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Sample records for hard mast production

  1. Long-term monitoring of fleshy fruit and hard mast production and seasonal bird distribution at the Savannah River Site, South Carolina.

    SciTech Connect

    Greenberg, Cathryn, H.; Levey, Douglas J.

    2009-06-15

    A final report of Fruit and hard mast production in five habitat types at SRS with a comparison of fruit consumption by fledgling versus adult birds at SRS and Relative importance of fruit, seeds, and insects in the diets of overwintering birds at SRS.

  2. Bait stations, hard mast, and black bear population growth in Great Smoky Mountains National Park

    USGS Publications Warehouse

    Clark, Joseph D.; van Manen, Frank T.; Pelton, Michael R.

    2005-01-01

    Bait-station surveys are used by wildlife managers as an index to American black bear (Ursus americanus) population abundance, but the relationship is not well established. Hard mast surveys are similarly used to assess annual black bear food availability which may affect mortality and natality rates. We used data collected in Great Smoky Mountains National Park (GSMNP) from 1989 to 2003 to determine whether changes in the bait-station index (ΔBSI) were associated with estimated rates of bear population growth (λ) and whether hard mast production was related to bear visitation to baits. We also evaluated whether hard mast production from previous years was related to λ. Estimates of λ were based on analysis of capture-recapture data with the Pradel temporal symmetry estimator. Using the Akaike's Information Criterion (AIC), our analysis revealed no direct relationship between ΔBSI and λ. A simulation analysis indicated that our data were adequate to detect a relationship had one existed. Model fit was marginally improved when we added total oak mast production of the previous year as an interaction term suggesting that the BSI was confounded with environmental variables. Consequently the utility of the bait-station survey as a population monitoring technique is questionable at the spatial and temporal scales we studied. Mast survey data, however, were valuable covariates of λ. Population growth for a given year was negatively related to oak mast production 4 and 5 years prior. That finding supported our hypothesis that mast failures can trigger reproductive synchrony, which may not be evident from the trapped sample until years later.

  3. New Kepler Data Products At MAST For Stellar Astrophysics

    NASA Astrophysics Data System (ADS)

    Fleming, Scott W.; Shiao, B.; Tseng, S.; Million, C.; Thompson, R.; Seibert, M.; Abney, F.; Donaldson, T.; Dower, T.; Fraquelli, D. A.; Handy, S.; Koekemoer, A. M.; Levay, K.; Matuskey, J.; McLean, B.; Quick, L.; Rogers, A.; Wallace, G.; White, R. L.

    2014-01-01

    The Kepler Mission has collected high-precision, time-series photometry of over 200,000 stars. The reduced lightcurves, target pixel files, and a variety of catalog metadata are already available at MAST. We present new data products and services at MAST that will further aid researchers as Kepler begins its transition to a legacy mission, particularly in the realm of stellar astrophysics. New photometric catalogs to accompany the Kepler targets have arrived at MAST within the past year, and several more will be coming in the relative future. These include the second half of the Kepler INT survey (U,g,r,i,H_alpha; available now), an improved GALEX source catalog (NUV and FUV; available now), PanSTARRS (g,r,i,z; available soon), and WISE (3.4, 4.6, 12, and 22 microns; planned). We expect searches for variability will become one of the most active areas of archive use, so MAST is including a wide range of variability statistics as part of the archive database. In addition to being searchable through database queries and web forms, each Preview page will now include a summary of these variability indices for each of the target's lightcurves within a Quarter. Along with updated NUV and FUV fluxes, a new tool at MAST called gPhoton will allow users to create time-series lightcurves, including animated movies and intensity images, from any set of GALEX photons with arbitrary aperture and bin sizes. We show some examples of the ways GALEX UV lightcurves generated with gPhoton can be used in conjunction with the Kepler data. Finally, MAST has released an initial version of its Data Discovery Portal. This one-stop, interactive web application gives users the ability to search and access data from any of MAST's missions (HST, GALEX, Kepler, FUSE, IUE, JWST, etc.), as well as any data available through the Virtual Observatory. It includes filtering options, access to interactive displays, an accompanying AstroViewer with data footprints on-sky, the ability to upload your own

  4. MAST 1 purchased products--components. Final report

    SciTech Connect

    Brown, R.J.

    1995-10-01

    AlliedSignal Inc., Kansas City Division, the production agency, was provided with funding to acquire purchased product components in support of the MAST (Multi-Application Surety Technology) Program. Implementation efforts, closing procurement status, and proposals for improvements in the procurement process are presented. The intent of this project was to fund the Purchased Product Team`s traditional procurement of components, with significantly reduced flowtime, in accordance with the Qualification Evaluation System, and to exercise the system to the extent possible. When funding was reduced, it became obvious that full implementation of the Qualification Evaluation System could not be achieved due to limited resources.

  5. The relationships between weather, mast production, and the breeding ecology of eastern wild turkeys in South Carolina

    SciTech Connect

    Carlisle, William, D.

    2003-02-26

    Carlisle, W.D. 2003. The relationship between weather, mast production, and the breeding ecology of eastern wild turkeys. MS Thesis. Clemson University, Clemson, South Carolina. 41 pp. From 1998 to 2001, 134 wild turkeys were captured, including 2 recaptures. Hens were fitted with radio transmitters to monitor nesting, brooding and movement activities. Of 37 known nests, including 6 renests, overall nest success was 28%. Causes of nest failure included abandonment, depredation, and fire. Mean clutch size was 11. Mean date of nest initiation was April 9 for first nests and May 14 for renests. Mean annual poult to hen ratios were determined for 1990 to 2000 from a South Carolina Department of Natural Resources roadside survey and ranged from 0.6 to 4.0 poults per hen. Soft mast and hard mast production data were provided by D.J. Levey, Univ. of Florida. Rainfall and temperature data were collected at 12 weather stations on Savannah River Site. Notable correlations were found between hard mast production and jake weight, and June rainfall and poult to hen ratio.

  6. First Results from a Charged Fusion Products Diagnostic at MAST

    NASA Astrophysics Data System (ADS)

    Perez, Ramona V.; Allan, Scott Y.; Boeglin, Werner U.; Cecconello, Marco; McClements, Ken G.; Darrow, Douglass S.; MAST Team

    2013-10-01

    We designed, built and installed in MAST a 4-channel solid-state detector array for the detection of the charged deuterium-deuterium fusion products protons and tritons. The array has been mounted at the end of the reciprocating probe arm in MAST allowing it to sample a range of radial positions. First data have been taken in August 2013. The detector signals have been digitized with a 60 MHz sampling rate and have been continuously recorded during plasma discharges. Protons and tritons were readily identified and counted. The observed count rates showed clear dependence on the neutral beam power and were modulated synchronous with saw-teeth. Comparison with data obtained from the MAST neutron camera and the fission chamber neutron detector is planned. We found that time resolutions as low as at least 1 ms were achievable. The detector performance and first analysis results for various plasma scenarios will be presented. Supported in part by DOE grant DE-SC0001157.

  7. New GALEX UV Data Products At MAST For Stellar Astrophysics

    NASA Astrophysics Data System (ADS)

    Shiao, Bernie; Fleming, S. W.; Million, C.; Seibert, M.; Bianchi, L.; Thompson, R.; Tseng, S.; Adler, W. J.; Hubbard, M.; Levay, K.; Madore, B. F.; Martin, C. D.; Nieto-Santisteban, M. A.; Sahai, R.; Schiminovich, D.; White, R. L.; Wyder, T. K.

    2014-01-01

    The Galaxy Evolution Explorer (GALEX) mission ended in June 2013 after ten years in orbit. Its FUV and NUV microchannel plate detectors were used to conduct a variety of direct imaging and spectroscopic astronomical surveys with various depths and sky coverage, recording individual photon events with a time resolution of five thousandths of a second. Although the mission has ended, MAST is continuing to provide new data products as the mission transitions to a legacy archive. One product is the GCAT (Seibert et al., in prep), a catalog of GALEX sources across the entire GR6 data release that removes duplicate objects found in the GALEX MCAT. The GCAT defines "primary" NUV and FUV fluxes within the AIS and MIS surveys 40 million and 22 million sources, respectively), accounting for tile overlaps, and with visual inspection of every tile to flag artifacts and conduct other quality control checks. Another catalog of unique sources is that of Bianchi et al. (2013). Similar to the GCAT, their catalog produces a list of distinct GALEX sources in both the FUV and NUV from the AIS and MIS surveys, and includes data from GR7 (through the end of 2012). They have also cross-matched their sources with SDSS DR9, GSC-II, PanSTARRS, and 2MASS. We review access options for these catalogs, including updated matches between the GCAT and SDSS / Kepler available at MAST. In addition to these unique GALEX source catalogs, MAST will provide a database and software package that archives each of the ~1.5 trillion photon events detected over the lifetime of the mission. For the first time, users will be able to create calibrated lightcurves, intensity maps, and animated movies from any set of photons selected across any tile, and with specified aperture sizes, coordinates, and time steps. Users can access the data using either a python-based command-line software package, through a web interface at MAST, or (eventually) through CasJobs using direct SQL queries. We present some example

  8. Mast Cells Mediate Acute Kidney Injury through the Production of TNF

    PubMed Central

    Summers, Shaun A.; Chan, Jacky; Gan, Poh-Yi; Dewage, Lakshi; Nozaki, Yuji; Steinmetz, Oliver M.; Nikolic-Paterson, David J.; Kitching, A. Richard

    2011-01-01

    Leukocyte recruitment contributes to acute kidney injury (AKI), but the mechanisms by which leukocytes promote injury are not completely understood. The degranulation of mast cells releases inflammatory molecules, including TNF, but whether these cells participate in the pathogenesis of AKI is unknown. Here, we induced AKI with cisplatin in mast cell-deficient and wild-type mice. Compared with wild-type mice, deficiency of mast cells attenuated renal injury, reduced serum levels of TNF, and reduced recruitment of leukocytes to the inflamed kidney. Mast cell-deficient mice also exhibited significantly lower intrarenal expression of leukocyte chemoattractants. Mast cell-deficient mice reconstituted with mast cells from wild-type mice exhibited similar cisplastin-induced renal damage and serum levels of TNF as wild-type mice. In contrast, mast cell-deficient mice reconstituted with mast cells from TNF-deficient mice continued to demonstrate significant attenuation of cisplatin-induced renal injury. Furthermore, the mast-cell stabilizer sodium chromoglycate also significantly abrogated renal injury in this model of AKI. Taken together, these results suggest that mast cells mediate AKI through the production of TNF. PMID:22021718

  9. Beyond The Prime Directive: The MAST Discovery Portal and High Level Science Products

    NASA Astrophysics Data System (ADS)

    Fleming, Scott W.; Abney, Faith; Donaldson, Tom; Dower, Theresa; Fraquelli, Dorothy A.; Koekemoer, Anton M.; Levay, Karen; Matuskey, Jacob; McLean, Brian; Quick, Lee; Rogers, Anthony; Shiao, Bernie; Thompson, Randy; Tseng, Shui-Ay; Wallace, Geoff; White, Richard L.

    2015-01-01

    The Mikulski Archive for Space Telescopes (MAST) is a NASA-funded archive for a wide range of astronomical missions, primarily supporting space-based UV and optical telescopes. What is less well-known is that MAST provides much more than just a final resting place for primary data products and documentation from these missions. The MAST Discovery Portal is our new search interface that integrates all the missions that MAST supports into a single interface, allowing users to discover (and retrieve) data from other missions that overlap with your targets of interest. In addition to searching MAST, the Portal allows users to search the Virtual Observatory, granting access to data from thousands of collections registered with the VO, including large missions spanning the electromagnetic spectrum (e.g., Chandra, SDSS, Spitzer, 2MASS, WISE). The Portal features table import/export, coordinate-based cross-matching, dynamic chart plotting, and the AstroView sky viewer with footprint overlays. We highlight some of these capabilities with science-driven examples. MAST also accepts High Level Science Products (HLSPs) from the community. These HLSPs are user-generated data products that can be related to a MAST-supported mission. MAST provides a permanent archive for these data with linked references, and integrates it within MAST infrastructure and services. We highlight some of the most recent HLSPs MAST has released, including the HST Frontier Fields, GALEX All-Sky Diffuse Radiation Mapping, a survey of the intergalactic medium with HST-COS, and one of the most complete line lists ever derived for a white dwarf using FUSE AND HST-STIS. These HLSPs generate substantial interest from the community, and are an excellent way to increase visibility and ensure the longevity of your data.

  10. Mast cells inhibit intramacrophage Francisella tularensis replication via contact and secreted products including IL-4

    PubMed Central

    Ketavarapu, Jyothi M.; Rodriguez, Annette R.; Yu, Jieh-Juen; Cong, Yu; Murthy, Ashlesh K.; Forsthuber, Thomas G.; Guentzel, M. Neal; Klose, Karl E.; Berton, Michael T.; Arulanandam, Bernard P.

    2008-01-01

    Francisella tularensis is an intracellular, Gram-negative bacterium that is the causative agent of pulmonary tularemia. The pathogenesis and mechanisms related to innate resistance against F. tularensis are not completely understood. Mast cells are strategically positioned within mucosal tissues, the major interface with the external environment, to initiate innate responses at the site of infection. Mast cell numbers in the cervical lymph nodes and the lungs progressively increased as early as 48 h after intranasal F. tularensis live vaccine strain (LVS) challenge. We established a primary bone marrow-derived mast cell–macrophage coculture system and found that mast cells significantly inhibit F. tularensis LVS uptake and growth within macrophages. Importantly, mice deficient in either mast cells or IL-4 receptor displayed greater susceptibility to the infection when compared with corresponding wild-type animals. Contact-dependent events and secreted products including IL-4 from mast cells, and IL-4 production from other cellular sources, appear to mediate the observed protective effects. These results demonstrate a previously unrecognized role for mast cells and IL-4 and provide a new dimension to our understanding of the innate immune mechanisms involved in controlling intramacrophage Francisella replication. PMID:18591675

  11. FK506 inhibition of histamine release and cytokine production by mast cells and basophils.

    PubMed

    Sengoku, T; Kishi, S; Sakuma, S; Ohkubo, Y; Goto, T

    2000-03-01

    Histamine release and cytokine production by mast cells and basophils are thought to be closely involved in the pathogenesis of allergic diseases. Some reports show that FK506 (tacrolimus hydrate) inhibited histamine release and cytokine production by mast cells and basophils. However, as the effects of FK506 has not been compared with those of clinically used drugs in those reports, the clinical relevancy of FK506 inhibition remained unclear. In this paper, we compared the actions of FK506 with those of steroids or disodium cromoglycate (DSCG) which has been clinically used. FK506 inhibited histamine release by Brown-Norway rat peritoneal mast cells more potently than steroids and especially DSCG. FK506 also inhibited histamine release by a mast rat basophilic leukemia (RBL)-1 cell line and human peripheral blood basophils, whereas steroids failed to inhibit histamine release by human basophils. FK506 as well as steroids inhibited TNF-alpha and IL-4 production by RBL-1 cells. FK506 was therefore more effective than steroids and DSCG in inhibiting histamine release, and it also had the ability of inhibiting cytokine production by mast cells as steroids do. We concluded that FK506 might regulate allergic diseases via these actions, judging from the viewpoint of clinical relevancy. PMID:10685002

  12. Airway epithelial cells activate Th2 cytokine production in mast cells via IL-1 and thymic stromal lymphopoietin

    PubMed Central

    Nagarkar, Deepti R.; Poposki, Julie A.; Comeau, Michael R.; Biyasheva, Assel; Avila, Pedro C.; Schleimer, Robert P.; Kato, Atsushi

    2012-01-01

    Background Airway epithelial cells are important regulators of innate and adaptive immunity. Although mast cells are known to play a central role in manifestations of allergic inflammation and are found in the epithelium in Th2-related diseases, their role is incompletely understood. Objectives The objective of this study was to investigate the role of airway epithelial cells in production of Th2 cytokines in mast cells. Methods Normal human bronchial epithelial cells (NHBE) were stimulated with TNF, IL-4, IFN-γ, IL -17A and dsRNA alone or in combination. Human mast cells were stimulated with epithelial cell-derived supernatants, or co-cultured with NHBE. Th2 cytokine responses were blocked with neutralizing antibodies. Results Supernatants from IL-4 and dsRNA stimulated NHBE significantly enhanced Th2 cytokine production from mast cells. The combination of IL-4 and dsRNA itself or supernatants from NHBE stimulated with other cytokines did not activate mast cells, suggesting that mast cell responses were induced by epithelial cell factors that were only induced by IL-4 and dsRNA. Epithelial supernatant-dependent Th2 cytokine production in mast cells was suppressed by anti-IL-1 and anti-TSLP, and was enhanced by anti-IL-1Ra. Similar results were observed in co-culture experiments. Finally, we found dsRNA-dependent production of IL-1, TSLP, and IL-1Ra in NHBE was regulated by Th cytokines, and their ratio in NHBE correlated with Th2 cytokine production in mast cells. Conclusions Pathogens producing dsRNA, such as respiratory viral infections, may amplify local Th2 inflammation in asthmatics via the production of TSLP and IL-1 by epithelial cells and subsequent activation of Th2 cytokine production by mast cells in the airways. PMID:22633328

  13. Regulatory T cells enhance mast cell production of IL-6 via surface-bound TGF-β.

    PubMed

    Ganeshan, Kirthana; Bryce, Paul J

    2012-01-15

    Mast cell degranulation is a hallmark of allergic reactions, but mast cells can also produce many cytokines that modulate immunity. Recently, CD25(+) regulatory T cells (Tregs) have been shown to inhibit mast cell degranulation and anaphylaxis, but their influence on cytokine production remained unknown. In this study, we show that, rather than inhibit, Tregs actually enhance mast cell production of IL-6. We demonstrate that, whereas inhibition of degranulation was OX40/OX40 ligand dependent, enhancement of IL-6 was due to TGF-β. Interestingly, our data demonstrate that the Treg-derived TGF-β was surface-bound, because the interaction was contact dependent, and no TGF-β was detectable in the supernatant. Soluble TGF-β1 alone was sufficient to enhance mast cell IL-6 production, and these supernatants were sufficient to promote Th17 skewing, but those from Treg-mast cell cultures were not, supporting this being surface-bound TGF-β from the Tregs. Interestingly, the augmentation of IL-6 production occurred basally or in response to innate stimuli (LPS or peptidoglycan), adaptive stimuli (IgE cross-linking by specific Ag), and cytokine activation (IL-33). We demonstrate that TGF-β led to enhanced transcription and de novo synthesis of IL-6 upon activation without affecting IL-6 storage or mRNA stability. In vivo, the adoptive transfer of Tregs inhibited mast cell-dependent anaphylaxis in a model of food allergy but promoted intestinal IL-6 and IL-17 production. Consequently, our findings establish that Tregs can exert divergent influences upon mast cells, inhibiting degranulation via OX40/OX40 ligand interactions while promoting IL-6 via TGF-β. PMID:22156492

  14. Human Lung Mast Cell Products Regulate Airway Smooth Muscle CXCL10 Levels

    PubMed Central

    Alkhouri, H.; Cha, V.; Tong, K.; Moir, L. M.; Armour, C. L.; Hughes, J. M.

