls. There was a positive correlation between the duration of illness and the percentage of CD3(+)DR(+) (r = 0.53, p = 0.03) expression. Some peripheral lymphocyte cell subsets show marked variation in patients with Sheehan's syndrome in comparison to matched healthy subjects, which may have implications for altered immune regulation in these patients. High CD3 (+) DR (+) expression that correlates with the duration of illness in Sheehan's patients is suggestive of an ongoing inflammation accompanying the slow progression of pituitary dysfunction in Sheehan's syndrome. It is not clear if these cellular alterations contribute to the cause or consequence of pituitary deficiency in Sheehan's syndrome.

  10. Aerobic Granulation in Sequencing Batch Reactor (SBR Treating Saline Wastewater

    Directory of Open Access Journals (Sweden)

    Ensieh Taheri

    2012-04-01

    Full Text Available Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background and Objectives: Aerobic sludge granulation is an advanced phenomenonin which its mechanisms have not been understood. Granulation can be a promising and novel biological wastewater treatment technology to eliminate organic and inorganic materials in future. High salinity is a parameter which leads to plasmolisatian and reduction of the cell activity. This could be a problem for biological treatment of the saline wastewater. Aerobic granule was formed and investigated during this study. Materials and Methods: This study is an intervention study on the treatment of wastewater with 500-10000 mg/L concentration of NaCl by sequencing batch reactor. Asynthesized wastewater including nutrient required for microorganism's growth was prepared. Input and output pH and EC were measured. Range of pH and DO varied between 7-8, and 2-5 mg/L, respectively. SEM technology was used to identify graduals properties.Results: In terms of color, granules divided into two groups of light brown and black. Granule ranged in 3-7mm with the sediment velocity of 0.9-1.35 m/s and density of 32-60 g/L.Properties of granules were varied. Filamentous bacteria and fungi were dominant in some granules. However non filamentous bacteria were dominant in others. EDX analysis indicated the presence of Ca and PO4.Conclusion: Granules with non filamentous bacterial were compact and settled faster. Presence of different concentrations of salinity leaded to plasmolysis of the bacterial cells and increased concentrations of EPS  in the system as a result  of which granulation accelerated. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso

  11. Adipose tissue lymphocytes: types and roles.

    Science.gov (United States)

    Caspar-Bauguil, S; Cousin, B; Bour, S; Casteilla, L; Castiella, L; Penicaud, L; Carpéné, C

    2009-12-01

    Besides adipocytes, specialized in lipid handling and involved in energy balance regulation, white adipose tissue (WAT) is mainly composed of other cell types among which lymphocytes represent a non-negligible proportion. Different types of lymphocytes (B, alphabetaT, gammadeltaT, NK and NKT) have been detected in WAT of rodents or humans, and vary in their relative proportion according to the fat pad anatomical location. The lymphocytes found in intra-abdominal, visceral fat pads seem representative of innate immunity, while those present in subcutaneous fat depots are part of adaptive immunity, at least in mice. Both the number and the activity of the different lymphocyte classes, except B lymphocytes, are modified in obesity. Several of these modifications in the relative proportions of the lymphocyte classes depend on the degree of obesity, or on leptin concentration, or even fat depot anatomical location. Recent studies suggest that alterations of lymphocyte number and composition precede the macrophage increase and the enhanced inflammatory state of WAT found in obesity. Lymphocytes express receptors to adipokines while several proinflammatory chemokines are produced in WAT, rendering intricate crosstalk between fat and immune cells. However, the evidences and controversies available so far are in favour of an involvement of lymphocytes in the control of the number of other cells in WAT, either adipocytes or immune cells and of their secretory and metabolic activities. Therefore, immunotherapy deserves to be considered as a promising approach to treat the endocrino-metabolic disorders associated to excessive fat mass development.

  12. Autoimmune hepatitis in association with lymphocytic colitis.

    LENUS (Irish Health Repository)

    Cronin, Edmond M

    2012-02-03

    Autoimmune hepatitis is a rare, chronic inflammatory disorder which has been associated with a number of other auto-immune conditions. However, there are no reports in the medical literature of an association with microscopic (lymphocytic) colitis. We report the case of a 53-year-old woman with several autoimmune conditions, including lymphocytic colitis, who presented with an acute hepatitis. On the basis of the clinical features, serology, and histopathology, we diagnosed autoimmune hepatitis. To our knowledge, this is the first report of autoimmune hepatitis in association with lymphocytic colitis, and lends support to the theory of an autoimmune etiology for lymphocytic colitis.

  13. Lymphocyte-platelet crosstalk in Graves' disease.

    Science.gov (United States)

    Kuznik, Boris I; Vitkovsky, Yuri A; Gvozdeva, Olga V; Solpov, Alexey V; Magen, Eli

    2014-03-01

    Platelets can modulate lymphocytes' role in the pathophysiology of thyroid autoimmune diseases. The present study was performed to clarify the status of platelet-lymphocyte subpopulations aggregation in circulating blood in patients with Graves' disease (GD). One hundred and fifty patients with GD (GD group) and 45 hyperthyroid patients with toxic multinodular goiter (TMG group) were recruited in the study. Control group consisted 150 healthy subjects. Immunophenotyping of lymphocytes was performed by flow cytometry. Detection of lymphocyte-platelet aggregates (LPAs) was done using light microscope after Ficoll-gradient centrifugation. The group of GD patients exhibited reduced CD8 lymphocyte and higher CD19 cell counts compared with TMG group and healthy controls. A greater number of activated CD3, HLA-DR+ lymphocytes were observed in GD than in TMG group and control group. GD group was characterized by lower blood platelet count (232 ± 89 × 10 cells/µL) than TMG group (251 ± 97 × 10 cells/µL; P < 0.05) and control group (262 ± 95 × 10 cells/µL; P < 0.05). In GD group, more platelet-bound lymphocytes (332 ± 91 /µL) were found than that in TMG group (116 ± 67/µL, P < 0.005) and control group (104 ± 58 /µL; P < 0.001). GD is associated with higher levels of activated lymphocytes and lymphocyte-platelet aggregates.

  14. Impact of fill-level in twin-screw granulation on critical quality attributes of granules and tablets.

    Science.gov (United States)

    Meier, Robin; Moll, Klaus-Peter; Krumme, Markus; Kleinebudde, Peter

    2017-02-15

    In a previous study a change of the fill-level in the barrel exerted a huge influence on the twin-screw granulation (TSG) process of a high drug loaded, simplified formulation. The present work investigated this influence systematically. The specific feed load (SFL) indicating the mass per revolution as surrogate parameter for the fill-level was applied and the correlation to the real volumetric fill level of an extruder could be demonstrated by a newly developed method. A design of experiments was conducted to examine the combined influence of SFL and screw speed on the process and on critical quality attributes of granules and tablets. The same formulation was granulated at constant liquid level with the same screw configuration and led to distinctively different results by only changing the fill-level and the screw speed. The power consumption of the extruder increased at higher SFLs with hardly any influence of screw speed. At low SFL the median residence time was mainly fill-level dependent and at higher SFL mainly screw speed dependent. Optimal values for the product characteristics were found at medium values for the SFL. Granule size distributions shifted from mono-modal and narrow shape to broader and even bimodal distributions of larger median granule sizes, when exceeding or falling below a certain fill-level. Deviating from the optimum fill-level, tensile strength of tablets decreased by about 25 % and disintegration times of tablets increased for more than one third. At low fill-levels, material accumulation in front of the kneading zone was detected by pressure measurements and was assumed to be responsible for the unfavored product performance. At high fill-levels, granule consolidation due to higher propensity of contact with the result of higher material temperature was accounted for inferior product performance. The fill-level was found to be an important factor in assessment and development of twin-screw granulation processes as it impacted

  15. Preparation of porcelain tile granulates by more environmentally sustainable processes

    Energy Technology Data Exchange (ETDEWEB)

    Gil, C.; Silvestre, D.; Piquer, J.; Garcia-Ten, J.; Quereda, E.; Vicente, M. J.

    2012-07-01

    This study examines the feasibility of manufacturing glazed porcelain tiles with a more environmentally friendly manufacturing process, by reducing water and thermal energy consumption. The process studied in this paper is dry milling in a pendulum mill, with subsequent granulation (in order to obtain a press powder with similar flow ability to that of spray dried powders). The different morphology of the new granulate with respect to the standard spray-dried granulate modifies the microstructure of the green compacts and thus, their behaviour and fired tile properties. In order to obtain porcelain tiles with the required properties (water absorption, mechanical strength,) changes have been made in the raw materials mixture and in the processing variables. Finally, porcelain tiles measuring 50x50 cm have been manufactured at industrial scale with the new granulate using a conventional firing cycle, obtaining quality levels identical to those provided by the spray-dried granulate. These results open the possibility of preparing porcelain tile body compositions through a manufacturing process alternative to the standard one, more environmentally friendly and with lower costs. (Author)

  16. THE KINETICS OF CYTOPLASMIC GRANULE SECRETION IN NATURAL KILLER CYTOTOXICITY

    Institute of Scientific and Technical Information of China (English)

    龚伊红; R.R.Hcrberman; C.W.Reynolds

    1994-01-01

    Antisexum against purified cytoplasmic granules from rat LGL tumor cells, and protein A-gold inmmnoelec-tron microscopy were used to study the secretory events in lysis of YAC-1 tumor cells by rat LGL tumor cells or by isolated LGL from normal rats. After 30 min incubation of effector and target cells together, gold-labeled cyto-plasmic granules were often seen concentrated in the area of the LGL adjacent to the ~ YAC-1 Within 60min,the grantees were observed to move to the cell border near the conjugazed site. At this point, fine granules were fused with file cell membrane, and subsequently released file gold-labeled contents into the junction between the LGL and the target cell. Gold particles could be seen at the B-T interface, on the surface,or sometimes on the target cell surface.These data provide direct evidence for the hypothesis that under conditions of active cytotoxicity,natural killer cells secrete their cytoplasmic granule contents leading to the deposition of granule material on the target cell surface and the eventual lysis of the cell.

  17. Fabrication and cytocompatibility of spherical magnesium ammonium phosphate granules.

    Science.gov (United States)

    Christel, Theresa; Geffers, Martha; Klammert, Uwe; Nies, Berthold; Höß, Andreas; Groll, Jürgen; Kübler, Alexander C; Gbureck, Uwe

    2014-09-01

    Magnesium phosphate compounds, as for example struvite (MgNH4PO4·6H2O), have comparable characteristics to calcium phosphate bone substitutes, but degrade faster under physiological conditions. In the present work, we used a struvite forming calcium doped magnesium phosphate cement with the formulation Ca0.75Mg2.25(PO4)2 and an ammonium phosphate containing aqueous solution to produce round-shaped granules. For the fabrication of spherical granules, the cement paste was dispersed in a lipophilic liquid and stabilized by surfactants. The granules were characterized with respect to morphology, size distribution, phase composition, compressive strength, biocompatibility and solubility. In general, it was seen that small granules can hardly be produced by means of emulsification, when the raw material is a hydraulic paste, because long setting times promote coalescence of initially small unhardened cement droplets. Here, this problem was solved by using an aqueous solution containing both the secondary (NH4)2HPO4 and primary ammonium phosphates NH4H2PO4 to accelerate the setting reaction. This resulted in granules with 97 wt.% having a size in the range between 200 and 1,000 μm. The novel solution composition doubled the compressive strength of the cement to 37 ± 5 MPa without affecting either the conversion to struvite or the cytocompatibility using human fetal osteoblasts.

  18. Platelet granule exocytosis: A comparison with chromaffin cells

    Directory of Open Access Journals (Sweden)

    Jennifer eFitch-Tewfik

    2013-06-01

    Full Text Available The rapid secretion of bioactive amines from chromaffin cells constitutes an important component of the fight or flight response of mammals to stress. Platelets respond to stresses within the vasculature by rapidly secreting cargo at sites of injury, inflammation, or infection. Although chromaffin cells derive from the neural crest and platelets from bone marrow megakaryocytes, both have evolved a heterogeneous assemblage of granule types and a mechanism for efficient release. This article will provide an overview of granule formation and exocytosis in platelets with an emphasis on areas in which the study of chromaffin cells has influenced that of platelets and on similarities between the two secretory systems. Commonalities include the use of transporters to concentrate bioactive amines and other cargos into granules, the role of cytoskeletal remodeling in granule exocytosis, and the use of granules to provide membrane for cytoplasmic projections. The SNAREs and SNARE accessory proteins used by each cell type will also be considered. Finally, we will discuss the newly appreciated role of dynamin family proteins in regulated fusion pore formation. This evaluation of the comparative cell biology of regulated exocytosis in platelets and chromaffin cells demonstrates a convergence of mechanisms between two disparate cell types both tasked with responding rapidly to physiological stimuli.

  19. Massively augmented hippocampal dentate granule cell activation accompanies epilepsy development

    Science.gov (United States)

    Dengler, Christopher G.; Yue, Cuiyong; Takano, Hajime; Coulter, Douglas A.

    2017-01-01

    In a mouse model of temporal lobe epilepsy, multicellular calcium imaging revealed that disease emergence was accompanied by massive amplification in the normally sparse, afferent stimulation-induced activation of hippocampal dentate granule cells. Patch recordings demonstrated reductions in local inhibitory function within the dentate gyrus at time points where sparse activation was compromised. Mimicking changes in inhibitory synaptic function and transmembrane chloride regulation was sufficient to elicit the dentate gyrus circuit collapse evident during epilepsy development. Pharmacological blockade of outward chloride transport had no effect during epilepsy development, and significantly increased granule cell activation in both control and chronically epileptic animals. This apparent occlusion effect implicates reduction in chloride extrusion as a mechanism contributing to granule cell hyperactivation specifically during early epilepsy development. Glutamine plays a significant role in local synthesis of GABA in synapses. In epileptic mice, sparse granule cell activation could be restored by glutamine application, implicating compromised GABA synthesis. Glutamine had no effect on granule cell activation earlier, during epilepsy development. We conclude that compromised feedforward inhibition within the local circuit generates the massive dentate gyrus circuit hyperactivation evident in animals during and following epilepsy development. However, the mechanisms underlying this disinhibition diverge significantly as epilepsy progresses. PMID:28218241

  20. Studi Awal Desain Pabrik Pupuk Organik Granul Dari Organic Waste

    Directory of Open Access Journals (Sweden)

    Zulfatul Hanna

    2015-12-01

    Full Text Available 800x600 Banyak pertanian di Indonesia yang masih bergantung pada penggunaan pupuk kimia. Padahal penggunaan pupuk kimia yang berlebihan dapat menyebabkan penurunan bahan organik tanah. Untuk menyeimbangkannnya saat ini petani juga sedang menggalakkan penggunaan pupuk organik. Sehingga membuat kebutuhan pupuk organik meningkat setiap tahunnya. Pendirian pabrik pupuk organik granul ini dapat memenuhi kebutuhan pupuk organik untuk petani. Prosess pembuatan pupuk organik granul terdiri dari pencampuran bahan baku, yakni sampah organik, kotoran sapi, kotoran domba, dan dipotong dengan rotary knife cutter. Tahap berikutnya adalah proses fermentasi, dengan penambahan bioactivator agar meningkatkan kandungan C-organik, phosphor, dan kalium. Selanjutnya adalah proses granulasi, pembesaran dari partikel dengan proses aglomerasi. Ukuran yang diharapkan pada proses granulasi ini adalah 2-4 mm sehingga produk undersize maupun oversize akan dikembalikan ke dalam granulator setelah melewati screener. Selanjutnya pupuk organik granul dikeringkan. Selanjutnya produk dipisahkan berdasarkan ukurannya lalu didinginkan di Rotary cooler. Setelah keluar dari Rotary Cooler suhu keluaran sekitar 40 oC dan masih mengandung kadar air sebesar 13,7%. Produk dari rotary cooler siap untuk di packaging dan masuk ke dalam pupuk organik granul storage. Dari analisa ekonomi didapatkan BEP sebesar 45% dengan POT sesudah pajak sebesar 4,8 tahun. Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4

  1. Asymmetric cell division of granule neuron progenitors in the external granule layer of the mouse cerebellum

    Directory of Open Access Journals (Sweden)

    Parthiv Haldipur

    2015-07-01

    Full Text Available The plane of division of granule neuron progenitors (GNPs was analysed with respect to the pial surface in P0 to P14 cerebellum and the results showed that there was a significant bias towards the plane of cell division being parallel to pial surface across this developmental window. In addition, the distribution of β-Catenin in anaphase cells was analysed, which showed that there was a significant asymmetry in the distribution of β-Catenin in dividing GNPs. Further, inhibition of Sonic Hedgehog (Shh signalling had an effect on plane of cell division. Asymmetric distribution of β-Catenin was shown to occur towards the source of a localized extracellular cue.

  2. Emperipolesis-like invasion of neoplastic lymphocytes into hepatocytes in feline T-cell lymphoma.

    Science.gov (United States)

    Suzuki, M; Kanae, Y; Kagawa, Y; Ano, N; Nomura, K; Ozaki, K; Narama, I

    2011-05-01

    Twelve cases of feline malignant lymphoma with emperipolesis-like invasion of neoplastic lymphocytes were examined microscopically, immunohistochemically and ultrastructurally. Intracytoplasmic invasion of neoplastic cells varied in severity between the cases, between hepatic lobules and between areas within the lobules. The number of infiltrating neoplastic cells ranged from one to several per hepatocyte. Neoplastic cells exhibited widely varying morphology from case-to-case and cell-to-cell within each case, and contained eosinophilic cytoplasmic granules in four cases. Immunohistochemical examination revealed that neoplastic cells in 11 of the 12 cases expressed one or both T-cell markers (CD3 and TIA-1). Diagnosis of T-cell lymphoma was also confirmed by assessment of clonality by polymerase chain reaction. Ultrastructural analysis revealed that the neoplastic lymphocytes were contained within an invagination of the cell membrane of the hepatocyte, rather than directly infiltrating into the cytoplasm of the cell. There was no evidence that the invasive neoplastic lymphocytes had a cytotoxic effect.

  3. Hantavirus-infection confers resistance to cytotoxic lymphocyte-mediated apoptosis.

    Directory of Open Access Journals (Sweden)

    Shawon Gupta

    2013-03-01

    Full Text Available Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS and hantavirus cardio-pulmonary syndrome (HCPS; also called hantavirus pulmonary syndrome (HPS, both human diseases with high case-fatality rates. Endothelial cells are the main targets for hantaviruses. An intriguing observation in patients with HFRS and HCPS is that on one hand the virus infection leads to strong activation of CD8 T cells and NK cells, on the other hand no obvious destruction of infected endothelial cells is observed. Here, we provide an explanation for this dichotomy by showing that hantavirus-infected endothelial cells are protected from cytotoxic lymphocyte-mediated induction of apoptosis. When dissecting potential mechanisms behind this phenomenon, we discovered that the hantavirus nucleocapsid protein inhibits the enzymatic activity of both granzyme B and caspase 3. This provides a tentative explanation for the hantavirus-mediated block of cytotoxic granule-mediated apoptosis-induction, and hence the protection of infected cells from cytotoxic lymphocytes. These findings may explain why infected endothelial cells in hantavirus-infected patients are not destroyed by the strong cytotoxic lymphocyte response.

  4. Hantavirus-infection confers resistance to cytotoxic lymphocyte-mediated apoptosis.

    Science.gov (United States)

    Gupta, Shawon; Braun, Monika; Tischler, Nicole D; Stoltz, Malin; Sundström, Karin B; Björkström, Niklas K; Ljunggren, Hans-Gustaf; Klingström, Jonas

    2013-03-01

    Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardio-pulmonary syndrome (HCPS; also called hantavirus pulmonary syndrome (HPS)), both human diseases with high case-fatality rates. Endothelial cells are the main targets for hantaviruses. An intriguing observation in patients with HFRS and HCPS is that on one hand the virus infection leads to strong activation of CD8 T cells and NK cells, on the other hand no obvious destruction of infected endothelial cells is observed. Here, we provide an explanation for this dichotomy by showing that hantavirus-infected endothelial cells are protected from cytotoxic lymphocyte-mediated induction of apoptosis. When dissecting potential mechanisms behind this phenomenon, we discovered that the hantavirus nucleocapsid protein inhibits the enzymatic activity of both granzyme B and caspase 3. This provides a tentative explanation for the hantavirus-mediated block of cytotoxic granule-mediated apoptosis-induction, and hence the protection of infected cells from cytotoxic lymphocytes. These findings may explain why infected endothelial cells in hantavirus-infected patients are not destroyed by the strong cytotoxic lymphocyte response.

  5. Changes of lymphocyte kinetics in the normal rat, induced by the lymphocyte mobilizing agent polymethacrylic acid

    NARCIS (Netherlands)

    Ormai, S.; Hagenbeek, A.; Palkovits, M.; Bekkum, D.W. van

    1973-01-01

    The changes in lymphocyte kinetics induced by the lymphocyte mobilizing agent polymethacrylic acid (PMAA) were studied in the normal rat. Quantitative data are presented concerning the degree of lymphocyte mobilization in the spleen and in various lymph nodes at different times after PMAA administra

  6. Summary of Granulation Matrix Testing for the Plutonium Immobilization Program

    Energy Technology Data Exchange (ETDEWEB)

    Herman, C.C.

    2001-10-19

    In FY00, a matrix for process development testing was created to identify those items related to the ceramic process that had not been fully developed or tested and to help identify variables that needed to be tested. This matrix, NMTP/IP-99-003, was jointly created between LLNL and SRTC and was issued to all affected individuals. The matrix was also used to gauge the progress of the development activities. As part of this matrix, several series of tests were identified for the granulation process. This summary provides the data and results from the granulation testing. The results of the granulation matrix testing were used to identify the baseline process for testing in the PuCTF with cold surrogates in B241 at LLNL.

  7. Arginine-rich cationic proteins of human eosinophil granules

    Energy Technology Data Exchange (ETDEWEB)

    Olsson, I.; Venge, P.; Spitznagel, J.K.; Lehrer, R.I.

    1977-01-01

    Several arginine-rich cationic proteins previously isolated from granules of leukemic myeloid cells have been found to reside primarily in human eosinophil leukocytes. The major component has a molecular weight of 21,000 and it contains approximately 2.6 moles of zinc per mole of protein. Velocity centrifugation of cytoplasm from leukocytes of patients with marked eosinophilia showed that this group of proteins is packaged in the crystalloid-containing large eosinophil granules. Approximately 30% of the protein content of eosinophil granules belonged to this group of cationic proteins. Bactericidal or esterolytic activities of the cationic proteins were not detected, nor did they inhibit guinea pig anaphylatoxin or histamine-induced contraction. The basic protein previously demonstrated in guinea pig eosinophils may be analogous to the group of basic proteins of human eosinophils but great differences are found for molecular weight and amino acid composition.

  8. Studies on preparation of aceclofenac pellets by centrifugal granulator

    Directory of Open Access Journals (Sweden)

    Zibin GAO

    Full Text Available To prepare aceclofenac pellets by centrifugal granulation. Using 90~100 g of starch pellets as the core pellets,100 g of aceclofenac mixed with 50 g of microcrystalline cellulose(MCC and 4 g talc, methyl cellulose (HPMC as binder,the aceclofenac pellets were prepared by centrifugal granulation .And evaluate the quality of the pellets. The aceclofenac pellets had high yield and less losses,the pellets had a partical size of 0.70~0.88 mm(18~24 mesh)and had uniform particle size .the moisture ,drug content and dissolution meet the requirement . Aceclofenac pellets were prepared by the process of centrifugal granulation .The preparation prescription and process parameters were optimized by single factor method .and the pellets meet the standard requirements.

  9. Enterovirus Control of Translation and RNA Granule Stress Responses

    Directory of Open Access Journals (Sweden)

    Richard E. Lloyd

    2016-03-01

    Full Text Available Enteroviruses such as poliovirus (PV and coxsackievirus B3 (CVB3 have evolved several parallel strategies to regulate cellular gene expression and stress responses to ensure efficient expression of the viral genome. Enteroviruses utilize their encoded proteinases to take over the cellular translation apparatus and direct ribosomes to viral mRNAs. In addition, viral proteinases are used to control and repress the two main types of cytoplasmic RNA granules, stress granules (SGs and processing bodies (P-bodies, PBs, which are stress-responsive dynamic structures involved in repression of gene expression. This review discusses these processes and the current understanding of the underlying mechanisms with respect to enterovirus infections. In addition, the review discusses accumulating data suggesting linkage exists between RNA granule formation and innate immune sensing and activation.

  10. Enterovirus Control of Translation and RNA Granule Stress Responses

    Science.gov (United States)

    Lloyd, Richard E.

    2016-01-01

    Enteroviruses such as poliovirus (PV) and coxsackievirus B3 (CVB3) have evolved several parallel strategies to regulate cellular gene expression and stress responses to ensure efficient expression of the viral genome. Enteroviruses utilize their encoded proteinases to take over the cellular translation apparatus and direct ribosomes to viral mRNAs. In addition, viral proteinases are used to control and repress the two main types of cytoplasmic RNA granules, stress granules (SGs) and processing bodies (P-bodies, PBs), which are stress-responsive dynamic structures involved in repression of gene expression. This review discusses these processes and the current understanding of the underlying mechanisms with respect to enterovirus infections. In addition, the review discusses accumulating data suggesting linkage exists between RNA granule formation and innate immune sensing and activation. PMID:27043612

  11. Paronychia and granulation tissue formation during treatment with isotretinoin*

    Science.gov (United States)

    Figueiras, Daniela de Almeida; Ramos, Ticiana Batista; Marinho, Ayana Karla de Oliveira Ferreira; Bezerra, Milena Soneley Mendonça; Cauas, Renata Cavalcanti

    2016-01-01

    This paper describes the association of two unusual side effects of treatment with isotretinoin for severe acne: paronychia and excess granulation tissue in the nails furrows. We report a case of male patient aged 19 years, who in the course of the 36th week of treatment with isotretinoin for acne grade III showed erythema, edema, excess granulation tissue and onychocryptosis in various nail beds of hands and feet, with no history of trauma associated. A literature review revealed few reports of these adverse events, and two clinical patterns of exuberant granulation tissue has been described: one in periungual location and other in lesions of previous acne. The rarity and lack of knowledge on the best treatment for granuloma-like reactions make this theme a considerable challenge. PMID:27192525

  12. Cystatin F Ensures Eosinophil Survival by Regulating Granule Biogenesis.

    Science.gov (United States)

    Matthews, Stephen P; McMillan, Sarah J; Colbert, Jeff D; Lawrence, Rachel A; Watts, Colin

    2016-04-19

    Eosinophils are now recognized as multifunctional leukocytes that provide critical homeostatic signals to maintain other immune cells and aid tissue repair. Paradoxically, eosinophils also express an armory of granule-localized toxins and hydrolases believed to contribute to pathology in inflammatory disease. How eosinophils deliver their supporting functions while avoiding self-inflicted injury is poorly understood. We have demonstrated that cystatin F (CF) is a critical survival factor for eosinophils. Eosinophils from CF null mice had reduced lifespan, reduced granularity, and disturbed granule morphology. In vitro, cysteine protease inhibitors restored granularity, demonstrating that control of cysteine protease activity by CF is critical for normal eosinophil development. CF null mice showed reduced pulmonary pathology in a model of allergic lung inflammation but also reduced ability to combat infection by the nematode Brugia malayi. These data identify CF as a "cytoprotectant" that promotes eosinophil survival and function by ensuring granule integrity. VIDEO ABSTRACT.

  13. Application of high OLR-fed aerobic granules for the treatment of low-strength wastewater: Performance, granule morphology and microbial community

    Institute of Scientific and Technical Information of China (English)

    Jingyun Ma; Xiangchun Quan; Huai Li

    2013-01-01

    Aerobic granules,pre-cultivated at the organic loading rate (OLR) of 3.0 kg COD/(m3·day),were used to treat low-strength wastewater in two sequencing batch reactors at low OLRs of 1.2 and 0.6 kg COD/(m3·day),respectively.Reactor performance,evolution of granule morphology,structure and microbial community at low OLRs under long-term operation (130 days) were investigated.Results showed that low OLRs did not cause significant damage to granule structure as a dominant granule morphology with size over 540 μm was maintained throughout the operation.Aerobic granules at sizes of about 750 μm were finally obtained at the low OLRs.The granule reactors operated at low OLRs demonstrated effective COD and ammonia removals (above 90%),smaller granule sizes and less biomass.The contents of extracellular polymeric substances in the granules were decreased while the ratios of exopolysaccharide/exoprotein were increased (above 1.0).The granules cultivated at the low OLRs showed a smoother surface and more compact structure than the seeded granules.A significant shift in microbial community was observed but the microbial diversity remained relatively stable.Confocal Laser Scanning Microscopy observation showed that the live cells were spread throughout the whole granule,while the dead cells were mainly concentrated in the outer layer of the granule,and the proteins,polysaccharides and lipids were mainly located in the central regime of the granule.In conclusion,granules cultivated at high OLRs show potential for treating low-strength organic wastewater steadily under long-term operation.

  14. UVC-induced stress granules in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Mohamed Taha Moutaoufik

    Full Text Available Stress granules (SGs are well characterized cytoplasmic RNA bodies that form under various stress conditions. We have observed that exposure of mammalian cells in culture to low doses of UVC induces the formation of discrete cytoplasmic RNA granules that were detected by immunofluorescence staining using antibodies to RNA-binding proteins. UVC-induced cytoplasmic granules are not Processing Bodies (P-bodies and are bone fide SGs as they contain TIA-1, TIA-1/R, Caprin1, FMRP, G3BP1, PABP1, well known markers, and mRNA. Concomitant with the accumulation of the granules in the cytoplasm, cells enter a quiescent state, as they are arrested in G1 phase of the cell cycle in order to repair DNA damages induced by UVC irradiation. This blockage persists as long as the granules are present. A tight correlation between their decay and re-entry into S-phase was observed. However the kinetics of their formation, their low number per cell, their absence of fusion into larger granules, their persistence over 48 hours and their slow decay, all differ from classical SGs induced by arsenite or heat treatment. The induction of these SGs does not correlate with major translation inhibition nor with phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α. We propose that a restricted subset of mRNAs coding for proteins implicated in cell cycling are removed from the translational apparatus and are sequestered in a repressed form in SGs.

  15. Influence of filler selection on twin screw foam granulation.

    Science.gov (United States)

    Rocca, K E; Weatherley, S; Sheskey, P J; Thompson, M R

    2015-01-01

    The influence of filler selection in wet granulation was studied for the novel case where the binder is delivered as an unstable, semi-rigid aqueous foam to an extrusion process. The work primarily examined the impact of differing concentrations of microcrystalline cellulose (Avicel PH® 101) in a formulation with spray-dried α-lactose monohydrate (Flowlac® 100) in regards to wetting and granule nucleation for this relatively new technique known as continuous foam granulation. Foam stability was varied within the work to change its drainage and coarsening behavior atop these powder excipients, by use of different foamable binding agents (METHOCEL™ F4 PLV and METHOCEL™ Premium VLV) as well as by adjusting the foam quality. A static bed penetration test was first used to study the foam behavior in wetting these powders without the processing constraints of an extruder which limit possible liquid-to-solids ratios as well as introduce shear which may complicate interpretation of the mechanism. The test found that the penetration time to saturate these powders decreased as their water absorption capacity increased which in turn decreased the size of the formed nuclei. Differences in the stability of the foamed binder had minimal influence on these attributes of wetting despite its high spread-to-soak behavior. The size of granules produced by extrusion similarly demonstrated sensitivity to the increasing water absorption capacity of the filler and little dependency on foam properties. The different liquid-to-solids ratios required to granulate these different formulations inside the extruder highlighted an evolving concept of powder lubricity for continuous foam granulation.

  16. Interpretation of NCCN Guideline: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (Version 1, 2017

    Directory of Open Access Journals (Sweden)

    Lei XIA

    2016-12-01

    Full Text Available Chronic lymphocytic leukemia (CLL is a kind of chronic lymphocyte proliferative disease with corresponding clinical symptoms caused by the accumulation of mature B lymphocytes in peripheral blood, bone marrow and lymphatic tissues. In recent years, great achievements have been reached on the basic research, new prognostic markers, diagnostic criteria and therapeutic methods in CLL. This study mainly interpreted the corresponding diagnosis and treatment of CLL in NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (Version 1, 2017.

  17. Genetics Home Reference: bare lymphocyte syndrome type I

    Science.gov (United States)

    ... Home Health Conditions bare lymphocyte syndrome type I bare lymphocyte syndrome type I Enable Javascript to view ... boxes. Download PDF Open All Close All Description Bare lymphocyte syndrome type I (BLS I) is an ...

  18. The Danish National Chronic Lymphocytic Leukemia Registry

    DEFF Research Database (Denmark)

    da Cunha-Bang, Caspar; Geisler, Christian Hartmann; Enggaard, Lisbeth

    2016-01-01

    AIM: In 2008, the Danish National Chronic Lymphocytic Leukemia Registry was founded within the Danish National Hematology Database. The primary aim of the registry is to assure quality of diagnosis and care of patients with chronic lymphocytic leukemia (CLL) in Denmark. Secondarily, to evaluate...

  19. Disruption of the langerin/CD207 Gene Abolishes Birbeck Granules without a Marked Loss of Langerhans Cell Function

    Science.gov (United States)

    Kissenpfennig, Adrien; Aït-Yahia, Smina; Clair-Moninot, Valérie; Stössel, Hella; Badell, Edgar; Bordat, Yann; Pooley, Joanne L.; Lang, Thierry; Prina, Eric; Coste, Isabelle; Gresser, Olivia; Renno, Toufic; Winter, Nathalie; Milon, Geneviève; Shortman, Ken; Romani, Nikolaus; Lebecque, Serge; Malissen, Bernard; Saeland, Sem; Douillard, Patrice

    2005-01-01

    Langerin is a C-type lectin expressed by a subset of dendritic leukocytes, the Langerhans cells (LC). Langerin is a cell surface receptor that induces the formation of an LC-specific organelle, the Birbeck granule (BG). We generated a langerin−/− mouse on a C57BL/6 background which did not display any macroscopic aberrant development. In the absence of langerin, LC were detected in normal numbers in the epidermis but the cells lacked BG. LC of langerin−/− mice did not present other phenotypic alterations compared to wild-type littermates. Functionally, the langerin−/− LC were able to capture antigen, to migrate towards skin draining lymph nodes, and to undergo phenotypic maturation. In addition, langerin−/− mice were not impaired in their capacity to process native OVA protein for I-Ab-restricted presentation to CD4+ T lymphocytes or for H-2Kb-restricted cross-presentation to CD8+ T lymphocytes. langerin−/− mice inoculated with mannosylated or skin-tropic microorganisms did not display an altered pathogen susceptibility. Finally, chemical mutagenesis resulted in a similar rate of skin tumor development in langerin−/− and wild-type mice. Overall, our data indicate that langerin and BG are dispensable for a number of LC functions. The langerin−/− C57BL/6 mouse should be a valuable model for further functional exploration of langerin and the role of BG. PMID:15601833

  20. Physical, electrochemical, and thermal properties of granulated natural graphite as anodes for Li-ion batteries.

    Science.gov (United States)

    Jo, Yong Nam; Park, Min-Sik; Kim, Jae-Hun; Kim, Young-Jun

    2013-05-01

    Two different types of granulated graphites were synthesized by blending and kneading of natural graphite with pitch followed by sintering methods. The electrochemical performances of granulated graphites were investigated as anode materials for use in Li-ion batteries. The blending type granulated graphite possesses a large amount of cavities and voids, while the kneading type granulated graphite has a relatively compact microstructure, which is responsible for a high tap density. Both granulated graphites show improved the initial coulombic efficiencies as a result of decrease of surface area by the granulations. In particular, the kneading type granulated graphite exhibits an excellent rate-capability without significant capacity loss. In addition, the thermal stabilities of both granulated graphites were also improved, which could be attributed to the decrease of active surface area due to pitch coating.

  1. Modeling of lithium granule injection in NSTX using M3D-C1

    Science.gov (United States)

    Fil, A.; Kolemen, E.; Ferraro, N.; Jardin, S.; Parks, P. B.; Lunsford, R.; Maingi, R.

    2017-05-01

    In this paper, we present simulations of pedestal control by lithium granule injection (LGI) in NSTX. A model for small granule ablation has been implemented in the M3D-C1 code (Jardin et al 2012 Comput. Sci. Discovery 5 014002), allowing the simulation of realistic lithium granule injections. 2D and 3D simulations of Li injections in NSTX H-mode plasmas are performed and the effect of granule size, injection angle and velocity on the pedestal gradient increase is studied. The amplitude of the local pressure perturbation caused by the granules is found to be highly dependent on the solid granule size. Adjusting the granule injection velocity allows one to inject more particles at the pedestal top. 3D simulations show the destabilization of high order MHD modes whose amplitude is directly linked to the localized pressure perturbation, which is found to depend on the toroidal localization of the granule density source.

  2. To prepare and characterize microcrystalline cellulose granules using water and isopropyl alcohol as granulating agents and determine its end-point by thermal and rheological tools.

    Science.gov (United States)

    Chaudhari, Smruti P; Dave, Rutesh H

    2015-05-01

    Microcrystalline cellulose (MCC-102) is one of the most commonly used excipient in the pharmaceutical industry. For this research purpose, authors have developed a different technique to determine the end point for MCC-102 using water and isopropyl alcohol 70% (IPA) as granulating agent. Wet and dry granules obtained were characterized for their flow properties using the powder rheometer and thermal analysis. Powder rheometer was used to measure basic flowability energy (BFE), specific energy (SE), percentage compressibility, permeability and aeration. Thermal analysis includes effusivity and differential scanning calorimetry (DSC) measurements. BFE and SE results showed water granules requires high energy as compared to IPA granules. Permeability and compressibility results suggest IPA forms more porous granules and have better compressibility as compared to water granules. Hardness data reveals interesting phenomena in which as the amount of water increases, hardness decreases and vice-versa for IPA. Optimal granules were obtained in the range of 45-55% w/w. DSC data supported the formation of optimal granules. Empirical measurements like angle of repose did not reveal any significant differences between powder flow among various granules. In this paper, with the help of thermal effusivity and powder rheology we were able to differentiate between various powder flows and determine the optimal range for granule formation.

  3. Lenalidomide and Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Ana Pilar González-Rodríguez

    2013-01-01

    Full Text Available Lenalidomide is an oral immunomodulatory drug used in multiple myeloma and myelodysplastic syndrome and most recently it has shown to be effective in the treatment of various lymphoproliferative disorders such as chronic lymphocytic leukemia (CLL and non-Hodgkin lymphoma. The mechanism of action of lenalidomide varies depending on the pathology, and in the case of CLL, it appears to primarily act by restoring the damaged mechanisms of tumour immunosurveillance. This review discusses the potential mechanism of action and efficacy of lenalidomide, alone or in combination, in treatment of CLL and its toxic effects such as tumor lysis syndrome (TLS and tumor flare reaction (TFR, that make its management different from other hematologic malignancies.

  4. The development of a growth regime map for a novel reverse-phase wet granulation process.

    Science.gov (United States)

    Wade, Jonathan B; Martin, Gary P; Long, David F

    2016-10-15

    The feasibility of a novel reverse-phase wet granulation process has been established and potential advantages identified. Granule growth in the reverse-phase process proceeds via a steady state growth mechanism controlled by capillary forces, whereas granule growth in the conventional process proceeds via an induction growth regime controlled by viscous forces. The resultant reverse-phase granules generally have greater mass mean diameter and lower intragranular porosity when compared to conventional granules prepared under the same liquid saturation and impeller speed conditions indicating the two processes may be operating under different growth regimes. Given the observed differences in growth mechanism and consolidation behaviour of the reverse-phase and conventional granules the applicability of the current conventional granulation regime map is unclear. The aim of the present study was therefore to construct and evaluate a growth regime map, which depicts the regime as a function of liquid saturation and Stokes deformation number, for the reverse-phase granulation process. Stokes deformation number was shown to be a good predictor of both granule mass mean diameter and intragranular porosity over a wide range of process conditions. The data presented support the hypothesis that reverse-phase granules have a greater amount of surface liquid present which can dissipate collision energy and resist granule rebound resulting in the greater granule growth observed. As a result the reverse-phase granulation process results in a greater degree of granule consolidation than that produced using the conventional granulation process. Stokes deformation number was capable of differentiating these differences in the granulation process.

  5. Discrete element modelling of fluidised bed spray granulation

    NARCIS (Netherlands)

    Goldschmidt, M.J.V.; Weijers, G.G.C.; Boerefijn, R.; Kuipers, J.A.M.

    2003-01-01

    A novel discrete element spray granulation model capturing the key features of fluidised bed hydrodynamics, liquid¿solid contacting and agglomeration is presented. The model computes the motion of every individual particle and droplet in the system, considering the gas phase as a continuum. Microsca

  6. Discrete element modelling of fluidised bed spray granulation

    NARCIS (Netherlands)

    Goldschmidt, M.J.V.; Weijers, G.G.C.; Boerefijn, R.; Kuipers, J.A.M.

    2002-01-01

    A novel discrete element spray granulation model capturing the key features of fluidised bed hydrodynamics, liquid-solid contacting and agglomeration is presented. The model computes the motion of every individual particle and droplet in the system, considering the gas phase as a continuum. Micro sc

  7. Arachnoid granules: Dandy was Dandy, Cushing and Weed were not.

    Science.gov (United States)

    Maurizi, Charles P

    2010-08-01

    Errors can be instructive. It seems that Harvey Cushing and Louis Weed provided the medical world with a faulty theory of cerebrospinal fluid absorption. Louis Weed, working in Harvey Cushing's laboratory, initially studied the movement of substances in the cerebrospinal fluid by using low-pressure studies. Results of the low-pressure studies were considered unsatisfactory and high pressure experiments were undertaken and these had results similar to earlier work done by others in human cadavers. High pressure results demonstrating movement of fluid through the arachnoid granules were deemed correct. Because of Cushing's position of authority, the theory became accepted as fact and in time proved to be entrenched dogma. Walter Dandy demonstrated in experiments on hydrocephalus and the surgical removal of the arachnoid granule system that the fluid was produced by the choroid plexuses and not absorbed by the arachnoid granules. His work was dismissed by Weed as unreliable. Examination of the pattern of deposition of corpora amylacea on the surface of the brain provides evidence that cerebrospinal fluid does not pass through arachnoid granules but passes through the choroid fissure and is recycled through choroid plexus portals. The choroid plexus portal theory can explain the findings in the low-pressure experiments of Weed. Bias and pride seem to be the source of the faulty theory. Entrenched dogma is resistant to challenge.

  8. F-Granulation Generalized Rough Entropy and Image Analysis

    Science.gov (United States)

    Pal, Sankar K.

    2012-12-01

    Role of f-granulation in handling uncertainty in machine intelligence and its significance as a facet of natural computation are discussed. Its modeling through judicious integration of rough and fuzzy sets is explained. Several tasks like case generation, clustering, classification and segmentation are described in rough-fuzzy framework demonstrating the role of f-granulation and the resulting merits. A definition of generalized rough sets is given considering both the set and granules as crisp and/or fuzzy. Based on that new entropy measures are defined using exponential and logarithmic gain functions. The superiority of rough-fuzzy integration, in terms of performance and computation time, is illustrated for the tasks of case mining in large data sets, segmenting brain MR images, and classifying remotely sensed images as examples. Neighbourhood rough sets are capable of better dimensionality reduction. The effect of fuzzy-granules and generalizations in rough sets is demonstrated for image segmentation. The article includes some of the results published elsewhere.

  9. Mechanisms underlying the beneficial effects of Kaiyu Granule for depression

    Institute of Scientific and Technical Information of China (English)

    Xi Jin; Yidan Zhang; Qiaoying Li; Jianjun Zhao

    2013-01-01

    The proprietary Chinese medicine preparation Kaiyu Granule is made of bupleurum, nutgrass ga-lingale rhizome, szechwan lovage rhizome, turmeric root tuber, white peony alba, cape jasmine fruit, fried semen ziziphi jujubae, and prepared liquorice root. It is a common recipe for the clinical treatment of depression in China. In this study, after 21 days of unpredictable stress exposure, Wistar rats exhibited similar behavioral changes to patients with depression. Moreover, G-protein-coupled inwardly rectifying K+channel 1 mRNA and protein expression were significantly reduced in rat hippocampal CA1 and CA3 regions. However, G-protein-coupled inwardly rectifying K+channel 1 mRNA, protein expression, and rat behavior were clearly better after administration of 12, 8, or 4 g/kg of Kaiyu Granule when depression model rats underwent stress. 12 g/kg of Kaiyu Granule had the most obvious effects on the increased expression of G-protein-coupled inwardly rectifying K+channel 1 mRNA and protein in rat hippocampal CA1 and CA3 regions. These results suggested that Kaiyu Granule improved depression by affecting G-protein-coupled inwardly fying K+channel 1 expression in the rat hippocampus.

  10. Spontaneous calcium waves in granule cells in cerebellar slice cultures

    DEFF Research Database (Denmark)

    Apuschkin, Mia; Ougaard, Maria; Rekling, Jens C

    2013-01-01

    and establishment of synaptic transmission. Here, we used calcium imaging in slice cultures of the postnatal cerebellum, and observe spontaneous propagating calcium waves in NeuN-positive granule-like cells. Wave formation was blocked by TTX and the AMPA antagonist NBQX, but persisted after NMDA receptor blockade...

  11. Block-based approach to modelling of granulated fertilizers' quality

    DEFF Research Database (Denmark)

    Kohonen, J.; Reinikainen, S. P.; Høskuldsson, Agnar

    2009-01-01

    Fertilizer manufacturing is a customer-driven industry, where the quality of a product is a key factor in order to survive the competition. However, measuring the most important feature with granulated fertilizers, flowability, is tedious, time-consuming and thus expensive. Flowability can...

  12. Comparison of torque measurements and near-infrared spectroscopy in characterization of a wet granulation process

    DEFF Research Database (Denmark)

    Jørgensen, Anna Cecilia; Luukkonen, Pirjo; Rantanen, Jukka

    2004-01-01

    The purpose of this study was to compare impeller torque measurements and near-infrared (NIR) spectroscopy in the characterization of the water addition phase of a wet granulation process. Additionally, the effect of hydrate formation during granulation on the impeller torque was investigated...... to process monitoring of wet granulation, also in cases where monitoring of impeller torque is difficult to apply....

  13. A model for the spray zone in early-stage fluidized bed granulation

    NARCIS (Netherlands)

    Schaafsma, S. H.; Vonk, P.; Kossen, N. W. F.; Hoffmann, A. C.

    2006-01-01

    The formation of granules in the spray zone of a top-spray fluid-bed granulation process using a known and uniform drop-size is studied experimentally and theoretically. Experimental results indicate a multi-modal size distribution of spherically-shaped granules. A model is presented to explain this

  14. Comparison of four enhancement strategies for aerobic granulation in sequencing batch reactors.

    Science.gov (United States)

    Gao, Dawen; Liu, Lin; Liang, Hong; Wu, Wei-Min

    2011-02-15

    Aerobic granules were developed in four identical sequencing batch reactors (SBRs) with synthetic wastewater to compare different strategies for the enhancement of granulation. The SBRs were operated by (a) increasing organic loading rate in R1; (b) reducing settling time in R2; (c) extending starvation period in R3; and (d) increasing shear force in R4. The results showed that four operational strategies were able to enhance aerobic granulation successfully in SBR, but that also showed different effect on the granulation process and characteristics of mature aerobic granules. The rapidest granulation was observed by using short settling time (R2) and the granules had higher extracellular polymeric substance (EPS) than other reactors. Extended starvation period (R3) and high shear force (R4) resulted in longer granulation period and the granules with higher integrity and smaller size. Higher organic loading rate (R1) resulted in the granules with larger size and higher K value. The maximum specific COD removal rates (q(max)) of the granules in all SBRs were at a similar level (0.13-0.16 g COD/h-g VSS) but the granules in R1 and R2 had higher apparent half rate constant (K) of 18 and 16 mg/L, than those in R3 and R4 (2.8 and 3.3 mg/L).

  15. Comparison of four enhancement strategies for aerobic granulation in sequencing batch reactors

    Energy Technology Data Exchange (ETDEWEB)

    Gao Dawen, E-mail: dawengao@gmail.com [School of Forestry, Northeast Forestry University, Harbin 150040 (China); State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150090 (China); Liu Lin; Liang Hong [School of Forestry, Northeast Forestry University, Harbin 150040 (China); Wu Weimin [Department of Civil and Environmental Engineering, Stanford University, Stanford, CA 94305-4020 (United States)

    2011-02-15

    Aerobic granules were developed in four identical sequencing batch reactors (SBRs) with synthetic wastewater to compare different strategies for the enhancement of granulation. The SBRs were operated by (a) increasing organic loading rate in R1; (b) reducing settling time in R2; (c) extending starvation period in R3; and (d) increasing shear force in R4. The results showed that four operational strategies were able to enhance aerobic granulation successfully in SBR, but that also showed different effect on the granulation process and characteristics of mature aerobic granules. The rapidest granulation was observed by using short settling time (R2) and the granules had higher extracellular polymeric substance (EPS) than other reactors. Extended starvation period (R3) and high shear force (R4) resulted in longer granulation period and the granules with higher integrity and smaller size. Higher organic loading rate (R1) resulted in the granules with larger size and higher K value. The maximum specific COD removal rates (q{sub max}) of the granules in all SBRs were at a similar level (0.13-0.16 g COD/h-g VSS) but the granules in R1 and R2 had higher apparent half rate constant (K) of 18 and 16 mg/L, than those in R3 and R4 (2.8 and 3.3 mg/L).

  16. TABLETING PROPERTIES OF EXPERIMENTAL AND COMMERCIALLY AVAILABLE LACTOSE GRANULATIONS FOR DIRECT COMPRESSION

    NARCIS (Netherlands)

    BOLHUIS, GK; ZUURMAN, K

    1995-01-01

    Lactose granulations (125-250 mu m) were prepared from two different alpha-lactose monohydrate powders and one roller dried beta-lactose powder respectively, by wet granulation with only water as a binder. As an effect of the granulation process, the flow properties improved, but the compactibility

  17. Morphology, structure and gelatinization properties of heterogeneous starch granules from high-amylose maize.

    Science.gov (United States)

    Cai, Canhui; Zhao, Lingxiao; Huang, Jun; Chen, Yifang; Wei, Cunxu

    2014-02-15

    High-amylose cereal endosperm is rich in heterogeneous starch granules. In this paper, we investigated the morphology, structure and gelatinization properties of high-amylose maize endosperm starch. Starch had individual, aggregate and elongated heterogeneous granules. Most of individual granules were round with small size and had one central hilum. Aggregate and elongated granules consisted of many subgranules with central hila, and had irregular and rod/filamentous shapes, respectively. Iodine stained starch granules showed five types of polarization colors: blue, purple, fuchsia, dark red, and interior dark blue and exterior brown. Most of individual and aggregate granules had the color of dark red, that of elongated granules the color of interior dark blue and exterior brown. Amylose was mainly distributed in the hilum region and the circumference of starch granules. Aggregate and elongated granules had higher amylose content than individual granules. Elongated and individual granules had the highest and the lowest gelatinization resistance among high-amylose maize heterogeneous starch granules, respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Spray freeze granulation of submicron alumina and its sintering behavior via spark plasma sintering

    Directory of Open Access Journals (Sweden)

    Liu Wei

    2015-01-01

    Full Text Available Spray freeze granulation is an improved method based on spray granulation, solving many limitations of spray granulation. In this work, spray freeze granulation of submicron alumina is performed to explore the possibility of industrial-scale production of dense alumina via spark plasma sintering. Powder pretreatment such as sedimentation and the selection of granules with the appropriate size are employed for the maximum use of the high qualified as-prepared granules and granule sliding, which would provide a guidance for the industrial-scale production. Debound granules were densified via SPS and the corresponding sintering behaviors such as the recorded shrinkage and shrinkage rate were discussed. The comparison of sintering behaviors between granulated and as-received powder are conducted to identify the role of spray freeze granulation in sinterability for dense alumina. The Vickers hardness (Hv and the fracture toughness (KIC of the freeze granulated body are higher than the corresponding properties of the as-received body due to the more homogenous microstructure with little agglomeration in the particle packing after freeze granulation.

  19. File list: ALL.Neu.20.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. File list: Oth.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

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  1. File list: Oth.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

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    Lifescience Database Archive (English)

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  14. File list: ALL.Neu.05.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

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    Lifescience Database Archive (English)

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  18. File list: Unc.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. File list: Unc.Neu.20.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: Oth.Neu.05.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Neu.05.AllAg.Cerebellar_granule_neurons mm9 TFs and others Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.05.AllAg.Cerebellar_granule_neurons.bed ...

  2. [Evolution and phylogeny of B lymphocytes].

    Science.gov (United States)

    Claudio-Piedras, Fabiola; Lanz-Mendoza, Humberto

    2016-01-01

    B lymphocytes are one of the most important cell types involved in the immune response of mammals. The origin and evolution of this cellular type is unknown, but the B lymphocyte bona fide appeared first in fish. In this review we analize the principal components of the immune response of invertebrates, their phylogenetic distribution and the permancence of some properties that allowed the emergence of the B lymphocyte. We started from the idea that many of the components that characterize the B lymphocyte are found distributed among the invertebrates, however, it is in the B lymphocyte, where all these components that give this type of cell its identity, converged. The actual knowledge we have in regards of the lymphocytes comes, in the most part, from physiological studies in mammals, being the mice the more representative. The origin of the B lymphocyte, its alternative mechanisms for generating receptor diversity, its immune effector response, and the generation of memory, require an evolutionary and multidisiplinary approach for its study.

  3. Surface Modification of Porous Titanium Granules for Improving Bioactivity.

    Science.gov (United States)

    Karaji, Zahra Gorgin; Houshmand, Behzad; Faghihi, Shahab

    The highly porous titanium granules are currently being used as bone substitute material and for bone tissue augmentation. However, they suffer from weak bone bonding ability. The aim of this study was to create a nanostructured surface oxide layer on irregularly shaped titanium granules to improve their bioactivity. This could be achieved using optimized electrochemical anodic oxidation (anodizing) and heat treatment processes. The anodizing process was done in an ethylene glycol-based electrolyte at an optimized condition of 60 V for 3 hours. The anodized granules were subsequently annealed at 450°C for 1 hour. Scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy (EDS), and x-ray diffraction (XRD) were used to characterize the surface structure and morphology of the granules. The in vitro bioactivity of the samples was evaluated by immersion of specimens in simulated body fluid (SBF) for 1, 2, and 3 weeks. The human osteoblastic sarcoma cell line, MG63, was used to evaluate cell viability on the samples using dimethylthiazol-diphenyl tetrazolium bromide (MTT) assay. The results demonstrated the formation of amorphous nanostructured titanium oxide after anodizing, which transformed to crystalline anatase and rutile phases upon heat treatment. After immersion in SBF, spherical aggregates of amorphous calcium phosphate were formed on the surface of the anodized sample, which turned into crystalline hydroxyapatite on the surface of the anodized annealed sample. No cytotoxicity was detected among the samples. It is suggested that anodic oxidation followed by heat treatment could be used as an effective surface treatment procedure to improve bioactivity of titanium granules implemented for bone tissue repair and augmentation.

  4. GRANULATION AND BRIQUETTING OF SOLID PRODUCTS FROM FLUE GAS DESULFURIZATION

    Directory of Open Access Journals (Sweden)

    Jan J. Hycnar

    2015-11-01

    Full Text Available Most flue gas desulfurization products can be characterized by significant solubility in water and dusting in dry state. These characteristics can cause a considerable pollution of air, water, and soil. Among many approaches to utilization of this waste, the process of agglomeration using granulation or briquetting has proved very effective. Using desulfurization products a new material of aggregate characteristics has been acquired, and this material is resistant to water and wind erosion as well as to the conditions of transportation and storage. The paper presents the results of industrial trials granulation and briquetting of calcium desulphurization products. The granulation of a mixture of phosphogypsum used with fly ash (in the share 1:5. The resulting granules characterized by a compressive strength of 41.6 MPa, the damping resistance of 70% and 14.2% abrasion. The granulate was used for the production of cement mix. The produced concrete mortar have a longer setting and hardening time, as compared to the traditional ash and gypsum mortar, and have a higher or comparable flexural and compressive strength during hardening. Briquetting trials made of a product called synthetic gypsum or rea-gypsum both in pure form and with the addition of 5% and 10% of the limestone dust. Briquettes have a high initial strength and resistance to abrasion. The values ​​of these parameters increased after 72 hours of seasoning. It was found that higher hardiness of briquettes with rea-gypsum was obtained with the impact of atmospheric conditions and higher resistance to elution of water-soluble components in comparison to ash briquettes.

  5. Clarithromycin highly-loaded gastro-floating fine granules prepared by high-shear melt granulation can enhance the efficacy of Helicobacter pylori eradication.

    Science.gov (United States)

    Aoki, Hajime; Iwao, Yasunori; Mizoguchi, Midori; Noguchi, Shuji; Itai, Shigeru

    2015-05-01

    In an effort to develop a new gastro-retentive drug delivery system (GRDDS) without a large amount of additives, 75% clarithromycin (CAM) loaded fine granules were prepared with three different hydrophobic binders by high-shear melt granulation and their properties were evaluated. Granules containing the higher hydrophobic binder showed sustained drug release and were able to float over 24h. The synchrotron X-ray CT measurement indicated that both the high hydrophobicity of the binder and the void space inside the granules might be involved in their buoyancy. In an in vivo experiment, the floating granules more effectively eradicated Helicobacter pylori than a CAM suspension by remaining in the stomach for a longer period. In short, CAM highly-loaded gastro-floating fine granules can enhance the eradication efficiency of H. pylori compared with CAM alone. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Metabolism of peripheral lymphocytes, interleukin-2-activated lymphocytes and tumor-infiltrating lymphocytes from sup 31 P NMR studies

    Energy Technology Data Exchange (ETDEWEB)

    Kaplan, O.; Cohen, J.S.; Aebersold, P.

    1989-11-20

    {sup 31}O NMR spectra of tumor-infiltrating lymphocytes (TILs) were found to be significantly diefferent form those of normal peripheral lymphocytes. The greatest difference was in the phosphodiester (PDE) region, mainly in the glycerophosphocholine (GPC) signal. Short-term activation of peripheral lymphocytes with interleukin-2 induced a small increase in ATP levels. In all lumphocytes the phosphomonoester (PME) region is dominated by phosphoethanolamine (PE), while there is an unusual absence of phosphocholine (PC). Perfusion of these cells with high concentrations of choline caused only a minimal increase in PC, indicating that choline kinase is not the rate limiting step of lecithin synthesis in lymphocytes. (author). 13 refs.; 3 figs.; 1 tab.

  7. Fine granules showing sustained drug release prepared by high-shear melt granulation using triglycerin full behenate and milled microcrystalline cellulose.

    Science.gov (United States)

    Aoki, Hajime; Iwao, Yasunori; Uchimoto, Takeaki; Noguchi, Shuji; Kajihara, Ryusuke; Takahashi, Kana; Ishida, Masayuki; Terada, Yasuko; Suzuki, Yoshio; Itai, Shigeru

    2015-01-30

    This study aimed to prepare fine granules with a diameter less than 200μm and sustained drug release properties by melt granulation. Triglycerin full behenate (TR-FB) was examined as a new meltable binder (MB) by comparison of its properties with those of glycerin monostearate (GM), widely used as MB. The effect of milling microcrystalline cellulose (MCC), an excipient for melt granulation, on the granule properties was also investigated. TR-FB was more stable during heating and storage than GM, and produced smaller granules with narrower particle size distribution, larger yield in the 106-200μm range, uniform roundness and better sustained drug release profile than those prepared with GM. Granules prepared with milled MCC had almost the same physicochemical properties as those produced with intact MCC. However, milled MCC produced granules with a more rigid structure and smaller void space than intact MCC. Consequently, the granules produced with milled MCC showed better sustained drug release behavior than those prepared with intact MCC. We successfully prepared fine granules with sustained drug release properties and diameter of less than 200μm using TR-FB and milled MCC. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Nitrifying and denitrifying bacteria in aerobic granules formed in sequencing batch airlift reactors

    Institute of Scientific and Technical Information of China (English)

    WANG Fang; YANG Fenglin; QI Aijiu

    2007-01-01

    The purpose of this study was to investigate nitrifying bacteria and denitrifying bacteria isolated from aerobic granules.Aerobic granules were formed in an internal-circulate sequencing batch airlift reactor(SBAR)and biodegradation of NH3 -N was analyzed in the reactor.Bacteria were isolated and determined from aerobic granules using selected media.The growth properties and morphology of bacteria colonies were observed by controlling aerobic or anaerobic conditions in the culture medium.It was found that bacteria in aerobic granules were diverse and some of them were facultative aerobes.The diversity of bacteria in aerobic granules was a premise of simultaneous nitrification and denitrification.

  9. Generalized multi-layered granulations and approximations based on neighborhood systems under incomplete information systems

    Institute of Scientific and Technical Information of China (English)

    HE Ming; FENG Bo-qin

    2005-01-01

    A generalized multi-layered granulation structure used by neighborhood systems is proposed. With granulated views, the concepts of approximations under incomplete information systems are studied, which are represented by covering of the universe. With respect to different levels of granulations, a pair of lower and upper approximations is defined and an approximation structure is investigated, which lead to a more general approximation structure. The generalized multi-layered granulation structure provides a basis of the proposed framework of granular computing. Using this framework, the interesting and useful results about information granulation and approximation reasoning can be obtained. This paper presents some useful explorations about the incomplete information systems from information views.

  10. Monoclonal antibodies in chronic lymphocytic leukemia.

    Science.gov (United States)

    Ferrajoli, Alessandra; Faderl, Stefan; Keating, Michael J

    2006-09-01

    Multiple options are now available for the treatment of chronic lymphocytic leukemia. Over the last 10 years, monoclonal antibodies have become an integral part of the management of this disease. Alemtuzumab has received approval for use in patients with fludarabine-refractory chronic lymphocytic leukemia. Rituximab has been investigated extensively in chronic lymphocytic leukemia both as a single agent and in combination with chemotherapy and other monoclonal antibodies. Epratuzumab and lumiliximab are newer monoclonal antibodies in the early phase of clinical development. This article will review the monoclonal antibodies more commonly used to treat chronic lymphocytic leukemia, the results obtained with monoclonal antibodies as single agents and in combination with chemotherapy, and other biological agents and newer compounds undergoing clinical trials.