    2014-01-01

    In asthma, the airway smooth muscle (ASM) produces CXCL10 which may attract CXCR3+ mast/T cells to it. Our aim was to investigate the effects of mast cell products on ASM cell CXCL10 production. ASM cells from people with and without asthma were stimulated with IL-1β, TNF-α, and/or IFNγ and treated with histamine (1–100 μM) ± chlorpheniramine (H1R antagonist; 1 μM) or ranitidine (H2R antagonist; 50 μM) or tryptase (1 nM) ± leupeptin (serine protease inhibitor; 50 μM), heat-inactivated tryptase, or vehicle for 4 h or 24 h. Human lung mast cells (MC) were isolated and activated with IgE/anti-IgE and supernatants were collected after 2 h or 24 h. The supernatants were added to ASM cells for 48 h and ASM cell CXCL10 production detected using ELISA (protein) and real-time PCR (mRNA). Histamine reduced IL-1β/TNF-α-induced CXCL10 protein, but not mRNA, levels independent of H1 and H2 receptor activation, whereas tryptase and MC 2 h supernatants reduced all cytokine-induced CXCL10. Tryptase also reduced CXCL10 levels in a cell-free system. Leupeptin inhibited the effects of tryptase and MC 2 h supernatants. MC 24 h supernatants contained TNF-α and amplified IFNγ-induced ASM cell CXCL10 production. This is the first evidence that MC can regulate ASM cell CXCL10 production and its degradation. Thus MC may regulate airway myositis in asthma. PMID:24648846

  15. Hard Exclusive Meson Production at COMPASS

    NASA Astrophysics Data System (ADS)

    Ter Wolbeek, Johannes

    2016-02-01

    The concept of Generalized Parton Distributions (GPDs) combines two-dimensional spatial information given by form factors, with longitudinal momentum information from Parton Distribution Functions. GPDs provide comprehensive description of the nucleon structure involving a wealth of new information. For instance, according to Ji’s sum rule, the GPDs H and E enable access to the total angular momenta of quarks, antiquarks and gluons. While H can be approached using measurements of electroproduction cross sections, asymmetry measurements in hard exclusive meson production off transversely polarized targets can help to constrain the GPD E and chiral-odd GPDs. In 2007 and 2010 the COMPASS experiment at CERN collected data by scattering a 160GeV/c muon beam off a transversely polarized NH3 target. Exclusive vector-meson production μ + p → μ‧ + p + V with a ρ0 or ω meson in the final state is studied and five single-spin and three double-spin azimuthal asymmetries are measured.

  16. Notch signaling enhances FcεRI-mediated cytokine production by mast cells through direct and indirect mechanisms.

    PubMed

    Nakano, Nobuhiro; Nishiyama, Chiharu; Yagita, Hideo; Hara, Mutsuko; Motomura, Yasutaka; Kubo, Masato; Okumura, Ko; Ogawa, Hideoki

    2015-05-01

    Th2-type cytokines and TNF-α secreted by activated mast cells upon cross-linking of FcεRI contribute to the development and maintenance of Th2 immunity to parasites and allergens. We have previously shown that cytokine secretion by mouse mast cells is enhanced by signaling through Notch receptors. In this study, we investigated the molecular mechanisms by which Notch signaling enhances mast cell cytokine production induced by FcεRI cross-linking. FcεRI-mediated production of cytokines, particularly IL-4, was significantly enhanced in mouse bone marrow-derived mast cells by priming with Notch ligands. Western blot analysis showed that Notch signaling augmented and prolonged FcεRI-mediated phosphorylation of MAPKs, mainly JNK and p38 MAPK, through suppression of the expression of SHIP-1, a master negative regulator of FcεRI signaling, resulting in the enhanced production of multiple cytokines. The enhancing effect of Notch ligand priming on multiple cytokine production was abolished by knockdown of Notch2, but not Notch1, and FcεRI-mediated production of multiple cytokines was enhanced by retroviral transduction with the intracellular domain of Notch2. However, only IL-4 production was enhanced by both Notch1 and Notch2. The enhancing effect of Notch signaling on IL-4 production was lost in bone marrow-derived mast cells from mice lacking conserved noncoding sequence 2, which is located at the distal 3' element of the Il4 gene locus and contains Notch effector RBP-J binding sites. These results indicate that Notch2 signaling indirectly enhances the FcεRI-mediated production of multiple cytokines, and both Notch1 and Notch2 signaling directly enhances IL-4 production through the noncoding sequence 2 enhancer of the Il4 gene. PMID:25821223

  17. Lipid droplets in activated mast cells - a significant source of triglyceride-derived arachidonic acid for eicosanoid production.

    PubMed

    Dichlberger, Andrea; Schlager, Stefanie; Kovanen, Petri T; Schneider, Wolfgang J

    2016-08-15

    Mast cells are potent effectors of immune reactions and key players in various inflammatory diseases such as atherosclerosis, asthma, and rheumatoid arthritis. The cellular defense response of mast cells represents a unique and powerful system, where external signals can trigger cell activation resulting in a stimulus-specific and highly coordinated release of a plethora of bioactive mediators. The arsenal of mediators encompasses preformed molecules stored in cytoplasmic secretory granules, as well as newly synthesized proteinaceous and lipid mediators. The release of mediators occurs in strict chronological order and requires proper coordination between the endomembrane system and various enzymatic machineries. For the generation of lipid mediators, cytoplasmic lipid droplets have been shown to function as a major intracellular pool of arachidonic acid, the precursor for eicosanoid biosynthesis. Recent studies have revealed that not only phospholipids in mast cell membranes, but also triglycerides in mast cell lipid droplets are a substrate source for eicosanoid formation. The present review summarizes current knowledge about mast cell lipid droplet biology, and discusses expansions and challenges of traditional mechanistic models for eicosanoid production. PMID:26164793

  18. Macelignan inhibits histamine release and inflammatory mediator production in activated rat basophilic leukemia mast cells.

    PubMed

    Han, Young Sun; Kim, Myung-Suk; Hwang, Jae-Kwan

    2012-10-01

    Type I allergy is characterized by the release of granule-associated mediators, lipid-derived substances, cytokines, and chemokines by activated mast cells. To evaluate the anti-allergic effects of macelignan isolated from Myristica fragrans Houtt., we determined its ability to inhibit calcium (Ca(2+)) influx, degranulation, and inflammatory mediator production in RBL-2 H3 cells stimulated with A23187 and phorbol 12-myristate 13-acetate. Macelignan inhibited Ca(2+) influx and the secretion of β-hexosaminidase, histamine, prostaglandin E(2), and leukotriene C(4); decreased mRNA levels of cyclooxygenase-2, 5-lipoxygenase, interleukin-4 (IL-4), IL-13, and tumor necrosis factor-α; and attenuated phosphorylation of Akt and the mitogen-activated protein kinases extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase. These results indicate the potential of macelignan as a type I allergy treatment. PMID:22729280

  19. Simultaneous detection of histamine release and lactate production in rat mast cells induced by compound 48/80 using sup 1 H NMR

    SciTech Connect

    Yoshizaki, Kazuo; Arizono, Naoki )

    1991-04-01

    {sup 1}H NMR spectroscopy was used to evaluate histamine release and lactate production in intact mast cells isolated from rats. The resonance lines of the aromatic histamine protons in mast cells, detected by the selective spin-excitation technique, were broader and located in a lower magnetic field than those in free histamine solution. When exocytosis of mast-cell granules was induced by compound 48/80, free histamine appeared, with a corresponding decrease in the amount of histamine in the mast cells; the lactate signal was also detected in the spectrum. On the addition of compound 48/ 80, there was a further release of histamine from mast cells, accompanied by further production of lactate. This result indicates that the mechanisms which induce the exocytosis of granules, and/or the events following exocytosis, activate glycolysis.

  20. Acidic environment augments FcεRI-mediated production of IL-6 and IL-13 in mast cells

    SciTech Connect

    Kamide, Yosuke; Ishizuka, Tamotsu; Tobo, Masayuki; Tsurumaki, Hiroaki; Aoki, Haruka; Mogi, Chihiro; Nakakura, Takashi; Yatomi, Masakiyo; Ono, Akihiro; Koga, Yasuhiko; Sato, Koichi; Hisada, Takeshi; Dobashi, Kunio; Yamada, Masanobu; Okajima, Fumikazu

    2015-08-28

    Although blood pH is maintained in a narrow range of around pH 7.4 in living organisms, inflammatory loci are characterized by acidic conditions. Mast cells tend to reside close to the surface of the body in areas such as the mucosa and skin where they may be exposed to exogenous acids, and they play an important role in immune responses. However, little is known about the effects of extracellular acidification on the functions of mast cell. Here, we found that extracellular acidification increased the dinitrophenyl-conjugated human serum albumin (DNP-HSA)-induced production of interleukin (IL)-6 and IL-13 in MC/9 cells or bone marrow-derived mouse mast cells sensitized with anti-DNP IgE. Extracellular acidification also inhibited migration of MC/9 cells toward DNP-HSA. In addition, acidic pH stimulated antigen-induced activation of p38 mitogen-activated protein kinase (MAPK) and protein kinase B (Akt). These findings suggest that extracellular acidification augmented antigen/IgE-induced and FcεRI-mediated production of IL-6 and IL-13 in mast cells, and that this was associated with the enhancement of p38 MAPK and Akt activation. - Highlights: • Antigen-induced IL-6 and IL-13 production was augmented by acidic pH in mast cells. • Acidic pH-induced actions were associated with activation of p38 MAPK and Akt. • Inhibition of p38 MAPK and Akt attenuated cytokine responses to acidic pH. • Acidic pH effects are not attributable to actions of known proton-sensing GPCRs.

  1. Mast cells enhance T cell activation: Importance of mast cell-derived TNF

    NASA Astrophysics Data System (ADS)

    Nakae, Susumu; Suto, Hajime; Kakurai, Maki; Sedgwick, Jonathon D.; Tsai, Mindy; Galli, Stephen J.

    2005-05-01

    Mast cells are not only important effector cells in immediate hypersensitivity reactions and immune responses to pathogens but also can contribute to T cell-mediated disorders. However, the mechanisms by which mast cells might influence T cells in such settings are not fully understood. We find that mast cells can enhance proliferation and cytokine production in multiple T cell subsets. Mast cell-dependent enhancement of T cell activation can be promoted by FcRI-dependent mast cell activation, TNF production by both mast cells and T cells, and mast cell-T cell contact. However, at high concentrations of cells, mast cells can promote T cell activation independent of IgE or TNF. Finally, mast cells also can promote T cell activation by means of soluble factors. These findings identify multiple mechanisms by which mast cells can influence T cell proliferation and cytokine production. allergy | asthma | autoimmunity | cytokines | immune response

  2. Activated mast cells release biological activities able to support eosinophil production from mouse hemopoietic precursors.

    PubMed

    Oskéritzian, C; Milon, G; Braquet, P; Mencia-Huerta, J M; David, B

    1996-02-01

    Mouse bone marrow cells cultured for 6 days in the presence of recombinant murine IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) were used as a source of precursors responsive to eosinopoietins. They were further cultured for 7 days in the presence of either a combination of recombinant cytokines or supernatants of bone marrow-derived mast cells (BMMC) activated with either immunological or nonimmunological stimuli. Cytosmears of collected cells were analyzed for eosinophil contents and allowed to demonstrate that supernatants of passively sensitized BMMC support both total cell proliferation and eosinophil production, after various periods of incubation with monoclonal rat anti-mouse IgE antibodies (the 6HD5 mAbs). In contrast, a stimulation with 100 ng/ml dinitrophenylated bovine serum albumin (DNP-BSA) did not generate supernatants displaying such bioactivities. Low doses of methyl ester of L (but not D)-leucine or of the calcium ionophore A23187 also allowed the release of eosinopoietic bioactivities. In addition, immunoreactive IL-5, GM-CSF, and IL-3 were quantified in the BMMC supernatants. These results demonstrate that activated BMMC are able to effect eosinophil production. PMID:8603429

  3. Expression, localization, and regulation of NOS in human mast cell lines: effects on leukotriene production.

    PubMed

    Gilchrist, Mark; McCauley, Scott D; Befus, A Dean

    2004-07-15

    Nitric oxide (NO) is a potent radical produced by nitric oxide synthase (NOS) and has pleiotrophic activities in health and disease. As mast cells (MCs) play a central role in both homeostasis and pathology, we investigated NOS expression and NO production in human MC populations. Endothelial NOS (eNOS) was ubiquitously expressed in both human MC lines and skin-derived MCs, while neuronal NOS (nNOS) was variably expressed in the MC populations studied. The inducible (iNOS) isoform was not detected in human MCs. Both growth factor-independent (HMC-1) and -dependent (LAD 2) MC lines showed predominant nuclear eNOS protein localization, with weaker cytoplasmic expression. nNOS showed exclusive cytoplasmic localization in HMC-1. Activation with Ca(2+) ionophore (A23187) or IgE-anti-IgE induced eNOS phosphorylation and translocation to the nucleus and nuclear and cytoplasmic NO formation. eNOS colocalizes with the leukotriene (LT)-initiating enzyme 5-lipoxygenase (5-LO) in the MC nucleus. The NO donor, S-nitrosoglutathione (SNOG), inhibited, whereas the NOS inhibitor, N(G)-nitro-l-arginine methyl ester (L-NAME), potentiated LT release in a dose-dependent manner. Thus, human MC lines produce NO in both cytoplasmic and nuclear compartments, and endogenously produced NO can regulate LT production by MCs. PMID:15044250

  4. Adipose triglyceride lipase regulates eicosanoid production in activated human mast cells.

    PubMed

    Dichlberger, Andrea; Schlager, Stefanie; Maaninka, Katariina; Schneider, Wolfgang J; Kovanen, Petri T

    2014-12-01

    Human mast cells (MCs) contain TG-rich cytoplasmic lipid droplets (LDs) with high arachidonic acid (AA) content. Here, we investigated the functional role of adipose TG lipase (ATGL) in TG hydrolysis and the ensuing release of AA as substrate for eicosanoid generation by activated human primary MCs in culture. Silencing of ATGL in MCs by siRNAs induced the accumulation of neutral lipids in LDs. IgE-dependent activation of MCs triggered the secretion of the two major eicosanoids, prostaglandin D2 (PGD2) and leukotriene C4 (LTC4). The immediate release of PGD2 from the activated MCs was solely dependent on cyclooxygenase (COX) 1, while during the delayed phase of lipid mediator production, the inducible COX-2 also contributed to its release. Importantly, when ATGL-silenced MCs were activated, the secretion of both PGD2 and LTC4 was significantly reduced. Interestingly, the inhibitory effect on the release of LTC4 was even more pronounced in ATGL-silenced MCs than in cytosolic phospholipase A2-silenced MCs. These data show that ATGL hydrolyzes AA-containing TGs present in human MC LDs and define ATGL as a novel regulator of the substrate availability of AA for eicosanoid generation upon MC activation. PMID:25114172

  5. Adipose triglyceride lipase regulates eicosanoid production in activated human mast cells

    PubMed Central

    Dichlberger, Andrea; Schlager, Stefanie; Maaninka, Katariina; Schneider, Wolfgang J.; Kovanen, Petri T.