  11. Segmental identity and cerebellar granule cell induction in rhombomere 1

    Directory of Open Access Journals (Sweden)

    Bell Esther

    2004-06-01

    Full Text Available Abstract Background Cerebellar granule cell precursors are specifically generated within the hindbrain segment, rhombomere 1, which is bounded rostrally by the midbrain/hindbrain isthmus and caudally by the boundary of the Hoxa2 expression domain. While graded signals from the isthmus have a demonstrable patterning role within this region, the significance of segmental identity for neuronal specification within rhombomere 1 is unexplored. We examined the response of granule cell precursors to the overexpression of Hoxa2, which normally determines patterns of development specific to the hindbrain. How much does the development of the cerebellum, a midbrain/hindbrain structure, reflect its neuromeric origin as a hindbrain segment? Results We show that a Gbx2-positive, Otx2-/Hoxa2-negative territory corresponding to rhombomere 1 forms prior to an identifiable isthmic organiser. Early global overexpression of Hoxa2 at embryonic day 0 has no effect on the expression of isthmic signalling molecules or the allocation of rhombomere 1 territory, but selectively results in the loss of granule cell markers at embryonic day 6 and the depletion of cell bodies from the external granule cell layer. By comparison the trochlear nucleus and locus coeruleus form normally in ventral rhombomere 1 under these conditions. Microsurgery, coupled with electroporation, to target Hoxa2 overexpression to rhombic lip precursors, reveals a profound, autonomous respecification of migration. Rhombic lip derivatives, normally destined to occupy the external granule cell layer, violate the cerebellar boundary to form a ventrolateral nucleus in a position comparable to that occupied by rhombic lip derived neurons in rhombomere 2. Conclusions Different overexpression strategies reveal that the recognition of migration cues by granule cell precursors is dependent on their identity as rhombomere 1 derivatives. Segmental patterning cues operate autonomously within the rhombic lip

  12. Granulation of sulfur-oxidizing bacteria for autotrophic denitrification.

    Science.gov (United States)

    Yang, Weiming; Lu, Hui; Khanal, Samir K; Zhao, Qing; Meng, Liao; Chen, Guang-Hao

    2016-11-01

    Sulfur-oxidizing bacteria (SOB) was successfully employed for effective autotrophic denitrification and sludge minimization in a full-scale application of saline sewage treatment in Hong Kong. In this study, a Granular Sludge Autotrophic Denitrification (GSAD) reactor was continuously operated over 600 days for SOB granulation, and to evaluate the long-term stability of SOB granules, microbial communities and denitrification efficacy. Sludge granulation initiated within the first 40 days of start-up with an average particle size of 186.4 μm and sludge volume index (SVI5) of 40 mL/g in 5 min. The sludge granules continued to grow reaching a nearly uniform size of mean diameter 1380 ± 20 μm with SVI5 of 30 mL/g during 600 days of GSAD reactor operation at hydraulic retention time of 5 h and nitrate loading rate of 0.33 kg-N/m(3)/d. The GSAD reactor with SOB granular sludge achieved 93.7 ± 2.1% nitrogen and complete sulfide removal with low sludge yield of 0.15 g-volatile suspended solids (VSS)/g-N, and much lower nitrous oxide (N2O) emission than the heterotrophic denitrifying process. Microbial community analysis using fluorescence in situ hybridization (FISH) technique revealed that granules were enriched with SOB contributing to autotrophic denitrification. Furthermore, 16S rRNA analysis showed diverse autotrophic denitrification related genera, namely Thiobacillus (32.6%), Sulfurimonas (31.3%), and Arcobacter (0.01%), accounting for 63.9% of total operational taxonomic units at the generic level. No heterotrophic denitrification related genera were detected. The results from this study could provide useful design and operating conditions with respect to SOB sludge granulation and its subsequent application in a full-scale autotrophic denitrification in the Sulfate reduction-Autotrophic denitrification-Nitrification Integrated (SANI) process. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Study growth kinetics in fluidized bed granulation with at-line FBRM.

    Science.gov (United States)

    Hu, Xinhui; Cunningham, John C; Winstead, Denita

    2008-01-22

    In this study, a novel at-line focused beam reflectance measurement (FBRM) technique was developed to investigate granule growth in a fluidized bed granulation (FBG). The chord length distribution (CLD) measured by the FBRM was used to represent granule particle size distribution (PSD). Through a systematic study, it was proved that the trends of the chord length measured by the at-line FBRM technique were identical to those measured by a laser diffraction instrument and sieve analysis in spite of different measurement mechanisms. The portable at-line FBRM technique was successfully applied to a granule growth kinetics study for a fluidized bed granulation performed in a Glatt GPCG-1 granulator. Granule size evolution was clearly exhibited by the at-line FBRM. Spray rate was found to be the most significant factor on the granule growth compared with the other two factors: binder solution concentration and intra- to extra-granular microcrystalline cellulose (MCC) ratio for the formulation studied in this work. The CLD evolution measured by the FBRM confirmed that the granule agglomeration was mainly dominated by the binder on the granule surface. The at-line FBRM enables us to select appropriate process parameters and effectively control the fluid bed granulation process.

  14. Investigation on side-spray fluidized bed granulation with swirling airflow.

    Science.gov (United States)

    Wong, Poh Mun; Chan, Lai Wah; Heng, Paul Wan Sia

    2013-03-01

    Top-spray fluidized bed granulation with axial fluidization airflow from the bottom of the granulator is well-established in the pharmaceutical industry. The application of swirling airflow for fluidized bed granulation was more recently introduced. This study examined the effects of various process parameters on the granules produced by side-spray fluidized bed with swirling airflow using the central composite and Box-Behnken design of experiment. Influence of the amount of binder solution, spray rate, and distance between spray nozzle and powder bed were initially studied to establish operationally viable values for these parameters. This was followed by an in-depth investigation on the effects of inlet airflow rate, atomizing air pressure and distance between spray nozzle and powder bed on granule properties. It was found that the amount of binder solution had a positive correlation with granule size and percentage of lumps but a negative correlation with size distribution and Hausner ratio of the granules. Binder solution spray rate was also found to affect the granules size. High drug content uniformity was observed in all the batches of granules produced. Both inlet airflow rate and atomizing air pressure were found to correlate negatively with granule size and percentage of lumps but correlate positively with the size distribution of the granule produced. Percentage of fines was found to be significantly affected by inlet airflow rate. Distance between spray nozzle and powder bed generally affected the percentage of lumps.

  15. Investigation of internal structure of fine granules by microtomography using synchrotron X-ray radiation.

    Science.gov (United States)

    Noguchi, Shuji; Kajihara, Ryusuke; Iwao, Yasunori; Fujinami, Yukari; Suzuki, Yoshio; Terada, Yasuko; Uesugi, Kentaro; Miura, Keiko; Itai, Shigeru

    2013-03-10

    Computed tomography (CT) using synchrotron X-ray radiation was evaluated as a non-destructive structural analysis method for fine granules. Two kinds of granules have been investigated: a bromhexine hydrochloride (BHX)-layered Celphere CP-102 granule coated with pH-sensitive polymer Kollicoat Smartseal 30-D, and a wax-matrix granule constructed from acetaminophen (APAP), dibasic calcium phosphate dehydrate, and aminoalkyl methacrylate copolymer E (AMCE) manufactured by melt granulation. The diameters of both granules were 200-300 μm. CT analysis of CP-102 granule could visualize the laminar structures of BHX and Kollicoat layers, and also visualize the high talc-content regions in the Kollicoat layer that could not be detected by scanning electron microscopy. Moreover, CT analysis using X-ray energies above the absorption edge of Br specifically enhanced the contrast in the BHX layer. As for granules manufactured by melt granulation, CT analysis revealed that they had a small inner void space due to a uniform distribution of APAP and other excipients. The distribution of AMCE revealed by CT analysis was also found to involve in the differences of drug dissolution from the granules as described previously. These observations demonstrate that CT analysis using synchrotron X-ray radiation is a powerful method for the detailed internal structure analysis of fine granules. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Effects of extracellular polymer substances on aerobic granulation in sequencing batch reactors

    Institute of Scientific and Technical Information of China (English)

    WANG Zhi-ping; LIU Li-li; YAO Jie; SUN Li-xin; CAI Wei-min

    2009-01-01

    The effects of extracellular polymeric substances (EPS) on aerobic granulation in sequencing batch reactors (SBR) were investigated by evaluating the EPS content, and the relationship between EPS composition and surface properties of glucose-fed aerobic granules. The results show that aerobic granular sludge contains more EPS than seed sludge, and it is about 47 mg/gMLSS. Corresponding to the changes of EPS, the surface charge of microorganisms in granules increases from -0. 732 to -0. 845 meq/gMLSS, whereas the hydrophobicry changes significantly from 48.46% to 73. 16%. It is obviously that changes of EPS in sludge alter the negative surface charge and hydrophobieity of microorganisms in granules, enhance the polymeric interaction and promote the aerobic granulation. Moreover, EPS can serve as carbon and energy reserves in granulation, thus the growth between the interior and exterior bacteria is balanced, and the integrality of granules is maintained.SEM observation of the granules exhibits that EPS in granules are ropy ; by mixing with bacteria, compact matrix structure can be formed. The distribution of EPS in granules profiles the importance of EPS storage. It can be concluded that EPS play a crucial role in aerobic granulation.

  17. Chronic lymphocytic leukemia: present status.

    Science.gov (United States)

    Montserrat, E; Rozman, C

    1995-03-01

    Chronic lymphocytic leukemia (CLL) is the form of leukemia which occurs most frequently in Western countries. Its etiology is unknown, and no relationship with viruses or genes has been demonstrated. Epidemiological data suggest that genetic and ambiental factors might be of some significance. Clinical features of CLL are due to the accumulation of leukemic cells in bone marrow and lymphoid organs as well as the immune disturbances that accompany the disease. The prognosis of patients with CLL varies. Treatment is usually indicated by the risk of the individual patient, which is clearly reflected by the stage of the disease. In the early stage (Binet A, Rai O) it is reasonable to defer therapy until disease progression is observed. By contrast, because their median survival is less than five years, patients with more advanced stages require therapy. For almost 50 years, no major advances in the management of CLL, which has revolved around the use of alkylating agents, have been made. In recent years, the therapeutic approach in patients with CLL has changed as a result of the introduction of combination chemotherapy regimens and, in particular, purine analogues. The latter are already the treatment of choice for patients not responding to standard therapies, and their role as front-line therapy is being investigated. Bone marrow transplants are also being increasingly used. It is to be hoped that in years to come the outcome of patients with CLL will be improved by these advances.

  18. Lymphocyte subsets in pediatric migraine.

    Science.gov (United States)

    Cseh, Aron; Farkas, Kristof Mark; Derzbach, Laszlo; Muller, Katalin; Vasarhelyi, Barna; Szalay, Balazs; Treszl, Andras; Farkas, Viktor

    2013-07-01

    Aseptic inflammation due to activated immune cells has been implicated in the pathomechanism of migraine. We measured the prevalence of regulatory T cells (Tregs), along with that of CD4(+)/CD8(+) lymphocytes and their Th1/Th2 commitment in pediatric migraine. Children and adolescents suffering from migraine without aura, migraine with aura and hemiplegic migraine ictally (n = 53, 27, and 20, respectively), also interictally (n = 33) were recruited and compared to 24 healthy children. Our results indicated comparable prevalence of Tregs, CD4(+) and Th1/Th2 committed cells. CD8(+) prevalence was lower, and CD4(+)/CD8(+) ratio was higher in ictal phase irrespective of the subtype of migraine. No association between CD8(+) prevalence and gender, body weight, disease onset and attack duration in migraine subtypes was found. CD8(+) prevalence was normal in patients in interictal phase. These results suggest the absence of major systemic alteration of adaptive immunity in children and adolescents suffering from migraine; however, a transient decrease of CD8(+) prevalence during the ictal phase was detected irrespective of the subtype of migraine.

  19. Obinutuzumab for chronic lymphocytic leukemia.

    Science.gov (United States)

    Rioufol, Catherine; Salles, Gilles

    2014-10-01

    Chronic lymphocytic leukemia (CLL) is a frequent hematological malignancy that is incurable using standard approaches. Two anti-CD20 monoclonal antibodies (mAb), rituximab and ofatumumab, have been approved for CLL treatment. A new glycoengineered type II humanized anti-CD20 mAb, obinutuzumab (GA101), has been developed and demonstrates increased activity against B-cell malignancies by inducing direct cell death and better antibody-dependent cellular cytotoxicity. In a recent randomized Phase III study in patients with newly diagnosed CLL and coexisting conditions, obinutuzumab plus chlorambucil demonstrated significant improvement in progression-free survival and several other outcome parameters, in contrast to rituximab plus chlorambucil. Grade 3-4 infusion-related reactions and neutropenia occurred more frequently in patients who received obinutuzumab compared with those who received rituximab; however, the rate of serious infections was similar. Obinutuzumab represents a promising new option for patients with CLL and must be investigated with other chemotherapy regimens or with new targeted agents.

  20. How T lymphocytes see antigen

    Science.gov (United States)

    Chakraborty, Arup K.

    2009-03-01

    Complex organisms, like humans, have an adaptive immune system that enables us to do battle with diverse pathogens. This flexible system can also go awry, and many diseases are the direct consequence of the adaptive immune system failing to discriminate between markers of self and non-self. The orchestrators of adaptive immunity are a class of cells called T lymphocytes (T cells). T cells recognize minute numbers of molecular signatures of pathogens, and T cell recognition of these molecular markers of non-self is both specific and degenerate. The specific (yet, cross-reactive), diverse, and self-tolerant T cell repertoire is designed in the thymus. I will describe how an approach that brings together theoretical and computational studies (rooted in statistical physics) with experiments (carried out by key collaborators) has allowed us to shed light on the mechanistic principles underlying how T cells respond to pathogens in a digital fashion (``on'' or ``off''), and how this molecular machinery coupled with frustration (a la spin glasses) plays a key role in designing the special properties of the T cell repertoire during development in the thymus.

  1. Study of the iron ores mixture granulation in the sintering process. Part 1. Granulation; Estudio de la granulacion de la mezcla de minerales de hierro en el proceso de sinterizacion. I parte. Granulacion

    Energy Technology Data Exchange (ETDEWEB)

    Formoso, A.; Jimenez, J.; Moro, A.; Cores, A. [Centro Nacional de Investigaciones Metalurgicas CENIM. Madrid (Spain); Moro, A. [Universidad de Oviedo (Spain); Fernandez-Pello, G.; Muniz, M. [ACERALIA. Gijon (Spain)

    2000-07-01

    The granulation process of the ore mixture is described and the fitness for granulation of several iron ores form part of the mixture is studied. With a good granulation and sintering maximum temperature control is possible to achieve the best sintered structure forming by a hematite nucleus bonded by acicular ferrites. The industrial experience of several types of granulation is described. (Author) 33 refs.

  2. MICROMORPHOLOGICAL STUDIES OF STARCH GRANULES IN SELECTED PROCESSED INDIGENOUS FLOUR OF SOUTH WESTERN NIGERIA

    Directory of Open Access Journals (Sweden)

    Adeniyi A. JAYEOLA

    2013-06-01

    Full Text Available Starch granules of yam stem tubers, plantain fruits and cassava root tubers were studied using the light microscope and then compared. Yam and plantain, both monocotyledons, had morphologically similar granules between locations, being mostly oval in shape while the granules of cassava, a dicot, were predominantly globular but varied between locations. Differences in processing methods between locations might be responsible for the observed variation in cassava granules. There is a suggestion that starch granule morphology might follow lineages in a broad sense. The unique micromorphology of cassava starch granule could make it easily detectable when adulterated, substituted or contaminated with yam or plantain granules and this could provide a cost effective clue in forensic determination.

  3. Granular computing classification algorithms based on distance measures between granules from the view of set.

    Science.gov (United States)

    Liu, Hongbing; Liu, Chunhua; Wu, Chang-an

    2014-01-01

    Granular computing classification algorithms are proposed based on distance measures between two granules from the view of set. Firstly, granules are represented as the forms of hyperdiamond, hypersphere, hypercube, and hyperbox. Secondly, the distance measure between two granules is defined from the view of set, and the union operator between two granules is formed to obtain the granule set including the granules with different granularity. Thirdly the threshold of granularity determines the union between two granules and is used to form the granular computing classification algorithms based on distance measures (DGrC). The benchmark datasets in UCI Machine Learning Repository are used to verify the performance of DGrC, and experimental results show that DGrC improved the testing accuracies.

  4. Artificial Intelligence Tools for Scaling Up of High Shear Wet Granulation Process.

    Science.gov (United States)

    Landin, Mariana

    2017-01-01

    The results presented in this article demonstrate the potential of artificial intelligence tools for predicting the endpoint of the granulation process in high-speed mixer granulators of different scales from 25L to 600L. The combination of neurofuzzy logic and gene expression programing technologies allowed the modeling of the impeller power as a function of operation conditions and wet granule properties, establishing the critical variables that affect the response and obtaining a unique experimental polynomial equation (transparent model) of high predictability (R(2) > 86.78%) for all size equipment. Gene expression programing allowed the modeling of the granulation process for granulators of similar and dissimilar geometries and can be improved by implementing additional characteristics of the process, as composition variables or operation parameters (e.g., batch size, chopper speed). The principles and the methodology proposed here can be applied to understand and control manufacturing process, using any other granulation equipment, including continuous granulation processes.

  5. GRANULATION TRIALS OF WASTE THE DUST SILICON CARBIDE FOR UTILIZATION IN METALLURGY

    Directory of Open Access Journals (Sweden)

    Gabriel Borowski

    2016-09-01

    Full Text Available The article presents the results of laboratory granulation tests of dust silicon carbide and the results of research on the selection of the binder and the properties of the granules obtained. The research material was a waste of the silicon carbide powder with a high fragmentation, mixed with a cement or an organic modified starch specimen. Six tests were performed in a disc granulator with 100 cm in diameter. In each series of trial specified: the type and share of the binder, the diameter of the granules, tenderness, type of structure and mechanical properties. Good granules of silicon carbide obtained with the addition of cement binder with 4% of the mass fraction and at least 24 hours of seasoning. The binder should be added twice by powdering, first in a stirred granulator, and again after manufacture. It was found that the resulting granules may be used as a replacement of ferrosilicon in the process of steelmaking.

  6. Bilateral dacryoadenitis complicated by lymphocytic hypophysitis.

    Science.gov (United States)

    Baoke, Hou; Shihui, Wei; Maonian, Zhang; Zhaohui, Li; Zhitong, Zou; Zhigang, Song; Yan, Hei

    2009-09-01

    Three patients developed dacryoadenitis (DA) or lymphocytic pneumonitis before the diagnosis of lymphocytic hypophysitis (LyH). There were two previous reports of concurrence of DA and LyH. Our patients add support to the idea that DA and LyH are manifestations of a systemic autoimmune disease. We suggest that the discovery of DA should prompt imaging and endocrine investigation of LyH.

  7. Expression of tenascin in lymphocytic autoimmune thyroiditis.

    OpenAIRE

    Back, W; Heubner, C; Winter, J.; Bleyl, U

    1997-01-01

    AIMS: To study the distribution of tenascin by immunocytochemistry in autoimmune diseases of the thyroid. METHODS: Thyroids from patients with inflammatory lesions of the thyroid (lymphocytic thyroiditis Hashimoto, Grave's disease, thyroiditis DeQuervain) were studied by immunocytochemistry using antibodies against tenascin, collagen III, and collagen IV. RESULTS: In autoimmune lymphocytic thyroiditis Hashimoto there was a characteristic corona-like staining pattern of tenascin around all act...

  8. Study of Viability of Phosphate Solubilizing Bacteria in Phosphate granules

    Directory of Open Access Journals (Sweden)

    hajar rajabi

    2017-06-01

    Full Text Available Introduction: sustainable development and the environment are interconnected. Sustainable agriculture is continuous utilization of a farm with respect to various aspects of environmental conditions by using fewer inputs (other than Bio-fertilizers. Phosphorus is one of the essential elements for the plants. Management of soil is possible by using biological fertilizers pillar of sustainable agriculture and providing some of the phosphorus needed by plants via bio-fertilizers. Phosphorus deficiency is extremely effective on the plant growth and productivity. The application of phosphorus fertilizers is expensive and dangerous. In addition, phosphorus in the soilmay become insoluble and will be unavailable to the plants. Studies showed that phosphate solubilizing bacteria in the soil rhizosphere are active and by root exudates solve insoluble phosphates such as tricalcium phosphate, and form absorbable P for plant. Consequently, the use of microbial fertilizers could reduce excessive use of chemical fertilizers and lead to decrease their harmful effects and protect the environment and conservation of available resources. The biological phosphate fertilizer industry uses sugar beet molasses as a binder and drying granules at high temperatures. Therefore, it is important to evaluate the durability of the bacteria in molasses at high temperature. Materials and Methods: This study was designed as completely randomized design in a factorial arrangement.10 isolates were selected and the ratios of 50%, 25%, 15% and 10% of the apatite, organic matter, sulfur and soluble granule (ratio 1: 1 and 2: 1 bacteria and molasses, respectively, for each isolate was prepared. The final product was dried at 28 and 40 °C and remained for 4 months and population counted at first day and 10, 20, 30, 60, 90 and 120 days after the preparing. The population was counted by the serial dilution technique and cultured at Sperber media. Results and Discussion:Comparing the

  9. Lymphocyte migration into syngeneic implanted lymph nodes

    Energy Technology Data Exchange (ETDEWEB)

    Gordeeva, M.S.

    1986-03-01

    To judge the functional activity of lymphocytes of an implanted lymph node (LN), the proliferative response of lymphocytes of the implanted organ in the blast-transformation reaction in vitro and their ability to induce a local graft versus host reaction (GVHR) were determined. The lymphocyte suspension for labeling with /sup 51/Cr was obtained from peripheral LN in different situations from syngeneic mice. The resulting lymphocyte suspension was labeled with a solution of sodium chromate-/sup 51/Cr in a concentration of 20-40 microCi/100.10/sup 6/ cells in 1 ml for 40 min at 37/sup 0/C. The proliferative activity of a suspension of lymphocytes was estimated as incorporation of /sup 3/H-thymidine into DNA during incubation of the cell suspension for 3 days. Data on migration of /sup 51/Cr-labeled cells and the results of the morphological observations revealed marked ability of lymphocytes of the peripheral pool to colonize the regenerating stroma.

  10. Prenatal ontogeny of lymphocyte subpopulations in pigs.

    Science.gov (United States)

    Sinkora, M; Sinkora, J; Reháková, Z; Splíchal, I; Yang, H; Parkhouse, R M; Trebichavsk, I

    1998-12-01

    Although porcine lymphocytes have been classified into numerous subpopulations in postnatal animals, little is known about the ontogeny of these complex cell subsets. Using double- and triple-colour flow cytometry (FCM), we investigated the surface phenotype of fetal lymphoid cells in the thymus, cord blood, spleen and mesenteric lymph nodes at different stages of gestation. It was found that the major lymphocyte subpopulations started to appear at the beginning of the second third of the gestation period, with B cells being the earliest lymphocyte subpopulation to appear in the periphery. The T-cell receptor (TCR) gamma delta+ cells were the earliest detectable T-cell subset, developing first in the thymus and subsequently arriving in the periphery. Later in ontogeny, however, the number of TCRalpha beta+ lymphocytes rapidly increased, becoming the predominant T cells both in the thymus and in the periphery. Cells with the phenotype of adult natural killer cells were also identified in pig fetuses, though their nature and functional roles remain to be investigated. In addition, CD2 was expressed on most B cells whilst very few CD4+ TCRalpha beta+ cells or CD2+ TCRgamma delta+ cells expressed CD8, suggesting that the expression of CD2 and CD8 may reflect the functional status of the cells in postnatal animals. Taken together, this study has provided a systematic analysis of fetal porcine lymphocyte subpopulations and may provide the base for studies to establish the physiological roles of these lymphocyte subsets.

  11. SHARPIN Regulates Uropod Detachment in Migrating Lymphocytes

    Directory of Open Access Journals (Sweden)

    Jeroen Pouwels

    2013-11-01

    Full Text Available SHARPIN-deficient mice display a multiorgan chronic inflammatory phenotype suggestive of altered leukocyte migration. We therefore studied the role of SHARPIN in lymphocyte adhesion, polarization, and migration. We found that SHARPIN localizes to the trailing edges (uropods of both mouse and human chemokine-activated lymphocytes migrating on intercellular adhesion molecule-1 (ICAM-1, which is one of the major endothelial ligands for migrating leukocytes. SHARPIN-deficient cells adhere better to ICAM-1 and show highly elongated tails when migrating. The increased tail lifetime in SHARPIN-deficient lymphocytes decreases the migration velocity. The adhesion, migration, and uropod defects in SHARPIN-deficient lymphocytes were rescued by reintroducing SHARPIN into the cells. Mechanistically, we show that SHARPIN interacts directly with lymphocyte-function-associated antigen-1 (LFA-1, a leukocyte counterreceptor for ICAM-1, and inhibits the expression of intermediate and high-affinity forms of LFA-1. Thus, SHARPIN controls lymphocyte migration by endogenously maintaining LFA-1 inactive to allow adjustable detachment of the uropods in polarized cells.

  12. Entospletinib and Obinutuzumab in Treating Patients With Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Non-Hodgkin Lymphoma

    Science.gov (United States)

    2017-07-24

    Anemia; B-Cell Prolymphocytic Leukemia; Fatigue; Fever; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Hairy Cell Leukemia; Lymphadenopathy; Lymphocytosis; Lymphoplasmacytic Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Night Sweats; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Small Lymphocytic Lymphoma; Richter Syndrome; Splenomegaly; Thrombocytopenia; Weight Loss

  13. Multivariate modelling of the tablet manufacturing process with wet granulation for tablet optimization and in-process control

    NARCIS (Netherlands)

    Westerhuis, J.A; Coenegracht, P.M J; Lerk, C.F

    1997-01-01

    The process of tablet manufacturing with granulation is described as a two-step process. The first step comprises wet granulation of the powder mixture, and in the second step the granules are compressed into tablets. For the modelling of the pharmaceutical process of wet granulation and tableting,

  14. A study on the production processes of granulated iron

    Science.gov (United States)

    Nokhrina, O. I.; Rozhikhina, I. D.; Khodosov, I. E.

    2016-09-01

    The results of theoretical and experimental studies on the production process of high-quality granulated iron using hematite-magnetite iron ore and coal of different brands as a raw material are presented. According to the research the optimal coal consumption, temperature and time parameters of the metallization process, necessary for obtaining metallized materials with the specified composition and metallization degree, are defined. The conditions for the formation of metal granules with high content (over 98%) of primary iron are found. The process includes two stages: initially the solid-phase reduction of iron from oxides with production of metallized sponge material is carried out, further as the temperature increases the separation of slag and metal phases takes place.

  15. A Novel Method Isolated Microorganisms in Soil Granule

    Institute of Scientific and Technical Information of China (English)

    Liu Bao-ping; Xiang Wen-sheng; Wang Hong-yan; Fu Shi-cong

    2012-01-01

    A novel method isolated microorganisms in soil granule was built. The key steps included: repeated elutriation of soil by sterilized water, inoculation on the plates with the elutriated sediments, incubation of the plates and isolation of the actinomycetes by using selected culture medium. We formulated that most microflora included the dominant actinomycetes in the soil were carried away with the sterilized water in the elutriation procedure, some rare actinomycetes and few other microflora included bacteria were remained in the elutriated sediments, the other microflora were excluded to grew into colonies on the plates by using selective culture medium for actinomycetes in the elutriated sediments. Results showed the supposition. Non-streptomycete actinomycetes were isolated both from black soil samples from Chinese northeast area and compost samples from Chinese central area. Soil fungi in granule were isolated by using the selective conditions to favor fungi. The results showed that the method was effective

  16. Self-organized criticality of liquefaction in saturated granules

    Institute of Scientific and Technical Information of China (English)

    吴爱祥; 孙业志; 李青松

    2003-01-01

    Utilizing the dissipative structure theory, the evolutionary process of vibrating liquefaction in saturatedgranules was analyzed. When the irreversible force increases to some degree, the system will be in a state far fromequilibrium, and the new structure probably occurs. According to synergetics, the equation of liquefaction evolutionwas deduced, and the evolutionary process was analyzed by dynamics. The evolutionary process of vibrating lique-faction is a process in which the period doubling accesses to chaos, and the fluctuation is the original driving force ofsystem evolution. The liquefaction process was also analyzed by fractal geometry. The steady process of vibratingliquefaction obeys the scaling form, and shows self-organized criticality in the course of vibration. With the incre-ment of the recurrence number, the stress of saturated granules will decrease rapidly or lose completely, and thestrain will increase rapidly, so that the granules can not sustain load and the "avalanche" phenomenon takes place.

  17. A PRELIMINARY PHARMACOGNOSTICAL AND PHYSICOCHEMICAL ASSAY OF VASAKHANDA KUSHMANDAKA GRANULES

    Directory of Open Access Journals (Sweden)

    Ghosh Kuntal

    2012-02-01

    Full Text Available Vasaka (Adhatoda vasica Nees of Acanthaceae family and Kushmanda (Benincasa hispida Thunb. of Cucurbitaceae family are the commonly used herbs in Ayurvedic system of medicine with its vivid action on various Systems. In Ayurveda, Vasaka is used in bronchial asthma, cough, diabetes mellitus and also in the pitta-kapha predominant diseases where as Kushmanda is used in Acid reflux syndrome, mental diseases, alcoholism, etc. Samsakara is a tool mentioned in Ayurveda which refers to modification or processing of drug to potentiate it, or to get desired action or to change its form. An attempt was made to change the form of Vasakhanda Kushmandaka avaleha into Vasakhanda Kushmandaka granules and assessed for its pharmacognostical and pharmaceutical characters. The present study provides the details of Vasakhanda Kushmandaka granules preparation, its pharmacognostical and physicochemical characters which may help in laying down a standard protocol for future research works.

  18. A constitutive model for sintering of granulated ceramic powders

    Science.gov (United States)

    Shinagawa, K.; Hirashima, Y.

    1998-05-01

    Sintering behavior of granulated powder is investigated to develop a constitutive model for deformation analysis of ceramic powder compacts during sintering. Spray-dried alumina is compacted by CIPing (cold isostatic pressing) and sintered at various temperatures. Shrinkage and the change in grain size of the compacts during sintering are revealed in relation to the inhomogeneous microstructure consisting of fractured and unfractured granules as a consequence of the compaction. A constitutive model for the ceramic powder compacts having the internal structure is presented; The difference in grain growth in dense and sparse regions of the compacts is taken into consideration to the model. The results calculated by the model show good agreement with that obtained by experiment.

  19. Relation between trees of fragmenting granules and supergranulation evolution

    CERN Document Server

    Roudier, Th; Rieutord, M; Frank, Z

    2016-01-01

    Context: The determination of the underlying mechanisms of the magnetic elements diffusion over the solar surface is still a challenge. Understanding the formation and evolution of the solar network (NE) is a challenge, because it provides a magnetic flux over the solar surface comparable to the flux of active regions at solar maximum. Aims: We investigate the structure and evolution of interior cells of solar supergranulation. From Hinode observations, we explore the motions on solar surface at high spatial and temporal resolution. We derive the main organization of the flows inside supergranules and their effect on the magnetic elements. Method: To probe the superganule interior cell, we used the Trees of Fragmenting Granules (TFG) evolution and their relations to horizontal Results: Evolution of TFG and their mutual interactions result in cumulative effects able to build horizontal coherent flows with longer lifetime than granulation (1 to 2 hours) over a scale up to 12\\arcsec. These flows clearly act on t...

  20. The Experimental Study on Enhancing Immunity of the Bovine Colostrum Granule%牛初乳冲剂增强免疫力的实验研究

    Institute of Scientific and Technical Information of China (English)

    徐冰; 高慧艳; 王海玉; 王燕; 张桂霞; 张聪恪

    2012-01-01

      Objective To observe the impact of the bovine colostrum granule on immune function in mice. Methods Given BALB/c mice the bovine colostrum granule intragastrically 30 days, we detected immune indicators, including carbon clearance ability, delayed type hypersensitivity, antibody-producing cell count, serum hemolysin level, macrophage phagocytosis of chicken erythrocytes capacity, NK cell activity and ConA-induced lymphocyte transformationability, etc. Results The bovine colostrum granule had no obvious influence on organ weight/body weight , carbon clearance and NK cell activity in mice. However, it had significant effect on delayed type hypersensitivity, antibody-producing cell count, HC50, macrophage phagocytosis of chicken erythrocytes capacity and ConA-induced lymphocyte transformationability. Conclusion The bovine colostrum granule could enhancing Immunity in mice.%  目的观察牛初乳冲剂对小鼠免疫功能的影响。方法BALB/c小鼠连续灌胃30d后检测碳廓清能力、迟发型变态反应、抗体生成细胞数、血清溶血素水平、巨噬细胞吞噬鸡红细胞能力、NK细胞活性及ConA诱导的脾淋巴细胞转化能力等免疫指标。结果牛初乳冲剂对小鼠的脏/体比值、碳廓清能力及NK细胞活性无明显影响;对迟发型变态反应、抗体生成细胞数、HC50、巨噬细胞吞噬鸡红细胞能力及ConA诱导的小鼠淋巴细胞转化有显著作用。结论牛初乳冲剂能增强小鼠免疫力。

  1. Isolating stromal stem cells from periodontal granulation tissues.

    Science.gov (United States)

    Hung, Tzu-Yuan; Lin, Hsiang-Chun; Chan, Ying-Jen; Yuan, Kuo

    2012-08-01

    Stem cell therapy is a promising area in regenerative medicine. Periodontal granulation tissues are often discarded during conventional surgery. If stromal stem cells can be isolated from these tissues, they can be used for subsequent surgery on the same patient. Fifteen human periodontal granulation tissue samples were obtained from intrabony defects during surgery. Immunohistochemistry (IHC) was carried out on five of the samples to identify STRO-1, a marker of mesenchymal stem cells. Five samples underwent flow cytometry analysis for the same marker. The remaining five samples were characterized by "colony formation unit-fibroblast" (CFU-f) assay and selected for proliferation assay, flow cytometry of stem cell markers, immunocytochemistry (ICC), multipotent differentiation assays, and repairing critical-size defects in mice. The ratio of STRO-1(+) cells detected by IHC was 5.91 ± 1.50%. The analysis of flow cytometry for STRO-1 was 6.70 ± 0.81%. Approximately two thirds of the CFU-f colonies had a strong reaction to STRO-1 in ICC staining. The cells were multipotent both in vitro and in vivo. Mice given bone grafts and stem cells showed significantly better bone healing than those without stem cells. Multipotent stromal stem cells can be isolated from human periodontal granulation tissues. These cells improve new bone formation when transplanted in mouse calvarial defects. Isolating stem cells from relatively accessible sites without extra procedures is clinically advantageous. This study demonstrated that human periodontal granulation tissues contain isolatable multipotent stem cells. The cells may be a good source for autotransplantation in subsequent treatment.

  2. Excess granulation tissue and hair loss following acitretin

    Directory of Open Access Journals (Sweden)

    Francesca Gaudiello

    2011-02-01

    Full Text Available Retinoids are routinely used in dermatology for various clinical entities including acne vulgaris, rosacea, hypertrophic scars, strie distensae, psoriasis, disorders of dyskeratinization, cancer prevention and other chronic hyperkeratotic disorders. Oral acitretin therapy is effective in the treatment of psoriasis normalizing cellular differentiation and maturation but clinical side-effects are reported. We describe the occurrence of excess granulation tissue in the nails sulcus and noncicatricial universal alopecia in a psoriatic patient receiving oral acitretin.

  3. Granule-Dependent Natural Killer Cell Cytotoxicity to Fungal Pathogens

    Science.gov (United States)

    Ogbomo, Henry; Mody, Christopher H.

    2017-01-01

    Natural killer (NK) cells kill or inhibit the growth of a number of fungi including Cryptococcus, Candida, Aspergillus, Rhizopus, and Paracoccidioides. Although many fungi are not dangerous, invasive fungal pathogens, such as Cryptococcus neoformans, cause life-threatening disease in individuals with impaired cell-mediated immunity. While there are similarities to cell-mediated killing of tumor cells, there are also important differences. Similar to tumor killing, NK cells directly kill fungi in a receptor-mediated and cytotoxic granule-dependent manner. Unlike tumor cell killing where multiple NK cell-activating receptors cooperate and signal events that mediate cytotoxicity, only the NKp30 receptor has been described to mediate signaling events that trigger the NK cell to mobilize its cytolytic payload to the site of interaction with C. neoformans and Candida albicans, subsequently leading to granule exocytosis and fungal killing. More recently, the NKp46 receptor was reported to bind Candida glabrata adhesins Epa1, 6, and 7 and directly mediate fungal clearance. A number of unanswered questions remain. For example, is only one NK cell-activating receptor sufficient for signaling leading to fungal killing? Are the signaling pathways activated by fungi similar to those activated by tumor cells during NK cell killing? How do the cytolytic granules traffic to the site of interaction with fungi, and how does this process compare with tumor killing? Recent insights into receptor use, intracellular signaling and cytolytic granule trafficking during NK cell-mediated fungal killing will be compared to tumor killing, and the implications for therapeutic approaches will be discussed. PMID:28123389

  4. Heterogeneous structure and spatial distribution in endosperm of high-amylose rice starch granules with different morphologies.

    Science.gov (United States)

    Cai, Canhui; Huang, Jun; Zhao, Lingxiao; Liu, Qiaoquan; Zhang, Changquan; Wei, Cunxu

    2014-10-15

    Starch granules from high-amylose cereal mutants or transgenic lines usually have different morphologies. It is not clear whether the structure and spatial distribution of starch granules with different morphologies in endosperm is homogeneous or heterogeneous. In the present study, the structure and spatial distribution in endosperm of morphologically different starch granules from high-amylose transgenic rice line (TRS) were investigated. The TRS endosperm had individual, aggregate, elongated, and interior hollow starch granules. The individual and interior hollow granules had the lowest and the highest amylose content and gelatinization resistance, respectively, among the four types of granules. The individual granules were mainly distributed in the middle of the endosperm; the aggregate granules in the starchy endosperm cells between the subaleurone layer and the middle of the endosperm; the elongated granules in the peripheral starchy endosperm cells adjacent to the subaleurone layer; and the interior hollow granules in the subaleurone layer cells.

  5. Microstructure and ultrastructure of high-amylose rice resistant starch granules modified by antisense RNA inhibition of starch branching enzyme.

    Science.gov (United States)

    Wei, Cunxu; Qin, Fengling; Zhu, Lijia; Zhou, Weidong; Chen, Yifang; Wang, Youping; Gu, Minghong; Liu, Qiaoquan

    2010-01-27

    A high-amylose transgenic rice line (TRS) modified by antisense RNA inhibition of starch branching enzymes revealed a resistant starch-rich quality. Compound starch granules in whole grains of the regular rice cultivar Teqing (TQ) were readily split during fracturing, whereas the starch granules in TRS were structurally intact and showed large voluminous, non-angular rounded bodies and elongated, filamentous structures tolerant of fracturing. In isolated preparation, TQ starch granules broke up into separate polygonal granules, whereas TRS starch granules kept their intactness. TRS starch granules consisted of packed smaller subgranules, some of which located at the periphery of starch granules were fused to each other with adjacent ones forming a thick band or wall encircling the entire circumference of the granules. TQ starch granules had a high concentration of amylose in the concentric hilum, whereas TRS starch granules showed a relatively even distribution of amylose with intense amylose in both hilum and band.

  6. FIB/SEM cell sectioning for intracellular metal granules characterization

    Science.gov (United States)

    Milani, Marziale; Brundu, Claudia; Santisi, Grazia; Savoia, Claudio; Tatti, Francesco

    2009-05-01

    Focused Ion Beams (FIBs) provide a cross-sectioning tool for submicron dissection of cells and subcellular structures. In combination with Scanning Electron Microscope (SEM), FIB provides complementary morphological information, that can be further completed by EDX (Energy Dispersive X-ray Spectroscopy). This study focus onto intracellular microstructures, particularly onto metal granules (typically Zn, Cu and Fe) and on the possibility of sectioning digestive gland cells of the terrestrial isopod P. scaber making the granules available for a compositional analysis with EDX. Qualitative and quantitative analysis of metal granules size, amount and distribution are performed. Information is made available of the cellular storing pattern and, indirectly, metal metabolism. The extension to human level is of utmost interest since some pathologies of relevance are metal related. Apart from the common metal-overload-diseases (hereditary hemochromatosis, Wilson's and Menkes disease) it has been demonstrated that metal in excess can influence carcinogenesis in liver, kidney and breast. Therefore protocols will be established for the observation of mammal cells to improve our knowledge about the intracellular metal amount and distribution both in healthy cells and in those affected by primary or secondary metal overload or depletion.

  7. High pressure impact on changes in potato starch granules

    Directory of Open Access Journals (Sweden)

    Słomińska Lucyna

    2015-12-01

    Full Text Available Air dry potato starch (84.9% d.s. was subjected to pressurizing under the pressure of 50, 100, 250, 500, 750, 1000 and 2000 MPa for 1 h. The physical properties of pressurized starch, such as morphology, surface and crystalline structure, gelatinization parameters, were studied by means of scanning and atomic force microscopy (SEM/AFM, X-ray diffraction (X-ray, differential scanning calorimetry (DSC. The susceptibility to the amylolytic enzyme (α-amylase was also measured. Application of pressure in the range of 50–2000 MPa results in an increase in the compressed potato starch bulk density, change in the contours of the granules from oval to polyhedral, increase in the roughness of the granule surface, vanishing of the X-ray reflexes generated by the orthogonal structure and weakening of the reflexes generated by the hexagonal structure, lowering of the enthalpy of starch gelatinization, and the enhancement of hydrolytic susceptibility of starch granules to the amylolytic enzyme.

  8. Soil Stabilisation Using Ground Granulated Blast Furnace Slag

    Directory of Open Access Journals (Sweden)

    Ashish Kumar Pathak

    2014-05-01

    Full Text Available Stabilisation is a broad sense for the various methods employed and modifying the properties of a soil to improve its engineering performance and used for a variety of engineering works. In today‟s day soil stabilisation is the major problem for civil engineers, either for construction of road and also for increasing the strength or stability of soil and reduces the construction cost. In this thesis the soil are stabilised by ground granulated blast furnace slag (GGBS and this material is obtained from the blast furnace of cement plant, which is the byproduct of iron (from ACC plant, sindri. It is generally obtained in three shaped one is air cooled, foamed shaped and another is in granulated shaped. The use of by-product materials for stabilisation has environmental and economic benefits. Ground granulated blast furnace slag (GGBS material is used in the current work to stabilise soil (clay. The main objectives of this research were to investigate the effect of GGBS on the engineering property (optimum moisture content and maximum dry density, plastic limit, liquid limit, compaction, unconfined compressive strength, triaxial and California bearing ratio test of the soil and determine the engineering properties of the stabilised.

  9. Modelling and simulation of nutrient dispersion from coated fertilizer granules

    Science.gov (United States)

    Razali, Radzuan; Daud, Hanita; Nor, Shafiq Mohd.

    2014-10-01

    The usage of Controlled-Release Fertilizer (CRF) is essential in plants and crops to fulfill the need and requirement for the modern agriculture which now feeds 6 billion people. Therefore modeling and simulation of nutrient release from coated fertilizer has become the best method to study the behavior of some parameters toward water saturation in and nutrient release from the coated-fertilizer granule. This paper is the improvement development of modeling and computer simulation by Basu [1] which include some of the factors affecting the water saturation time and nutrient release time from a coated-fertilizer. The effect of granule radius, the diffusivity of water and nutrient, the temperature of surrounding, the contact areas and the characteristic of the coating are studied and the simulation was developed using MATLAB software. The studies and understanding of this project is very important and useful especially to determine the important parameters in the manufacturing process of the coated-fertilizer granule and also will be useful for the farmers/users in the selection of the best fertilizers for their crops.

  10. Enhanced aerobic sludge granulation with layered double hydroxide

    Directory of Open Access Journals (Sweden)

    Jizhi Zhou

    2014-06-01

    Full Text Available Aerobic granular sludge technology has been developed for the biochemical treatment of wastewater in the present study. A fast cultivation of aerobic granular sludge was realized in Sequencing Batch Reactor (SBR, where Mg-Al layered double hydroxide (LDH was used as a carrier for granules growth. In comparison, the sludge particle size with LDH addition was bigger than those without LDH, with more than 50% of compact granular sludge >1.4 mm in size. This indicatestheLDH improved the growth ofthegranular sludge. The frequency of LDH addition had little effect on the granule growth. Moreover, the formation of granules led to the low sludge volume index (SVI and high mixed liquid suspended solids (MLSS in SBR reactor. With the formation of granular sludge, more than 80% of COD was removed in SBR reactor. The high COD removal efficiency of wastewater was observed regardless of various COD loading strength. The results suggest that the growth of granular sludge with LDH as a carrier enhanced the treatment efficiency. Therefore, our results have provided a promising way to prepare the granular sludge for wastewater treatment.

  11. ATP storage and uptake by isolated pancreatic zymogen granules

    DEFF Research Database (Denmark)

    Haanes, Kristian Agmund; Novak, Ivana

    2010-01-01

    ATP is released from pancreatic acini in response to cholinergic and hormonal stimulation. The same stimuli cause exocytosis of ZG (zymogen granules) and release of digestive enzymes. The aim of the present study was to determine whether ZG stored ATP and to characterize the uptake mechanism...... for ATP transport into the ZG. ZG were isolated and the ATP content was measured using luciferin/luciferase assays and was related to protein in the sample. The estimate of ATP concentration in freshly isolated granules was 40-120 µM. The ATP uptake had an apparent Km value of 4.9±2.1 mM when granules...... were incubated without Mg2+ and a Km value of 0.47±0.05 mM in the presence of Mg2+, both in pH 6.0 buffers. The uptake of ATP was significantly higher at pH 7.2 compared with pH 6.0 solutions. The anion transport blockers DIDS (4,4'-di-isothiocyanostilbene-2,2'-disulfonate) and Evans Blue inhibited ATP...

  12. Spatial Circular Granulation Method Based on Multimodal Finger Feature

    Directory of Open Access Journals (Sweden)

    Jinfeng Yang

    2016-01-01

    Full Text Available Finger-based personal identification has become an active research topic in recent years because of its high user acceptance and convenience. How to reliably and effectively fuse the multimodal finger features together, however, has still been a challenging problem in practice. In this paper, viewing the finger trait as the combination of a fingerprint, finger vein, and finger-knuckle-print, a new multimodal finger feature recognition scheme is proposed based on granular computing. First, the ridge texture features of FP, FV, and FKP are extracted using Gabor Ordinal Measures (GOM. Second, combining the three-modal GOM feature maps in a color-based manner, we then constitute the original feature object set of a finger. To represent finger features effectively, they are granulated at three levels of feature granules (FGs in a bottom-up manner based on spatial circular granulation. In order to test the performance of the multilevel FGs, a top-down matching method is proposed. Experimental results show that the proposed method achieves higher accuracy recognition rate in finger feature recognition.

  13. Organellar proteomics: analysis of pancreatic zymogen granule membranes.

    Science.gov (United States)

    Chen, Xuequn; Walker, Angela K; Strahler, John R; Simon, Eric S; Tomanicek-Volk, Sarah L; Nelson, Bradley B; Hurley, Mary C; Ernst, Stephen A; Williams, John A; Andrews, Philip C

    2006-02-01

    The zymogen granule (ZG) is the specialized organelle in pancreatic acinar cells for digestive enzyme storage and regulated secretion and has been a model for studying secretory granule functions. In an initial effort to comprehensively understand the functions of this organelle, we conducted a proteomic study to identify proteins from highly purified ZG membranes. By combining two-dimensional gel electrophoresis and two-dimensional LC with tandem mass spectrometry, 101 proteins were identified from purified ZG membranes including 28 known ZG proteins and 73 previously unknown proteins, including SNAP29, Rab27B, Rab11A, Rab6, Rap1, and myosin Vc. Moreover several hypothetical proteins were identified that represent potential novel proteins. The ZG localization of nine of these proteins was further confirmed by immunocytochemistry. To distinguish intrinsic membrane proteins from soluble and peripheral membrane proteins, a quantitative proteomic strategy was used to measure the enrichment of intrinsic membrane proteins through the purification process. The iTRAQ ratios correlated well with known or Transmembrane Hidden Markov Model-predicted soluble or membrane proteins. By combining subcellular fractionation with high resolution separation and comprehensive identification of proteins, we have begun to elucidate zymogen granule functions through proteomic and subsequent functional analysis of its membrane components.

  14. Calcium dynamics in the secretory granules of neuroendocrine cells.

    Science.gov (United States)

    Alvarez, Javier

    2012-01-01

    Cellular Ca(2+)signaling results from a complex interplay among a variety of Ca(2+) fluxes going across the plasma membrane and across the membranes of several organelles, together with the buffering effect of large numbers of Ca(2+)-binding sites distributed along the cell architecture. Endoplasmic and sarcoplasmic reticulum, mitochondria and even nucleus have all been involved in cellular Ca(2+) signaling, and the mechanisms for Ca(2+) uptake and release from these organelles are well known. In neuroendocrine cells, the secretory granules also constitute a very important Ca(2+)-storing organelle, and the possible role of the stored Ca(2+) as a trigger for secretion has attracted considerable attention. However, this possibility is frequently overlooked, and the main reason for that is that there is still considerable uncertainty on the main questions related with granular Ca(2+) dynamics, e.g., the free granular [Ca(2+)], the physical state of the stored Ca(2+) or the mechanisms for Ca(2+) accumulation and release from the granules. This review will give a critical overview of the present state of knowledge and the main conflicting points on secretory granule Ca(2+) homeostasis in neuroendocrine cells.

  15. Study on Predrying by Spin Flash Dryer for Granulation

    Institute of Scientific and Technical Information of China (English)

    王晓静; 叶鸣; 钱树德

    2004-01-01

    Spin flash dryer has the advantages of both fluidized bed dryer and pneumatic dryer.It has predominance in dealing with thermal sensitive materials.In this paper,the distribution of the air velocity in the spin flash dryer is discussed,which indicates that the rotating air in the dryer chamber can be divided into two areas,potential flow area and plane swirl area.Experiments show that air tangent velocity effects the process of granulation most remarkably.The radial distribution and moisture content of the particles have their intrinsic rules along either the diameter or height of the drying chamber.Besides,the operating parameters of predrying on bleaching powder are optimized.To meet the strict standard of the wet-pressing granulator on the moisture content of the feeder,a narrow lap is made at proper height in the wall of the drying chamber,where a chute and a rotating valve are installed in order to predry the filter cake and remove a part of water.Then the material is fed into the wet-pressing granulator.

  16. Monoclonal Antibody Therapy in Treating Patients With Chronic Lymphocytic Leukemia, Lymphocytic Lymphoma, Acute Lymphoblastic Leukemia, or Acute Myeloid Leukemia

    Science.gov (United States)

    2013-06-03

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma

  17. Granzyme B-dependent and perforin-independent DNA fragmentation in intestinal epithelial cells induced by anti-CD3 mAb-activated intra-epithelial lymphocytes.

    Science.gov (United States)

    Ogata, Masaki; Ota, Yuta; Matsutani, Takaji; Nanno, Masanobu; Suzuki, Ryuji; Itoh, Tsunetoshi

    2013-05-01

    We previously found that an i.p. injection of anti-CD3 monoclonal antibody (mAb) into mice caused DNA fragmentation in the intestinal villous epithelial cells (IVECs) of the duodenum and the jejunum. In this study, in order to elucidate the mechanism of DNA fragmentation in IVECs, we searched for the inducer(s) of DNA fragmentation by using immunohistochemistry. The release of cytoplasmic granules from intraepithelial lymphocytes (IELs) and the formation of large gaps between IELs and IVECs were observed electron microscopically after antibody administration. The presence and distribution pattern of Granzyme B (GrB), a serine protease in cytolytic granules present in cytotoxic T lymphocytes and natural killer cells and considered to be the responsible molecule for DNA fragmentation in target cells, was examined in detail in intestinal villi by immunohistology. GrB was detected in cytoplasmic granules in nearly all IELs. The time-kinetics of granule release from IELs after mAb injection coincided not only with that of the extracellular diffusion of GrB, but also with that of DNA fragmentation in IVECs. On the other hand, perforin (Pfn), assumed to cooperate with GrB in DNA fragmentation, could not be detected in IELs, and its release was not confirmed after the anti-CD3 mAb injection. Anti-CD3 mAb injection also induced DNA fragmentation in IVECs in Pfn-knockout mice. These results support the notion that DNA fragmentation in IVECs by the stimulated IELs in the present study is induced by a mechanism involving GrB, but independent of Pfn.

  18. Model-based analysis of a twin-screw wet granulation system for continuous solid dosage manufacturing

    DEFF Research Database (Denmark)

    Kumar, Ashish; Vercruysse, Jurgen; Mortier, Severine T. F. C.

    2016-01-01

    Implementation of twin-screw granulation in a continuous from-powder-to-tablet manufacturing line requires process knowledge development. This is often pursued by application of mechanistic models incorporating the underlying mechanisms. In this study, granulation mechanisms considered...... the granulator under certain process conditions. Such a physical separation between the granulation regimes is promising for future design and advanced control of the continuous granulation process. (C) 2016 Elsevier Ltd. All rights reserved....

  19. Selective effects of alpha interferon on human T-lymphocyte subsets during mixed lymphocyte cultures

    DEFF Research Database (Denmark)

    Hokland, M; Hokland, P; Heron, I

    1983-01-01

    Mixed lymphocyte reaction (MLR) cultures of human lymphocyte subsets with or without the addition of physiological doses of human alpha interferon (IFN-alpha) were compared with respect to surface marker phenotypes and proliferative capacities of the responder cells. A selective depression on the T...

  20. Fluidized Bed Hot Melt Granulation with Hydrophilic Materials Improves Enalapril Maleate Stability.

    Science.gov (United States)

    Guimarães, Thiago F; Comelli, Amanda C C; Tacón, Luciana A; Cunha, Talita A; Marreto, Ricardo N; Freitas, Luís A P

    2017-05-01

    This work aimed at developing enalapril maleate granules in order to improve its stability in solid dosage form. Granules were prepared by hot melt granulation using a fluidized bed apparatus. Gelucire 50/13®, polyethylene glycol 6000 e Poloxamer 407® were studied and compared as binders in 2 × 2 factorial designs where the proportions of enalapril maleate, binders and spray dried lactose were varied. The granulation process resulted in high yields and granule sizes that indicated the prevalence of particles coating. Furthermore, the granules obtained showed adequate flowability and a fast dissolution rate of enalapril maleate with almost 100% of the drug released in 10 min. The stability of enalapril maleate in hard gelatin capsules showed that the drug stability was greatly increased in granules, since for raw drug, the remaining content of enalapril maleate after 91 days was 68.4% and, for granules, the content was always above 93%. This result was confirmed by the quantification of the degradation products, enalaprilat and diketopiperazine, which were found in very low content in granules samples. The results demonstrate that fluidized bed hot melt granulation with hydrophilic binders is a suitable alternative for improving the chemical stability of enalapril maleate.

  1. Control over the morphology and segregation of Zebrafish germ cell granules during embryonic development

    Directory of Open Access Journals (Sweden)

    Nakkrasae La-Iad

    2008-05-01

    Full Text Available Abstract Background Zebrafish germ cells contain granular-like structures, organized around the cell nucleus. These structures share common features with polar granules in Drosophila, germinal granules in Xenopus and chromatoid bodies in mice germ cells, such as the localization of the zebrafish Vasa, Piwi and Nanos proteins, among others. Little is known about the structure of these granules as well as their segregation in mitosis during early germ-cell development. Results Using transgenic fish expressing a fluorescently labeled novel component of Zebrafish germ cell granules termed Granulito, we followed the morphology and distribution of the granules. We show that whereas these granules initially exhibit a wide size variation, by the end of the first day of development they become a homogeneous population of medium size granules. We investigated this resizing event and demonstrated the role of microtubules and the minus-end microtubule dependent motor protein Dynein in the process. Last, we show that the function of the germ cell granule resident protein the Tudor domain containing protein-7 (Tdrd7 is required for determination of granule morphology and number. Conclusion Our results suggest that Zebrafish germ cell granules undergo a transformation process, which involves germ cell specific proteins as well as the microtubular network.

  2. Rice starch granule amylolysis--differentiating effects of particle size, morphology, thermal properties and crystalline polymorph.

    Science.gov (United States)

    Dhital, Sushil; Butardo, Vito M; Jobling, Stephen A; Gidley, Michael J

    2015-01-22

    The underlying mechanism of amylolysis of rice starch granules was investigated using isolated starch granules from wild-type, as well as SBEIIb mutant and down-regulated lines. Fused granule agglomerates isolated from mutant and transgenic lines were hydrolysed at similar rates by amylases, and had similar crystalline patterns and thermal properties as individual granules. Surface pores, a feature previously only reported for A-polymorphic starch granules, were also observed in B- and C-polymorphic rice starch granules. Although the microscopic patterns of hydrolysis among granules with different crystalline polymorphs were qualitatively similar, the extent and the rate of amylolysis were different, suggesting that B-type crystalline polymorphs are intrinsically more resistant to enzymatic hydrolysis than A-type in rice starch granules. It is proposed that the slightly longer branch lengths of amylopectin which leads to the formation of more stable B-type double helical structures compared to their A-type counterparts is the major parameter, with other factors such as granule size, surface pores and interior channels having secondary roles, in determining the rate of enzymatic hydrolysis of rice starch granules.

  3. Validation of a continuous granulation process using a twin-screw extruder.

    Science.gov (United States)

    Van Melkebeke, B; Vervaet, C; Remon, J P

    2008-05-22

    Using twin-screw granulation as particle size enlargement technique, the effect of modifying the screw configuration (number of mixing zones, configuration of kneading block) on granule quality, tablet properties and mixing efficiency was investigated. The amount of oversized agglomerates and yield was significantly influenced by the presence of an extra conveying element at the screw end. Changing the staggering angle of the kneading block significantly affected yield and granule friability. The 90 degrees configuration resulted in a lower yield and granule friability. Disintegration time was the only tablet property significantly influenced by the screw configuration as disintegration was significantly faster when an extra conveying element was placed at the screw end. The influence of tracer addition method (wet vs. dry) on mixing efficiency inside the extruder barrel was investigated by means of different tracers: riboflavin (0.05%) suspended in the granulation liquid and hydrochlorothiazide (2.5%) added separately as powder. Mixing efficiency in function of time and granule size (above and below 1400 microm) was tested using riboflavine sodium phosphate (0.05%) dissolved in the granulation liquid. Since a good mixing efficiency was obtained independent of tracer addition method, tracer solubility, granulation time and granule size, continuous granulation using a twin-screw extruder was identified as a robust process.

  4. Inline real-time near-infrared granule moisture measurements of a continuous granulation-drying-milling process.

    Science.gov (United States)

    Chablani, Lipika; Taylor, Michael K; Mehrotra, Amit; Rameas, Patrick; Stagner, William C

    2011-12-01

    The purpose of this research was to use inline real-time near-infrared (NIR) to measure the moisture content of granules manufactured using a commercial production scale continuous twin-screw granulator fluid-bed dryer milling process. A central composite response surface statistical design was used to study the effect of inlet air temperature and dew point on granule moisture content. The NIR moisture content was compared to Karl Fischer (KF) and loss on drying (LOD) moisture determinations. Using multivariate analysis, the data showed a statistically significant correlation between the conventional methods and NIR. The R(2) values for predicted moisture content by NIR versus KF and predicted moisture values by NIR versus LOD were 0.94 (p < 0.00001) and 0.85 (p < 0.0002), respectively. The adjusted R(2) for KF versus LOD correlation was 0.85 (p < 0.0001). Analysis of the response surface design data showed that inlet air temperature over a range of 35-55°C had a significant linear impact on granule moisture content as measured by predicted NIR (adjusted R(2) = 0.84, p < 0.02), KF (adjusted R(2) = 0.91, p < 0.0001), and LOD (adjusted R(2) = 0.85, p < 0.0006). The inlet air dew point range of 10-20°C did not have a significant impact on any of the moisture measurements.

  5. High-rate hydrogenotrophic methanogenesis for biogas upgrading: the role of anaerobic granules.

    Science.gov (United States)

    Xu, Heng; Gong, Shufen; Sun, Yuanzi; Ma, Hailing; Zheng, Mingyue; Wang, Kaijun

    2015-01-01

    Hydrogenotrophic methanogenesis has been proved to be a feasible biological method for biogas upgrading. To improve its performance, the feasibility of typical anaerobic granules as the inoculum was investigated in both batch and continuous experiments. The results from batch experiments showed that glucose-acclimated granules seemed to perform better than granules acclimated to acidified products (AP, i.e. acetate, propionate and ethanol) in in situ biogas upgrading systems and a slightly higher H2 consumption rate (1.5 mmol H2 g VSS(-1) h(-1)) was obtained for glucose-acclimated granules. For AP-acclimated granules, the inhibition on anaerobic digestion and pH increase (up to 9.55±0.16) took place, and the upgrading performance was adversely affected. In contrast, better performance for AP-acclimated granules was observed in ex situ systems, possibly due to their higher hydrogenotrophic methanogenic activities (HMA). Moreover, when gas-liquid mass transfer limitations were alleviated, the upgrading performance was significantly improved (three-fold) for both glucose-acclimated and AP-acclimated granules. The HMA of anaerobic granules could be further enhanced to improve biogas upgrading performance via continuous cultivation with H2/CO2 as the sole substrate. During the three months' cultivation, secondary granulation and microbial population shift were observed, but anaerobic granules still remained intact and their HMA increased from 0.2 to 0.6 g COD g VSS(-1) d(-1). It indicated that the formation of hydrogenotrophic methanogenic granules, a new type of anaerobic granules specialized for high-rate hydrogenotrophic methanogenesis and biogas upgrading, might be possible. Conclusively, anaerobic granules showed great potential for biogas upgrading.

  6. β-TCP granules mixed with reticulated hyaluronic acid induce an increase in bone apposition.

    Science.gov (United States)

    Aguado, Eric; Pascaretti-Grizon, Florence; Gaudin-Audrain, Christine; Goyenvalle, Eric; Chappard, Daniel

    2014-02-01

    β beta-tricalcium phosphate (β-TCP) granules are suitable for repair of bone defects. They have an osteoconductive effect shortly after implantation. However, dry granules are difficult to handle in the surgical room because of low weight and lack of cohesion. Incorporation of granules in a hydrogel could be a satisfactory solution. We have investigated the use of hyaluronic acid (HyA) as an aqueous binder of the granules. β-TCP granules were prepared by the polyurethane foam technology. Commercially available linear (LHya) and reticulated hyaluronic acid (RHyA) in aqueous solution were used to prepare a pasty mixture that can be handled more easily than granules alone. Thirteen New Zealand White rabbits (3.5-3.75 kg) were used; a 4 mm hole was drilled in each femoral condyle. After flushing, holes were filled with either LHyA, RHyA, dry β-TCP granules alone, β-TCP granules + LHyA and β-TCP granules + RHyA. Rabbits were allowed to heal for one month, sacrificed and femurs were harvested and analysed by microCT and histomorphometry. The net amount of newly formed bone was derived from measurements done after thresholding the microCT images for the material and for the material+bone. LHyA and RHyA did not result in healing of the grafted area. LHyA was rapidly eluted from the grafted zone but allowed deposition of more granules, although the amount of formed bone was not significantly higher than with β-TCP granules alone. RHyA permitted the deposition of more granules which induced significantly more bone trabeculae without inducing an inflammatory reaction. RHyA appears to be a good vehicle to implant granules of β-TCP, since HyA does not interfere with bone remodeling.