    2014-01-01

    Human mast cells (MCs) contain TG-rich cytoplasmic lipid droplets (LDs) with high arachidonic acid (AA) content. Here, we investigated the functional role of adipose TG lipase (ATGL) in TG hydrolysis and the ensuing release of AA as substrate for eicosanoid generation by activated human primary MCs in culture. Silencing of ATGL in MCs by siRNAs induced the accumulation of neutral lipids in LDs. IgE-dependent activation of MCs triggered the secretion of the two major eicosanoids, prostaglandin D2 (PGD2) and leukotriene C4 (LTC4). The immediate release of PGD2 from the activated MCs was solely dependent on cyclooxygenase (COX) 1, while during the delayed phase of lipid mediator production, the inducible COX-2 also contributed to its release. Importantly, when ATGL-silenced MCs were activated, the secretion of both PGD2 and LTC4 was significantly reduced. Interestingly, the inhibitory effect on the release of LTC4 was even more pronounced in ATGL-silenced MCs than in cytosolic phospholipase A2-silenced MCs. These data show that ATGL hydrolyzes AA-containing TGs present in human MC LDs and define ATGL as a novel regulator of the substrate availability of AA for eicosanoid generation upon MC activation. PMID:25114172

  6. Interspeaker Variability in Hard Palate Morphology and Vowel Production

    ERIC Educational Resources Information Center

    Lammert, Adam; Proctor, Michael; Narayanan, Shrikanth

    2013-01-01

    Purpose: Differences in vocal tract morphology have the potential to explain interspeaker variability in speech production. The potential acoustic impact of hard palate shape was examined in simulation, in addition to the interplay among morphology, articulation, and acoustics in real vowel production data. Method: High-front vowel production from…

  7. Informativeness Improvement of Hardness Test Methods for Metal Product Assessment

    NASA Astrophysics Data System (ADS)

    Osipov, S.; Podshivalov, I.; Osipov, O.; Zhantybaev, A.

    2016-06-01

    The paper presents a combination of theoretical suggestions, results, and observations allowing to improve the informativeness of hardness testing process in solving problems of metal product assessment while in operation. The hardness value of metal surface obtained by a single measurement is considered to be random. Various measures of location and scattering of the random variable were experimentally estimated for a number of test samples using the correlation analysis, and their close interaction was studied. It was stated that in metal assessment, the main informative characteristics of hardness testing process are its average value and mean-square deviation for measures of location and scattering, respectively.

  8. Inhibitory effects of geranium essential oil and its major component, citronellol, on degranulation and cytokine production by mast cells.

    PubMed

    Kobayashi, Yuko; Sato, Harumi; Yorita, Mika; Nakayama, Hiroto; Miyazato, Hironari; Sugimoto, Keiichiro; Jippo, Tomoko

    2016-06-01

    We investigated the effects of geranium essential oil (GEO) on anaphylaxis. GEO can exert antioxidant and anti-inflammatory effects, but its roles in allergic reactions are incompletely understood. Here, we used mouse cells to show that GEO inhibited the degranulation of cultured mast cells (CMCs). Citronellol is the major component of GEO and inhibited CMC degranulation. The l-enantiomer of citronellol more effectively suppressed CMC degranulation than did d-citronellol. We also examined whether citronellol could inhibit the immunoglobulin (Ig) E-induced production of tumor necrosis factor (TNF)-α. Treatment with various concentrations of citronellol before CMC activation with IgE significantly inhibited the induction of TNF-α in a dose-dependent manner. Mechanistically, citronellol suppressed the phosphorylation of mitogen-activated protein kinase (ERK), which is critical for ERK activation and the production of inflammatory cytokines in mast cells. These findings suggest that citronellol may represent a candidate compound for the effective treatment of allergic diseases. PMID:26927807

  9. Mast cells and COPD.

    PubMed

    Mortaz, Esmaeil; Folkerts, Gert; Redegeld, Frank

    2011-08-01

    The pathogenesis of chronic obstructive pulmonary disease (COPD) is based on the innate and adaptive inflammatory immune response to the inhalation of toxic particles and gases. Although tobacco smoking is the primary cause of this inhalation injury, many other environmental and occupational exposures contribute to the pathology of COPD. The immune inflammatory changes associated with COPD are linked to a tissue-repair and -remodeling process that increases mucus production and causes emphysematous destruction of the gas-exchanging surface of the lung. The common form of emphysema observed in smokers begins in the respiratory bronchioles near the thickened and narrowed small bronchioles that become the major site of obstruction in COPD. The inflamed airways of COPD patients contain several inflammatory cells including neutrophils, macrophages, T lymphocytes, and dendritic cells. The relative contribution of mast cells to airway injury and remodeling is not well documented. In this review, an overview is given on the possible role of mast cells and their mediators in the pathogenesis of COPD. Activation of mast cells and mast cell signaling in response to exposure to cigarette smoke is further discussed. PMID:21463700

  10. MAPK-dependent regulation of IL-1- and β-adrenoreceptor-induced inflammatory cytokine production from mast cells: Implications for the stress response

    PubMed Central

    Chi, David S; Fitzgerald, S Matthew; Pitts, Shannon; Cantor, Karen; King, Ellis; Lee, Steven A; Huang, Shau-Ku; Krishnaswamy, Guha

    2004-01-01

    Background Catecholamines, such as epinephrine, are elaborated in stress responses, and mediate vasoconstriction to cause elevation in systemic vascular resistance and blood pressure. Our previous study has shown that IL-1 can induce mast cells to produce proinflammatory cytokines which are involved in atherogenesis. The aim of this study was to determine the effects of epinephrine on IL-1-induced proatherogenic cytokine production from mast cells. Results Two ml of HMC-1 (0.75 × 106 cells/ml) were cultured with epinephrine (1 × 10-5 M) in the presence or absence of IL-1β (10 ng/ml) for 24 hrs. HMC-1 cultured alone produced none to trace amounts of IL-6, IL-8, and IL-13. IL-1β significantly induced production of these cytokines in HMC-1, while epinephrine alone did not. However, IL-6, IL-8, and IL-13 production induced by IL-1β were significantly enhanced by addition of epinephrine. The enhancing effect appears to involve NF-κB and p38 MAPK pathways. Flow cytometry showed the presence of β1 and β2 adrenoreceptors on resting mast cells. The enhancing effect of proatherogenic cytokine production by epinephrine was down regulated by the β1 and β2 adrenoceptor antagonist, propranolol, but not by the β1 adrenoceptor antagonist, atenolol, suggesting the effect involved β2 adrenoceptors. The enhancing effect of epinephrine on proatherogenic cytokine production was also down regulated by the immunosuppressive drug, dexamethasone. Conclusions These results not only confirm that an acute phase cytokine, IL-1β, regulates mast cell function, but also show that epinephrine up regulates the IL-1β induction of proatherogenic cytokines in mast cells. These data provide a novel role for epinephrine, a stress hormone, in inflammation and atherogenesis. PMID:15383152

  11. Stimulus-Selective Regulation of Human Mast Cell Gene Expression, Degranulation and Leukotriene Production by Fluticasone and Salmeterol

    PubMed Central

    Catalli, Adriana; Karpov, Victor; Erdos, Levente E.; Tancowny, Brian P.; Schleimer, Robert P.; Kulka, Marianna

    2014-01-01

    Despite the fact that glucocorticoids and long acting beta agonists are effective treatments for asthma, their effects on human mast cells (MC) appear to be modest. Although MC are one of the major effector cells in the underlying inflammatory reactions associated with asthma, their regulation by these drugs is not yet fully understood and, in some cases, controversial. Using a human immortalized MC line (LAD2), we studied the effects of fluticasone propionate (FP) and salmeterol (SM), on the release of early and late phase mediators. LAD2 cells were pretreated with FP (100 nM), SM (1 µM), alone and in combination, at various incubation times and subsequently stimulated with agonists substance P, C3a and IgE/anti-IgE. Degranulation was measured by the release of β-hexosaminidase. Cytokine and chemokine expression were measured using quantitative PCR, ELISA and cytometric bead array (CBA) assays. The combination of FP and SM synergistically inhibited degranulation of MC stimulated with substance P (33% inhibition compared to control, n = 3, P<.05). Degranulation was inhibited by FP alone, but not SM, when MC were stimulated with C3a (48% inhibition, n = 3, P<.05). As previously reported, FP and SM did not inhibit degranulation when MC were stimulated with IgE/anti-IgE. FP and SM in combination inhibited substance P-induced release of tumor necrosis factor (TNF), CCL2, and CXCL8 (98%, 99% and 92% inhibition, respectively, n = 4, P<.05). Fluticasone and salmeterol synergistically inhibited mediator production by human MC stimulated with the neuropeptide substance P. This synergistic effect on mast cell signaling may be relevant to the therapeutic benefit of combination therapy in asthma. PMID:24819142

  12. Stimulus-selective regulation of human mast cell gene expression, degranulation and leukotriene production by fluticasone and salmeterol.

    PubMed

    Catalli, Adriana; Karpov, Victor; Erdos, Levente E; Tancowny, Brian P; Schleimer, Robert P; Kulka, Marianna

    2014-01-01

    Despite the fact that glucocorticoids and long acting beta agonists are effective treatments for asthma, their effects on human mast cells (MC) appear to be modest. Although MC are one of the major effector cells in the underlying inflammatory reactions associated with asthma, their regulation by these drugs is not yet fully understood and, in some cases, controversial. Using a human immortalized MC line (LAD2), we studied the effects of fluticasone propionate (FP) and salmeterol (SM), on the release of early and late phase mediators. LAD2 cells were pretreated with FP (100 nM), SM (1 µM), alone and in combination, at various incubation times and subsequently stimulated with agonists substance P, C3a and IgE/anti-IgE. Degranulation was measured by the release of β-hexosaminidase. Cytokine and chemokine expression were measured using quantitative PCR, ELISA and cytometric bead array (CBA) assays. The combination of FP and SM synergistically inhibited degranulation of MC stimulated with substance P (33% inhibition compared to control, n = 3, P<.05). Degranulation was inhibited by FP alone, but not SM, when MC were stimulated with C3a (48% inhibition, n = 3, P<.05). As previously reported, FP and SM did not inhibit degranulation when MC were stimulated with IgE/anti-IgE. FP and SM in combination inhibited substance P-induced release of tumor necrosis factor (TNF), CCL2, and CXCL8 (98%, 99% and 92% inhibition, respectively, n = 4, P<.05). Fluticasone and salmeterol synergistically inhibited mediator production by human MC stimulated with the neuropeptide substance P. This synergistic effect on mast cell signaling may be relevant to the therapeutic benefit of combination therapy in asthma. PMID:24819142

  13. MAST in the Context of VO Activities

    NASA Astrophysics Data System (ADS)

    Kamp, I.; Thompson, R.; Conti, A.; Fraquelli, D.; Kimball, T.; Levay, K.; Shiao, B.; Smith, M.; Somerville, R.; White, R. L.

    2005-12-01

    In the past year, the Multimission Archive at the Space Telescope Science Institute (MAST) has taken major steps in making MAST's holdings available using VO-defined protocols and standards, and in implementing VO-based tools. For example, MAST has implemented the Simple Cone Search protocol, and all MAST mission searches may be returned in the VOTable format, allowing other archives to use MAST data for their VO applications. We have made many of our popular High Level Science Products available through Simple Image Access Protocol (SIAP), and are implementing the VO Simple Spectral Access Protocol (SSAP). The cross correlation of VizieR catalogs with MAST missions is now possible and illustrates the integration of VO services into MAST. The user can easily display the results from searches within MAST using the plotting tool VOPlot. MAST also participates in the NVO registry service. Thus, the user can harvest MAST holdings simultaneously with data from many other surveys and missions through the VO DataScope Data Inventory Service.

  14. The Importance of Mast Cells in Dermal Scarring

    PubMed Central

    Wilgus, Traci A.; Wulff, Brian C.

    2014-01-01

    Significance: Mast cells are resident inflammatory cells present in high numbers in the skin. They are one of the first cell types to respond to damage and they do so by quickly releasing a variety of preformed mediators that are stored within mast cell granules. Mast cells are not only active early on, where they help induce inflammation, but they also stimulate the proliferation of several important cell types and influence the production and remodeling of collagen. Recent Advances: Recent studies have highlighted the importance of mast cells in determining the amount of scar tissue that forms as a result of the repair process. Mast cells are found in low numbers and in a less activated state in scarless wounds, whereas high numbers of activated mast cells are associated with scarring and fibrosis. Furthermore, animals that lack mast cells or have been treated with degranulation inhibitors or drugs that block the activity of mast cell proteases have been shown to heal with reduced scar tissue. Critical Issues: Despite evidence suggesting that mast cells regulate scar tissue development, the entire range of mast cell activities during wound repair and scar formation has not been completely characterized. In addition, the potential therapeutic benefits of targeting mast cells clinically have yet to be fully explored. Future Directions: More studies are needed to determine whether inhibiting mast cell activation and blocking the function of mast cell mediators are viable options to prevent or reduce the appearance of scars. PMID:24757590

  15. Mosla dianthera inhibits mast cell-mediated allergic reactions through the inhibition of histamine release and inflammatory cytokine production

    SciTech Connect

    Lee, Dong-Hee; Kim, Sang-Hyun . E-mail: shkim72@knu.ac.kr; Eun, Jae-Soon; Shin, Tae-Yong . E-mail: tyshin@woosuk.ac.kr

    2006-11-01

    In this study, we investigated the effect of the aqueous extract of Mosla dianthera (Maxim.) (AEMD) on the mast cell-mediated allergy model and studied the possible mechanism of action. Mast cell-mediated allergic disease is involved in many diseases such as asthma, sinusitis and rheumatoid arthritis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. AEMD inhibited compound 48/80-induced systemic reactions in mice. AEMD decreased immunoglobulin E-mediated local allergic reactions, passive cutaneous anaphylaxis. AEMD attenuated intracellular calcium level and release of histamine from rat peritoneal mast cells activated by compound 48/80. Furthermore, AEMD attenuated the phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-stimulated TNF-{alpha}, IL-8 and IL-6 secretion in human mast cells. The inhibitory effect of AEMD on the pro-inflammatory cytokines was nuclear factor-{kappa}B (NF-{kappa}B) dependent. AEMD decreased PMA and A23187-induced degradation of I{kappa}B{alpha} and nuclear translocation of NF-{kappa}B. Our findings provide evidence that AEMD inhibits mast cell-derived immediate-type allergic reactions and involvement of pro-inflammatory cytokines and NF-{kappa}B in these effects.

  16. T helper 2 and regulatory T-cell cytokine production by mast cells: a key factor in the pathogenesis of IgG4-related disease.

    PubMed

    Takeuchi, Mai; Sato, Yasuharu; Ohno, Kyotaro; Tanaka, Satoshi; Takata, Katsuyoshi; Gion, Yuka; Orita, Yorihisa; Ito, Toshihiro; Tachibana, Tomoyasu; Yoshino, Tadashi

    2014-08-01

    IgG4-related disease is a systemic disorder with unique clinicopathological features and uncertain etiological features and is frequently related to allergic disease. T helper 2 and regulatory T-cell cytokines have been reported to be upregulated in the affected tissues; thus, the production of these cytokines by T helper 2 and regulatory T cells has been suggested as an important factor in the pathogenesis of IgG4-related disease. However, it is not yet clear which cells produce these cytokines in IgG4-related disease, and some aspects of the disorder cannot be completely explained by T-cell-related processes. To address this, we analyzed paraffin-embedded sections of tissues from nine cases of IgG4-related submandibular gland disease, five cases of submandibular sialolithiasis, and six cases of normal submandibular gland in order to identify potential key players in the pathogenesis of IgG4-related disease. Real-time polymerase chain reaction analysis confirmed the significant upregulation of interleukin (IL)4, IL10, and transforming growth factor beta 1 (TGFβ1) in IgG4-related disease. Interestingly, immunohistochemical studies indicated the presence of mast cells expressing these cytokines in diseased tissues. In addition, dual immunofluorescence assays identified cells that were double-positive for each cytokine and for KIT, which is expressed by mast cells. In contrast, the distribution of T cells did not correlate with cytokine distribution in affected tissues. We also found that the mast cells were strongly positive for IgE. This observation supports the hypothesis that mast cells are involved in IgG4-related disease, as mast cells are known to be closely related to allergic reactions and are activated in the presence of elevated non-specific IgE levels. In conclusion, our results indicate that mast cells produce T helper 2 and regulatory T-cell cytokines in tissues affected by IgG4-related disease and possibly have an important role in disease

  17. Houttuynia cordata Thunb inhibits the production of pro-inflammatory cytokines through inhibition of the NFκB signaling pathway in HMC-1 human mast cells.