  7. Quantitative Assessment of Mass Flow Boundaries in Continuous Twin-screw Granulation.

    Science.gov (United States)

    Schmidt, Adrian; de Waard, Hans; Moll, Klaus-Peter; Krumme, Markus; Kleinebudde, Peter

    2016-01-01

    In pharmaceutical manufacturing, there is an increasing interest in continuous manufacturing. As an example for fast continuous processes in general of considerable complexity, this study was focussed on improving the understanding of twin-screw wet granulation. The impact of the liquid-to-solid (L/S) mass flow ratio on product quality (granules) as well as on downstream process operations (tableting) was investigated in detail. Initially two methods were used to define L/S ratio boundaries for the granulation regime in twin-screw wet granulation. It was shown that the first method, which is based on measuring the wet granule mass flow variation, can be used to define the upper L/S ratio boundary of the granulation regime. The second method, based on measuring the granule size distribution, can be used to define the lower L/S ratio boundary of the regime. Using these methods, the granulation regime for different formulations could be established. This information was then used to show that the formulation could be optimised such that the process is more robust (i.e. wider L/S ratio boundaries for the granulation regime). Also it could be used to optimise the formulation considering further downstream processing such as drying (using as little water as possible to reduce drying efforts) or tableting (obtain granules with optimised tableting properties). Preferably, the process should be performed close to the lower L/S ratio boundary of the granulation regime. In summary, these tools enabled the quantitative establishment of granulation regime boundaries in a twin-screw wet granulation process and can be used to optimise formulation and to create a robust process. Analogies to other continuous processes in completely different applications can be conceived.

  8. Characterization of the atypical lymphocytes in African swine fever

    Directory of Open Access Journals (Sweden)

    Z. A. Karalyan

    2016-07-01

    Full Text Available Aim: Atypical lymphocytes usually described as lymphocytes with altered shape, increased DNA amount, and larger size. For analysis of cause of genesis and source of atypical lymphocytes during African swine fever virus (ASFV infection, bone marrow, peripheral blood, and in vitro model were investigated. Materials and Methods: Atypical lymphocytes under the influence of ASFV were studied for morphologic, cytophotometric, and membrane surface marker characteristics and were used in vivo and in vitro models. Results: This study indicated the increased size, high metabolic activity, and the presence of additional DNA amount in atypical lymphocytes caused by ASFV infection. Furthermore, in atypical lymphocytes, nuclear-cytoplasmic ratio usually decreased, compared to normal lymphocytes. In morphology, they looking like lymphocytes transformed into blasts by exposure to mitogens or antigens in vitro. They vary in morphologic detail, but most of them are CD2 positive. Conclusions: Our data suggest that atypical lymphocytes may represent an unusual and specific cellular response to ASFV infection.

  9. Characterization of the atypical lymphocytes in African swine fever

    Science.gov (United States)

    Karalyan, Z. A.; Ter-Pogossyan, Z. R.; Abroyan, L. O.; Hakobyan, L. H.; Avetisyan, A. S.; Karalyan, N. Yu; Karalova, E. M.

    2016-01-01

    Aim: Atypical lymphocytes usually described as lymphocytes with altered shape, increased DNA amount, and larger size. For analysis of cause of genesis and source of atypical lymphocytes during African swine fever virus (ASFV) infection, bone marrow, peripheral blood, and in vitro model were investigated. Materials and Methods: Atypical lymphocytes under the influence of ASFV were studied for morphologic, cytophotometric, and membrane surface marker characteristics and were used in vivo and in vitro models. Results: This study indicated the increased size, high metabolic activity, and the presence of additional DNA amount in atypical lymphocytes caused by ASFV infection. Furthermore, in atypical lymphocytes, nuclear-cytoplasmic ratio usually decreased, compared to normal lymphocytes. In morphology, they looking like lymphocytes transformed into blasts by exposure to mitogens or antigens in vitro. They vary in morphologic detail, but most of them are CD2 positive. Conclusions: Our data suggest that atypical lymphocytes may represent an unusual and specific cellular response to ASFV infection. PMID:27536044

  10. Flow cytometric analysis of lymphocytes and lymphocyte subpopulations in induced sputum from patients with asthma

    Directory of Open Access Journals (Sweden)

    Yutaro Shiota

    2000-01-01

    Full Text Available Study objectives were to compare the numbers of lymphocytes and lymphocyte subpopulations in induced sputum from asthmatic patients and from healthy subjects, and to determine the effect of inhaled anti-asthmatic steroid therapy on these cell numbers. Hypertonic saline inhalation was used to non-invasively induce sputum samples in 34 patients with bronchial asthma and 21 healthy subjects. The sputum samples were reduced with dithioerythritol and absolute numbers of lymphocytes and lymphocyte subpopulations were assessed by direct immunofluorescence and flow cytometry. To assess the effect of beclomethasone dipropionate (BDP on induced sputum, numbers of lymphocytes and lymphocyte subpopulations in sputum also were evaluated after 4 weeks of BDP inhalation treatment in seven asthmatic patients. An adequate sample was obtained in 85.3% of patients with asthma and in 79.2% of the healthy subjects. Induced sputum from patients with asthma had increased numbers of lymphocytes (P = 0.009; CD4+ cells (P = 0.044; CD4+ cells-bearing interleukin-2 receptor (CD25; P = 0.016; and CD4+ cells bearing human histocompatibility leukocyte antigen (HLA-DR (P = 0.033. CD8+ cells were not increased in asthmatic patients. In patients treated with inhaled steroids, numbers of lymphocytes, CD4+ cells, CD25-bearing CD4+ cells and HLA-DR-bearing CD4+ cells in sputum decreased from pretreatment numbers (P = 0.016, 0.002, 0.003 and 0.002, respectively. Analysis of lymphocytes in induced sputum by flow cytometry is useful in assessing bronchial inflammation, and activated CD4+ lymphocytes may play a key role in the pathogenesis of airway inflammation in bronchial asthma.

  11. Granzyme release and caspase activation in activated human T-lymphocytes.

    Science.gov (United States)

    Zapata, J M; Takahashi, R; Salvesen, G S; Reed, J C

    1998-03-20

    Recently it has been reported that caspase-3 activation occurs in stimulated T-lymphocytes without associated apoptosis (Miossec, C., Dutilleul, V., Fassy, F., and Diu-Hercend, A. (1997) J. Biol. Chem. 272, 13459-13462). To explore this phenomenon, human peripheral blood lymphocytes (PBLs) were stimulated with mitogenic lectins or anti-CD3 antibody, and the proteolytic processing of different caspases and caspase substrates was analyzed by immunoblotting. Proteolytic processing of caspases-3 and -7 and the caspase substrates poly(ADP-ribose) polymerase, GDP dissociation inhibitor, and PKCdelta was observed when PBLs were activated in vitro, and lysates were prepared using RIPA buffer which contains 1% Nonidet P-40, 0.5% deoxycholate, and 0.1% SDS. In contrast, when a lysis buffer containing 2% SDS was used, the caspases remained in their zymogen pro-forms, and no proteolytic processing of caspase substrates was detected. Moreover, in experiments using intact cells and a cell-permeable fluorigenic caspase substrate, no caspase activity was observed in activated T-cells, whereas it was clearly detected when PBLs were treated with the apoptosis-inducing anticancer drug etoposide. Since the granzyme B is a direct activator of caspase-3 and its expression is induced following T-cell activation, we tested the effects of anti-GraB, an engineered serpin that specifically inhibits GraB. When the activated T-lymphocytes were lysed in RIPA buffer containing anti-GraB, no proteolytic processing or activation of caspase-3 was observed, strongly suggesting that release of GraB or similar proteases from their storage sites in cytotoxic granules during the lysis procedure is responsible for caspase activation. These findings demonstrate that T-cells do not process caspases upon activation and caution about the method of cell lysis used when studying granzyme-expressing cells.

  12. Effects of hydraulic retention time on aerobic granulation and granule growth kinetics at steady state with a fast start-up strategy.

    Science.gov (United States)

    Liu, Yong-Qiang; Zhang, Xing; Zhang, Rui; Liu, Wen-Tso; Tay, Joo-Hwa

    2016-01-01

    A hydraulic retention time (HRT) of 4, 6, and 8 h was employed, respectively, in three reactors to study the effects of HRT on granulation with a newly developed fast granulation strategy, i.e., a strategy by combining strong hydraulic selection pressure with high organic loading rate (OLR). Granules with clear boundary appeared within 24 h after reactor start-up and all reactors reached a pseudo steady state after 6-day operation. A 4-h HRT resulted in a relatively higher increasing rate in terms of granule size during granule development period, i.e., 208 μm day(-1), and the bigger granule size and the higher sludge volume index at the pseudo steady state. For HRT of 6 or 8 h, no obvious difference was observed. However, it was found that HRT influenced sludge retention time (SRT) and kinetics significantly. A HRT changing from 4 to 8 h led to an increased SRT from 3 to 21 days, a decreased observed specific biomass growth rate (μ obs) and an decreased observed biomass yield (Y obs) of stable granules from 0.37 to 0.062 days(-1), and 0.177 to 0.055 g MLVSS g(-1) COD, respectively. Both μ obs and Y obs had a linear relationship with the reciprocal of HRT. In addition, the great difference of microbial community between seed sludge, sludge retained in the reactors, and sludge washed out indicated a strong microbial selection for fast granulation within 24 h. However, during the granule development period from day 1 to 6, no more microbial selection was observed except an adjustment of microbial community. Little influence of HRT on microbial population in granular sludge indicated a minor role of HRT played for granulation with the fast start-up strategy adopted in this study. The results demonstrated that hydraulic selection pressure for granulation was mainly from short settling time, which led to strong microbial selection during the granulation period. Meanwhile, although HRT did not affect granulation with the fast start-up strategy, it played an

  13. An observation on sludge granulation in an enhanced biological phosphorus removal process.

    Science.gov (United States)

    Ong, Ying Hui; Chua, Adeline Seak May; Lee, Boon Pin; Ngoh, Gek Cheng; Hashim, Mohd Ali

    2012-01-01

    A sequencing batch reactor (SBR) seeded with flocculated sludge and fed with synthetic wastewater was operated for an enhanced biological phosphorus removal (EBPR) process. Eight weeks after reactor startup, sludge granules were observed. The granules had a diameter of 0.5 to 3.0 mm and were brownish in color and spherical or ellipsoidal in shape. No significant change was observed in sludge granule size when operational pH was changed from 7 to 8. The 208-day continuous operation of the SBR showed that sludge granules were stably maintained with a sludge volume index (SVI) between 30 to 55 mL/g while securing a removal efficiency of 83% for carbon and 97% for phosphorus. Fluorescent in situ hybridization (FISH) confirmed the enrichment of polyphosphate accumulating organisms (PAOs) in the SBR. The observations of sludge granulation in this study encourage further studies in the development of granules-based EBPR process.

  14. Theoretical and Experimental Studies on a Cylinder Containing Granules Rolling Down an Inclined Plane

    CERN Document Server

    Wibowo, Edy; Rokhmat, Mamat; Yuliza, Elfi; Khairurrijal,; Abdullah, Mikrajuddin

    2014-01-01

    The dynamics of a hollow cylinder containing granules and rolling down an inclined plane was investigated. A theoretical approach for investigating the behaviour of such a cylinder was proposed. The critical angle of the plane that allows the system to roll downward is presented. A simple experiment using six types of granules consistently confirmed the theoretical predictions. We showed that the critical angle is independent of the size distribution of the granules. We observed that the sliding angle of granules inside the cylinder is constant and, surprisingly, similar to the avalanche angle of the granules. Our theoretical prediction can be used to determine the critical angle without considering the shape, surface roughness and size distribution of the granules. Additionally, we derived the oscillation frequency of the system when it is slightly deviated from equilibrium, showing the frequency initially increases and then decreases with increasing granular volume. The oscillation is absent when the cylind...

  15. Single granule cells reliably discharge targets in the hippocampal CA3 network in vivo.

    Science.gov (United States)

    Henze, Darrell A; Wittner, Lucia; Buzsáki, György

    2002-08-01

    Processing of neuronal information depends on interactions between the anatomical connectivity and cellular properties of single cells. We examined how these computational building blocks work together in the intact rat hippocampus. Single spikes in dentate granule cells, controlled intracellularly, generally failed to discharge either interneurons or CA3 pyramidal cells. In contrast, trains of spikes effectively discharged both CA3 cell types. Increasing the discharge rate of the granule cell increased the discharge probability of its target neuron and decreased the delay between the onset of a granule cell train and evoked firing in postsynaptic targets. Thus, we conclude that the granule cell to CA3 synapses are 'conditional detonators,' dependent on granule cell firing pattern. In addition, we suggest that information in single granule cells is converted into a temporal delay code in target CA3 pyramidal cells and interneurons. These data demonstrate how a neural circuit of the CNS may process information.

  16. Evaluation of an in-line particle imaging tool for monitoring twin-screw granulation performance

    DEFF Research Database (Denmark)

    Kumar, Ashish; Dhondt, Jens; De Leersnyder, Fien;

    2015-01-01

    ). The volumetric size distribution obtained from the in-line measurements of the granules leaving the twin-screw granulator using the Eyecon™ camera was compared with the off-line measurements obtainedby sieving of the granule samples collected before and after the drying unit operation. For the intermediate size...... range (diameter 250–1000 μm), the Eyecon™ measurements showed to be promising as they were in agreement with off-line measurement results obtained before the drying unit. However, the image analysis algorithm and data post-processing of the Eyecon™ images for the fines and oversized ranges require......Twin-screw granulation is an emerging continuous wet granulation technique in the pharmaceutical industry due to several advantages over batch granulation. However, for the implementation of a fully continuous linein an industrial environment, in-process measurement tools are required to monitor...

  17. Nodular lymphocyte-predominant Hodgkin lymphoma.

    Science.gov (United States)

    Savage, Kerry J; Mottok, Anja; Fanale, Michelle

    2016-07-01

    Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma with distinct clinicopathologic features. It is typified by the presence of lymphocyte predominant (LP) cells, which are CD20(+) but CD15(-) and CD30(-) and are found scattered amongst small B lymphocytes arranged in a nodular pattern. Despite frequent and often late or multiple relapses, the prognosis of NLPHL is very favorable. There is an inherent risk of secondary aggressive non-Hodgkin lymphoma (NHL) and studies support that risk is highest in those with splenic involvement at presentation. Given disease rarity, the optimal management is unclear and opinions differ as to whether treatment paradigms should be similar to or differ from those for classical Hodgkin lymphoma (CHL). This review provides an overview of the existing literature describing pathological subtypes, outcome and treatment approaches for NLPHL.

  18. T cell immunity using transgenic B lymphocytes

    Science.gov (United States)

    Gerloni, Mara; Rizzi, Marta; Castiglioni, Paola; Zanetti, Maurizio

    2004-03-01

    Adaptive immunity exists in all vertebrates and plays a defense role against microbial pathogens and tumors. T cell responses begin when precursor T cells recognize antigen on specialized antigen-presenting cells and differentiate into effector cells. Currently, dendritic cells are considered the only cells capable of stimulating T lymphocytes. Here, we show that mature naïve B lymphocytes can be genetically programmed by using nonviral DNA and turned into powerful antigen-presenting cells with a dual capacity of synthesis and presentation of antigen to T cells in vivo. A single i.v. injection of transgenic lymphocytes activates T cell responses reproducibly and specifically even at very low cell doses (102). We also demonstrate that T cell priming can occur in the absence of dendritic cells and results in immunological memory with protective effector functions. These findings disclose aspects in the regulation of adaptive immunity and indicate possibilities for vaccination against viruses and cancer in humans.

  19. An intrinsic GABAergic system in human lymphocytes.

    Science.gov (United States)

    Dionisio, Leonardo; José De Rosa, María; Bouzat, Cecilia; Esandi, María Del Carmen

    2011-01-01

    γ-amino butyric acid (GABA) is an ubiquitous neurotransmitter in the central nervous system and it is also present in non-neuronal cells. In this study we investigated the presence of neuronal components of the GABAergic system in lymphocytes and its functional significance. By using RT-PCR we detected mRNA expression of different components of the GABAergic system in resting and mitogen-activated lymphocytes: i) GAD67, an isoform of the enzyme that synthetizes GABA; ii) VIAAT, the vesicular protein involved in GABA storage; iii) GABA transporters (GAT-1 and GAT-2); iv) GABA-T, the enzyme that catabolizes GABA; and v) subunits that conform ionotropic GABA receptors. The presence of VIAAT protein in resting and activated cells was confirmed by immunocytochemistry. The functionality of GABA transporters was evaluated by measuring the uptake of radioactive GABA. The results show that [(3)H]GABA uptake is 5-fold higher in activated than in resting lymphocytes. To determine if GABA subunits assemble into functional channels, we performed whole-cell recordings in activated lymphocytes. GABA and muscimol, a specific agonist of ionotropic GABA receptors, elicit macroscopic currents in about 10-15% of the cells. Finally, by using [(3)H]thymidine incorporation assays, we determined that the presence of agonists of GABA receptor during activation inhibits lymphocyte proliferation. Our results reveal that lymphocytes have a functional GABAergic system, similar to the neuronal one, which may operate as a modulator of T-cell activation. Pharmacological modulation of this system may provide new approaches for regulation of T-cell response. Copyright © 2010 Elsevier Ltd. All rights reserved.

  20. Effect of bioglass granules on the physico-chemical properties of brushite cements

    Energy Technology Data Exchange (ETDEWEB)

    Bohner, M. [Robert Mathys Foundation, Bettlach (Switzerland); Matter, S. [Stratec Medical, Oberdorf (Switzerland)

    2001-07-01

    Bioglass granules were added to a brushite cement in an attempt to neutralize the cement paste after setting. Results show that the pH of the cement paste was drastically increased by the addition of these granules. However, the setting time and the mechanical properties of the cement were strongly reduced. Therefore, the addition of bioglass granules is not a good way to modify the acidity of the cement paste after setting. (orig.)

  1. Characteristics of aerobic granules grown on glucose a sequential batch shaking reactor

    Institute of Scientific and Technical Information of China (English)

    CAI Chun-guang; ZHU Nan-wen; LIU Jun-shen; WANG Zhen-peng; CAI Wei-min

    2004-01-01

    Aerobic heterotrophic granular sludge was cultivated in a sequencing batch shaking reactor(SBSR) in which a synthetic wastewater containing glucose as carbon source was fed. The characteristics of the aerobic granules were investigated. Compared with the conventional activated sludge flocs, the aerobic granules exhibit excellent physical characteristics in terms of settleability, size, shape, biomass density, and physical strength.Scanning electron micrographs revealed that in mature granules little filamentous bacteria could be found, rodshaped and coccoid bacteria were the dominant microorganisms.

  2. Developing wax-based granule formulations for mating disruption of oriental beetles (Coleoptera: Scarabaeidae) in turfgrass.

    Science.gov (United States)

    Behle, R W; Cossé, A A; Dunlap, C; Fisher, J; Koppenhöfer, A M

    2008-12-01

    Oriental beetle, Anomala orientalis Waterhouse (Coleoptera: Scarabaeidae), is a pest of turfgrass that may be controlled by applications of synthetic pheromone (Z)-/ (E)-7-tetradecen-2-one to disrupt mating. Laboratory experiments were conducted to determine release profiles of pheromone from experimental wax-based granules, a proprietary wax granule, and rubber septa commonly used in pheromone traps. Rubber septa loaded with 10, 100, and 300 microg per septum provided steady rates of pheromone release (zero-order) over 4 wk of laboratory evaluation (total = 1.1, 9.0, and 26.9 microg/4 wk, respectively). Septa with 1,000 microg per septum had a significant decline in the rate of pheromone release for this 4-wk exposure time (total = 119 microg/4 wk). A large proprietary wax granule (44 mg per granule, 25% wt:wt pheromone) provided a steady rate of pheromone release (total = 2,347 microg/4 wk per granule). Experimental granules (16 mg per granule) made of soywax with higher pheromone loads (10% wt:wt) approached zero-order release (steady state) (total = 69 microg/4 wk per granule), whereas smaller granules (4 mg per granule) with less pheromone (0.1% wt:wt) provided first-order release profiles (decreasing rate with longer exposure time) (total = 0.35 microg/4 wk per granule). A field trial in turfgrass demonstrated the potential of selected granular formulations to provide effective mating disruption for up to 4 wk, as measured by pheromone trap shutdown. Documenting pheromone release profiles for these experimental granules and rubber septa provides valuable information that will support future field evaluations of mating disruption as a control strategy.

  3. Treatment of gouty arthritis in different phases by a series of Tongfeng granule: an efficacy observation

    Institute of Scientific and Technical Information of China (English)

    周蜜

    2014-01-01

    Objective To evaluate the clinical efficacy of a series of Tongfeng Granule(TG)in treating gouty arthritis patients in different stages.Methods Ninety primary gout patients were randomly assigned to two groups,the TCM treatment group(60 cases)and the Western medicine control group(30 cases).Huzhang Tongfeng Granule in combination with external application of Jinhuang Ointment was given to those in the TCM treatment group in the acute phase,and Yinlian Tongfeng Granule in the

  4. Comparison of A and B Starch Granules from Three Wheat Varieties

    Directory of Open Access Journals (Sweden)

    Haiyan Gao

    2011-12-01

    Full Text Available Three starches from the wheat varieties AK58, ZM18 and YZ4110 were separated into large (A and small (B granules, which were characterized structurally and evaluated for their functional properties. SEM results showed that the size of A-granules from ZM18 and YZ4110 were about the same, but the sizes of A-granules and B-granules from AK58 were larger than those of ZM18 and YZ4110. FTIR spectra showed that all the samples exhibited a similar pattern, with seven main modes with maximum absorbance peaks near 3,500, 3,000, 1,600, 1,400, 1,000, 800, 500 cm−1. The B-granules of ZM18 and YZ4110 had less amylose content, although the difference among the total amylose contents of the three unfractionated starches was not significant. X-ray diffraction (XRD patterns showed predominantly A-type crystallinity for all the starches. The A-granules showed sharper XRD patterns than the other starches. DSC analysis showed that the A-granules had broader ranges of gelatinization temperatures than the B-granules from the same wheat variety. The gelatinization enthalpy (ΔH of A-granules was higher than that of B-granules. AK58 exhibited the smallest enthalpy, while ZM18 showed the largest enthalpy. In pasting tests, the A-granule starch of AK58 had higher peak, final and setback viscosity, lower breakdown and pasting temperature, and the B-granule starch and unfractionated starch of AK58 had lower peak, breakdown, final and setback viscosity and higher pasting temperature than ZM18 and YZ4110.

  5. Continuous twin screw granulation of controlled release formulations with various HPMC grades.

    Science.gov (United States)

    Vanhoorne, V; Janssens, L; Vercruysse, J; De Beer, T; Remon, J P; Vervaet, C

    2016-09-25

    HPMC is a popular matrix former to formulate tablets with extended drug release. Tablets with HPMC are preferentially produced by direct compression. However, granulation is often required prior to tableting to overcome poor flowability of the formulation. While continuous twin screw granulation has been extensively evaluated for granulation of immediate release formulations, twin screw granulation of controlled release formulations including the dissolution behavior of the formulations received little attention. Therefore, the influence of the HPMC grade (viscosity and substitution degree) and the particle size of theophylline on critical quality attributes of granules (continuously produced via twin screw granulation) and tablets was investigated in the current study. Formulations with 20 or 40% HPMC, 20% theophylline and lactose were granulated with water at fixed process parameters via twin screw granulation. The torque was influenced by the viscosity and substitution degree of HPMC, but was not a limiting factor for the granulation process. An optimal L/S ratio was selected for each formulation based on the granule size distribution. The granule size distributions were influenced by the substitution degree and concentration of HPMC and the particle size of theophylline. Raman and UV spectroscopic analysis on 8 sieve fractions of granules indicated an inhomogeneous distribution of theophylline over the size fractions. However, this phenomenon was not correlated with the hydration rate or viscosity of HPMC. Controlled release of theophylline could be obtained over 24h with release profiles close to zero-order. The release of theophylline could be tailored via selection of the substitution degree and viscosity of HPMC.

  6. Lymphocytic adenohypophysitis: skull radiographs and MRI

    Energy Technology Data Exchange (ETDEWEB)

    Saiwai, S.; Miyamoto, T. [Department of Radiology, Kobe Central Municipal Hospital, Hyogo (Japan); Inoue, Y.; Nemoto, Y.; Tashiro, T. [Department of Radiology, Osaka City University Medical School (Japan); Ishihara, T. [Department of Endocrinology, Kobe Central Municipal Hospital, Hyogo (Japan); Matsumoto, S. [Department of Neurosurgery, Kobe Central Municipal Hospital, Hyogo (Japan); Hakuba, A. [Department of Neurosurgery, Osaka City University Medical School, 1-5-7 Asahimachi, Abeno, Osaka, 545 (Japan)

    1998-02-01

    We report the skull radiograph, CT and MRI findings in three patients with lymphocytic adenohypophysitis mimicking pituitary adenoma. All cases were associated with pregnancy. CT demonstrated a pituitary mass but did not differentiate lymphocytic adenohypophysitis from pituitary adenoma. The skull radiographs showed either a normal sella turcica or minimal abnormalities; they did not show ballooning or destruction. The MRI appearances were distinctive: relatively low signal on T1-weighted images; preservation of the bright posterior pituitary lobe despite the presence of a relatively large pituitary mass, less common in macroadenomas; marked contrast enhancement compared with pituitary macroadenomas; and dural enhancement adjacent to a pituitary mass. (orig.) With 3 figs., 1 tab., 40 refs.

  7. Expression of an engineered granule-bound Escherichia coli glycogen branching enzyme in potato results in severe morphological changes in starch granules.

    Science.gov (United States)

    Huang, Xing-Feng; Nazarian-Firouzabadi, Farhad; Vincken, Jean-Paul; Ji, Qin; Suurs, Luc C J M; Visser, Richard G F; Trindade, Luisa M

    2013-05-01

    The Escherichia coli glycogen branching enzyme (GLGB) was fused to either the C- or N-terminus of a starch-binding domain (SBD) and expressed in two potato genetic backgrounds: the amylose-free mutant (amf) and an amylose-containing line (Kardal). Regardless of background or construct used, a large amount of GLGB/SBD fusion protein was accumulated inside the starch granules, however, without an increase in branching. The presence of GLGB/SBD fusion proteins resulted in altered morphology of the starch granules in both genetic backgrounds. In the amf genetic background, the starch granules showed both amalgamated granules and porous starch granules, whereas in Kardal background, the starch granules showed an irregular rough surface. The altered starch granules in both amf and Kardal backgrounds were visible from the initial stage of potato tuber development. High-throughput transcriptomic analysis showed that expression of GLGB/SBD fusion protein in potato tubers did not affect the expression level of most genes directly involved in the starch biosynthesis except for the up-regulation of a beta-amylase gene in Kardal background. The beta-amylase protein could be responsible for the degradation of the extra branches potentially introduced by GLGB.

  8. Understanding the impact of influent nitrogen concentration on granule size and microbial community in a granule-based enhanced biological phosphorus removal system.

    Science.gov (United States)

    Zou, Jinte; Li, Yongmei; Zhang, Lili; Wang, Ruyi; Sun, Jing

    2015-02-01

    To better understand the effect of influent nitrogen concentration on granule size and microbial community in a granule-based enhanced biological phosphorus removal system, three influent nitrogen concentrations were tested while carbon concentration was an unlimited factor. The results show that although ammonium and phosphate were well removed in the tested nitrogen concentration range (20-50 mg L(-1)), granule size, the amount of phosphate accumulating organisms (PAOs) and microbial activity were affected significantly. A possible mechanism for the effect of influent nitrogen concentration on granule size is proposed based on the experimental results. The increase in proteins/polysaccharides ratio caused by high influent nitrogen concentration plays a crucial role in granule breakage. The small granule size then weakens simultaneous nitrification-denitrification, which further causes higher nitrate concentration in the effluent and lower amount of PAOs in sludge. Consequently, phosphate concentration in the anaerobic phase decreases, which plays the secondary role in granule breakage. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. DEM Modelling of Granule Rearrangement and Fracture Behaviours During a Closed-Die Compaction.

    Science.gov (United States)

    Furukawa, Ryoichi; Kadota, Kazunori; Noguchi, Tetsuro; Shimosaka, Atsuko; Shirakawa, Yoshiyuki

    2017-01-26

    The closed-die compaction behaviour of D-mannitol granules has been simulated by the discrete element method (DEM) to investigate the granule rearrangement and fracture behaviour during compaction which affects the compactibility of the tablet. The D-mannitol granules produced in a fluidized bed were modelled as agglomerates of primary particles connected by linear spring bonds. The validity of the model granule used in the DEM simulation was demonstrated by comparing to the experimental results of a uniaxial compression test. During uniaxial compression, the numerical results of the force-displacement curve corresponded reasonably well to the experimental data. The closed-die compaction of the modelled granules was carried out to investigate the rearrangement and fracture behaviours of the granule at different upper platen velocities. The forces during closed-die compaction calculated by DEM fluctuated in the low-pressure region due to the rearrangement of granules. A Heckel analysis showed that the force fluctuation occurred at the initial bending region of the Heckel plot, which represents the granule rearrangement and fracture. Furthermore, the upper platen velocity affected the trend of compaction forces, which can lead to compaction failure due to capping. These results could contribute to designing the appropriate granules during closed-die compaction.

  10. Digital image analysis of starch granules for recognizing hard red and soft red winter wheats

    Science.gov (United States)

    Zayas, Inna Y.; Bechtel, D. B.; Wilson, J. D.; Dempster, Richard E.

    1993-05-01

    The relationship between isolated starch granule morphometry and wheat hardness was studied. Starch granule size and shape may relate to grain millability, rheological properties of dough, and baking quality. Twenty four Kansas wheats were studied: 14 hard red winter (HRW) and 10 soft red winter (SRW). Isolated starch granules were viewed with light microscopy to obtain black and white images which were recorded on video tape. A program was designed to keep track of the taped images and measure starch granules without operator intervention. The data base of starch granule size and shape features of the 24 samples contained 152,237 granule observations. The number of observations per sample varied from 3,238 to 14,671. Distinguishing HRW from SRW wheat samples was accomplished by evaluation of starch granule morphometry. Several data manipulations and transformations were performed in analysis of the data. Information carried in two shape descriptors, which reflect aspect ratio and equivalent diameter distribution, was used to distinguish starch granules of HRW and SRW wheats. The percentage of starch granules in the aspect ratio range of 1.65 - 1.95 was 25.8 - 31.5% for HRW and 19.9 - 25.4% for SRW.

  11. CSR-1 and P granules suppress sperm-specific transcription in the C. elegans germline.

    Science.gov (United States)

    Campbell, Anne C; Updike, Dustin L

    2015-05-15

    Germ granules (P granules) in C. elegans are required for fertility and function to maintain germ cell identity and pluripotency. Sterility in the absence of P granules is often accompanied by the misexpression of soma-specific proteins and the initiation of somatic differentiation in germ cells. To investigate whether this is caused by the accumulation of somatic transcripts, we performed mRNA-seq on dissected germlines with and without P granules. Strikingly, we found that somatic transcripts do not increase in the young adult germline when P granules are impaired. Instead, we found that impairing P granules causes sperm-specific mRNAs to become highly overexpressed. This includes the accumulation of major sperm protein (MSP) transcripts in germ cells, a phenotype that is suppressed by feminization of the germline. A core component of P granules, the endo-siRNA-binding Argonaute protein CSR-1, has recently been ascribed with the ability to license transcripts for germline expression. However, impairing CSR-1 has very little effect on the accumulation of its mRNA targets. Instead, we found that CSR-1 functions with P granules to prevent MSP and sperm-specific mRNAs from being transcribed in the hermaphrodite germline. These findings suggest that P granules protect germline integrity through two different mechanisms, by (1) preventing the inappropriate expression of somatic proteins at the level of translational regulation, and by (2) functioning with CSR-1 to limit the domain of sperm-specific expression at the level of transcription.