    PubMed

    Lee, Hee Joe; Seo, Hye-Sook; Kim, Gyung-Jun; Jeon, Chan Yong; Park, Jong Hyeong; Jang, Bo-Hyoung; Park, Sun-Ju; Shin, Yong-Cheol; Ko, Seong-Gyu

    2013-09-01

    Houttuynia cordata Thunb (HCT) is widely used in oriental medicine as a remedy for inflammation. However, at present there is no explanation for the mechanism by which HCT affects the production of inflammatory cytokines. The current study aimed to determine the effect of an essence extracted from HCT on mast cell-mediated inflammatory responses. Inflammatory cytokine production induced by phorbol myristate acetate (PMA) plus a calcium ionophore, A23187, was measured in the human mast cell line, HMC-1, incubated with various concentrations of HCT. TNF-α, IL-6 and IL-8 secreted protein levels were measured using an ELISA assay. TNF-α, IL-6 and IL-8 mRNA levels were measured using RT-PCR analysis. Nuclear and cytoplasmic proteins were examined by western blot analysis. The NF-κB promoter activity was examined by luciferase assay. It was observed that HCT inhibited PMA plus A23187-induced TNF-α and IL-6 secretion and reduced the mRNA levels of TNF-α, IL-6 and IL-8. It was also noted that HCT suppressed the induction of NF-κB activity, inhibited nuclear translocation of NF-κB and blocked the phosphorylation of IκBα in stimulated HMC-1 cells. It was concluded that HCT is an inhibitor of NF-κB and cytokines blocking mast cell-mediated inflammatory responses. These results indicate that HCT may be used for the treatment of mast cell-derived allergic inflammatory diseases. PMID:23846481

  18. Genitourinary mast cells and survival.

    PubMed

    Theoharides, Theoharis C; Stewart, Julia M

    2015-10-01

    Mast cells (MCs) are ubiquitous in the body, but they have historically been associated with allergies, and most recently with regulation of immunity and inflammation. However, it remains a puzzle why so many MCs are located in the diencephalon, which regulates emotions and in the genitourinary tract, including the bladder, prostate, penis, vagina and uterus that hardly ever get allergic reactions. A number of papers have reported that MCs have estrogen, gonadotropin and corticotropin-releasing hormone (CRH) receptors. Moreover, animal experiments have shown that diencephalic MCs increase in number during courting in doves. We had reported that allergic stimulation of nasal MCs leads to hypothalamic-pituitary adrenal (HPA) activation. Interestingly, anecdotal information indicates that female patients with mastocytosis or mast cell activation syndrome may have increased libido. Preliminary evidence also suggests that MCs may have olfactory receptors. MCs may, therefore, have been retained phylogenetically not only to "smell danger", but to promote survival and procreation. PMID:26813805

  19. Genitourinary mast cells and survival

    PubMed Central

    Stewart, Julia M.

    2015-01-01

    Mast cells (MCs) are ubiquitous in the body, but they have historically been associated with allergies, and most recently with regulation of immunity and inflammation. However, it remains a puzzle why so many MCs are located in the diencephalon, which regulates emotions and in the genitourinary tract, including the bladder, prostate, penis, vagina and uterus that hardly ever get allergic reactions. A number of papers have reported that MCs have estrogen, gonadotropin and corticotropin-releasing hormone (CRH) receptors. Moreover, animal experiments have shown that diencephalic MCs increase in number during courting in doves. We had reported that allergic stimulation of nasal MCs leads to hypothalamic-pituitary adrenal (HPA) activation. Interestingly, anecdotal information indicates that female patients with mastocytosis or mast cell activation syndrome may have increased libido. Preliminary evidence also suggests that MCs may have olfactory receptors. MCs may, therefore, have been retained phylogenetically not only to “smell danger”, but to promote survival and procreation. PMID:26813805

  20. Effects of cigarette smoke on degranulation and NO production by mast cells and epithelial cells

    PubMed Central

    Wei, Xiu M; Kim, Henry S; Kumar, Rakesh K; Heywood, Gavin J; Hunt, John E; McNeil, H Patrick; Thomas, Paul S

    2005-01-01

    Exhaled nitric oxide (eNO) is decreased by cigarette smoking. The hypothesis that oxides of nitrogen (NOX) in cigarette smoke solution (CSS) may exert a negative feedback mechanism upon NO release from epithelial (AEC, A549, and NHTBE) and basophilic cells (RBL-2H3) was tested in vitro. CSS inhibited both NO production and degranulation (measured as release of beta-hexosaminidase) in a dose-dependent manner from RBL-2H3 cells. Inhibition of NO production by CSS in AEC, A549, and NHTBE cells was also dose-dependent. In addition, CSS decreased expression of NOS mRNA and protein expression. The addition of NO inhibitors and scavengers did not, however, reverse the effects of CSS, nor did a NO donor (SNP) or nicotine mimic CSS. N-acetyl-cysteine, partially reversed the inhibition of beta-hexosaminidase release suggesting CSS may act via oxidative free radicals. Thus, some of the inhibitory effects of CSS appear to be via oxidative free radicals rather than a NOX -related negative feedback. PMID:16168067

  1. Mast cells and inflammation.

    PubMed

    Theoharides, Theoharis C; Alysandratos, Konstantinos-Dionysios; Angelidou, Asimenia; Delivanis, Danae-Anastasia; Sismanopoulos, Nikolaos; Zhang, Bodi; Asadi, Shahrzad; Vasiadi, Magdalini; Weng, Zuyi; Miniati, Alexandra; Kalogeromitros, Dimitrios

    2012-01-01

    Mast cells are well known for their role in allergic and anaphylactic reactions, as well as their involvement in acquired and innate immunity. Increasing evidence now implicates mast cells in inflammatory diseases where they are activated by non-allergic triggers, such as neuropeptides and cytokines, often exerting synergistic effects as in the case of IL-33 and neurotensin. Mast cells can also release pro-inflammatory mediators selectively without degranulation. In particular, IL-1 induces selective release of IL-6, while corticotropin-releasing hormone secreted under stress induces the release of vascular endothelial growth factor. Many inflammatory diseases involve mast cells in cross-talk with T cells, such as atopic dermatitis, psoriasis and multiple sclerosis, which all worsen by stress. How mast cell differential responses are regulated is still unresolved. Preliminary evidence suggests that mitochondrial function and dynamics control mast cell degranulation, but not selective release. Recent findings also indicate that mast cells have immunomodulatory properties. Understanding selective release of mediators could explain how mast cells participate in numerous diverse biologic processes, and how they exert both immunostimulatory and immunosuppressive actions. Unraveling selective mast cell secretion could also help develop unique mast cell inhibitors with novel therapeutic applications. This article is part of a Special Issue entitled: Mast cells in inflammation. PMID:21185371

  2. Overview of MAST results

    NASA Astrophysics Data System (ADS)

    Chapman, I. T.; Adamek, J.; Akers, R. J.; Allan, S.; Appel, L.; Asunta, O.; Barnes, M.; Ben Ayed, N.; Bigelow, T.; Boeglin, W.; Bradley, J.; Brünner, J.; Cahyna, P.; Carr, M.; Caughman, J.; Cecconello, M.; Challis, C.; Chapman, S.; Chorley, J.; Colyer, G.; Conway, N.; Cooper, W. A.; Cox, M.; Crocker, N.; Crowley, B.; Cunningham, G.; Danilov, A.; Darrow, D.; Dendy, R.; Diallo, A.; Dickinson, D.; Diem, S.; Dorland, W.; Dudson, B.; Dunai, D.; Easy, L.; Elmore, S.; Field, A.; Fishpool, G.; Fox, M.; Fredrickson, E.; Freethy, S.; Garzotti, L.; Ghim, Y. C.; Gibson, K.; Graves, J.; Gurl, C.; Guttenfelder, W.; Ham, C.; Harrison, J.; Harting, D.; Havlickova, E.; Hawke, J.; Hawkes, N.; Hender, T.; Henderson, S.; Highcock, E.; Hillesheim, J.; Hnat, B.; Holgate, J.; Horacek, J.; Howard, J.; Huang, B.; Imada, K.; Jones, O.; Kaye, S.; Keeling, D.; Kirk, A.; Klimek, I.; Kocan, M.; Leggate, H.; Lilley, M.; Lipschultz, B.; Lisgo, S.; Liu, Y. Q.; Lloyd, B.; Lomanowski, B.; Lupelli, I.; Maddison, G.; Mailloux, J.; Martin, R.; McArdle, G.; McClements, K.; McMillan, B.; Meakins, A.; Meyer, H.; Michael, C.; Militello, F.; Milnes, J.; Morris, A. W.; Motojima, G.; Muir, D.; Nardon, E.; Naulin, V.; Naylor, G.; Nielsen, A.; O'Brien, M.; O'Gorman, T.; Ono, Y.; Oliver, H.; Pamela, S.; Pangione, L.; Parra, F.; Patel, A.; Peebles, W.; Peng, M.; Perez, R.; Pinches, S.; Piron, L.; Podesta, M.; Price, M.; Reinke, M.; Ren, Y.; Roach, C.; Robinson, J.; Romanelli, M.; Rozhansky, V.; Saarelma, S.; Sangaroon, S.; Saveliev, A.; Scannell, R.; Schekochihin, A.; Sharapov, S.; Sharples, R.; Shevchenko, V.; Silburn, S.; Simpson, J.; Storrs, J.; Takase, Y.; Tanabe, H.; Tanaka, H.; Taylor, D.; Taylor, G.; Thomas, D.; Thomas-Davies, N.; Thornton, A.; Turnyanskiy, M.; Valovic, M.; Vann, R.; Walkden, N.; Wilson, H.; Wyk, L. V.; Yamada, T.; Zoletnik, S.; MAST; MAST Upgrade Teams

    2015-10-01

    in solenoid-free start-up. A new proton detector has characterized escaping fusion products. Langmuir probes and a high-speed camera suggest filaments play a role in particle transport in the private flux region whilst coherence imaging has measured scrape-off layer (SOL) flows. BOUT++ simulations show that fluxes due to filaments are strongly dependent on resistivity and magnetic geometry of the SOL, with higher radial fluxes at higher resistivity. Finally, MAST Upgrade is due to begin operation in 2016 to support ITER preparation and importantly to operate with a Super-X divertor to test extended leg concepts for particle and power exhaust.

  3. Mast cells and inflammation

    PubMed Central

    Theoharides, Theoharis C.; Alysandratos, Konstantinos-Dionysios; Angelidou, Asimenia; Delivanis, Danae-Anastasia; Sismanopoulos, Nikolaos; Zhang, Bodi; Asadi, Shahrzad; Vasiadi, Magdalini; Weng, Zuyi; Miniati, Alexandra; Kalogeromitros, Dimitrios

    2012-01-01

    Mast cells are well known for their role in allergic and anaphylactic reactions, as well as their involvement in acquired and innate immunity. Increasing evidence now implicates mast cells in inflammatory diseases where they are activated by non-allergic triggers, such as neuropeptides and cytokines, often exerting synergistic effects as in the case of IL-33. Mast cells can also release pro-inflammatory mediators selectively without degranulation. In particular, IL-1 induces selective release of IL-6, while corticotropin-releasing hormone secreted under stress induces the release of vascular endothelial growth factor. Many inflammatory diseases involve mast cells in cross-talk with T cells, such as atopic dermatitis, psoriasis and multiple sclerosis, which all worsen by stress. How mast cell differential responses are regulated is still unresolved. Preliminary evidence suggests that mitochondrial function and dynamics control mast cell degranulation, but not selective release. Recent findings also indicate that mast cells have immunomodulatory properties. Understanding selective release of mediators could explain how mast cells participate in numerous diverse biologic processes, and how they exert both immunostimulatory and immunosuppressive actions. Unraveling selective mast cell secretion could also help develop unique mast cell inhibitors with novel therapeutic applications. PMID:21185371

  4. 46. BASE OF UMBILICAL MAST FROM UMBILICAL MAST TRENCH. ERECTION ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    46. BASE OF UMBILICAL MAST FROM UMBILICAL MAST TRENCH. ERECTION AND RETRACTION CYLINDERS BETWEEN MAST AND TRENCH WALL. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  5. Mast cells contribute to peripheral tolerance and attenuate autoimmune vasculitis.

    PubMed

    Gan, Poh-Yi; Summers, Shaun A; Ooi, Joshua D; O'Sullivan, Kim M; Tan, Diana S Y; Muljadi, Ruth C M; Odobasic, Dragana; Kitching, A Richard; Holdsworth, Stephen R

    2012-12-01

    Mast cells contribute to the modulation of the immune response, but their role in autoimmune renal disease is not well understood. Here, we induced autoimmunity resulting in focal necrotizing GN by immunizing wild-type or mast cell-deficient (Kit(W-sh/W-sh)) mice with myeloperoxidase. Mast cell-deficient mice exhibited more antimyeloperoxidase CD4+ T cells, enhanced dermal delayed-type hypersensitivity responses to myeloperoxidase, and more severe focal necrotizing GN. Furthermore, the lymph nodes draining the sites of immunization had fewer Tregs and reduced production of IL-10 in mice lacking mast cells. Reconstituting these mice with mast cells significantly increased the numbers of Tregs in the lymph nodes and attenuated both autoimmunity and severity of disease. After immunization with myeloperoxidase, mast cells migrated from the skin to the lymph nodes to contact Tregs. In an ex vivo assay, mast cells enhanced Treg suppression through IL-10. Reconstitution of mast cell-deficient mice with IL-10-deficient mast cells led to enhanced autoimmunity to myeloperoxidase and greater disease severity compared with reconstitution with IL-10-intact mast cells. Taken together, these studies establish a role for mast cells in mediating peripheral tolerance to myeloperoxidase, protecting them from the development of focal necrotizing GN in ANCA-associated vasculitis. PMID:23138486

  6. Mast Cell Stabilization Ameliorates Autoimmune Anti-Myeloperoxidase Glomerulonephritis.

    PubMed

    Gan, Poh-Yi; O'Sullivan, Kim M; Ooi, Joshua D; Alikhan, Maliha A; Odobasic, Dragana; Summers, Shaun A; Kitching, A Richard; Holdsworth, Stephen R

    2016-05-01

    Observations in experimental murine myeloperoxidase (MPO)-ANCA-associated vasculitis (AAV) show mast cells degranulate, thus enhancing injury as well as producing immunomodulatory IL-10. Here we report that, compared with biopsy specimens from control patients, renal biopsy specimens from 44 patients with acute AAV had more mast cells in the interstitium, which correlated with the severity of tubulointerstitial injury. Furthermore, most of the mast cells were degranulated and spindle-shaped in patients with acute AAV, indicating an activated phenotype. We hypothesized that the mast cell stabilizer disodium cromoglycate would attenuate mast cell degranulation without affecting IL-10 production. We induced anti-MPO GN by immunizing mice with MPO and a low dose of anti-glomerular basement membrane antibody. When administered before or after induction of MPO autoimmunity in these mice, disodium cromoglycate attenuated mast cell degranulation, development of autoimmunity, and development of GN, without diminishing IL-10 production. In contrast, administration of disodium cromoglycate to mast cell-deficient mice had no effect on the development of MPO autoimmunity or GN. MPO-specific CD4(+) effector T cell proliferation was enhanced by co-culture with mast cells, but in the presence of disodium cromoglycate, proliferation was inhibited and IL-10 production was enhanced. These results indicate that disodium cromoglycate blocks injurious mast cell degranulation specifically without affecting the immunomodulatory role of these cells. Thus as a therapeutic, disodium cromoglycate may substantially enhance the regulatory role of mast cells in MPO-AAV. PMID:26374606

  7. Method for Developing Descriptions of Hard-to-Price Products: Results of the Telecommunications Product Study

    SciTech Connect

    Conrad, F.; Tonn, B.

    1999-05-01

    This report presents the results of a study to test a new method for developing descriptions of hard-to-price products. The Bureau of Labor Statistics (BLS) is responsible for collecting data to estimate price indices such as the Consumers Price Index (BLS) is responsible for collecting data to estimate price indices such as the Consumers Price Index (CPI). BLS accomplishes this task by sending field staff to places of business to price actual products. The field staff are given product checklists to help them determine whether products found today are comparable to products priced the previous month. Prices for non-comparable products are not included in the current month's price index calculations. A serious problem facing BLS is developing product checklists for dynamic product areas, new industries, and the service sector. It is difficult to keep checklists up-to-date and quite often simply to develop checklists for service industry products. Some people estimates that upwards of 50 % of US economic activity is not accounted for in the CPI

  8. Resveratrol Suppresses Cytokine Production Linked to FcεRI-MAPK Activation in IgE-Antigen Complex-Exposed Basophilic Mast Cells and Mice.

    PubMed

    Han, Seon-Young; Choi, Yean-Jung; Kang, Min-Kyung; Park, Jung Han Yoon; Kang, Young-Hee

    2015-01-01

    A complicated interplay between resident mast cells and other recruited inflammatory cells contributes to the development and progression of allergic inflammation entailing the promotion of T helper 2 (Th2) cytokine responses. The current study examined whether resveratrol suppressed the production of inflammatory Th2 cytokines in cultured rat basophilic leukemia RBL-2H3 cells. Cells pre-treated with resveratrol nontoxic at 1–25 μM were sensitized with anti-dinitrophenyl (anti-DNP), and subsequently stimulated by dinitrophenyl-human serum albumin (DNP–HSA) antigen. Resveratrol dose-dependently diminished the secretion of interleukin (IL)-3, IL-4, IL-13 as well as tumor necrosis factor (TNF)-α by the antigen stimulation from sensitized cells. It was found that resveratrol mitigated the phosphorylation of p38 MAPK, ERK, and JNK elevated in mast cells exposed to Fc epsilon receptor I (FcεRI)-mediated immunoglobulin E (IgE)-antigen complex. The FcεRI aggregation was highly enhanced on the surface of mast cells following the HSA stimulation, which was retarded by treatment with 1–25 μM resveratrol. The IgE-receptor engagement rapidly induced tyrosine phosphorylation of c-Src-related focal adhesion protein paxillin involved in the cytoskeleton rearrangement. The FcεRI-mediated rapid activation of c-Src and paxillin was attenuated in a dose-dependent manner. In addition, the paxillin activation entailed p38 MAPK and ERK-responsive signaling, but the JNK activation was less involved. Consistently, oral administration of resveratrol reduced the tissue level of phosphorylated paxillin in the dorsal skin of DNP–HSA-challenged mice. The other tyrosine kinase Tyk2-STAT1 signaling was activated in the dorsal epidermis of antigen-exposed mice, which was associated with allergic inflammation. These results showed that resveratrol inhibited Th2 cytokines- and paxillin-linked allergic responses dependent upon MAPK signaling. Therefore, resveratrol may possess the

  9. Mast Cell Function

    PubMed Central

    da Silva, Elaine Zayas Marcelino; Jamur, Maria Célia

    2014-01-01

    Since first described by Paul Ehrlich in 1878, mast cells have been mostly viewed as effectors of allergy. It has been only in the past two decades that mast cells have gained recognition for their involvement in other physiological and pathological processes. Mast cells have a widespread distribution and are found predominantly at the interface between the host and the external environment. Mast cell maturation, phenotype and function are a direct consequence of the local microenvironment and have a marked influence on their ability to specifically recognize and respond to various stimuli through the release of an array of biologically active mediators. These features enable mast cells to act as both first responders in harmful situations as well as to respond to changes in their environment by communicating with a variety of other cells implicated in physiological and immunological responses. Therefore, the critical role of mast cells in both innate and adaptive immunity, including immune tolerance, has gained increased prominence. Conversely, mast cell dysfunction has pointed to these cells as the main offenders in several chronic allergic/inflammatory disorders, cancer and autoimmune diseases. This review summarizes the current knowledge of mast cell function in both normal and pathological conditions with regards to their regulation, phenotype and role. PMID:25062998

  10. Mast cells: potential positive and negative roles in tumor biology.

    PubMed

    Marichal, Thomas; Tsai, Mindy; Galli, Stephen J

    2013-11-01

    Mast cells are immune cells that reside in virtually all vascularized tissues. Upon activation by diverse mechanisms, mast cells can secrete a broad array of biologically active products that either are stored in the cytoplasmic granules of the cells (e.g., histamine, heparin, various proteases) or are produced de novo upon cell stimulation (e.g., prostaglandins, leukotrienes, cytokines, chemokines, and growth factors). Mast cells are best known for their effector functions during anaphylaxis and acute IgE-associated allergic reactions, but they also have been implicated in a wide variety of processes that maintain health or contribute to disease. There has been particular interest in the possible roles of mast cells in tumor biology. In vitro studies have shown that mast cells have the potential to influence many aspects of tumor biology, including tumor development, tumor-induced angiogenesis, and tissue remodeling, and the shaping of adaptive immune responses to tumors. Yet, the actual contributions of mast cells to tumor biology in vivo remain controversial. Here, we review some basic features of mast cell biology with a special emphasis on those relevant to their potential roles in tumors. We discuss how using in vivo tumor models in combination with models in which mast cell function can be modulated has implicated mast cells in the regulation of host responses to tumors. Finally, we summarize data from studies of human tumors that suggest either beneficial or detrimental roles for mast cells in tumors. PMID:24777963

  11. Anaplasma phagocytophilum Infects Mast Cells via α1,3-Fucosylated but Not Sialylated Glycans and Inhibits IgE-Mediated Cytokine Production and Histamine Release ▿

    PubMed Central

    Ojogun, Nore; Barnstein, Brian; Huang, Bernice; Oskeritzian, Carole A.; Homeister, Jonathon W.; Miller, Daniel; Ryan, John J.; Carlyon, Jason A.

    2011-01-01

    Mast cells are sentinels for infection. Upon exposure to pathogens, they release their stores of proinflammatory cytokines, chemokines, and histamine. Mast cells are also important for the control of certain tick-borne infections. Anaplasma phagocytophilum is an obligate intracellular tick-transmitted bacterium that infects neutrophils to cause the emerging disease granulocytic anaplasmosis. A. phagocytophilum adhesion to and infection of neutrophils depend on sialylated and α1,3-fucosylated glycans. We investigated the hypotheses that A. phagocytophilum invades mast cells and inhibits mast cell activation. We demonstrate that A. phagocytophilum binds and/or infects murine bone marrow-derived mast cells (BMMCs), murine peritoneal mast cells, and human skin-derived mast cells. A. phagocytophilum infection of BMMCs depends on α1,3-fucosylated, but not sialylated, glycans. A. phagocytophilum binding to and invasion of BMMCs do not elicit proinflammatory cytokine secretion. Moreover, A. phagocytophilum-infected cells are inhibited in the release of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), IL-13, and histamine following stimulation with IgE or antigen. Thus, A. phagocytophilum mitigates mast cell activation. These findings potentially represent a novel means by which A. phagocytophilum usurps host defense mechanisms and shed light on the interplay between mast cells and vector-borne bacterial pathogens. PMID:21536789

  12. Mast cell stabilisers.

    PubMed

    Zhang, Tao; Finn, Deirdre Frances; Barlow, James William; Walsh, John Jarlath

    2016-05-01

    Mast cells play a critical role in type 1 hypersensitivity reactions. Indeed, mast cell mediators are implicated in many different conditions including allergic rhinitis, conjunctivitis, asthma, psoriasis, mastocytosis and the progression of many different cancers. Thus, there is intense interest in the development of agents which prevent mast cell mediator release or which inhibit the actions of such mediators once released into the environment of the cell. Much progress into the design of new agents has been made since the initial discovery of the mast cell stabilising properties of khellin from Ammi visnaga and the clinical approval of cromolyn sodium. This review critically examines the progress that has been made in the intervening years from the design of new agents that target a specific signalling event in the mast cell degranulation pathway to those agents which have been developed where the precise mechanism of action remains elusive. Particular emphasis is also placed on clinically used drugs for other indications that stabilise mast cells and how this additional action may be harnessed for their clinical use in disease processes where mast cells are implicated. PMID:26130122

  13. Human and rat mast cell high-affinity immunoglobulin E receptors: Characterization of putative. alpha. -chain gene products

    SciTech Connect

    Shimizu, Akira; Benfey, P.N.; Leder, P. ); Tepler, I. Brigham and Women's Hospital, Boston, MA ); Berenstein, E.H.; Siraganian, R.P. )

    1988-03-01

    The authors have cloned and determined the entire nucleotide sequence of cDNAs corresponding to the putative {alpha} subunits of the human and rat mast cell high-affinity IgE receptors. Both human and rat cDNAs encode an NH{sub 2}-terminal signal peptide, two immunoglobulin-like extracellular domains (encoded by discrete exons), a hydrophobic transmembrane region, and a positively charged cytoplasmic tail. The human and rat {alpha} subunits share an overall homology with one another and the immunoglobulin gene family, suggesting that they arose from a common ancestral gene and continue to share structural homology with their ligands. In addition, the rat gene is transcribed into at least three distinct forms, each of which yields a somewhat different coding sequence.

  14. Recent PHENIX results on hard probes and direct photon production

    NASA Astrophysics Data System (ADS)

    Riabov, V.; PHENIX Collaboration

    2016-02-01

    A hot and dense matter called strongly interacting quark-gluon plasma (sQGP) is created in heavy ion collisions at RHIC energies. Detailed study of the properties of this new state of matter is a driving force of recent research at RHIC. In these proceedings we present most recent PHENIX results for system size and energy dependence of hadron and jet production at high transverse momentum in heavy ion collisions at RHIC. We also report latest results for direct photon production including soft direct photon yields and anisotropic flow.

  15. Increased local IgE production induced by common aeroallergens and phenotypic alteration of mast cells in Chinese eosinophilic, but not non-eosinophilic, chronic rhinosinusitis with nasal polyps

    PubMed Central

    Cao, Ping-Ping; Zhang, Ya-Na; Liao, Bo; Ma, Jin; Wang, Bao-Feng; Wang, Heng; Zeng, Ming; Liu, Wei-Hong; Schleimer, Robert P.; Liu, Zheng

    2014-01-01

    Background Eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) display distinct patterns of inflammation. However, the pathogenic mechanisms underlying the heterogeneity of CRSwNP need further investigation. Objective To investigate local immunoglobulin E (IgE) production and phenotype of mast cells in eosinophilic and non-eosinophilic CRSwNP in Chinese. Methods Total and specific IgE levels were analyzed by means of the ImmunoCAP system. The molecular steps involved in class switch recombination to IgE were investigated using RT-PCR assays. Mast cell phenotypes, IgE- and high affinity IgE receptor (FcεRI)-positive cells, and allergen binding to specific IgE in sinonasal mucosa were determined by means of immunohistochemistry. Results Compared with controls and non-eosinophilic CRSwNP, local total IgE levels were increased, and local specific IgE to common aeroallergens was more frequently found, in Chinese eosinophilic CRSwNP independent of atopy and without significant association with Staphylococcus aureus enterotoxins. The ε germline gene transcript was also more frequently detected in eosinophilic CRSwNP. The number of IgE- and FcεRI-positive cells was increased in eosinophilic CRSwNP. Most IgE- and FcεRI-positive cells were mast cells. Dust mite antigens could bind to IgE on mast cells in situ. The number of mast cells positive for both tryptase and chymase and activated mast cells was increased in eosinophilic CRSwNP and the number of activated mast cells positively correlated with local IgE level, eotaxin-1 level, and eosinophil count in CRSwNP. Conclusions and Clinical Relevance The local IgE induced by common aeroallergens may mediate mast cell activation and contribute to subsequent eosinophilic inflammation in Chinese CRSwNP. This study offers a rationale for considering intervention strategies designed to target “local allergy” in eosinophilic CRSwNP. PMID:24597471

  16. Delta-Isobar Production in the Hard Photodisintegration of a Deuteron

    NASA Astrophysics Data System (ADS)

    Granados, Carlos; Sargsian, Misak

    2010-02-01

    Hard photodisintegration of the deuteron in delta-isobar production channels is proposed as a useful process in identifying the quark structure of hadrons and of hadronic interactions at large momentum and energy transfer. The reactions are modeled using the hard re scattering model, HRM, following previous works on hard breakup of a nucleon nucleon (NN) system in light nuclei. Here,quantitative predictions through the HRM require the numerical input of fits of experimental NN hard elastic scattering cross sections. Because of the lack of data in hard NN scattering into δ-isobar channels, the cross section of the corresponding photodisintegration processes cannot be predicted in the same way. Instead, the corresponding NN scattering process is modeled through the quark interchange mechanism, QIM, leaving an unknown normalization parameter. The observables of interest are ratios of differential cross sections of δ-isobar production channels to NN breakup in deuteron photodisintegration. Both entries in these ratios are derived through the HRM and QIM so that normalization parameters cancel out and numerical predictions can be obtained. )

  17. The Comprehension and Production of Wh-Questions in Deaf and Hard-of-Hearing Children

    ERIC Educational Resources Information Center

    Friedmann, Naama; Szterman, Ronit

    2011-01-01

    Hearing loss during the critical period for language acquisition restricts spoken language input. This input limitation, in turn, may hamper syntactic development. This study examined the comprehension, production, and repetition of Wh-questions in deaf or hard-of-hearing (DHH) children. The participants were 11 orally trained Hebrew-speaking…

  18. 45. VIEW OF UMBILICAL MAST TRENCH FROM BASE OF MAST, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    45. VIEW OF UMBILICAL MAST TRENCH FROM BASE OF MAST, FROM SOUTH. ACTUATORS FOR MAST TRENCH DOORS VISIBLE CONNECTING DOORS AND WALL. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  19. Imaging the proton via hard exclusive production in diffractive pp scattering

    SciTech Connect

    Charles Hyde; Leonid Frankfurt; Mark Strikman; Christian Weiss

    2007-05-21

    We discuss the prospects for probing Generalized Parton Distributions (GPDs) via exclusive production of a high-mass system (H = heavy quarkonium, di-photon, di-jet, Higgs boson) in diffractive pp scattering, pp -> p + H + p. In such processes the interplay of hard and soft interactions gives rise to a diffraction pattern in the final-state proton transverse momenta, which is sensitive to the transverse spatial distribution of partons in the colliding protons. We comment on the plans for diffractive pp measurements at RHIC and LHC. Such studies could complement future measurements of GPDs in hard exclusive ep scattering (JLab, COMPASS, EIC).

  20. Mast cells and mastocytosis

    PubMed Central

    2008-01-01

    Mast cells have been recognized for well over 100 years. With time, human mast cells have been documented to originate from CD34+ cells, and have been implicated in host responses in both innate and acquired immunity. In clinical immunology, they are recognized for their central role in IgE-mediated degranulation and allergic inflammation by virtue of their expression of the high-affinity receptor for IgE and release of potent proinflammatory mediators. In hematology, the clinical disease of mastocytosis is characterized by a pathologic increase of mast cells in tissues, often associated with mutations in KIT, the receptor for stem cell factor. More recently, and with increased understanding of how human mast cells are activated through receptors including the high-affinity receptor for IgE and KIT, specific tyrosine kinase inhibitors have been identified with the potential to interrupt signaling pathways and thus limit the proliferation of mast cells as well as their activation through immunoglobulin receptors. PMID:18684881

  1. Mast Cells and Neuroinflammation

    PubMed Central

    Dong, Hongquan; Zhang, Xiang; Qian, Yanning

    2014-01-01

    It has been determined that there is extensive communication between the immune system and the central nervous system (CNS). Proinflammatory cytokines play a key role in this communication. There is an emerging realization that glia and microglia, in particular, (which are the brain’s resident macrophages), are an important source of inflammatory mediators and may have fundamental roles in CNS disorders. Microglia respond also to proinflammatory signals released from other non-neuronal cells, principally those of immune origin, such as mast cells. Mast cells reside in the CNS and are capable of migrating across the blood-brain barrier (BBB) in situations where the barrier is compromised as a result of CNS pathology. Mast cells are both sensors and effectors in communication among nervous, vascular, and immune systems. In the brain, they reside on the brain side of the BBB, and interact with astrocytes, microglia, and blood vessels via their neuroactive stored and newly synthesized chemicals. They are first responders, acting as catalysts and recruiters to initiate, amplify, and prolong other immune and nervous responses upon activation. Mast cells both promote deleterious outcomes in brain function and contribute to normative behavioral functioning, particularly cognition and emotion. Mast cells may play a key role in treating systemic inflammation or blockade of signaling pathways from the periphery to the brain. PMID:25529562

  2. Mast cells and metabolic syndrome

    PubMed Central

    Zhang, Jie; Shi, Guo-Ping

    2011-01-01

    Mast cells are critical effectors in the development of allergic diseases and in many immunoglobulin E–mediated immune responses. These cells exert their physiological and pathological activities by releasing granules containing histamine, cytokines, chemokines, and proteases, including mast cell-specific chymase and tryptase. Like macrophages and T lymphocytes, mast cells are inflammatory cells, and they participate in the pathogenesis of inflammatory diseases such as cardiovascular complications and metabolic disorders. Recent observations suggested that mast cells are involved in insulin resistance and type 2 diabetes. Data from animal models proved the direct participation of mast cells in diet-induced obesity and diabetes. Although the mechanisms by which mast cells participate in these metabolic diseases are not fully understood, established mast cell pathobiology in cardiovascular diseases and effective mast cell inhibitor medications used in pre-formed obesity and diabetes in experimental models offer hope to patients with these common chronic inflammatory diseases. PMID:21185370

  3. Process for casting hard-faced, lightweight camshafts and other cylindrical products

    DOEpatents

    Hansen, Jeffrey S.; Turner, Paul C.; Argetsinger, Edward R.; Wilson, Rick D.