  12. Layered growth with bottom-spray granulation for spray deposition of drug.

    Science.gov (United States)

    Er, Dawn Z L; Liew, Celine V; Heng, Paul W S

    2009-07-30

    The gap in scientific knowledge on bottom-spray fluidized bed granulation has emphasized the need for more studies in this area. This paper comparatively studied the applicability of a modified bottom-spray process and the conventional top-spray process for the spray deposition of a micronized drug during granulation. The differences in circulation pattern, mode of growth and resultant granule properties between the two processes were highlighted. The more ordered and consistent circulation pattern of particles in a bottom-spray fluidized bed was observed to give rise to layered granule growth. This resulted in better drug content uniformity among the granule batches and within a granule batch. The processes' sensitivities to wetting and feed material characteristics were also compared and found to differ markedly. Less robustness to differing process conditions was observed for the top-spray process. The resultant bottom-spray granules formed were observed to be less porous, more spherical and had good flow properties. The bottom-spray technique can thus be potentially applied for the spray deposition of drug during granulation and was observed to be a good alternative to the conventional technique for preparing granules.

  13. [Solution kinetics of magnesium oxide containing granules produced by laboratory scale fluidization].

    Science.gov (United States)

    Rácz, I; Zelkó, R; Bihari, E

    1994-09-01

    In practice of manufacturing industrial pharmaceutical products, the technique of fluidization has been used extensively in the past decades. The authors studied the magnesium oxide-containing granulates made by fluidization granulation in laboratory, to optimize the process, to determine the neutralization kinetic parameters of granulates, to establish the connections between the method of granulation and the release of active substances. According to our findings, the pharmaceutical product's characteristics in the aspects of physics, chemistry, stability and bioavailability may remarkably change without fixing the border conditions of parameters within limits.

  14. Who Regulates Whom? An Overview of RNA Granules and Viral Infections

    Directory of Open Access Journals (Sweden)

    Natalia Poblete-Durán

    2016-06-01

    Full Text Available After viral infection, host cells respond by mounting an anti-viral stress response in order to create a hostile atmosphere for viral replication, leading to the shut-off of mRNA translation (protein synthesis and the assembly of RNA granules. Two of these RNA granules have been well characterized in yeast and mammalian cells, stress granules (SGs, which are translationally silent sites of RNA triage and processing bodies (PBs, which are involved in mRNA degradation. This review discusses the role of these RNA granules in the evasion of anti-viral stress responses through virus-induced remodeling of cellular ribonucleoproteins (RNPs.

  15. Biodegradation of p-cresol by aerobic granules in sequencing batch reactor

    Institute of Scientific and Technical Information of China (English)

    Farrukh Basheer; I.H.Farooqi

    2012-01-01

    The cultivation of aerobic granules in sequencing batch reactor for the biodegradation of p-cresol was studied.The reactor was started with 100 mg/L of p-cresol.Aerobic granules first appeared within one month of start up.The granules were large and strong and had a compact structure.The diameter of stable granules was in the range of 1-5 mm.The integrity coefficient and granules density was found to be 96% and 1046 kg/m3,respectively.The settling velocity of granules was found to be in the range of 2×10-2-6×10-2 m/sec.The aerobic granules were able to degrade p-cresol upto 800 mg/L at a removal efficiency of 88%.Specific p-cresol degradation rate in aerobic granules followed Haldane model for substrate inhibition.High specific p-cresol degradation rate up to 0.96 g pcresol/(g VSS.day) were sustained upto p-cresol concentration of 400 mg/L.Higher removal efficiency,good settling characteristics of aerobic granules,makes sequencing batch reactor suitable for enhancing the microorganism potential for biodegradation of inhibitory compounds.

  16. Role of the Caenorhabditis elegans multidrug resistance gene, mrp-4, in gut granule differentiation.

    Science.gov (United States)

    Currie, Erin; King, Brian; Lawrenson, Andrea L; Schroeder, Lena K; Kershner, Aaron M; Hermann, Greg J

    2007-11-01

    Caenorhabditis elegans gut granules are lysosome-related organelles with birefringent contents. mrp-4, which encodes an ATP-binding cassette (ABC) transporter homologous to mammalian multidrug resistance proteins, functions in the formation of gut granule birefringence. mrp-4(-) embryos show a delayed appearance of birefringent material in the gut granule but otherwise appear to form gut granules properly. mrp-4(+) activity is required for the extracellular mislocalization of birefringent material, body-length retraction, and NaCl sensitivity, phenotypes associated with defective gut granule biogenesis exhibited by embryos lacking the activity of GLO-1/Rab38, a putative GLO-1 guanine nucleotide exchange factor GLO-4, and the AP-3 complex. Multidrug resistance protein (MRP)-4 localizes to the gut granule membrane, consistent with it playing a direct role in the transport of molecules that compose and/or facilitate the formation of birefringent crystals within the gut granule. However, MRP-4 is also present in oocytes and early embryos, and our genetic analyses indicate that its site of action in the formation of birefringent material may not be limited to just the gut granule in embryos. In a search for genes that function similarly to mrp-4(+), we identified WHT-2, another ABC transporter that acts in parallel to MRP-4 for the formation of birefringent material in the gut granule.

  17. Comparison of Ca{sup 2+} and Mg{sup 2+} enhancing aerobic granulation in SBR

    Energy Technology Data Exchange (ETDEWEB)

    Liu Lin [School of Forestry, Northeast Forestry University, Harbin 150040 (China); Gao Dawen, E-mail: dawengao@gmail.com [School of Forestry, Northeast Forestry University, Harbin 150040 (China); State Key Laboratory of Urban Water Resource and Environment, 73 Huanghe Rd., Harbin 150090 (China); Zhang Min [School of Forestry, Northeast Forestry University, Harbin 150040 (China); Fu Yuan [State Key Laboratory of Urban Water Resource and Environment, 73 Huanghe Rd., Harbin 150090 (China)

    2010-09-15

    Two sequencing batch reactors (SBRs) were operated to investigate the effect of Ca{sup 2+} and Mg{sup 2+} augmentation on aerobic granulation. Reactor R1 was augmented with Ca{sup 2+} at 40 mg/L, while Mg{sup 2+} was added to the reactor R2 with 40 mg/L. Results showed that the reactor R1 had a faster granulation process compared with R2, and the mature granules in R1 showed better physical characteristics. However, the mature granules in R2 had the higher production yield of polysaccharides and proteins, and aerobic granules in R2 experienced a faster substrate biodegradation. Microbial and genetic characteristics in mature granules were analyzed using polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE) techniques. The results revealed that Mg{sup 2+} addition led to higher microbial diversity in mature granules. In addition, an uncultured bacterium (AB447697) was major specie in R1, and {beta}-proteobacterium was dominant in R2. It can be concluded that Ca{sup 2+} had an important effect on physical properties of aerobic granules, while Mg{sup 2+} played a key role on biological properties during the sludge granulation.

  18. Foam granulation: new developments in pharmaceutical solid oral dosage forms using twin screw extrusion machinery.

    Science.gov (United States)

    Thompson, M R; Weatherley, S; Pukadyil, R N; Sheskey, P J

    2012-07-01

    This paper investigates foam granulation in a twin screw extruder as a new continuous wet granulation technique for pharmaceutical powder drug formulations. Foamed aqueous binder has a reportedly lower soak-to-spread ratio than drop or spray liquid addition in batch granulation. This work demonstrates a twin screw extruder configuration for foam granulation and subsequently compares the new approach against liquid injection in the granulation of α-lactose monohydrate with a methylcellulose binder. Trials were conducted at high powder output rates (20-40 kg/h) and high screw speeds (220-320 RPM) with two screw configurations. Process stability improved with the new technique allowing granulation with less binder. The extruded mass maintained a low exit temperature, being insensitive to operating conditions unlike the liquid injection approach, where temperatures rose significantly as flow rate increased. The particle size distribution by foam granulation reflected a more uniformly wetted mass with larger granule growth noted even for conditions where dry powder exited by liquid injection. Other factors were found similar between the two binder delivery methods such as consumed mechanical energy, as well as fracture strength and compressibility of produced granules.

  19. The stealthy nano-machine behind mast cell granule size distribution.

    Science.gov (United States)

    Hammel, Ilan; Meilijson, Isaac

    2015-01-01

    The classical model of mast cell secretory granule formation suggests that newly synthesized secretory mediators, transported from the rough endoplasmic reticulum to the Golgi complex, undergo post-transitional modification and are packaged for secretion by condensation within membrane-bound granules of unit size. These unit granules may fuse with other granules to form larger granules that reside in the cytoplasm until secreted. A novel stochastic model for mast cell granule growth and elimination (G&E) as well as inventory management is presented. Resorting to a statistical mechanics approach in which SNAP (Soluble NSF Attachment Protein) REceptor (SNARE) components are viewed as interacting particles, the G&E model provides a simple 'nano-machine' of SNARE self-aggregation that can perform granule growth and secretion. Granule stock is maintained as a buffer to meet uncertainty in demand by the extracellular environment and to serve as source of supply during the lead time to produce granules of adaptive content. Experimental work, mathematical calculations, statistical modeling and a rationale for the emergence of nearly last-in, first out inventory management, are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. The diverse functions of germline P-granules in Caenorhabditis elegans.

    Science.gov (United States)

    Voronina, Ekaterina

    2013-08-01

    P-granules are conserved cytoplasmic organelles, similar to nuage, that are present in Caenorhabditis elegans germ cells. Based on the prevailing sterility phenotype of the component mutants, P-granules have been seen as regulators of germ cell development and function. Yet, specific germline defects resulting from P-granule failure vary, depending on which component(s) are inactivated, at which stage of development, as well as on the presence of stress factors during animal culture. This review discusses the unifying themes in many P-granule functions, with the main focus on their role as organizing centers nucleating RNA regulation in the germ cell cytoplasm.

  1. P granules phase transition induced by cytoplasmic streaming in Caenorhabditis elegans embryo

    Science.gov (United States)

    Wang, Hang; Hu, GuoHui

    2017-01-01

    P granules are germ granules contained in Caenorhabditis elegans germ cells. The first germ cell is specified by the one-cell embryo in which P granules localize to the posterior. Previous studies suggested that the mechanism of the localization phenomena is induced by liquid-liquid phase transition (LLPT), in which the polarity proteins control the saturation point of P granules. In the present study, we propose that the P granules phase transition can be triggered by the cytoplasmic streaming. A two-phase flow model is employed to simulate the localization of P granules, i.e., the cytoplasm is considered as a liquid phase, and the droplet-like P granules are another liquid phase. With the presence of the cytoplasmic streaming, P granules, initially distributing uniformly in the entire one-cell embryo, eventually condense/dissolve in the cytoplasm phase, regulated by difference between the saturation pressure and the hydrodynamic pressure. The numerical results reveal that the cytoplasmic streaming has significant effects on the localization of P granules, as well as the embryo division.

  2. Who Regulates Whom? An Overview of RNA Granules and Viral Infections

    Science.gov (United States)

    Poblete-Durán, Natalia; Prades-Pérez, Yara; Vera-Otarola, Jorge; Soto-Rifo, Ricardo; Valiente-Echeverría, Fernando

    2016-01-01

    After viral infection, host cells respond by mounting an anti-viral stress response in order to create a hostile atmosphere for viral replication, leading to the shut-off of mRNA translation (protein synthesis) and the assembly of RNA granules. Two of these RNA granules have been well characterized in yeast and mammalian cells, stress granules (SGs), which are translationally silent sites of RNA triage and processing bodies (PBs), which are involved in mRNA degradation. This review discusses the role of these RNA granules in the evasion of anti-viral stress responses through virus-induced remodeling of cellular ribonucleoproteins (RNPs). PMID:27367717

  3. Role of adaptor proteins in secretory granule biogenesis and maturation

    Directory of Open Access Journals (Sweden)

    Mathilde L Bonnemaison

    2013-08-01

    Full Text Available In the regulated secretory pathway, secretory granules (SGs store peptide hormones that are released on demand. SGs are formed at the trans-Golgi network (TGN and must undergo a maturation process to become responsive to secretagogues. The production of mature SGs requires concentrating newly synthesized soluble content proteins in granules whose membranes contain the appropriate integral membrane proteins. The mechanisms underlying the sorting of soluble and integral membrane proteins destined for SGs from other proteins are not yet well understood. For soluble proteins, luminal pH and divalent metals can affect aggregation and interaction with surrounding membranes. The trafficking of granule membrane proteins can be controlled by both luminal and cytosolic factors. Cytosolic adaptor proteins, which recognize the cytosolic domains of proteins that span the SG membrane, have been shown to play essential roles in the assembly of functional SGs. Adaptor protein 1A (AP-1A is known to interact with specific motifs in its cargo proteins and with the clathrin heavy chain, contributing to the formation of a clathrin coat. AP-1A is present in patches on immature SG membranes, where it removes cargo and facilitates SG maturation. AP-1A recruitment to membranes can be modulated by PACS-1 (Phosphofurin Acidic Cluster Sorting protein 1, a cytosolic protein which interacts with both AP-1A and cargo that has been phosphorylated by casein kinase II. A cargo/PACS-1/AP-1A complex is necessary to drive the appropriate transport of several cargo proteins within the regulated secretory pathway. The GGA (Golgi-localized, -ear containing, ADP-ribosylation factor binding family of adaptor proteins serve a similar role. We review the functions of AP-1A, PACS-1 and GGAs in facilitating the retrieval of proteins from immature SGs and review examples of cargo proteins whose trafficking within the regulated secretory pathway is governed by adaptor proteins.

  4. The Uptake and Utilization of Chlorambucil by Lymphocytes from Patients with Chronic Lymphocytic Leukaemia

    Science.gov (United States)

    Hill, Bridget T.; Harrap, K. R.

    1972-01-01

    It has been shown that lymphocytes isolated from the peripheral blood of patients with chronic lymphocytic leukaemia do not modify the mustard group of chlorambucil, as has been demonstrated previously in Yoshida ascites cells. However, lymphocytes from patients with an unsatisfactory clinical course or poor response to treatment were able to modify the aromatic region of the drug molecule; little change occurred in the aromatic absorption of intracellular chlorambucil in patients who responded to treatment. This simple test may provide a rapid assessment of a patient's potential response to chemotherapy. PMID:4647395

  5. Lymphocytic adrenal medullitis and lymphocytic thyroiditis in a laboratory beagle dog.

    Science.gov (United States)

    Doi, Takuya; Tomonari, Yuki; Kawasako, Kazufumi; Yamada, Naoaki; Tsuchitani, Minoru

    2017-02-04

    Lymphocytic adrenal medullitis characterized by inflammation and atrophy in the medulla of the bilateral adrenal glands was observed in an 18-month-old male laboratory beagle dog. It might be that the present lymphocytic adrenal medullitis is an autoimmune-mediated disease as the histological characteristics are consistent with an autoimmune pathogenesis. However, the actual cause remains unclear as the existence of serum autoantibodies against the adrenal medulla could not be confirmed. Although this dog also contracted lymphocytic thyroiditis along with serum thyroglobulin autoantibodies, indicating that the thyroiditis occurred with an autoimmune basis; the relation between the adrenal medullitis and thyroiditis is unknown.

  6. Lipofuscin Granules in the Epileptic Human Temporal Neocortex with Age.

    Science.gov (United States)

    Merlo, Suélen; Nakayama, Ana Beatriz S; Brusco, Janaina; Rossi, Marcos A; Carlotti, Carlos G; Moreira, Jorge E

    2015-01-01

    Lipofuscin granules (LGs), the "age pigments", are autofluorescent cell products from lysosomes that diverge in number and size among brain regions. Human temporal cortex from 20- to 55-year-old epileptic subjects were studied with the fat soluble dye Sudan Black, under confocal and electron microscopy. Ultrastructural analysis showed that with age LGs increase in area, but not in number. Proportionally to the LGs area, the electron lucid portion increases and the electron dense reduces over time. The robust increase in lipid components is possibly due to modifications in the neuronal metabolism with age in physiological and pathological conditions.

  7. Stochastic differential equation model for cerebellar granule cell excitability.

    Science.gov (United States)

    Saarinen, Antti; Linne, Marja-Leena; Yli-Harja, Olli

    2008-02-29

    Neurons in the brain express intrinsic dynamic behavior which is known to be stochastic in nature. A crucial question in building models of neuronal excitability is how to be able to mimic the dynamic behavior of the biological counterpart accurately and how to perform simulations in the fastest possible way. The well-established Hodgkin-Huxley formalism has formed to a large extent the basis for building biophysically and anatomically detailed models of neurons. However, the deterministic Hodgkin-Huxley formalism does not take into account the stochastic behavior of voltage-dependent ion channels. Ion channel stochasticity is shown to be important in adjusting the transmembrane voltage dynamics at or close to the threshold of action potential firing, at the very least in small neurons. In order to achieve a better understanding of the dynamic behavior of a neuron, a new modeling and simulation approach based on stochastic differential equations and Brownian motion is developed. The basis of the work is a deterministic one-compartmental multi-conductance model of the cerebellar granule cell. This model includes six different types of voltage-dependent conductances described by Hodgkin-Huxley formalism and simple calcium dynamics. A new model for the granule cell is developed by incorporating stochasticity inherently present in the ion channel function into the gating variables of conductances. With the new stochastic model, the irregular electrophysiological activity of an in vitro granule cell is reproduced accurately, with the same parameter values for which the membrane potential of the original deterministic model exhibits regular behavior. The irregular electrophysiological activity includes experimentally observed random subthreshold oscillations, occasional spontaneous spikes, and clusters of action potentials. As a conclusion, the new stochastic differential equation model of the cerebellar granule cell excitability is found to expand the range of dynamics

  8. Study on quality control method for compound Shanzha Granules

    Institute of Scientific and Technical Information of China (English)

    付延伟; 程艳芹

    2015-01-01

    Objective:To establish the quality standard of Compound Shanzha Granules. Methods:Crataegi Fructus and Cassiae Semen were identified by TLC. The contents of Autrantio- obtusin and Chrysophanol in Cassiae Semen were determined by HPLC. Results:The relevant spots on TLC plates were clear by the blank reference. The contents showed good linearitis in the range of 0.0357~0.3570μg for Autrantio- obtusin and 0.0520~0.5200μg for Chrysophanol.Conclusions:The method are simple, accurate and reproducible.

  9. Simulator for a packing and weighing system of granulated powders.

    Science.gov (United States)

    Couto Rodrigues de Oliveira, Rafael; Garcia, Claudio

    2013-09-01

    The development of a simulator for a packing and weighing system (PWS) of granulated powder is described. It employed system identification to obtain the deterministic part of the model and stochastic processes to reproduce disturbances. It reproduces the fluctuations in carton weight observed in real packing systems. Its final use is to evaluate proposed improvements in the PWS, aiming at reducing overweight and underweight. Its performance is satisfactory, as the oscillations observed in the carton weights, due to powder density variability, are close to reality as well as the monetary losses due to overweight and underweight and the power spectral density graphs of the real and simulated weights.

  10. Proximate analysis for determination of micropores in granulated activated carbon

    Energy Technology Data Exchange (ETDEWEB)

    Berman, Ya. G.; Nikolaev, V.B.; Shepelev, A.N.

    1987-02-01

    A method is discussed for determining the specific micropore volume of granulated activated carbon used for water treatment in Soviet coking plants. Toluene molecules with a diameter of 0.67 nm are sorbed by activated carbon with micropore diameter ranging from 0.7 to 1.4 nm. Therefore, sorptive properties of activated carbon in relation to toluene supply information on micropore volume in carbon. A formula which describes this relation is derived. The method for determining micropore volume on the basis of toluene adsorption was tested using 8 types of activated carbon produced from coal and petroleum. Types of activated carbon characterized by the highest adsorption were selected. 1 ref.

  11. Additives for granulating and removing ash from finely dispersed coal

    Energy Technology Data Exchange (ETDEWEB)

    Ivabutin, K.; Fukuda, T.; Goto, M.; Miva, K.; Murata, T.; Taguti, D.

    1982-07-31

    One to thirty percent of a 0.01 to 10 percent solution of synthetic polymers (SPL) of ethylene and vinylacetate or methacrylate, polybutadiene rubbers, resins based on vinylchloride, low molecular PA and so on in an organic solvent mixed with high boiling point bottoms of coal distillation or that of crude oil and or an inorganic electrolyte (a sulfate or phosphate of an alkaline metal) is added to an aqueous suspension of coal powder in order to utilize the dust particles of the coal and to make low ash granules from them.

  12. [Quantitative structure characteristics and fractal dimension of Chinese medicine granules measured by synchrotron radiation X-ray computed micro tomography].

    Science.gov (United States)

    Lu, Xiao-long; Zheng, Qin; Yin, Xian-zhen; Xiao, Guang-qing; Liao, Zu-hua; Yang, Ming; Zhang, Ji-wen

    2015-06-01

    The shape and structure of granules are controlled by the granulation process, which is one of the main factors to determine the nature of the solid dosage forms. In this article, three kinds of granules of a traditional Chinese medicine for improving appetite and promoting digestion, namely, Jianwei Granules, were prepared using granulation technologies as pendular granulation, high speed stirring granulation, and fluidized bed granulation and the powder properties of them were investigated. Meanwhile, synchrotron radiation X-ray computed micro tomography (SR-µCT) was applied to quantitatively determine the irregular internal structures of the granules. The three-dimensional (3D) structure models were obtained by 3D reconstruction, which were more accurately to characterize the three-dimensional structures of the particles through the quantitative data. The models were also used to quantitatively compare the structural differences of granules prepared by different granulation processes with the same formula, so as to characterize how the production process plays a role in the pharmaceutical behaviors of the granules. To focus on the irregularity of the particle structure, the box counting method was used to calculate the fractal dimensions of the granules. The results showed that the fractal dimension is more sensitive to reflect the minor differences in the structure features than the conventional parameters, and capable to specifically distinct granules in structure. It is proved that the fractal dimension could quantitatively characterize the structural information of irregular granules. It is the first time suggested by our research that the fractal dimension difference (Df,c) between two fractal dimension parameters, namely, the volume matrix fractal dimension and the surface matrix fractal dimension, is a new index to characterize granules with irregular structures and evaluate the effects of production processes on the structures of granules as a new

  13. Assessment of illness-related indicators in peripheral blood and skin lesion tissue of patients with vitiligo after NB-UVB, triamcinolone acetonide and vitiligo granules triple treatment

    Institute of Scientific and Technical Information of China (English)

    Wei-Liang Wang; Yan Chen; Feng-Bin Liu; Yuan-Zuo Huang; Ju-Zhen Lin; Guan-Biao Lyu

    2016-01-01

    Objective:To study the changes of illness-related indicators in peripheral blood and skin lesion tissue of patients with vitiligo after NB-UVB, triamcinolone acetonide and vitiligo granules triple treatment.Methods: Patients with vitiligo were selected as research subjects and randomly divided into two groups, observation group received NB-UVB, triamcinolone acetonide and vitiligo granules triple treatment, control group received combined therapy of NB-UVB and triamcinolone acetonide, and then the contents of lymphocyte subsets and cytokines in peripheral blood as well as the expression of illness-related molecules in skin lesion tissue were detected.Results:After treatment, the percentage of CD3+ CD28+, CD3+CD4+CD28+, CD3+CD8+CD28+ and Th17cells as well as the contents of IL-17 and IL-6 in peripheral blood of observation group were significantly lower than those of control group, and the percentage of CD3+ CTLA4+, CD3+CD4+ CTLA4+, CD3+CD8+ CTLA4+ and Treg cells as well as the contents of IL-10 and TGF-β were significantly higher than those of control group; the expression levels of Nrf-2, SCF, c-kit and InnVit in skin lesion tissue of observation group were higher than those of control group, and CLEC2B expression level was lower than that of control group.Conclusion:NB-UVB, triamcinolone acetonide and vitiligo granules triple treatment can more effectively regulate immune function and expression of illness-related molecules in skin lesion tissue of patients with vitiligo.

  14. Dual character of interaction between lymphocytes and allogeneic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Petrov, R.V.; Dozmorov, I.M.; Kochetkova, M.O.; Nikolaeva, I.S.

    1986-10-01

    The mechanisms of stimulation of colony formation by small doses of allogeneic lymphocytes were studied in mice. When interaction of lymphocytes with allogeneic stem cells was studied, bone marrow cells of mice were injected into lethally irradiated recipients in the control, and mixtures of bone marrow cells with varied numbers of lymphocytes were injected in the experiment. Dependence of the inactivation indices on the number of lymphocytes injected, based on the results of counting macro- and microcolonies in the spleen, is shown.

  15. Morphometric Characterization of Small Cell Lymphocytic Lymphoma

    Directory of Open Access Journals (Sweden)

    Chisoi Anca

    2014-11-01

    Full Text Available The morphometry in histopathology is used to characterize cell populations belonging to different tissues and to identify differences in their parameters with prognostic implications. To achieve morphometric examination were selected 6 of 24 cases identified as small cell lymphocytic lymphoma. For each case analysis was done on five fields, for each field measuring the parameters of 20 cells. The studied parameters were for cytoplasm: cytoplasmic area, maximum and minimum cytoplasmic diameter, cytoplasmic perimeter; for nucleus were measured: nuclear area, minimum and maximum nuclear diameter, nuclear perimeter, nuclear contour index, nuclear ellipticity index, nuclear irregularity index. Also the nucleocytoplasmic ratio was calculated in all studied cases. Small cell lymphocytic lymphoma is characterized in morphometric terms having a small cytoplasmic area (average 29.206 and also a small nuclear area (mean 28.939 having a nucleo-cytoplasmic ratio appearance suggestive for adult lymphocyte. A nuclear contour index small value (3.946, ellipticity index value also small (3.521 and small nuclear irregularity index (3.965. Standard deviations, in any of the studied morphometric categories, is around or below 1 suggesting monomorphic cell appearance. These morphometric and microscopic features characterized mainly by a small population of adult lymphocytes, monomorphic, with rounded hipercromic nuclei, dense chromatin, support the framing into indolent lymphoma group in terms of clinical outcome.

  16. Targeting cytotoxic T lymphocytes for cancer immunotherapy

    OpenAIRE

    Maher, J; Davies, E. T.

    2004-01-01

    In light of their preeminent role in cellular immunity, there is considerable interest in targeting of cytotoxic T-lymphocytes to cancer. This review summarises the active and passive immunotherapeutic approaches under development to achieve this goal, emphasising how recent advances in tumour immunology and gene transfer have impacted upon this field.

  17. Immunophenotypic lymphocyte profiles in human african trypanosomiasis.

    Directory of Open Access Journals (Sweden)

    Caroline Boda

    Full Text Available Human African trypanosomiasis (HAT is a deadly vector-born disease caused by an extracellular parasite, the trypanosome. Little is known about the cellular immune responses elicited by this parasite in humans. We used multiparameter flow cytometry to characterize leukocyte immunophenotypes in the blood and cerebrospinal fluid (CSF of 33 HAT patients and 27 healthy controls identified during a screening campaign in Angola and Gabon. We evaluated the subsets and activation markers of B and T lymphocytes. Patients had a higher percentage of CD19+ B lymphocytes and activated B lymphocytes in the blood than did controls, but lacked activated CD4+ T lymphocytes (CD25+. Patients displayed no increase in the percentage of activated CD8+ T cells (HLA-DR+, CD69+ or CD25+, but memory CD8 T-cell levels (CD8+CD45RA2 were significantly lower in patients than in controls, as were effector CD8 T-cell levels (CD8+CD45RA+CD62L2. No relationship was found between these blood immunophenotypes and disease severity (stage 1 vs 2. However, CD19+ B-cell levels in the CSF increased with disease severity. The patterns of T and B cell activation in HAT patients suggest that immunomodulatory mechanisms may operate during infection. Determinations of CD19+ B-cell levels in the CSF could improve disease staging.

  18. SnapShot: chronic lymphocytic leukemia.

    Science.gov (United States)

    Ciccone, Maria; Ferrajoli, Alessandra; Keating, Michael J; Calin, George A

    2014-11-10

    Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults in western countries. This SnapShot depicts the origins and evolution of this B cell malignancy, describes prognostic factors and CLL animal models, and illustrates therapies in preclinical and clinical development against CLL.

  19. Regulatory T-lymphocytes in asthma

    NARCIS (Netherlands)

    van Oosterhout, AJM; Bloksma, N

    2005-01-01

    T-helper cell type (Th)2 lymphocytes play an important role in the initiation, progression and persistence of allergic diseases, including asthma. However, little is known about immunoregulatory mechanisms that determine susceptibility to, severity of, or persistence of asthma. The concept of a dist

  20. Lymphocyte dynamics in health and disease

    NARCIS (Netherlands)

    van Gent, R.

    2009-01-01

    Following immune depletion, it is vital that the immune system recovers rapidly to avoid severe or life-threatening infections. In adults, full recovery of CD4+ and CD8+ T-cell counts, important cell types of the immune system, may take years. Similar to other lymphocytes, T cells start their develo

  1. Peripheral lymphocyte subpopulations in recurrent aphthous ulceration

    DEFF Research Database (Denmark)

    Pedersen, A; Klausen, B; Hougen, H P

    1991-01-01

    Peripheral lymphocyte subsets--T-helper (CD4+), T-suppressor/cytotoxic (CD8+), and naive/virgin T cells/natural killer cells (CD45RA)--were studied quantitatively in 30 patients with recurrent aphthous ulceration (RAU) and 29 sex- and age-matched RAU-free control donors. The CD4+ percentage was s...

  2. Effect of chloroquine on human lymphocyte proliferation

    DEFF Research Database (Denmark)

    Bygbjerg, Ib Christian; Flachs, H

    1986-01-01

    the response to pokeweed mitogen. The response to concanavalin A and to various antigens was suppressed, especially the response to large particulate antigens. Oral intake of 300 mg of chloroquine base/week did not affect the lymphocyte proliferative responses. 600 mg of base/week decreased the response...

  3. Improved tabletability after a polymorphic transition of delta-mannitol during twin screw granulation.

    Science.gov (United States)

    Vanhoorne, V; Bekaert, B; Peeters, E; De Beer, T; Remon, J-P; Vervaet, C

    2016-06-15

    In most formulations processed via continuous twin screw granulation microcrystalline cellulose (MCC) and/or lactose are used as excipients, but mannitol is also a preferred excipient for wet granulation and tableting due to its non-hygroscopicity and inertness. Therefore, the aim of the current study was to investigate the influence of process parameters on critical quality attributes of granules (moisture content, solid state, morphology, size distribution, specific surface area, friability, flowability and hygroscopicity) and tablets (tensile strength and friability) after twin screw granulation of δ-mannitol. The δ-polymorph was selected since a moisture-induced transformation to β-mannitol was observed during batch wet granulation, which exhibited a unique morphology with a large surface area and improved tabletability. A full factorial experimental design was performed, varying screw speed (400-900rpm), granulation temperature (25-40°C), number of kneading elements (6 or 12) and liquid-to-solid (L/S) ratio, on the granulation unit of a ConsiGma™-25 line (a continuous powder-to-tablet manufacturing system). After tray drying the granules were milled and tableted. The results showed that the polymorphic transition from δ- to β-mannitol also occurred during twin screw granulation, although the residence time and L/S ratios were much lower in continuous twin screw granulation compared to batch processing. However, the polymorphic transition was not complete in all experiments and depended on the L/S ratio, screw speed and number of kneading elements. Nevertheless all granules exhibited the unique morphology linked to the polymorphic transition and had a superior tabletability compared to granules produced with β-mannitol as starting material. This was attributed to enhanced plastic deformation of the granules manufactured using δ-mannitol as starting material. In addition, it was concluded that mannitol was granulated via a different mechanism than

  4. Stability and repeatability of a continuous twin screw granulation and drying system.

    Science.gov (United States)

    Vercruysse, J; Delaet, U; Van Assche, I; Cappuyns, P; Arata, F; Caporicci, G; De Beer, T; Remon, J P; Vervaet, C

    2013-11-01

    The aim of this study was to investigate the process transfer of a commercially available product from the current batch fluid bed granulation and drying production method to an innovative continuously operating "from powder to tablet" production line using twin screw granulation as an intermediate granulation step. By monitoring process outcomes (torque, water temperature at the granulator jacket inlet, differential pressure over the dryer filters, and temperature mill screen) and granule and tablet quality in function of process time, the stability and repeatability during long production runs were determined. Three consecutive 5h "from powder to tablet" production runs were performed using the ConsiGma™-25 system (GEA Pharma Systems, Collette™, Wommelgem, Belgium). A premix of two active ingredients, powdered cellulose, maize starch, pregelatinized starch, and sodium starch glycolate was granulated with distilled water. After drying and milling (1000 μm and 800 rpm), granules were in-line blended with magnesium stearate and directly compressed using a Modul™ P tablet press (tablet weight: 430 mg, main compression force: 12 kN). Granule (loss on drying, particle size distribution, friability, flow) and tablet (weight uniformity, hardness, thickness, friability, content uniformity, disintegration time, and dissolution) quality was evaluated in function of process time. For each of the logged process outcomes, a stabilization period was needed to reach steady-state conditions. Slightly deviating particle size distribution and friability results for milled granules were observed during start-up due to initial layering of the mill screen. However, no deviating tablet quality was detected in function of process time. For multiple hours, granule and tablet quality was constant in function of process time. Furthermore, process data trends were highly repeatable. Consequently, the ConsiGma™-25 system can be considered as a stable and repeatable system for the

  5. Respiratory Syncytial Virus Induces Host RNA Stress Granules To Facilitate Viral Replication▿

    Science.gov (United States)

    Lindquist, Michael E.; Lifland, Aaron W.; Utley, Thomas J.; Santangelo, Philip J.; Crowe, James E.