    1996-01-01

    A process for casting a hard-faced cylindrical product such as an automobile camshaft includes the steps of: (a) preparing a composition formed from a molten base metal and an additive in particle form and having a hardness value greater than the hardness value of the base metal; (b) introducing the composition into a flask containing a meltable pattern of a cylindrical product such as an automobile camshaft to be manufactured and encased in sand to allow the composition to melt the pattern and assume the shape of the pattern within the sand; and (c) rotating the flask containing the pattern about the longitudinal axes of both the flask and the pattern as the molten base metal containing the additive in particle form is introduced into the flask to cause particles of the additive entrained in the molten base metal to migrate by centrifugal action to the radial extremities of the pattern and thereby provide a cylindrical product having a hardness value greater at it's radial extremities than at its center when the molten base metal solidifies.

  4. Chemical Characterization of Beer Aging Products Derived from Hard Resin Components in Hops (Humulus lupulus L.).

    PubMed

    Taniguchi, Yoshimasa; Yamada, Makiko; Taniguchi, Harumi; Matsukura, Yasuko; Shindo, Kazutoshi

    2015-11-25

    The bitter taste of beer originates from resins in hops (Humulus lupulus L.), which are classified into two subtypes (soft and hard). Whereas the nature and reactivity of soft-resin-derived compounds, such as α-, β-, and iso-α-acids, are well studied, there is only a little information on the compounds in hard resin. For this work, hard resin was prepared from stored hops and investigated for its compositional changes in an experimental model of beer aging. The hard resin contained a series of α-acid oxides. Among them, 4'-hydroxyallohumulinones were unstable under beer storage conditions, and their transformation induced primary compositional changes of the hard resin during beer aging. The chemical structures of the products, including novel polycyclic compounds scorpiohumulinols A and B and dicyclohumulinols A and B, were determined by HRMS and NMR analyses. These compounds were proposed to be produced via proton-catalyzed cyclization reactions of 4'-hydroxyallohumulinones. Furthermore, they were more stable than their precursor 4'-hydroxyallohumulinones during prolonged storage periods. PMID:26507444

  5. Mast Cells and Anaphylaxis.

    PubMed

    Lieberman, Phil; Garvey, Lene Heise

    2016-03-01

    For half a century, it has been known that the mast cell is the cell responsible for the majority of anaphylactic events. Its mediators, taken as a whole, are capable of producing all of the clinical manifestations of these events. With the discovery of immunoglobulin E (IgE), it was originally felt that the vast majority of anaphylactic episodes were due to antigen coupling with two cell-bound IgE molecules. More recently it has been learned that many episodes are produced by direct activation of mast cells, not involving antigen binding to IgE, and that monomeric IgE under certain conditions can also cause degranulation. Of note--in regard to antigen independent degranulation--are recent reports that the human G-protein-coupled receptor, MRGPRX2, may be the receptor for many drugs and cationic proteins capable of producing direct mast cell degranulation and anaphylactic events. PMID:26857018

  6. Mast Cell and Autoimmune Diseases

    PubMed Central

    Xu, Yunzhi; Chen, Guangjie

    2015-01-01

    Mast cells are important in innate immune system. They have been appreciated as potent contributors to allergic reaction. However, increasing evidence implicates the important role of mast cells in autoimmune disease like rheumatoid arthritis and multiple sclerosis. Here we review the current stage of knowledge about mast cells in autoimmune diseases. PMID:25944979

  7. Analytical Expressions for the Hard-Scattering Production of Massive Partons

    SciTech Connect

    Wong, Cheuk-Yin

    2016-01-01

    We obtain explicit expressions for the two-particle differential cross section $E_c E_\\kappa d\\sigma (AB \\to c\\kappa X) /d\\bb c d \\bb \\kappa$ and the two-particle angular correlation function \\break $d\\sigma(AB$$ \\to$$ c\\kappa X)/d\\Delta \\phi \\, d\\Delta y$ in the hard-scattering production of massive partons in order to exhibit the ``ridge" structure on the away side in the hard-scattering process. The single-particle production cross section $d\\sigma(AB \\to cX) /dy_c c_T dc_T $ is also obtained and compared with the ALICE experimental data for charm production in $pp$ collisions at 7 TeV at LHC.

  8. Canine mast cell tumors.

    PubMed

    Macy, D W

    1985-07-01

    Despite the fact that the mast cell tumor is a common neoplasm of the dog, we still have only a meager understanding of its etiology and biologic behavior. Many of the published recommendations for treatment are based on opinion rather than facts derived from careful studies and should be viewed with some skepticism. Because of the infrequent occurrence of this tumor in man, only a limited amount of help can be expected from human oncologists; therefore, burden of responsibility for progress in predicting behavior and developing treatment effective for canine mast cell tumors must fall on the shoulders of the veterinary profession. PMID:3929444

  9. What drives masting? The phenological synchrony hypothesis.

    PubMed

    Koenig, Walter D; Knops, Johannes M H; Carmen, William J; Pearse, Ian S

    2015-01-01

    Annually variable and synchronous seed production, or masting behavior, is a widespread phenomenon with dramatic effects on wildlife populations and their associated communities. Proximally, masting is often correlated with environmental factors and most likely involves differential pollination success and resource allocation, but little is known about how these factors interact or how they influence seed production. We studied masting in the valley oak (Quercus lobata Née), a California endemic tree, and report evidence that phenological synchrony in flowering driven by microclimatic variability determines the size of the acorn crop through its effects on pollen availability and fertilization success. These findings integrate two of the major factors believed to influence seed production in wind-pollinated species-environmental conditions and pollen limitation-by means of a coherent mechanistic hypothesis for how highly variable and synchronized annual seed production is accomplished. We illustrate how, by means of a simulation based on the mechanism proposed here, climate change may influence masting patterns through its effects on environmental variability. PMID:26236903

  10. Knockout of the Trpc1 gene reveals that TRPC1 can promote recovery from anaphylaxis by negatively regulating mast-cell TNF-α production

    PubMed Central

    Medic, Nevenka; Desai, Avanti; Olivera, Ana; Abramowitz, Joel; Birnbaumer, Lutz; Beaven, Michael A.; Gilfillan, Alasdair M.; Metcalfe, Dean D.

    2013-01-01

    Antigen-mediated mast cell (MC) degranulation is the critical early event in the induction of allergic reactions. Transient receptor potential channels (TRPC), particularly TRPC1, are thought to contribute to such MC activation. To explore the contribution of TRPC1 in MC-driven allergic reactions, we examined antigen-mediated anaphylaxis in Trpc1−/− and WT mice, and TRPC1 involvement in the activation of MCs derived from the bone marrow (BMMCs) of these mice. In vivo, we observed a similar induction of passive systemic anaphylaxis in the Trpc1−/− mice compared to WT controls. Nevertheless, there was delayed recovery from this response in Trpc1−/− mice. Furthermore, contrary to expectations, Trpc1−/− BMMCs responded to antigen with enhanced calcium signalling but with little defect in degranulation or associated signalling. In contrast, antigen-mediated production of TNF-α, and other cytokines, was enhanced in the Trpc1−/− BMMCs, as were calcium-dependent events required for these responses. Additionally, circulating levels of TNF-α in response to antigen were preferentially elevated in the Trpc1−/− mice, and administration of an anti-TNF-α antibody blocked the delay in recovery from anaphylaxis in these mice. These data thus provide evidence that, in this model, TRPC1 promotes recovery from the anaphylactic response by repressing antigen-mediated TNF-α release from MCs. PMID:23489970

  11. Mast cells: Versatile regulators of inflammation, tissue remodeling, host defense and homeostasis

    PubMed Central

    Galli, Stephen J.; Tsai, Mindy

    2009-01-01

    Summary The possible roles of mast cells in heath and disease have been a topic of interest for over one hundred and twenty five years. Many adaptive or pathological processes affecting the skin or other anatomical sites have been associated with morphological evidence of mast cell activation, and/or with changes in mast cell numbers or phenotype. Such observations, taken together with the known functions of the diverse mediators, cytokines and growth factors which can be secreted by mast cells, have suggested many potential functions for mast cells in health and disease. Definitively identifying the importance of mast cells in biological responses in humans is difficult. However, mutant mice which are profoundly mast cell-deficient, especially those which can undergo engraftment with wild type or genetically-altered mast cells, provide an opportunity to investigate the importance of mast cells, and specific mast cell functions or products, in various adaptive or pathological responses in mice. Such work has shown that mast cells can significantly influence multiple features of inflammatory or immune responses, through diverse effects that can either promote or, surprisingly, suppress, aspects of these responses. Through such functions, mast cells can significantly influence inflammation, tissue remodeling, host defense and homeostasis. PMID:18024086

  12. Cross-Talk between Human Mast Cells and Bronchial Epithelial Cells in Plasminogen Activator Inhibitor-1 Production via Transforming Growth Factor-β1

    PubMed Central

    Lee, Sun H.; Kato, Atsushi; Takabayashi, Tetsuji; Kulka, Marianna; Shin, Soon C.; Schleimer, Robert P.

    2015-01-01

    Previous reports suggest that plasminogen activator inhibitor-1 (PAI-1) promotes airway remodeling and that human and mouse mast cells (MCs) are an important source of PAI-1. In the present study we investigated MC–epithelial cell (EC) interactions in the production of PAI-1. We stimulated the human MC line LAD2 with IgE-receptor cross-linking and collected the supernatants. We incubated the human bronchial EC line BEAS-2B with the LAD2 supernatants and measured the level of PAI-1. When the supernatants from IgE-stimulated LAD2 were added to BEAS-2B, there was a significant enhancement of PAI-1 production by BEAS-2B. When we treated the MC supernatants with a transforming growth factor (TGF)-β1 neutralizing antibody, the MC-derived induction of PAI-1 from BEAS-2B was completely abrogated. Although TGF-β1 mRNA was constitutively expressed in resting LAD2, it was not highly induced by IgE-mediated stimulation. Nonetheless, active TGF-β1 protein was significantly increased in LAD2 after IgE-mediated stimulation. Active TGF-β1 produced by primary cultured human MCs was significantly reduced in the presence of a chymase inhibitor, suggesting a role of MC chymase as an activator of latent TGF-β1. This study indicates that stimulation of human MCs by IgE receptor cross-linking triggers activation of TGF-β1, at least in part via chymase, which in turn induces the production of PAI-1 by bronchial ECs. Our data suggest that human MCs may play an important role in airway remodeling in asthma as a direct source of PAI-1 and by activating bronchial ECs to produce further PAI-1 via a TGF-β1–mediated activation pathway. PMID:24987792

  13. Cross-talk between human mast cells and bronchial epithelial cells in plasminogen activator inhibitor-1 production via transforming growth factor-β1.

    PubMed

    Cho, Seong H; Lee, Sun H; Kato, Atsushi; Takabayashi, Tetsuji; Kulka, Marianna; Shin, Soon C; Schleimer, Robert P

    2015-01-01

    Previous reports suggest that plasminogen activator inhibitor-1 (PAI-1) promotes airway remodeling and that human and mouse mast cells (MCs) are an important source of PAI-1. In the present study we investigated MC-epithelial cell (EC) interactions in the production of PAI-1. We stimulated the human MC line LAD2 with IgE-receptor cross-linking and collected the supernatants. We incubated the human bronchial EC line BEAS-2B with the LAD2 supernatants and measured the level of PAI-1. When the supernatants from IgE-stimulated LAD2 were added to BEAS-2B, there was a significant enhancement of PAI-1 production by BEAS-2B. When we treated the MC supernatants with a transforming growth factor (TGF)-β1 neutralizing antibody, the MC-derived induction of PAI-1 from BEAS-2B was completely abrogated. Although TGF-β1 mRNA was constitutively expressed in resting LAD2, it was not highly induced by IgE-mediated stimulation. Nonetheless, active TGF-β1 protein was significantly increased in LAD2 after IgE-mediated stimulation. Active TGF-β1 produced by primary cultured human MCs was significantly reduced in the presence of a chymase inhibitor, suggesting a role of MC chymase as an activator of latent TGF-β1. This study indicates that stimulation of human MCs by IgE receptor cross-linking triggers activation of TGF-β1, at least in part via chymase, which in turn induces the production of PAI-1 by bronchial ECs. Our data suggest that human MCs may play an important role in airway remodeling in asthma as a direct source of PAI-1 and by activating bronchial ECs to produce further PAI-1 via a TGF-β1-mediated activation pathway. PMID:24987792

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

    PubMed Central

    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. PMID:27378825

  15. Growth and Saxitoxin Production by Cylindrospermopsis raciborskii (Cyanobacteria) Correlate with Water Hardness

    PubMed Central

    Carneiro, Ronaldo Leal; Pacheco, Ana Beatriz Furlanetto; Azevedo, Sandra Maria Feliciano de Oliveira e

    2013-01-01

    The cosmopolitan and increasing distribution of Cylindrospermopsis raciborskii can be attributed to its ecophysiological plasticity and tolerance to changing environmental factors in water bodies. In reservoirs in the semi-arid region of Brazil, the presence and common dominance of C. raciborskii have been described in waters that are considered hard. We investigated the response of a Brazilian C. raciborskii strain to water hardness by evaluating its growth and saxitoxin production. Based on environmental data, a concentration of 5 mM of different carbonate salts was tested. These conditions affected growth either positively (MgCO3) or negatively (CaCO3 and Na2CO3). As a control for the addition of cations, MgCl2, CaCl2 and NaCl were tested at 5 or 10 mM, and MgCl2 stimulated growth, NaCl slowed but sustained growth, and CaCl2 inhibited growth. Most of the tested treatments increased the saxitoxin (STX) cell quota after six days of exposure. After 12 days, STX production returned to concentrations similar to that of the control, indicating an adaptation to the altered water conditions. In the short term, cell exposure to most of the tested conditions favored STX production over neoSTX production. These results support the noted plasticity of C. raciborskii and highlight its potential to thrive in hard waters. Additionally, the observed relationship between saxitoxin production and water ion concentrations characteristic of the natural environments can be important for understanding toxin content variation in other harmful algae that produce STX. PMID:23955286

  16. A hard x-ray prototype production exposure station at NSLS

    SciTech Connect

    Johnson, E.D.; Milne, J.C.

    1997-07-01

    Exposures conducted at the NSLS R and D beamline (X-27B) for High Aspect Ratio Precision Manufacture have proven sufficiently successful that the authors are constructing a dedicated hard x-ray exposure beamline. The new beamline (X-14B) provides an exposure field {approximately} 120 mm wide, three times larger than that of X-27B. The scanner is based on the hydraulic system from the X-27B program. It is optimized for planar exposures and takes advantage of the full 525 mm stroke available. Exposures of multiple substrates and masks will be possible, with the fixturing supporting mounting of substrate holders from other groups (ALS, APS, CAMD, and UW). The function of this beamline is to establish a hard x-ray exposure station where manufacturing scale protocols can be developed and ultimately exploited for production runs.

  17. ASI/MET Mast

    NASA Technical Reports Server (NTRS)

    1997-01-01

    The Mars Pathfinder meteorology mast casts a shadow on the lander solar array, as seen in this superpan mosaic. Looking to the southeast during the morning, the windsocks are slightly tilted, indicating the presence of a light wind from the southwest. The MET mast measured the temperature, pressure, and wind speed at the Pathfinder landing site. During the mission, the instrument returned 8.5 million individual measurements from the surface of Mars.

    Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is a division of the California Institute of Technology (Caltech). The IMP was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator.

  18. Role of mast cells in gastrointestinal mucosal defense.

    PubMed

    Penissi, Alicia B; Rudolph, María I; Piezzi, Ramón S

    2003-08-01

    The purpose of this review, based on studies from our laboratory as well as from others, is to summarize salient features of mast cell immunobiology and to describe their associations with gastrointestinal mucosal defense. Gastrointestinal mast cells are involved in many pathologic effects, such as food hypersensitivity. On the other hand, they also play a protective role in defense against parasitic and microbial infections. Thus, they have both positive and negative effects, but presently the mechanisms that control the balance of these various effects are poorly known. It has been suggested that stabilization of mast cells may be a key mechanism to protect the gastrointestinal tract from injury. Few molecules are known to possess both mast cell stabilizing and gastrointestinal cytoprotective activity. These include zinc compounds, sodium cromoglycate, FPL 52694, ketotifen, aloe vera, certain flavonoids such as quercetin, some sulfated proteoglycans such as chondroitin sulfate and dehydroleucodine. Dehydroleucodine, a sesquiterpene lactone isolated from Artemisia douglasiana Besser, exhibits anti-inflammatory and gastrointestinal cytoprotective action. The lactone stimulates mucus production, and inhibits histamine and serotonin release from intestinal mast cells. The lactone could act as a selective mast cell stabilizer by releasing cytoprotective factors and inhibiting pro-inflammatory mast cell mediators. PMID:14510234

  19. Emerging concepts: mast cell involvement in allergic diseases.

    PubMed

    Modena, Brian D; Dazy, Kristen; White, Andrew A

    2016-08-01

    In a process known as overt degranulation, mast cells can release all at once a diverse array of products that are preformed and present within cytoplasmic granules. This occurs typically within seconds of stimulation by environmental factors and allergens. These potent, preformed mediators (ie, histamine, heparin, serotonin, and serine proteases) are responsible for the acute symptoms experienced in allergic conditions such as allergic conjunctivitis, allergic rhinitis, allergy-induced asthma, urticaria, and anaphylaxis. Yet, there is reason to believe that the actions of mast cells are important when they are not degranulating. Mast cells release preformed mediators and inflammatory cytokines for periods after degranulation and even without degranulating at all. Mast cells are consistently seen at sites of chronic inflammation, including nonallergic inflammation, where they have the ability to temper inflammatory processes and shape tissue morphology. Mast cells can trigger actions and chemotaxis in other important immune cells (eg, eosinophils and the newly discovered type 2 innate lymphocytes) that then make their own contributions to inflammation and disease. In this review, we will discuss the many known and theorized contributions of mast cells to allergic diseases, focusing on several prototypical allergic respiratory and skin conditions: asthma, chronic rhinosinusitis, aspirin-exacerbated respiratory disease, allergic conjunctivitis, atopic dermatitis, and some of the more common medication hypersensitivity reactions. We discuss traditionally accepted roles that mast cells play in the pathogenesis of each of these conditions, but we also delve into new areas of discovery and research that challenge traditionally accepted paradigms. PMID:26976119

  20. Speech Sound Production in Two-Year-Olds who are Hard of Hearing

    PubMed Central

    Ambrose, Sophie E.; Unflat Berry, Lauren M.; Walker, Elizabeth A.; Harrison, Melody; Oleson, Jacob; Moeller, Mary Pat

    2014-01-01

    Purpose The purpose of the study was to 1) compare the speech sound production abilities of 2-year-old children who are hard of hearing (HH) to children with normal hearing (NH), 2) identify sources of risk for individual children who are HH, and 3) determine whether speech sound production skills at age two were predictive of speech sound production skills at age three. Method Seventy children with bilateral, mild-to-severe hearing loss who use hearing aids and 37 age- and SES-matched children with NH participated. Children’s speech sound production abilities were assessed at 2 and 3 years of age. Results At age two, the HH group demonstrated vowel production abilities on par with their NH peers, but weaker consonant production abilities. Within the HH group, better outcomes were associated with hearing aid fittings by 6 months of age, hearing loss of less than 45 dB HL, stronger vocabulary scores, and being female. Positive relationships existed between children’s speech sound production abilities at 2 and 3 years of age. Conclusions Assessment of early speech sound production abilities in combination with demographic, audiologic, and linguistic variables may be useful in identifying HH children who are at risk of delays in speech sound production. PMID:24686852

  1. Interleukin-33 and Mast Cells Bridge Innate and Adaptive Immunity: From the Allergologist’s Perspective

    PubMed Central

    Jang, Tae Young; Kim, Young Hyo

    2015-01-01

    Interleukin (IL) 33, a member of the IL-1 superfamily, is an “alarmin” protein and is secreted in its active form from damaged cells undergoing necrotic cell death. Mast cells are one of the main effector cell types in allergic disorders. They secrete a variety of mediators, including T helper 2 cytokines. As mast cells have high-affinity IgE receptors (FcεRI) on their surface, they can capture circulating IgE. IgE-bound mast cells degranulate large amounts of histamine, heparin, and proteases when they encounter antigens. As IL-33 is an important mediator of innate immunity and mast cells play an important role in adaptive immune responses, interactions between the two could link innate and adaptive immunity. IL-33 promotes the adhesion of mast cells to laminin, fibronectin, and vitronectin. IL-33 increases the expression of adhesion molecules, such as intracellular adhesion molecule-1 and vascular cell adhesion molecule-1, in endothelial cells, thus enhancing mast cell adhesion to blood vessel walls. IL-33 stimulates mast cell proliferation by activating the ST2/Myd88 pathway; increases mast cell survival by the activation of survival proteins such as Bcl-XL; and promotes the growth, development, and maturation of mast cell progenitors. IL-33 is also involved in the activation of mature mast cells and production of different proinflammatory cytokines. The interaction of IL-33 and mast cells could have important clinical implications in the field of clinical urology. Epithelial dysfunction and mast cells could play an important role in the pathogenesis of interstitial cystitis. Urinary levels of IL-33 significantly increase in patients with interstitial cystitis. In addition, the number of mast cells significantly increase in the urinary bladders of patients with interstitial cystitis. Therefore, inhibition of mast cell activation and degranulation in response to increase in IL-33 is a potential therapeutic target in the treatment of interstitial cystitis

  2. Mast cells in rheumatic disease.

    PubMed

    Suurmond, Jolien; van der Velden, Daniël; Kuiper, Johan; Bot, Ilze; Toes, René E M

    2016-05-01

    Rheumatoid Arthritis is a chronic autoimmune disease with a complex disease pathogenesis leading to inflammation and destruction of synovial tissue in the joint. Several molecules lead to activation of immune pathways, including autoantibodies, Toll-Like Receptor ligands and cytokines. These pathways can cooperate to create the pro-inflammatory environment that results in tissue destruction. Each of these pathways can activate mast cells, inducing the release of a variety of inflammatory mediators, and in combination can markedly enhance mast cell responses. Mast cell-derived cytokines, chemokines, and proteases have the potential to induce recruitment of other leukocytes able to evoke tissue remodeling or destruction. Likewise, mast cells can secrete a plethora of factors that can contribute to tissue remodeling and fibroblast activation. Although the functional role of mast cells in arthritis pathogenesis in mice is not yet elucidated, the increased numbers of mast cells and mast cell-specific mediators in synovial tissue of rheumatoid arthritis patients suggest that mast cell activation in rheumatoid arthritis may contribute to its pathogenesis. PMID:25943290

  3. Confinement & Stability in MAST

    NASA Astrophysics Data System (ADS)

    Akers, Rob

    2001-10-01

    Transition to H-mode has been achieved in the MAST spherical tokamak (ST) for both ohmically and neutral beam heated plasmas (P_NBI ~ 0.5-1.5MW), resulting in double-null diverted discharges containing both regular and irregular edge localised modes (ELMs). The observed L-H power threshold is ~10 times higher than predicted by established empirical scalings. L-H transition in MAST is accompanied by a sharp increase in edge density gradient, the efficient conversion of internal electron Bernstein waves into free space waves, the onset and saturation of edge poloidal rotation and a marked decrease in turbulence. During ELM free periods, a reduction in outboard power deposition width is observed using a Langmuir probe array. A novel divertor structure has been installed to counter the resulting increase in target heat-flux by applying a toroidally varying potential to the divertor plasma, theory suggesting that convective broadening of the scrape off layer will take place. Global confinement in H-mode is found to routinely exceed the international IPB(y,2) scaling, even for discharges approaching the Greenwald density. In an attempt to further extend the density range (densities in excess of Greenwald having been achieved for plasma currents up to 0.8MA) a multi-pellet injector has been installed at the low-field-side. In addition, high field side fuelling can be supplied via a gas-feed located at the centre-column mid-plane, this technique having been found to significantly enhance H-mode accessibility and quality. A range of stability issues will be discussed, including vertical displacement events, the rich variety of high frequency MHD seen in MAST and the physics of the Neoclassical Tearing Mode. This work was funded by the UK Department of Trade and Industry and by EURATOM. The NBI equipment is on loan from ORNL and the pellet injector was provided by FOM.

  4. Mast cells in gastrointestinal disorders.

    PubMed

    Bischoff, Stephan C

    2016-05-01

    Mast cells are constitutively found in the gastrointestinal (GI) tract. The three major physiological functions of GI mast cells comprise of - as far as we know - regulation of GI functions, namely epithelial and endothelial functions, crosstalk with the enteric nervous system, and contribution to the host defense against bacterial, viral and parasitic agents. A number of chronic GI diseases, including inflammatory bowel disease (Crohn's disease, ulcerative colitis), celiac disease, irritable bowel syndrome, and food allergies, are thought to be associated with mast cell hyperplasia and humoral activity. Clinical conditions characterized by a decrease in mast cell functionality are not known so far. In the present review, we summarize current evidence which show that human mast cells play a central role at the GI barrier, both in health and disease. PMID:26852959

  5. Heavy-Quark Associated Production with One Hard Photon at Hadron Colliders

    SciTech Connect

    Hartanto, Heribertus Bayu

    2013-01-01

    We present the calculation of heavy-quark associated production with a hard photon at hadron colliders, namely $pp(p\\bar p) → Q\\bar Q +X$γ (for $Q=t,b$), at Next-to-Leading Order (NLO) in Quantum Chromodynamics (QCD). We study the impact of NLO QCD corrections on the total cross section and several differential distributions at both the Tevatron and the Large Hadron Collider (LHC). For $t\\bar t$γ production we observe a sizeable reduction of the renormalization and factorization scale dependence when the NLO QCD corrections are included, while for $b\\bar b$γ production a considerable scale dependence still persists at NLO in QCD. This is consistent with what emerges in similar processes involving $b$ quarks and vector bosons and we explain its origin in detail. For $b\\bar b$γ production we study both the case in which at least one $b$ jet and the case in which at least two $b$ jets are observed. We perform the $b\\bar b$γ calculation using the Four Flavor Number Scheme (4FNS) and compare the case where at least one $b$ jet is observed with the corresponding results from the Five Flavor Number Scheme (5FNS) calculation. Finally we compare our results for $p\\bar p →+b+X$γ with the Tevatron data.

  6. Heavy-quark associated production with one hard photon at hadron colliders

    NASA Astrophysics Data System (ADS)

    Hartanto, Heribertus Bayu

    We present the calculation of heavy-quark associated production with a hard photon at hadron colliders, namely pp( pp) → QQgamma + X (for Q = t, b), at Next-to-Leading Order (NLO) in Quantum Chromodynamics (QCD). We study the impact of NLO QCD corrections on the total cross section and several differential distributions at both the Tevatron and the Large Hadron Collider (LHC). For ttgamma production we observe a sizeable reduction of the renormalization and factorization scale dependence when the NLO QCD corrections are included, while for bbgamma production a considerable scale dependence still persists at NLO in QCD. This is consistent with what emerges in similar processes involving b quarks and vector bosons and we explain its origin in detail. For bbgamma production we study both the case in which at least one b jet and the case in which at least two b jets are observed. We perform the bbgamma calculation using the Four Flavor Number Scheme (4FNS) and compare the case where at least one b jet is observed with the corresponding results from the Five Flavor Number Scheme (5FNS) calculation. Finally we compare our results for p p → gamma + b + X with Tevatron data.

  7. Singular Values of Products of Ginibre Random Matrices, Multiple Orthogonal Polynomials and Hard Edge Scaling Limits

    NASA Astrophysics Data System (ADS)

    Kuijlaars, Arno B. J.; Zhang, Lun

    2014-12-01

    Akemann, Ipsen and Kieburg recently showed that the squared singular values of products of M rectangular random matrices with independent complex Gaussian entries are distributed according to a determinantal point process with a correlation kernel that can be expressed in terms of Meijer G-functions. We show that this point process can be interpreted as a multiple orthogonal polynomial ensemble. We give integral representations for the relevant multiple orthogonal polynomials and a new double contour integral for the correlation kernel, which allows us to find its scaling limits at the origin (hard edge). The limiting kernels generalize the classical Bessel kernels. For M = 2 they coincide with the scaling limits found by Bertola, Gekhtman, and Szmigielski in the Cauchy-Laguerre two-matrix model, which indicates that these kernels represent a new universality class in random matrix theory.

  8. ASI/MET mast

    NASA Technical Reports Server (NTRS)

    1997-01-01

    The Atmospheric Structure Instrument/Meteorology Package (ASI/MET) mast is visible against a backdrop of rocky Martian terrain in this image, taken by the Imager for Mars Pathfinder (IMP). The windsocks are slightly tilted, showing some wind activity. Distortions in the background are due to parallax.

    Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is an operating division of the California Institute of Technology (Caltech). The Imager for Mars Pathfinder (IMP) was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator.

  9. Subthreshold IKK activation modulates the effector functions of primary mast cells and allows specific targeting of transformed mast cells.

    PubMed

    Drube, Sebastian; Weber, Franziska; Loschinski, Romy; Beyer, Mandy; Rothe, Mandy; Rabenhorst, Anja; Göpfert, Christiane; Meininger, Isabel; Diamanti, Michaela A; Stegner, David; Häfner, Norman; Böttcher, Martin; Reinecke, Kirstin; Herdegen, Thomas; Greten, Florian R; Nieswandt, Bernhard; Hartmann, Karin; Krämer, Oliver H; Kamradt, Thomas

    2015-03-10

    Mast cell differentiation and proliferation depends on IL-3. IL-3 induces the activation of MAP-kinases and STATs and consequently induces proliferation and survival. Dysregulation of IL-3 signaling pathways also contribute to inflammation and tumorigenesis. We show here that IL-3 induces a SFK- and Ca²⁺-dependent activation of the inhibitor of κB kinases 2 (IKK2) which results in mast cell proliferation and survival but does not induce IκBα-degradation and NFκB activation. Therefore we propose the term "subthreshold IKK activation".This subthreshold IKK activation also primes mast cells for enhanced responsiveness to IL-33R signaling. Consequently, co-stimulation with IL-3 and IL-33 increases IKK activation and massively enhances cytokine production induced by IL-33.We further reveal that in neoplastic mast cells expressing constitutively active Ras, subthreshold IKK activation is associated with uncontrolled proliferation. Consequently, pharmacological IKK inhibition reduces tumor growth selectively by inducing apoptosis in vivo.Together, subthreshold IKK activation is crucial to mediate the full IL-33-induced effector functions in primary mast cells and to mediate uncontrolled proliferation of neoplastic mast cells. Thus, IKK2 is a new molecularly defined target structure. PMID:25749030

  10. Subthreshold IKK activation modulates the effector functions of primary mast cells and allows specific targeting of transformed mast cells

    PubMed Central

    Drube, Sebastian; Beyer, Mandy; Rothe, Mandy; Rabenhorst, Anja; Göpfert, Christiane; Meininger, Isabel; Diamanti, Michaela A.; Stegner, David; Häfner, Norman; Böttcher, Martin; Reinecke, Kirstin; Herdegen, Thomas; Greten, Florian R.; Nieswandt, Bernhard; Hartmann, Karin; Krämer, Oliver H.; Kamradt, Thomas

    2015-01-01

    Mast cell differentiation and proliferation depends on IL-3. IL-3 induces the activation of MAP-kinases and STATs and consequently induces proliferation and survival. Dysregulation of IL-3 signaling pathways also contribute to inflammation and tumorigenesis. We show here that IL-3 induces a SFK- and Ca2+-dependent activation of the inhibitor of κB kinases 2 (IKK2) which results in mast cell proliferation and survival but does not induce IκBα-degradation and NFκB activation. Therefore we propose the term “subthreshold IKK activation”. This subthreshold IKK activation also primes mast cells for enhanced responsiveness to IL-33R signaling. Consequently, co-stimulation with IL-3 and IL-33 increases IKK activation and massively enhances cytokine production induced by IL-33. We further reveal that in neoplastic mast cells expressing constitutively active Ras, subthreshold IKK activation is associated with uncontrolled proliferation. Consequently, pharmacological IKK inhibition reduces tumor growth selectively by inducing apoptosis in vivo. Together, subthreshold IKK activation is crucial to mediate the full IL-33-induced effector functions in primary mast cells and to mediate uncontrolled proliferation of neoplastic mast cells. Thus, IKK2 is a new molecularly defined target structure. PMID:25749030

  11. Twenty-first century mast cell stabilizers

    PubMed Central

    Finn, D F; Walsh, J J

    2013-01-01

    Mast cell stabilizing drugs inhibit the release of allergic mediators from mast cells and are used clinically to prevent allergic reactions to common allergens. Despite the relative success of the most commonly prescribed mast cell stabilizer, disodium cromoglycate, in use for the preventative treatment of bronchial asthma, allergic conjunctivitis and vernal keratoconjunctivitis, there still remains an urgent need to design new substances that are less expensive and require less frequent dosing schedules. In this regard, recent developments towards the discovery of the next generation of mast cell stabilizing drugs has included studies on substances isolated from natural sources, biological, newly synthesized compounds and drugs licensed for other indications. The diversity of natural products evaluated range from simple phenols, alkaloids, terpenes to simple amino acids. While in some cases their precise mode of action remains unknown it has nevertheless sparked interest in the development of synthetic derivatives with improved pharmacological properties. Within the purely synthetic class of inhibitors, particular attention has been devoted to the inhibition of important signalling molecules including spleen TK and JAK3. The statin class of cholesterol-lowering drugs as well as nilotinib, a TK inhibitor, are just some examples of clinically used drugs that have been evaluated for their anti-allergic properties. Here, we examine each approach under investigation, summarize the test data generated and offer suggestions for further preclinical evaluation before their therapeutic potential can be realized. Linked Articles This article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2013.170.issue-1 PMID:23441583

  12. Influence of the magnetic properties and repetitions on the energy product in layered thin film hard soft magnetic nanocomposites

    NASA Astrophysics Data System (ADS)

    Zagardo, David; Beik Mohammadi, Jamileh; Tuggle, Andrew; Mewes, Claudia; Mewes, Tim; Suzuki, Takao; MINT Center Team

    2015-03-01

    Exchange spring composites (hard-soft magnetic composites) are interesting for many applications such as rare-earth free permanent magnets and information storage. One key aspect is the figure of merit, the energy product, also called (BH)max. The system of study is a magnetic nano composite where each bilayer consists of a soft and hard magnetic material of total height of 22 nm. Using micromagnetic simulations we have investigated the influence of different ratios of the volume of the hard and soft layers on the energy product and the number of bilayer repetitions. Our findings indicate that the maximum energy product depends strongly on the volume ratio as well as on the number of repetitions. In addition we have studied the influence of different anisotropy contributions of the hard and soft magnetic layer on the energy product. Finally we have studied the influence of the interlayer exchange coupling on the energy product, which show that strong interlayer exchange coupling is necessary to reach a high energy product.