    2010-01-01

    Mammalian cell cytoplasmic RNA stress granules are induced during various conditions of stress and are strongly associated with regulation of host mRNA translation. Several viruses induce stress granules during the course of infection, but the exact function of these structures during virus replication is not well understood. In this study, we showed that respiratory syncytial virus (RSV) induced host stress granules in epithelial cells during the course of infection. We also showed that stress granules are distinct from cytoplasmic viral inclusion bodies and that the RNA binding protein HuR, normally found in stress granules, also localized to viral inclusion bodies during infection. Interestingly, we demonstrated that infected cells containing stress granules also contained more RSV protein than infected cells that did not form inclusion bodies. To address the role of stress granule formation in RSV infection, we generated a stable epithelial cell line with reduced expression of the Ras-GAP SH3 domain-binding protein (G3BP) that displayed an inhibited stress granule response. Surprisingly, RSV replication was impaired in these cells compared to its replication in cells with intact G3BP expression. In contrast, knockdown of HuR by RNA interference did not affect stress granule formation or RSV replication. Finally, using RNA probes specific for RSV genomic RNA, we found that viral RNA predominantly localized to viral inclusion bodies but a small percentage also interacted with stress granules during infection. These results suggest that RSV induces a host stress granule response and preferentially replicates in host cells that have committed to a stress response. PMID:20844027

  6. Rosette formation of pig T lymphocytes with sheep erythrocytes.

    Science.gov (United States)

    Escajadillo, C; Binns, R M

    1975-01-01

    The relationship of sheep RBC rosette formation to density of thymus and blood lymphocytes was investigated. Thymocyte density was unimodal and cells of all densities rosetted equally. Blood lymphocyte density was bimodal with most rosette-forming cells in the denser ficoll layers. Papain treatment of SRBC increases rosette formation with blood lymphocytes while apparently maintaining specificity of T cells.

  7. 21 CFR 864.8500 - Lymphocyte separation medium.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lymphocyte separation medium. 864.8500 Section 864.8500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... medium. (a) Identification. A lymphocyte separation medium is a device used to isolate lymphocytes from...

  8. DMPD: Developmental plasticity of lymphocytes. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18472258 Developmental plasticity of lymphocytes. Cobaleda C, Busslinger M. Curr Op...in Immunol. 2008 Apr;20(2):139-48. Epub 2008 May 9. (.png) (.svg) (.html) (.csml) Show Developmental plastic...ity of lymphocytes. PubmedID 18472258 Title Developmental plasticity of lymphocytes. Authors Cobaleda C, Bus

  9. A preliminary pharmacognostical and pharmaceutical assay of Yastimadhu granules

    Directory of Open Access Journals (Sweden)

    Srihari Sheshagiri

    2012-01-01

    Full Text Available Aim: Yastimadhu (Glycyrrhizha glabra Linn. of Fabaceae family is one of the most commonly used herb in various Ayurvedic preparations with its vivid actions on various systems. It is also used as a flavouring agent and taste corrigent in pharmaceutical as well as confectionery industries. In a study conducted to evaluate the role of Yastimadhu in enhancing intellect and memory of school going children, the drug was used in the form of granules so ask to mask the issue of palatability. Pharmacognostical and physico-chemical properties were explored to assess the genuine nature of the raw drug in this new formulation after it underwent the pharmaceutical procedure. Materials and Methods: The present study provides the details of preparation of granules and methods employed in pharmacognostical and physic-chemical qualities. Results: The results obtained revealed that the genuine properties of raw drug did not change even after it underwent the pharmaceutical procedure into a new form which was easily palatable. Conclusion: As the drug possesses multiple actions and qualities, the new form would be of potential benefit to all age group of patients with issue of palatability. This study can also be used as a reference for further quality-control researches.

  10. Enteric coating of granules containing the probiotic Lactobacillus acidophilus

    Directory of Open Access Journals (Sweden)

    Pyar Hassan

    2014-06-01

    Full Text Available In the present study, a capsule formulation composed of enteric coated granules of Lactobacillus acidophilus ATCC 4962 was developed using Eudragit L30D-55 as enteric polymer. Optimization of the capsule formulation was achieved with a maximum viable cell count after 2 h of incubation in acid medium and disintegration time of 1 h in buffer pH 6.8. The amount of Eudragit L30D-55 in the capsules correlated with gastric juice resistance. The best protective qualities against artificial gastric juice were observed when capsules were prepared from granules composed of L. acidophilus, corn starch, lactose monohydrate, polyvinylpyrrolidone and coated with 12.5 % (m/V of Eudragit L30D-55. Capsule formulation of L. acidophilus in edible broth medium suspension serves as a cheap alternative to the expensive freeze-drying procedure for preparing L. acidophilus. In addition, the enteric coating using Eudragit L30D-55 could protect probiotics from the acidic gastric environment and enhance the bioactivity of probiotics along with replacement of pathogenic microbes in human intestine

  11. Mechanisms of ethanol-induced death of cerebellar granule cells.

    Science.gov (United States)

    Luo, Jia

    2012-03-01

    Maternal ethanol exposure during pregnancy may cause fetal alcohol spectrum disorders (FASD). FASD is the leading cause of mental retardation. The most deleterious effect of fetal alcohol exposure is inducing neuroapoptosis in the developing brain. Ethanol-induced loss of neurons in the central nervous system underlies many of the behavioral deficits observed in FASD. The cerebellum is one of the brain areas that are most susceptible to ethanol during development. Ethanol exposure causes a loss of both cerebellar Purkinje cells and granule cells. This review focuses on the toxic effect of ethanol on cerebellar granule cells (CGC) and the underlying mechanisms. Both in vitro and in vivo studies indicate that ethanol induces apoptotic death of CGC. The vulnerability of CGC to ethanol-induced death diminishes over time as neurons mature. Several mechanisms for ethanol-induced apoptosis of CGC have been suggested. These include inhibition of N-methyl-D-aspartate receptors, interference with signaling by neurotrophic factors, induction of oxidative stress, modulation of retinoid acid signaling, disturbance of potassium channel currents, thiamine deficiency, and disruption of translational regulation. Cultures of CGC provide an excellent system to investigate cellular/molecular mechanisms of ethanol-induced neurodegeneration and to evaluate interventional strategies. This review will also discuss the approaches leading to neuroprotection against ethanol-induced neuroapoptosis.

  12. A high temperature granulation process for ecological ash recirculation

    Energy Technology Data Exchange (ETDEWEB)

    Sundqvist, Thomas

    1999-07-01

    This thesis is a summary of three papers dealing with new technologies for facilitating ecological biomass ash recirculation back to forest and farm lands. The present outtake of biomass for paper and energy production may be incompatible with a sustainable forestry. The cycle of nutrients contained in the biomass extracted must be closed by ash recirculation in an environmental compatible way. This implies stabilization of the loose ashes/rest-products to a product with low heavy metal contents, controlled leaching properties and a high spreadability. In the present work, two different techniques were evaluated for the possibilities to separate heavy metals from the nutrient elements by utilizing high process temperatures to vaporize the unwanted metals from the condensed bulk materials. The results indicated that direct in-situ separation in fluidized bed combustion systems is possible, but requires too high process temperatures to be practically attractive. On the other hand, the new proposed high temperature treatment method for granulated raw materials was found to significantly separate As, Cd and Pb, with separation efficiencies exceeding 90 % at optimal operating conditions. In addition, the results indicated that the treatment method could be used to significantly delay and control the leaching characteristics, as well as the content of products of incomplete combustion of the produced granules.

  13. Modifying the properties of finely ground limestone by tumbling granulation

    Science.gov (United States)

    Macho, Oliver; Eckert, Maroš; Tomášová, Barbora; Peciar, Peter; Ščasný, Martin; Fekete, Roman; Peciar, Marián

    2016-06-01

    Calcium carbonate in the form of finely ground limestone is a material that has found its application in a wide range of industries, in the chemical, rubber, agricultural, and paper industries, is used for desulfurization of boilers and other. In civil engineering, ground limestone is used for the production of building materials, plaster and mortar mixtures, as a filler in concrete mixtures, in road construction, and as an essential component of mastic asphalt. This paper deals with examining the modification of the properties of finely ground limestone by the tumbling agglomeration method. It has been shown that the components of concrete with a round grain have a positive effect on the pumping of concrete in comparison with an elongated grain or the rough surface of crushed stone. The experiments will be carried out on a granulation plate using a variety of granulation liquid. The agglomerates and their properties were compared with untreated finely ground limestone, with a focus on detecting changes in compressibility, density and particle size. The output of this paper is a description and graphical representation of the changes in the properties of ground limestone before and after the agglomeration process.

  14. Tribology of swollen starch granule suspensions from maize and potato.

    Science.gov (United States)

    Zhang, Bin; Selway, Nichola; Shelat, Kinnari J; Dhital, Sushil; Stokes, Jason R; Gidley, Michael J

    2017-01-02

    The tribological properties of suspensions of cooked swollen starch granules are characterised for systems based on maize starch and potato starch. These systems are known as granule 'ghosts' due to the release (and removal) of polymer from their structure during cooking. Maize starch ghosts are less swollen than potato starch ghosts, resulting in a higher packing concentration and greater mechanical stability. In a soft-tribological contact, maize ghost suspensions reduce friction compared to the solvent (water), generate bell-shaped tribological profiles characteristic of particle entrainment and show a marked concentration dependence, whereas potato ghost suspensions exhibit lubrication behaviour similar to water. Microscopy analysis of the samples following tribological testing suggests that this is due to the rapid break-up of potato ghosts under the shear and rolling conditions within the tribological contact. A reduction in the small deformation moduli (associated with a weak gel structure) is also observed when the potato ghost suspensions are subjected to steady shear using parallel plate rheometry; both microscopy and particle size analysis show that this is accompanied by the partial shear-induced breakage of ghost particles. This interplay between particle microstructure and the resultant rheological and lubrication dynamics of starch ghost suspensions contributes to an enhanced mechanistic understanding of textural and other functional properties of cooked starches in food and other applications.

  15. Modifying the properties of finely ground limestone by tumbling granulation

    Directory of Open Access Journals (Sweden)

    Macho Oliver

    2016-06-01

    Full Text Available Calcium carbonate in the form of finely ground limestone is a material that has found its application in a wide range of industries, in the chemical, rubber, agricultural, and paper industries, is used for desulfurization of boilers and other. In civil engineering, ground limestone is used for the production of building materials, plaster and mortar mixtures, as a filler in concrete mixtures, in road construction, and as an essential component of mastic asphalt. This paper deals with examining the modification of the properties of finely ground limestone by the tumbling agglomeration method. It has been shown that the components of concrete with a round grain have a positive effect on the pumping of concrete in comparison with an elongated grain or the rough surface of crushed stone. The experiments will be carried out on a granulation plate using a variety of granulation liquid. The agglomerates and their properties were compared with untreated finely ground limestone, with a focus on detecting changes in compressibility, density and particle size. The output of this paper is a description and graphical representation of the changes in the properties of ground limestone before and after the agglomeration process.

  16. Mechanism of phenol adsorption onto electro-activated carbon granules.

    Science.gov (United States)

    Lounici, H; Aioueche, F; Belhocine, D; Drouiche, M; Pauss, A; Mameri, N

    2004-01-01

    The main purpose of this paper is to determine the mechanisms which govern the adsorption of the phenol onto electro-activated carbon granules. This new activation technique allowed an increase of the performance of the adsorbent. Two models were utilised to understand the improvement in the performance of electroactivated carbon granules. The first, a simple external resistance model based on film resistance, gave acceptable predictions, with an error of less than 15%, between the theoretical results and experimental data independent of the activation potential and phenol initial concentration. The second linear model, based on diffusion phenomena, was more representative in describing the experiment than the first model. It was observed that the electro-activation method did not change the mechanism which governs phenol adsorption onto granular carbon. Indeed, the same mathematical model based on diffusion phenomena made it possible to predict with a very low error (less than 5%) the experimental data obtained for the favourable activation potential, without activation potential and with an unfavourable activation potential. The electro-activation technique makes it possible to increase the number of active sites that improve the performance of the electro-activated granular carbon compared with conventional granular activated carbon.

  17. Enhancement of sludge granulation in hydrolytic acidogenesis by denitrification.

    Science.gov (United States)

    Li, Yang; Zhang, Yaobin; Zhao, Zisheng; Sun, Songlan; Quan, Xie; Zhao, Huimin

    2016-04-01

    Acidogenesis is an important pretreatment process for various industrial wastewater treatments. Granular sludge is an efficient form of a microbial community in anaerobic methanogenic reactors, such as upflow anaerobic sludge blanket (UASB), but it is hard to develop in the acidogenic process due to the short hydraulic retention times (HRTs) of acidogenesis. In this study, nitrate was added into an acidogenic reactor as an electron acceptor to enhance electron exchange between acidogenic and denitrifying bacteria to accelerate sludge growth in the acidogenesis process. The results showed that it developed solid and mature granular sludge with a mean size of 410 ± 35 μm over 84 days of operation. Comparatively, the sludge in a no-nitrate acidogenic reactor showed a flocculent appearance with a mean size of 110 ± 18 μm. Analysis of the microbial community indicated that denitrifying bacteria interwoven with propionate-oxidizing bacteria were distributed in the outer granule layer, which provided an ideal shield for susceptible microorganisms inside the granules. This microbial structure was favorable for the development of granular sludge and made the system possible to respond well to shocks in the operation.

  18. Chronic lymphocytic leukemia/small lymphocytic lymphoma presenting as septic arthritis of the shoulder

    Energy Technology Data Exchange (ETDEWEB)

    Donovan, Andrea; Schweitzer, Mark E.; Nomikos, George [NYU Hospital for Joint Diseases, New York, NY (United States); Garcia, Roberto A. [Bellevue Hospital Center, New York, NY (United States)

    2008-11-15

    We report a case of a 53-year-old man presenting with shoulder pain mimicking septic arthritis. Laboratory findings were atypical. Biopsy performed to assess for possible osteomyelitis demonstrated chronic lymphocytic leukemia/small lymphocytic lymphoma. Intra-articular lymphoma is a rare but important consideration in patients with atypical clinical presentation. Imaging alone may be insufficient to render diagnosis as lymphoma can mimic infection, synovial hypertrophic processes, and depositional arthropathy. (orig.)

  19. NEUTROPHIL/LYMPHOCYTE RATIO AND PLATELET/LYMPHOCYTE RATIO IN PATIENTS WITH NSCLC

    OpenAIRE

    Cukic, Vesna

    2016-01-01

    Objective: to compare neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in patients with NSCLC (Non- Small- Cell Lung Cancer): with and without metastases at the time of diagnosis to find out if there is the importance of these cell ratios in the assessment of severity NSCLC. Material and Methods: this is the retrospective analysis of NRL and PRL in patients with NSCLC at the time of the diagnosis of disease before any anti tumor treatment (chemotherapy, radiotherapy, surg...

  20. Lymphocytic colitis: A clue to bacterial etiology

    Institute of Scientific and Technical Information of China (English)

    Thanaa EA Helal; Naglaa S Ahmed; Osama Abo El Fotoh

    2005-01-01

    AIM: To find out the role of bacteria as a possible etiological factor in lymphocytic colitis.METHODS: Twenty patients with histopathological diagnosis of lymphocytic colitis and 10 normal controls were included in this study. Colonoscopic biopsies were obtained from three sites (hepatic and splenic flexures and rectosigmoid region). Each biopsy was divided into two parts. A fresh part was incubated on special cultures for bacterial growth. The other part was used for the preparation of histologic tissue sections that were examined for the presence of bacteria with the help of Giemsa stain.RESULTS: Culture of tissue biopsies revealed bacterial growth in 18 out of 20 patients with lymphocytic colitis mostly Escherichia coli(14/18), which was found in all rectosigmoid specimens (14/14), but only in 8/14 and 6/14 of splenic and hepatic flexure specimens respectively. In two of these cases, E coliwas associated with proteus. Proteus was found only in one case, Klebsiella in two cases, and Staphylococcus aureus in one case. In the control group, only 2 out of 10 controls showed the growth of E coliin their biopsy cultures.Histopathology showed rod-shaped bacilli in the tissue sections of 12 out of 14 cases with positive E coliin their specimen's culture. None of the controls showed these bacteria in histopathological sections.CONCLUSION: This preliminary study reports an association between E coliand lymphocytic colitis, based on histological and culture observations. Serotyping and molecular studies are in process to assess the role of E coliin the pathogenesis of lymphocytic colitis.

  1. Lymphocyte transformation studies in drug hypersensitivity.

    Science.gov (United States)

    Warrington, R J; Tse, K S

    1979-05-05

    In a group of patients with clinically diagnosed drug hypersensitivity the in vitro lymphocyte response to the suspected drug was assessed by the lymphocyte transformation test. The test gave positive results in all 15 patients with penicillin-induced immediate or accelerated allergic reactions and positive immediate skin-test reactivity to the major or the minor antigenic determinant of penicillin, or both, but in only 3 of the 12 patients with delayed-onset maculopapular rashes induced by penicillin, despite positive immediate reactivity to the skin-test reagents.Lymphocyte stimulation greater than five times the control level was demonstrated for five patients with penicillin-induced erythroderma, Stevens-Johnson syndrome or a serum-sickness-like illness, or with methicillin-induced interstitial nephritis, all of whom had negative reactions to the appropriate skin-test reagents. A low level of stimulation was seen in eight other skin-test-negative patients with possible allergic reactions induced by penicillins. However, in all subjects tested the stimulation was significantly greater than the mean for control subjects.For 9 of 11 patients with isoniazid-induced hepatitis or maculopapular rashes, but for only 8 of 31 patients with eruptions induced by a variety of drugs other than penicillins and isoniazid, significant stimulation occurred in the lymphocyte transformation test.It is concluded that the lymphocyte transformation test is useful in the detection of hypersensitivity to the penicillins (although in IgE-mediated reactions skin testing is clearly preferable) and isoniazid but is of limited value in the demonstration of hypersensitivity to other drugs.

  2. Preparation of porcelain tile granulates by more environmentally sustainable processes

    Directory of Open Access Journals (Sweden)

    García-Ten, J.

    2012-04-01

    Full Text Available This study examines the feasibility of manufacturing glazed porcelain tiles with a more environmentally friendly manufacturing process, by reducing water and thermal energy consumption. The process studied in this paper is dry milling in a pendulum mill, with subsequent granulation (in order to obtain a press powder with similar flowability to that of spraydried powders. The different morphology of the new granulate with respect to the standard spray-dried granulate modifies the microstructure of the green compacts and thus, their behaviour and fired tile properties. In order to obtain porcelain tiles with the required properties (water absorption, mechanical strength,… changes have been made in the raw materials mixture and in the processing variables. Finally, porcelain tiles measuring 50x50 cm have been manufactured at industrial scale with the new granulate using a conventional firing cycle, obtaining quality levels identical to those provided by the spray-dried granulate. These results open the possibility of preparing porcelain tile body compositions through a manufacturing process alternative to the standard one, more environmentally friendly and with lower costs.

    En el presente trabajo se ha estudiado la viabilidad de fabricar gres porcelánico esmaltado utilizando un sistema de preparación de la composición del soporte más respetuoso con el medio ambiente, lo que implica una reducción importante de los consumos de agua y de energía térmica. El proceso que se estudia en el presente trabajo es el consistente en la molienda vía seca en molino pendular y en la posterior granulación (para obtener un polvo de prensas con fluidez similar a la de los polvos atomizados. La distinta morfología de los nuevos gránulos obtenidos respecto al polvo atomizado actual, modifica la microestuctura en crudo de las piezas y, con ello, el comportamiento y propiedades finales de las baldosas obtenidas. Por ello, ha sido necesario

  3. Isopentenyl pyrophosphate-activated CD56+ {gamma}{delta} T lymphocytes display potent antitumor activity toward human squamous cell carcinoma.

    Science.gov (United States)

    Alexander, Alan A Z; Maniar, Amudhan; Cummings, Jean-Saville; Hebbeler, Andrew M; Schulze, Dan H; Gastman, Brian R; Pauza, C David; Strome, Scott E; Chapoval, Andrei I

    2008-07-01

    The expression of CD56, a natural killer cell-associated molecule, on alphabeta T lymphocytes correlates with their increased antitumor effector function. CD56 is also expressed on a subset of gammadelta T cells. However, antitumor effector functions of CD56(+) gammadelta T cells are poorly characterized. To investigate the potential effector role of CD56(+) gammadelta T cells in tumor killing, we used isopentenyl pyrophosphate and interleukin-2-expanded gammadelta T cells from peripheral blood mononuclear cells of healthy donors. Thirty to 70% of expanded gammadelta T cells express CD56 on their surface. Interestingly, although both CD56(+) and CD56(-) gammadelta T cells express comparable levels of receptors involved in the regulation of gammadelta T-cell cytotoxicity (e.g., NKG2D and CD94), only CD56(+) gammadelta T lymphocytes are capable of killing squamous cell carcinoma and other solid tumor cell lines. This effect is likely mediated by the enhanced release of cytolytic granules because CD56(+) gammadelta T lymphocytes expressed higher levels of CD107a compared with CD56(-) controls following exposure to tumor cell lines. Lysis of tumor cell lines is blocked by concanamycin A and a combination of anti-gammadelta T-cell receptor + anti-NKG2D monoclonal antibody, suggesting that the lytic activity of CD56(+) gammadelta T cells involves the perforin-granzyme pathway and is mainly gammadelta T-cell receptor/NKG2D dependent. Importantly, CD56-expressing gammadelta T lymphocytes are resistant to Fas ligand and chemically induced apoptosis. Our data indicate that CD56(+) gammadelta T cells are potent antitumor effectors capable of killing squamous cell carcinoma and may play an important therapeutic role in patients with head and neck cancer and other malignancies.

  4. The use of rheology to elucidate the granulation mechanisms of a miscible and immiscible system during continuous twin-screw melt granulation.

    Science.gov (United States)

    Monteyne, Tinne; Heeze, Liza; Mortier, Séverine Thérèse F C; Oldörp, Klaus; Nopens, Ingmar; Remon, Jean-Paul; Vervaet, Chris; De Beer, Thomas

    2016-08-20

    Twin-screw hot melt granulation (TS HMG) is a valuable, but still unexplored alternative to granulate temperature and moisture sensitive drugs in a continuous way. Recently, the material behavior of an immiscible drug-binder blend during TS HMG was unraveled by using a rheometer and differential scanning calorimetry (DSC). Additionally, vibrational spectroscopic techniques proved the link between TS HMG and rheology since equal interactions at molecular level did occur in both processes. This allowed to use a rheometer to gain knowledge of the material behavior during hot melt processing of an immiscible drug-binder blend. However, miscibility of a drug-binder formulation and drug-binder interactions appear to influence the rheological properties and, hence conceivably also the granulation mechanism. The aim of this research was to examine if the TS HMG process of a miscible formulation system is comparable with the mechanism of an immiscible system and to evaluate whether rheology still serves as a useful tool to understand and optimize the hot melt granulation (HMG) process. The executed research (thermal analysis, rheological parameters and spectroscopic data) demonstrated the occurrence of a high and broad tan(δ) curve without a loss peak during the rheological temperature ramp which implies a higher material deformability without movement of the softened single polymer chains. Spectroscopic analysis revealed drug-polymer interactions which constrain the polymer to flow independently. As a result, the binder distribution step, which generally follows the immersion step, was hindered. This insight assisted the understanding of the granule properties. Inhomogeneous granules were produced due to large initial nuclei or adhesion of multiple smaller nuclei. Consequently, a higher granulation temperature was required in order to get the binder more homogeneously distributed within the granules. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Starch granule size strongly determines starch noodle processing and nnodle quality.

    NARCIS (Netherlands)

    Chen Zenghong,; Schols, H.A.; Voragen, A.G.J.

    2003-01-01

    Chemical compositions, physical properties, and suitability for starch noodle making of different granule size fractions from potato and sweet potato starches were studied. The ash content, amylose content, phosphorus content, gel firmness, and freeze-thaw stability of small-size granule fractions

  6. Endobrevin/VAMP-8-dependent dense granule release mediates thrombus formation in vivo.

    Science.gov (United States)

    Graham, Gwenda J; Ren, Qiansheng; Dilks, James R; Blair, Price; Whiteheart, Sidney W; Flaumenhaft, Robert

    2009-07-30

    Individuals whose platelets lack dense or alpha-granules suffer various degrees of abnormal bleeding, implying that granule cargo contributes to hemostasis. Despite these clinical observations, little is known regarding the effects of impaired platelet granule secretion on thrombus formation in vivo. In platelets, SNARE proteins mediate the membrane fusion events required for granule cargo release. Endobrevin/VAMP-8 is the primary vesicle-SNARE (v-SNARE) responsible for efficient release of dense and alpha-granule contents; thus, VAMP-8(-/-) mice are a useful model to evaluate the importance of platelet granule secretion in thrombus formation. Thrombus formation, after laser-induced vascular injury, in these mice is delayed and decreased, but not absent. In contrast, thrombus formation is almost completely abolished in the mouse model of Hermansky-Pudlak syndrome, ruby-eye, which lacks dense granules. Evaluation of aggregation of VAMP-8(-/-) and ruby-eye platelets indicates that defective ADP release is the primary abnormality leading to impaired aggregation. These results demonstrate the importance of dense granule release even in the earliest phases of thrombus formation and validate the distal platelet secretory machinery as a potential target for antiplatelet therapies.

  7. Endobrevin/VAMP-8–dependent dense granule release mediates thrombus formation in vivo

    Science.gov (United States)

    Graham, Gwenda J.; Ren, Qiansheng; Dilks, James R.; Blair, Price; Flaumenhaft, Robert

    2009-01-01

    Individuals whose platelets lack dense or α-granules suffer various degrees of abnormal bleeding, implying that granule cargo contributes to hemostasis. Despite these clinical observations, little is known regarding the effects of impaired platelet granule secretion on thrombus formation in vivo. In platelets, SNARE proteins mediate the membrane fusion events required for granule cargo release. Endobrevin/VAMP-8 is the primary vesicle-SNARE (v-SNARE) responsible for efficient release of dense and α-granule contents; thus, VAMP-8−/− mice are a useful model to evaluate the importance of platelet granule secretion in thrombus formation. Thrombus formation, after laser-induced vascular injury, in these mice is delayed and decreased, but not absent. In contrast, thrombus formation is almost completely abolished in the mouse model of Hermansky-Pudlak syndrome, ruby-eye, which lacks dense granules. Evaluation of aggregation of VAMP-8−/− and ruby-eye platelets indicates that defective ADP release is the primary abnormality leading to impaired aggregation. These results demonstrate the importance of dense granule release even in the earliest phases of thrombus formation and validate the distal platelet secretory machinery as a potential target for antiplatelet therapies. PMID:19395672

  8. Hypoglycemic and anti-hyperglycemic activity of Triphalādi granules in mice

    Directory of Open Access Journals (Sweden)

    Ankush Gunjal

    2016-01-01

    Conclusion: Triphalādi granules have significant hypoglycemic and anti-hyperglycemic activity in mice with minimal effect on BSL below normal range. The studies suggest the potential role of Triphalādi granules as an alternative adjuvant therapy in diabetic individuals for the control of the blood glucose level.

  9. Automatic Method for Identifying Photospheric Bright Points and Granules Observed by Sunrise

    CERN Document Server

    Javaherian, Mohsen; Amiri, Ali; Ziaei, Shervin

    2014-01-01

    In this study, we propose methods for the automatic detection of photospheric features (bright points and granules) from ultra-violet (UV) radiation, using a feature-based classifier. The methods use quiet-Sun observations at 214 nm and 525 nm images taken by Sunrise on 9 June 2009. The function of region growing and mean shift procedure are applied to segment the bright points (BPs) and granules, respectively. Zernike moments of each region are computed. The Zernike moments of BPs, granules, and other features are distinctive enough to be separated using a support vector machine (SVM) classifier. The size distribution of BPs can be fitted with a power-law slope -1.5. The peak value of granule sizes is found to be about 0.5 arcsec^2. The mean value of the filling factor of BPs is 0.01, and for granules it is 0.51. There is a critical scale for granules so that small granules with sizes smaller than 2.5 arcsec^2 cover a wide range of brightness, while the brightness of large granules approaches unity. The mean...

  10. Low temperature fabrication of spherical brushite granules by cement paste emulsion.

    Science.gov (United States)

    Moseke, Claus; Bayer, Christoph; Vorndran, Elke; Barralet, Jake E; Groll, Jürgen; Gbureck, Uwe

    2012-11-01

    Secondary protonated calcium phosphates such as brushite (CaHPO(4)·2H(2)O) or monetite (CaHPO(4)) have a higher resorption potential in bone defects than sintered ceramics, e.g. tricalcium phosphate or hydroxyapatite. However, processing of these phosphates to monolithic blocks or granules is not possible by sintering due to thermal decomposition of protonated phosphates at higher temperatures. In this study a low temperature technique for the preparation of spherical brushite granules in a cement setting reaction is presented. These granules were synthesized by dispersing a calcium phosphate cement paste composed of β-tricalcium phosphate and monocalcium phosphate together with a surfactant to an oil/water emulsion. The reaction products were characterized regarding their size distribution, morphology, and phase composition. Clinically relevant granule sizes ranging from 200 μm to 1 mm were obtained, whereas generally smaller granules were received with higher oil viscosity, increasing temperature or higher powder to liquid ratios of the cement paste. The hardened granules were microporous with a specific surface area of 0.7 m(2)/g and consisted of plate-like brushite (>95 % according to XRD) crystals of 0.5-7 μm size. Furthermore it was shown that the granules may be also used for drug delivery applications. This was demonstrated by adsorption of vancomycin from an aqueous solution, where a load of 1.45-1.88 mg drug per g granules and an almost complete release within 2 h was obtained.

  11. Metatranscriptomics reveals the molecular mechanism of large granule formation in granular anammox reactor

    KAUST Repository

    Bagchi, Samik

    2016-06-20

    Granules enriched with anammox bacteria are essential in enhancing the treatment of ammonia-rich wastewater, but little is known about how anammox bacteria grow and multiply inside granules. Here, we combined metatranscriptomics, quantitative PCR and 16S rRNA gene sequencing to study the changes in community composition, metabolic gene content and gene expression in a granular anammox reactor with the objective of understanding the molecular mechanism of anammox growth and multiplication that led to formation of large granules. Size distribution analysis revealed the spatial distribution of granules in which large granules having higher abundance of anammox bacteria (genus Brocadia) dominated the bottom biomass. Metatranscriptomics analysis detected all the essential transcripts for anammox metabolism. During the later stage of reactor operation, higher expression of ammonia and nitrite transport proteins and key metabolic enzymes mainly in the bottom large granules facilitated anammox bacteria activity. The high activity resulted in higher growth and multiplication of anammox bacteria and expanded the size of the granules. This conceptual model for large granule formation proposed here may assist in the future design of anammox processes for mainstream wastewater treatment.

  12. Discrete element study of granulation in a spout-fluidized bed

    NARCIS (Netherlands)

    Link, J.M.; Godlieb, W.; Deen, N.G.; Kuipers, J.A.M.

    2007-01-01

    In this work a discrete element model (DEM) is presented for the description of the gas–liquid–solid flow in a spout-fluidized bed including all relevant phenomena for the study of granulation. The model is demonstrated for the case of a granulation process in a flat spout-fluidized bed, containing

  13. In vivo Anomalous Diffusion and Weak Ergodicity Breaking of Lipid Granules

    DEFF Research Database (Denmark)

    Jeon, J.-H.; Tejedor, V.; Burov, S.;

    2011-01-01

    Combining extensive single particle tracking microscopy data of endogenous lipid granules in living fission yeast cells with analytical results we show evidence for anomalous diffusion and weak ergodicity breaking. Namely we demonstrate that at short times the granules perform subdiffusion accord...

  14. N-methyl-D-aspartate promotes the survival of cerebellar granule cells in culture

    DEFF Research Database (Denmark)

    Balázs, R; Jørgensen, Ole Steen; Hack, N

    1988-01-01

    Our previous studies on the survival-promoting influence of elevated concentrations of extracellular K+ ([K+]e) on cultured cerebellar granule cells led to the proposal that depolarization in vitro mimics the effect of the earliest afferent inputs received by the granule cells in vivo. This, in t...

  15. Tangzhiqing Granules Alleviate Podocyte Epithelial-Mesenchymal Transition in Kidney of Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Haiyan Xu

    2017-01-01

    Full Text Available This study discussed the effect of Tangzhiqing granules on podocyte epithelial-mesenchymal transition in kidney of diabetic rats. The diabetic rats were divided randomly into five groups: DM group treated with vehicle, Tangzhiqing granules low-dose treatment group, Tangzhiqing granules middle-dose treatment group, and Tangzhiqing granules high-dose treatment group. Eight Wistar rats used as control group were given saline solution. The intervention was all intragastric administration for 8 weeks. At the end of the 8 weeks, biochemical parameters and kidney weight/body weight ratio were measured. The kidney tissues were observed under light microscope and transmission electron microscopy. To search for the underlying mechanism, we examined the epithelial-to-mesenchymal transition (EMT related molecular markers and TGF-β/smad signaling pathway key proteins expression. The results showed that Tangzhiqing granules relieved the structural damage and functional changes of diabetic kidneys. Kidney podocyte EMT related molecular markers nephrin and CD2AP expression were increased, when desmin and α-SMA levels were decreased by Tangzhiqing granules in diabetic rats. Further TGF-β/smad signaling pathway key proteins TGF-β1 and p-smad2/3 levels were decreased in diabetic rats after treatment with Tangzhiqing granules. These findings suggest that Tangzhiqing granules may protect the podocytes of diabetic nephropathy rats via alleviating podocyte EMT and likely activating TGFβ/smad signaling pathway.

  16. Proteome profiling of human neutrophil granule subsets, secretory vesicles, and cell membrane

    DEFF Research Database (Denmark)

    Rørvig, Sara; Østergaard, Ole; Heegaard, Niels Henrik Helweg;

    2013-01-01

    granules, SVs, and plasma membrane has been performed before. Here, we performed subcellular fractionation on freshly isolated human neutrophils by nitrogen cavitation and density centrifugation on a four-layer Percoll gradient. Granule subsets were pooled and subjected to SDS-PAGE, and gel pieces were in...

  17. Metatranscriptomics reveals the molecular mechanism of large granule formation in granular anammox reactor

    Science.gov (United States)

    Bagchi, Samik; Lamendella, Regina; Strutt, Steven; van Loosdrecht, Mark C. M.; Saikaly, Pascal E.

    2016-06-01

    Granules enriched with anammox bacteria are essential in enhancing the treatment of ammonia-rich wastewater, but little is known about how anammox bacteria grow and multiply inside granules. Here, we combined metatranscriptomics, quantitative PCR and 16S rRNA gene sequencing to study the changes in community composition, metabolic gene content and gene expression in a granular anammox reactor with the objective of understanding the molecular mechanism of anammox growth and multiplication that led to formation of large granules. Size distribution analysis revealed the spatial distribution of granules in which large granules having higher abundance of anammox bacteria (genus Brocadia) dominated the bottom biomass. Metatranscriptomics analysis detected all the essential transcripts for anammox metabolism. During the later stage of reactor operation, higher expression of ammonia and nitrite transport proteins and key metabolic enzymes mainly in the bottom large granules facilitated anammox bacteria activity. The high activity resulted in higher growth and multiplication of anammox bacteria and expanded the size of the granules. This conceptual model for large granule formation proposed here may assist in the future design of anammox processes for mainstream wastewater treatment.

  18. Partitioning and Exocytosis of Secretory Granules during Division of PC12 Cells

    Directory of Open Access Journals (Sweden)

    Nickolay Vassilev Bukoreshtliev

    2012-01-01

    Full Text Available The biogenesis, maturation, and exocytosis of secretory granules in interphase cells have been well documented, whereas the distribution and exocytosis of these hormone-storing organelles during cell division have received little attention. By combining ultrastructural analyses and time-lapse microscopy, we here show that, in dividing PC12 cells, the prominent peripheral localization of secretory granules is retained during prophase but clearly reduced during prometaphase, ending up with only few peripherally localized secretory granules in metaphase cells. During anaphase and telophase, secretory granules exhibited a pronounced movement towards the cell midzone and, evidently, their tracks colocalized with spindle microtubules. During cytokinesis, secretory granules were excluded from the midbody and accumulated at the bases of the intercellular bridge. Furthermore, by measuring exocytosis at the single granule level, we showed, that during all stages of cell division, secretory granules were competent for regulated exocytosis. In conclusion, our data shed new light on the complex molecular machinery of secretory granule redistribution during cell division, which facilitates their release from the F-actin-rich cortex and active transport along spindle microtubules.

  19. Multi-species impurity granule injection and mass deposition projections in NSTX-U discharges

    Science.gov (United States)

    Lunsford, R.; Bortolon, A.; Roquemore, A. L.; Mansfield, D. K.; Jaworski, M. A.; Kaita, R.; Maingi, R.; Nagy, A.

    2017-07-01

    By employing a neutral gas shielding (NGS) model to characterize impurity granule injection, the ablation rates for three different species of granule: lithium, boron, and carbon, are determined. Utilizing the duration of ablation events recorded on experiments performed at DIII-D to calibrate the NGS model, we quantify the ablation rate with respect to the plasma density profile. The species-specific granule shielding constant is then used to model granule ablation within NSTX-U discharges. Simulations of 300, 500 and 700 micron diameter granules injected at 50 m s-1 are presented for NSTX-U L-mode type plasmas, as well as H-mode discharges with low natural ELM frequency. Additionally, ablation calculations of 500 micron granules of each species are presented at velocities ranging from 50-150 m s-1. In H-mode discharges these simulations show that the majority of the injected granule is ablated within or just past the edge steep gradient region. At this radial position, the perturbation to the background plasma generated by the ablating granule can lead to conditions advantageous for the rapid triggering of ELM crashes.

  20. Conceptual framework for model-based analysis of residence time distribution in twin-screw granulation.

    Science.gov (United States)

    Kumar, Ashish; Vercruysse, Jurgen; Vanhoorne, Valérie; Toiviainen, Maunu; Panouillot, Pierre-Emmanuel; Juuti, Mikko; Vervaet, Chris; Remon, Jean Paul; Gernaey, Krist V; De Beer, Thomas; Nopens, Ingmar

    2015-04-25

    Twin-screw granulation is a promising continuous alternative for traditional batchwise wet granulation processes. The twin-screw granulator (TSG) screws consist of transport and kneading element modules. Therefore, the granulation to a large extent is governed by the residence time distribution within each module where different granulation rate processes dominate over others. Currently, experimental data is used to determine the residence time distributions. In this study, a conceptual model based on classical chemical engineering methods is proposed to better understand and simulate the residence time distribution in a TSG. The experimental data were compared with the proposed most suitable conceptual model to estimate the parameters of the model and to analyse and predict the effects of changes in number of kneading discs and their stagger angle, screw speed and powder feed rate on residence time. The study established that the kneading block in the screw configuration acts as a plug-flow zone inside the granulator. Furthermore, it was found that a balance between the throughput force and conveying rate is required to obtain a good axial mixing inside the twin-screw granulator. Although the granulation behaviour is different for other excipients, the experimental data collection and modelling methods applied in this study are generic and can be adapted to other excipients.

  1. Investigating the Properties of Granulation in the Red Giants Observed by Kepler

    DEFF Research Database (Denmark)

    Mathur, S.; Hekker, S.; Trampedach, R.;

    2012-01-01

    More than 1000 red giants have been observed by NASA/Kepler mission during a nearly continuous period of ˜ 13 months. The resulting high-frequency resolution (<0.03 μHz) allows us to study the granulation parameters of these stars. The granulation pattern results from the convection motions leadi...

  2. Bone growth response with porous hydroxyapatite granules in a critical sized lapine tibial-defect model

    Indian Academy of Sciences (India)

    Annie John; S Abiraman; H K Varma; T V Kumari; P R Umashankar

    2002-04-01

    This study evaluated the tissue reaction to porous hydroxyapatite (HA) granules in a critical sized tibial-defect of New Zealand white rabbits for a period of 2, 6, 12 and 24 weeks. Physicochemical characterizations of the granules were done using transmission electron microscopy, scanning electron microscopy, X-ray diffraction, and fourier transform infrared spectroscopy to analyse the microstrucutre, composition, phase purity crystallinity and functional groups of HA. Prior to in vivo testing, the HA granules had proved to be biocompatible and cytocompatible en route in vitro studies using L929 mouse fibroblast cells. In the histologic evaluation, as early as 2 weeks, bone ingrowth was observed in the pores and interstices of the granules forming a network of bony trabeculae and over 6, 12 and 24 weeks, it was seen that the granules assisted in bone formation. Fluorochrome multilabels of yellow, red and orange lines showed active sites of bone mineralization in progress in the pores and periphery of the granules. Good osteointegration of the granules with the host bone was observed. There was neither inflammation nor fibreous tissue interposition while resorption of the material was in effect a slow process, since the HA granules still persisted after 24 weeks.

  3. Agglomeration of mesoporous silica by melt and steam granulation. part II: screening of steam granulation process variables using a factorial design.

    Science.gov (United States)

    Vialpando, Monica; Albertini, Beatrice; Passerini, Nadia; Vander Heyden, Yvan; Rombaut, Patrick; Martens, Johan A; Van Den Mooter, Guy

    2013-11-01

    The objectives of this study were to identify the key process parameters during steam granulation of disordered mesoporous silica material Syloid® 244 FP (244) and to compare two different binders: polyvinylpyrrolidone (PVP) K25 and hydroxypropylmethyl cellulose (HPMC). Itraconazole (ITZ) was selected as the model compound for the development of an oral dosage form for enhanced release. Six factors: binder content, steam amount, mixing time, impeller speed, spray pause time, and filler content were investigated using a two-level quarter-fraction factorial design of experiment (DOE) for each binder type. As experimental responses, characteristics correlating to both granules and tablets were selected. Granules prepared from PVP resulted in an overall higher bulk density, granule size, increased flow properties, and better compression and compaction behavior. Although granulation with PVP resulted in the most ITZ to extract from the pores during processing, the premature drug release was less than 5%. The results of the DOE indicate that the risk of extracting the drug from the pores during processing is governed both by the process parameters and the binder properties. Centerpoint replicates of granules prepared with HPMC were highly variable.

  4. The Role of Granule Size on the Kinetics of Electrochemical Reduction of SiO2 Granules in Molten CaCl2

    Science.gov (United States)

    Yang, Xiao; Yasuda, Kouji; Nohira, Toshiyuki; Hagiwara, Rika; Homma, Takayuki

    2016-02-01

    As a fundamental study to develop a new process for producing solar-grade silicon, the effect of granule size on the kinetics of the electrochemical reduction of SiO2 granules in molten CaCl2 was investigated. SiO2 granules with different size ranges were electrolyzed in molten CaCl2 at 1123 K (850 °C). The reduction kinetics was evaluated on the basis of the growth rate of the reduced Si layer and the behavior of the current during electrolysis. The results indicated that finer SiO2 granules are more favorable for a high reduction rate because the contact resistance between the bottom Si plate and the reduced Si particles is small and the diffusion of O2- ions in CaCl2 inside the porous Si shell is easy. Electrolysis using SiO2 granules less than 0.1 mm in size maintained a current density of no less than 0.4 A cm-2 within 20 minutes, indicating that the electrochemical reduction of fine SiO2 granules in molten CaCl2 has the potential of becoming a high-yield production process for solar-grade silicon.

  5. Effects of activated sludge flocs and pellets seeds on aerobic granule properties

    Institute of Scientific and Technical Information of China (English)

    Huacheng Xu; Pinjing He; Guanzhao Wang; Liming Shao

    2011-01-01

    Aerobic granules seeded with activated sludge fiocs and pellets (obtained from activated sludge flocs) were cultivated in two sequencing batch reactors and their characteristics were compared.Compared with granules seeded with activated sludge flocs, those seeded with pellets had shorter start-up time, larger diameter, better chemical oxygen demand removal efficiency, and higher hydrophobicity, suspended solid concentration, and Mg2+ content.The different inocula led the granule surface with different microbial morphologies, but did not result in different distribution patterns of extracellular polymeric substances and cells.The anaerobic bacterium Anoxybacillus sp.was detected in the granules seeded with pellets.These results highlighted the advantage of pellet over activated sludge floc as the seed for aerobic granulation and wastewater treatment.

  6. TRANSFORMATION OF EFFUSION AND FORMATION OF GRANULATION TISSUE IN PATHOLOGIC PROCESS OF OTITIS MEDIA WITH EFFUSION

    Institute of Scientific and Technical Information of China (English)

    韦俊荣; 张青; 张全安

    2003-01-01

    Objective To explore the diversity of stagnant effusions and the pathologic processes leading to granulation tissue formation in otitis media with effusion(OME). Methods Temporal bone slides from 306 ears with OME were studied histopathologically under the light microscope. Results Results of this study revealed a pathologic process in witch the type and the condition of stagnant effusion in the middle ear cleft was a variable in the dynamics of OME progression from an early stage to an advanced stage. The location of granulation tissue and retentive effusion were found to be closely related. Conclusion Early stage granulation tissue formation exhibited a pathologic process in which granulation tissue formation occurred only in areas where effusion had stagnated or was absorbed. The incidence of the retentive effusion and formation of granulation tissue was much higher and the pathologic changes most extensive in the area around the ossicular chain.

  7. [Self-aggregation property of bacterial alginates extracted from aerobic granules].

    Science.gov (United States)

    Lin, Yue-Mei; Wang, Lin

    2008-05-01

    To explore bacterial alginates role in aerobic granules' formation, the alginate was extracted from aerobic granules and identified. Its aggregation property in 50 mg x L(-1) CaCl2 solution was investigated by the atomic force microscopy (AFM). Bacterial alginates amounted to 35.1% +/- 1.9% of granules' dry mass. With the concentration increased from 10 mg x L(-1) to 500 mg x L(-1) in 50 mg x L(-1) CaCl2, the extracted alginates tended to form ordered aggregations, with the shape changed from randomly distributed globules, to rod-like and flower-shaped aggregations, and finally to weblike networks due to their supramolecular self-assembly property. The three dimensional alginate-metal gel is the structural polymer of aerobic granules, and the alginates-Ca2+ gel formation plays an important role in granules' formation and structure stabilization.

  8. Translation and silencing in RNA granules: a tale of sand grains.

    Science.gov (United States)

    Pimentel, Jerónimo; Boccaccio, Graciela L

    2014-01-01

    The transcriptome at the synapse consists of thousands of messengers encoding several cellular functions, including a significant number of receptors and ion channels and associated proteins. The concerted translational regulation of all these molecules contributes to the dynamic control of synaptic strength. Cumulative evidence supports that dendritic RNA granules and mRNA-silencing foci play an important role in translational regulation. Several relevant RBPs - FMRP; FUS/TLS; TDP-43; Staufen; Smaug; Pumilio; CPEB; HuD; ZBP1; and DDX6 among others - form granules that contain dormant mRNAs repressed by multiple pathways. Recent reports indicate that dendritic granules may contain stalled polysomes, and furthermore, active translation may occur in association with RNA granules. Here, we discuss the molecules and pathways involved in this continuum of RNA granules that contain masked mRNAs, mRNAs trapped in inactive polysomes or mRNAs engaged in translation.

  9. Syntaxin clusters assemble reversibly at sites of secretory granules in live cells.

    Science.gov (United States)

    Barg, S; Knowles, M K; Chen, X; Midorikawa, M; Almers, Wolfhard

    2010-11-30

    Syntaxin resides in the plasma membrane, where it helps to catalyze membrane fusion during exocytosis. The protein also forms clusters in cell-free and granule-free plasma-membrane sheets. We imaged the interaction between syntaxin and single secretory granules by two-color total internal reflection microscopy in PC12 cells. Syntaxin-GFP assembled in clusters at sites where single granules had docked at the plasma membrane. Clusters were intermittently present at granule sites, as syntaxin molecules assembled and disassembled in a coordinated fashion. Recruitment to granules required the N-terminal domain of syntaxin, but not the entry of syntaxin into SNARE complexes. Clusters facilitated exocytosis and disassembled once exocytosis was complete. Syntaxin cluster formation defines an intermediate step in exocytosis.

  10. Recovery of amorphous polyhydroxybutyrate granules from Cupriavidus necator cells grown on used cooking oil.

    Science.gov (United States)

    Martino, Lucrezia; Cruz, Madalena V; Scoma, Alberto; Freitas, Filomena; Bertin, Lorenzo; Scandola, Mariastella; Reis, Maria A M

    2014-11-01

    Used cooking oil (UCO) was employed as the sole carbon source for the production of polyhydroxybutyrate (PHB) by cultivation in batch mode of Cupriavidus necator DSM 428. The produced biomass was used for extraction of the PHB granules with a solvent-free approach using sodium dodecyl sulfate (SDS), ethylenediaminetetraacetic acid (EDTA), and the enzyme Alcalase in an aqueous medium. The recovered PHB granules showed a degree of purity higher than 90% and no crystallization (i.e., granules were recovered in their 'native' amorphous state) as demonstrated by wide angle X-ray diffraction (WAXS). Granules were characterized according to their thermal properties and stability by differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Results show that UCO can be used as a renewable resource to produce amorphous PHB granules with excellent properties in a biocompatible manner. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Morphological variations and population density of membrane-coating granules in human gingival sulcular epithelium.

    Science.gov (United States)

    Braun, T B; Ashrafi, S H; Waterhouse, J P

    1990-01-01

    Surgically excised specimens of sulcular wall with minimal inflammatory response as judged by clinical then histological criteria were processed for electron microscopy. The specimens were divided into crestal, middle and cervical areas of the sulcular epithelium. The highest concentration of membrane-coating granules was found in the upper spinous cell layers of sulcular epithelium. The profiles of these granules showed examples of both classical keratinized (lamellated) and non-keratinized (non-lamellated) forms but also other appearances that were not derived from them through differences in the plane of section. The population of granules decreased between the crestal and cervical zones, and the decrease in number was marked for the lamellated granules. This decrease in numbers of membrane-coating granules, together with the wider intercellular spaces, may be the reason why the sulcular epithelium is most permeable in the cervical region.

  12. Cultivation and characters of aerobic granules for pentachlorophenol (PCP) degradation under microaerobic condition

    Institute of Scientific and Technical Information of China (English)

    LAN Hui-xia; CHEN Yuan-cai; CHEN Zhong-hao; CHEN Rong

    2005-01-01

    Cultivation of aerobic granular sludge for pentachlorophenol (PCP) degradation under microaerobic condition ( DO concentration was controlled at 0.2-0.7 mg/L) was studied in this paper. Anaerobic granules were selected as inoculum. The changes of appearance were observed and the variations of SVI, VSS/TSS, PN/PS and the size of sludge were measured during cultivating. The capabilities for degradation of PCP, AOX and CODcr were also studied. Observations on mature granules were carried out by scanning electron microscope, and the results indicated bacillus was dominant on the surface of granules while in the inner of granules both bacillus and coccus were the dominant microorganisms. K, Na, Fe, Ca, Mg, Ni, Co, Mn, Cu and Zn were detected in the granules by element analysis.

  13. Is lymphocytic (hashimoto) thyroiditis associated with suicide?

    Science.gov (United States)

    Cina, Stephen J; Perper, Joshua A

    2009-09-01

    The histologic diagnosis of lymphocytic (Hashimoto) thyroiditis requires lymphocytic inflammation of the thyroid gland in combination with Hourthle cell metaplasia of follicular epithelial cells. Clinically, this autoimmune process has been associated with hypothyroidism and psychiatric conditions including depression. This retrospective study was designed to quantify the incidence and severity of lymphocytic thyroiditis in a series of nonconsecutive suicides compared with a cohort of motor vehicle accident victim controls. Eighty-one suicide victims (61 male, 20 female; age range 13-79 years, average 43) were compared with 88 age and gender matched controls (64 males, 24 females; age range 19-85 years, average 36). The degree of lymphocytic inflammation of the thyroid gland was graded on a scale of 0 to 3 (0 = no inflammation, 1 = mild inflammation, 2-3 moderate-to-marked inflammation with Hourthle cell metaplasia). Slides from each case were reviewed while blinded to the cause and manner of death in each case. Of these 169 total cases, 8 (4.7%) received a score of 3, whereas additional 7 (4.1%) received a grade of 2. Eighty-six percent of all of the cases showed no significant inflammation and recorded a score of 0. Of the 81 suicides, 3 had a score of 3, and 3 had a score of 2 (combined incidence of 7.4%). Within the control group, 5 of 88 cases scored 3 and another 4 scored 2 (combined incidence = 10.2%). Three males and 5 females scored 3 with an age range of 23 to 63 years, average 42. Incidental data tabulated showed that 19% of suicide victims were on psychoactive medications compared with 6% in the motor vehicle accident control group. No one on this study was on thyroid hormone replacement therapy. Depression is strongly linked to suicide and lymphocytic thyroiditis may be a cause of depression. Based on this study, however, the presence of lymphocytic thyroiditis cannot be used as a histologic adjunct to discriminate between suicide and accident in

  14. Formation of tRNA granules in the nucleus of heat-induced human cells

    Energy Technology Data Exchange (ETDEWEB)

    Miyagawa, Ryu [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Department of Biological Science, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8654 (Japan); Mizuno, Rie [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Watanabe, Kazunori, E-mail: watanabe@ric.u-tokyo.ac.jp [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Ijiri, Kenichi [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Department of Biological Science, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8654 (Japan)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer tRNAs are tranlocated into the nucleus in heat-induced HeLa cells. Black-Right-Pointing-Pointer tRNAs form the unique granules in the nucleus. Black-Right-Pointing-Pointer tRNA ganules overlap with nuclear stress granules. -- Abstract: The stress response, which can trigger various physiological phenomena, is important for living organisms. For instance, a number of stress-induced granules such as P-body and stress granule have been identified. These granules are formed in the cytoplasm under stress conditions and are associated with translational inhibition and mRNA decay. In the nucleus, there is a focus named nuclear stress body (nSB) that distinguishes these structures from cytoplasmic stress granules. Many splicing factors and long non-coding RNA species localize in nSBs as a result of stress. Indeed, tRNAs respond to several kinds of stress such as heat, oxidation or starvation. Although nuclear accumulation of tRNAs occurs in starved Saccharomyces cerevisiae, this phenomenon is not found in mammalian cells. We observed that initiator tRNA{sup Met} (Meti) is actively translocated into the nucleus of human cells under heat stress. During this study, we identified unique granules of Meti that overlapped with nSBs. Similarly, elongator tRNA{sup Met} was translocated into the nucleus and formed granules during heat stress. Formation of tRNA granules is closely related to the translocation ratio. Then, all tRNAs may form the specific granules.

  15. Isolation of Egg Yolk Granules as Low-Cholesterol Emulsifying Agent in Mayonnaise.

    Science.gov (United States)

    Motta-Romero, Hollman; Zhang, Zhong; Tien Nguyen, An; Schlegel, Vicki; Zhang, Yue

    2017-07-01

    Egg yolk is an essential ingredient for many food products due to its excellent functional properties such as emulsification. However, the consumers' concern of its cholesterol level has led food industry to seek solutions for its replacement. Utilization of low-fat egg yolk granules as emulsifier can be an alternative strategy. In this study, granules with low cholesterol content were separated from egg yolk by a simple method under easily scalable centrifugal conditions. The egg yolk granules isolated within 0.17 M NaCl solution achieved a 22.5% yield that was similar to that using higher centrifugation speeds and longer time. The yield of egg yolk granules increased from 25% to 32% when the yolk:water ratio was changed from 1:1 to 1:2. Mayonnaise was prepared to evaluate the emulsifying capacity of the egg yolk granules. It was found that egg yolk granules exhibited similar emulsifying activity as that of whole egg yolk, but a better emulsion stabilizing property that is evidenced by the higher viscosity of mayonnaise prepared with the granules. In addition, the viscosities of mayonnaise prepared by spray dried yolk and granules were slightly higher than the liquid counterpart, showing a further improvement by spray drying on the emulsion stabilizing properties. The mechanical spectra of mayonnaise samples by frequency sweep also suggested that granules favored the formation of stronger 3-dimensional arrangements of oil droplets and therefore a more stable emulsion. Results suggest that granules isolated within 0.17 M NaCl solution present best emulsifying properties and can be applied as whole yolk replacer in food emulsions. © 2017 Institute of Food Technologists®.

  16. Altered Morphology of Hippocampal Dentate Granule Cell Presynaptic and Postsynaptic Terminals Following Conditional Deletion of TrkB

    OpenAIRE

    Danzer, Steve C.; Kotloski, Robert J.; Walter, Cynthia; Hughes, Maya; McNamara, James O.

    2008-01-01

    Dentate granule cells play a critical role in the function of the entorhinal-hippocampal circuitry in health and disease. Dentate granule cells are situated to regulate the flow of information into the hippocampus, a structure required for normal learning and memory. Correspondingly, impaired granule cell function leads to memory deficits, and, interestingly, altered granule cell connectivity may contribute to the hyperexcitability of limbic epilepsy. It is important, therefore, to understand...

  17. 芪杞参颗粒对小鼠的细胞免疫和体液免疫功能的影响%The Influence of Qiqishen Granules on the Cellular and Humoral Immune Function

    Institute of Scientific and Technical Information of China (English)

    李宏; 戴学文; 房志仲; 高卫真

    2013-01-01

      目的研究芪杞参颗粒对小鼠的细胞免疫和体液免疫功能的影响。方法6周龄昆明种小鼠分空白对照组、芪杞参颗粒高、中、低剂量组,小鼠腹腔注射鸡红细胞混悬液,观察芪杞参颗粒对小鼠腹腔巨噬细胞吞噬功能的影响;制备绵羊红细胞(SRBC),观察血球凝集程度,测定血清溶血素;以靶细胞(YAC-1细胞)与脾细胞(效应细胞)的反应检测芪杞参颗粒对小鼠自然杀伤(NK)细胞活性的影响;采用淋巴细胞转化法观察芪杞参颗粒对细胞免疫的影响;计算小鼠胸腺质量/体质量及脾脏质量/体质量为脏器系数观察芪杞参颗粒对小鼠脏器的影响。结果与对照组比较,芪杞参颗粒显著增加小鼠腹腔巨噬细胞吞噬功能;对小鼠体液免疫功能有一定的增强作用;可增强小鼠NK细胞活性;对刀豆蛋白(Con)A诱导下的小鼠淋巴细胞转化有增强作用;对脏器系数没有显著的影响。结论芪杞参颗粒具有明显的免疫调节作用,预示其有良好的应用前景。%Objective To study the influence of qiqishen granules on the cellular and humoral immune functions in model mice. Methods Six-week-old mice were divided into control group and qiqishen granule (high, medium and low dose) groups. The suspension of chicken red blood cells was injected into the mouse abdominal cavity. The influence of qiq-ishen granules on the phagocytic function of the macrophages in mouse abdominal cavity was observed. The sheep red blood cells (SRBC) were prepared. The blood corpuscle coagulation was observed, and the serum hemolysin was detected. The ac-tivity of the mouse natural killer (NK) cells were detected by the interaction between the target cell (YAC-1) and spleen cell (the response cell). The influence of qiqishen granules on the cellular immunity was detected by the lymphocyte transforming assay. The influence of qiqishen granules on organ/body weight ratio

  18. Mean dose to lymphocytes during radiotherapy treatments

    Energy Technology Data Exchange (ETDEWEB)

    Brandan, M.E.; Perez-Pastenes, M.A. [Instituto de Fisica (Mexico); Ostrosky-Wegman, P.; Gonsebatt, M.E. [Instituto de Investigaciones Biomedicas (Mexico); Diaz-Perches, R. [Hospital General de Mexico (Mexico)

    1994-10-01

    Using a probabilistic model with parameters from four radiotherapy protocols used in Mexican hospitals for the treatment of cervical cancer, the authors have calculated the distribution of dose to cells in peripheral blood of patients. Values of the mean dose to the lymphocytes during and after a {sup 60}Co treatment are compared to estimates from an in vivo chromosome aberration study performed on five patients. Calculations indicate that the mean dose to the circulating blood is about 2% of the tumor dose, while the mean dose to recirculating lymphocytes may reach up to 7% of the tumor dose. Differences up to a factor of two in the dose to the blood are predicted for different protocols delivering equal tumor doses. The data suggest mean doses higher than the predictions of the model. 10 refs., 3 figs., 2 tabs.

  19. Cell Death Mechanisms Induced by Cytotoxic Lymphocytes

    Institute of Scientific and Technical Information of China (English)

    Ch(a)vez-Gal(a)n L; Arenas-Del Angel MC; Zenteno E; Ch(a)vez R; Lascurain R

    2009-01-01

    One of the functions of the immune system is to recognize and destroy abnormal or infected cells to maintain homeostasis. This is accomplished by cytotoxic lymphocytes. Cytotoxicity is a highly organized multifactor process. Here, we reviewed the apoptosis pathways induced by the two main cytotoxic lymphocyte subsets, natural killer (NK) cells and CD8+T cells. In base to recent experimental evidence, we reviewed NK receptors involved in recognition of target-cell, as well as lytic molecules such as perforin, granzymes-A and -B, and granulysin. In addition, we reviewed the Fas-FasL intercellular linkage mediated pathway, and briefly the cross-linking of tumor necrosis factor (TNF) and TNF receptor pathway. We discussed three models of possible molecular interaction between lyric molecules from effector cytotoxic cells and target-cell membrane to induction of apoptosis.

  20. Bioluminescent assay for human lymphocyte blast transformation.

    Science.gov (United States)

    Bulanova, E G; Budagyan, V M; Romanova, N A; Brovko LYu; Ugarova, N N

    1995-05-01

    One of the basic tests of in vitro evaluation of immune cell functional activity is a proliferative response of lymphocytes on the action of external stimuli such as mitogenic lectines, antigens, etc. We compared two methods used to assess the lymphocyte functional status. (1) [3H]thymidine incorporation and (2) bioluminescence for determination of intracellular ATP in blast cells. Comparison has been done for healthy donors and patients with proven low immunological status. The proposed bioluminescent method for evaluation of the proliferative response was shown to be sensitive enough for diagnostic purposes. This method allows one to process a large number of samples at the same time and correlates highly with the radionuclide test use hazardous radioactive materials.