  13. Choroidal mast cells in retinal pathology: a potential target for intervention.

    PubMed

    Bousquet, Elodie; Zhao, Min; Thillaye-Goldenberg, Brigitte; Lorena, Viera; Castaneda, Beatriz; Naud, Marie Christine; Bergin, Ciara; Besson-Lescure, Bernadette; Behar-Cohen, Francine; de Kozak, Yvonne

    2015-08-01

    Mast cells are important in the initiation of ocular inflammation, but the consequences of mast cell degranulation on ocular pathology remain uncharacterized. We induced mast cell degranulation by local subconjunctival injection of compound 48/80. Initial degranulation of mast cells was observed in the choroid 15 minutes after the injection and increased up to 3 hours after injection. Clinical signs of anterior segment inflammation paralleled mast cell degranulation. With the use of optical coherence tomography, dilation of choroidal vessels and serous retinal detachments (SRDs) were observed and confirmed by histology. Subconjunctival injection of disodium cromoglycate significantly reduced the rate of SRDs, demonstrating the involvement of mast cell degranulation in posterior segment disorders. The infiltration of polymorphonuclear and macrophage cells was associated with increased ocular media concentrations of tumor necrosis factor-α, CXCL1, IL-6, IL-5, chemokine ligand 2, and IL-1β. Analysis of the amounts of vascular endothelial growth factor and IL-18 showed an opposite evolution of vascular endothelial growth factor compared with IL-18 concentrations, suggesting that they regulate each other's production. These findings suggest that the local degranulation of ocular mast cells provoked acute ocular inflammation, dilation, increased vascular permeability of choroidal vessels, and SRDs. The involvement of mast cells in retinal diseases should be further investigated. The pharmacologic inhibition of mast cell degranulation may be a potential target for intervention. PMID:26166807

  14. The dark side of mast cell-targeted therapy in prostate cancer.

    PubMed

    Pittoni, Paola; Colombo, Mario Paolo

    2012-02-15

    Tumor development requires accomplices among white blood cells. Other than macrophages, mast cells have been observed to support the outgrowth of certain neoplasias because of their proangiogenic properties. In some tumor settings, however, mast cells may have a protective role, exerted by their proinflammatory mediators. In prostate cancer, no conclusive data on mast cell function were available. Here, we discuss recent work on the role of mast cells in mouse and human prostate cancer, showing that mast cells can behave alternatively as dangerous promoters, innocent bystanders, or essential guardians of tumors, according to the stage and origin of transformed cells. In particular, mast cells are essential for the outgrowth of early-stage tumors due to their matrix metalloproteinase-9 production, become dispensable in advanced-stage, post-epithelial-to-mesenchymal transition, and are protective against neuroendocrine prostate tumor variants. The common expression of c-Kit by mast cells and neuroendocrine clones suggests a possible competition for the ligand Stem cell factor and offers the chance of curing early-stage disease while preventing neuroendocrine tumors using c-Kit-targeted therapy. This review discusses the implications of these findings on the advocated mast cell-targeted cancer therapy and considers future directions in the study of mast cells and their interactions with other c-Kit-expressing cells. PMID:22307838

  15. Vitamin D3 represses IgE-dependent mast cell activation via mast cell-CYP27B1 and -vitamin D receptor activity

    PubMed Central

    Yip, Kwok-Ho; Kolesnikoff, Natasha; Yu, Chunping; Hauschild, Nicholas; Taing, Houng; Biggs, Lisa; Goltzman, David; Gregory, Philip A.; Anderson, Paul H.; Samuel, Michael S.; Galli, Stephen J.; Lopez, Angel F.; Grimbaldeston, Michele A.

    2014-01-01

    Background Mast cells have gained notoriety based on their detrimental contributions to IgE-mediated allergic disorders. Although mast cells express the vitamin D receptor (VDR), it is not clear to what extent 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), or its predominant inactive precursor metabolite in circulation, 25-hydroxyvitamin D3 (25OHD3), can influence IgE-mediated mast cell activation and passive cutaneous anaphylaxis (PCA) in vivo. Objective We sought to assess whether the vitamin D3 metabolites, 25OHD3 and 1α,25(OH)2D3, can repress IgE-dependent mast cell activation via mast cell-CYP27B1 and -vitamin D receptor activity. Methods We measured the extent of vitamin D3 suppression of IgE-mediated mast cell degranulation and mediator production in vitro, as well as the vitamin D3-induced curtailment of PCA responses in WBB6F1-KitW/W-v or C57BL/6J-KitW-sh/W-sh mice engrafted with mast cells that did or did not express VDR or CYP27B1. Results Here we show that mouse and human mast cells can convert 25OHD3 to 1α,25(OH)2D3 via 25-hydroxyvitamin D-1α–hydroxylase (CYP27B1) activity, and that both of these vitamin D3 metabolites suppressed IgE-induced mast cell-derived pro-inflammatory and vasodilatory mediator production in a VDR-dependent manner in vitro. Furthermore, epicutaneously applied vitamin D3 metabolites significantly reduced the magnitude of skin swelling associated IgE-mediated PCA reactions in vivo; a response that required functional mast cell-VDRs and mast cell-CYP27B1. Conclusion Taken together, our findings provide a mechanistic explanation for the anti-inflammatory effects of vitamin D3 on mast cell function by demonstrating that mast cells can actively metabolize 25OHD3 to dampen IgE-mediated mast cell activation in vitro and in vivo. PMID:24461581

  16. Conversion of pesticides to biologically active products on urban hard surfaces.

    PubMed

    Jiang, Weiying; Gan, Jay

    2016-06-15

    Impervious pavements such as concrete are a dominant feature of urban landscapes, but their role in the fate of environmental contaminants is largely ignored. This study considered the case of urban-use pesticides, and demonstrated for the first time that surfaces such as concrete were capable of converting pesticides to other biologically active intermediates. Rapid transformation of pesticides was observed in both bench and field scale setups. Under outdoor conditions, permethrin, a heavily used pyrethroid insecticide, quickly formed 3-phenoxybenzoic acid (3-PBA) that is a known endocrine disruptor, and the level of 3-PBA was >100μg/L in the runoff water even 3months after the treatment. Fipronil, a product used for termite and ant control, was quickly transformed to desulfinyl and sulfone derivatives, with the desulfinyl level exceeding that of parent in the runoff water only 1week after treatment. Fipronil derivatives have aquatic toxicity similar or even greater than the parent fipronil. Direct sampling of deposited particles from residential exterior pavements revealed widespread presence of fipronil sulfone and desulfinyl and demonstrated their in-situ formation and accumulation on concrete. The extensive transformations were likely caused by the alkalinity and metal oxides in concrete and conducive photolytic conditions at the hard surfaces. The study findings highlight the role of urban pavements and urbanization in the geochemical cycling of anthropogenic contaminants. PMID:26971210

  17. Blockade of Mast Cell Activation Reduces Cutaneous Scar Formation

    PubMed Central

    Ranzer, Matthew J.; Wilgus, Traci A.; DiPietro, Luisa A.

    2014-01-01

    Damage to the skin initiates a cascade of well-orchestrated events that ultimately leads to repair of the wound. The inflammatory response is key to wound healing both through preventing infection and stimulating proliferation and remodeling of the skin. Mast cells within the tissue are one of the first immune cells to respond to trauma, and upon activation they release pro-inflammatory molecules to initiate recruitment of leukocytes and promote a vascular response in the tissue. Additionally, mast cells stimulate collagen synthesis by dermal fibroblasts, suggesting they may also influence scar formation. To examine the contribution of mast cells in tissue repair, we determined the effects the mast cell inhibitor, disodium cromoglycate (DSCG), on several parameters of dermal repair including, inflammation, re-epithelialization, collagen fiber organization, collagen ultrastructure, scar width and wound breaking strength. Mice treated with DSCG had significantly reduced levels of the inflammatory cytokines IL-1α, IL-1β, and CXCL1. Although DSCG treatment reduced the production of inflammatory mediators, the rate of re-epithelialization was not affected. Compared to control, inhibition of mast cell activity caused a significant decrease in scar width along with accelerated collagen re-organization. Despite the reduced scar width, DSCG treatment did not affect the breaking strength of the healed tissue. Tryptase β1 exclusively produced by mast cells was found to increase significantly in the course of wound healing. However, DSCG treatment did not change its level in the wounds. These results indicate that blockade of mast cell activation reduces scar formation and inflammation without further weakening the healed wound. PMID:24465509

  18. Blockade of mast cell activation reduces cutaneous scar formation.

    PubMed

    Chen, Lin; Schrementi, Megan E; Ranzer, Matthew J; Wilgus, Traci A; DiPietro, Luisa A

    2014-01-01

    Damage to the skin initiates a cascade of well-orchestrated events that ultimately leads to repair of the wound. The inflammatory response is key to wound healing both through preventing infection and stimulating proliferation and remodeling of the skin. Mast cells within the tissue are one of the first immune cells to respond to trauma, and upon activation they release pro-inflammatory molecules to initiate recruitment of leukocytes and promote a vascular response in the tissue. Additionally, mast cells stimulate collagen synthesis by dermal fibroblasts, suggesting they may also influence scar formation. To examine the contribution of mast cells in tissue repair, we determined the effects the mast cell inhibitor, disodium cromoglycate (DSCG), on several parameters of dermal repair including, inflammation, re-epithelialization, collagen fiber organization, collagen ultrastructure, scar width and wound breaking strength. Mice treated with DSCG had significantly reduced levels of the inflammatory cytokines IL-1α, IL-1β, and CXCL1. Although DSCG treatment reduced the production of inflammatory mediators, the rate of re-epithelialization was not affected. Compared to control, inhibition of mast cell activity caused a significant decrease in scar width along with accelerated collagen re-organization. Despite the reduced scar width, DSCG treatment did not affect the breaking strength of the healed tissue. Tryptase β1 exclusively produced by mast cells was found to increase significantly in the course of wound healing. However, DSCG treatment did not change its level in the wounds. These results indicate that blockade of mast cell activation reduces scar formation and inflammation without further weakening the healed wound. PMID:24465509

  19. Mast Cell Chemotaxis – Chemoattractants and Signaling Pathways

    PubMed Central

    Halova, Ivana; Draberova, Lubica; Draber, Petr

    2012-01-01

    Migration of mast cells is essential for their recruitment within target tissues where they play an important role in innate and adaptive immune responses. These processes rely on the ability of mast cells to recognize appropriate chemotactic stimuli and react to them by a chemotactic response. Another level of intercellular communication is attained by production of chemoattractants by activated mast cells, which results in accumulation of mast cells and other hematopoietic cells at the sites of inflammation. Mast cells express numerous surface receptors for various ligands with properties of potent chemoattractants. They include the stem cell factor (SCF) recognized by c-Kit, antigen, which binds to immunoglobulin E (IgE) anchored to the high affinity IgE receptor (FcεRI), highly cytokinergic (HC) IgE recognized by FcεRI, lipid mediator sphingosine-1-phosphate (S1P), which binds to G protein-coupled receptors (GPCRs). Other large groups of chemoattractants are eicosanoids [prostaglandin E2 and D2, leukotriene (LT) B4, LTD4, and LTC4, and others] and chemokines (CC, CXC, C, and CX3C), which also bind to various GPCRs. Further noteworthy chemoattractants are isoforms of transforming growth factor (TGF) β1–3, which are sensitively recognized by TGF-β serine/threonine type I and II β receptors, adenosine, C1q, C3a, and C5a components of the complement, 5-hydroxytryptamine, neuroendocrine peptide catestatin, tumor necrosis factor-α, and others. Here we discuss the major types of chemoattractants recognized by mast cells, their target receptors, as well as signaling pathways they utilize. We also briefly deal with methods used for studies of mast cell chemotaxis and with ways of how these studies profited from the results obtained in other cellular systems. PMID:22654878

  20. Mast cells in mammalian brain.

    PubMed

    Dropp, J J

    1976-01-01

    Mast cells, which had until recently been believed to be not present in the mammalian brain, were studied in the brains of 29 mammalian species. Although there was considerable intraspecific and interspecific variation, mast cells were most numerous within the leptomeninges (especially in those overlying the cerebrum and the dorsal thalamus - most rodents, most carnivores, chimpanzees, squirrel monkeys and elephant), the cerebral cortex (most rodents, tiger, fox, chimpanzee, tarsier, and elephant) and in many nuclei of the dorsal thalamus (most rodents, tiger, lion, and fox). In some mammals, mast cells were also numerous in the stroma of the telencephalic choroid plexuses (chimpanzee, squirrel monkey), the putamen and the claustrum (chimpanzee), the subfornical organ (pack rat, tiger, chimpanzee), the olfactory peduncles (hooded rat, albino rat), the stroma of the diencephalic choroid plexus (lion, chimpanzee, squirrel monkey), the pineal organ (chimpanzee, squirrel monkey), some nuclei of the hypothalamus (tiger), the infundibulum (hooded rat, tiger, fox) the area postrema (pack rat, chinchilla, lion, spider monkey, chimpanzee, fox) and some nuclei and tracts of the metencephalon and the myelencephalon (tiger). Neither the sex of the animal nor electrolytic lesions made in the brains of some of the animals at various times prior to sacrifice appeared to effect the number and the distribution of mast cells. Age-related changes in mast cell number and distribution were detected in the albino rat. PMID:961335

  1. Cytoskeleton in Mast Cell Signaling

    PubMed Central

    Dráber, Pavel; Sulimenko, Vadym; Dráberová, Eduarda

    2012-01-01

    Mast cell activation mediated by the high affinity receptor for IgE (FcεRI) is a key event in allergic response and inflammation. Other receptors on mast cells, as c-Kit for stem cell factor and G protein-coupled receptors (GPCRs) synergistically enhance the FcεRI-mediated release of inflammatory mediators. Activation of various signaling pathways in mast cells results in changes in cell morphology, adhesion to substrate, exocytosis, and migration. Reorganization of cytoskeleton is pivotal in all these processes. Cytoskeletal proteins also play an important role in initial stages of FcεRI and other surface receptors induced triggering. Highly dynamic microtubules formed by αβ-tubulin dimers as well as microfilaments build up from polymerized actin are affected in activated cells by kinases/phosphatases, Rho GTPases and changes in concentration of cytosolic Ca2+. Also important are nucleation proteins; the γ-tubulin complexes in case of microtubules or Arp 2/3 complex with its nucleation promoting factors and formins in case of microfilaments. The dynamic nature of microtubules and microfilaments in activated cells depends on many associated/regulatory proteins. Changes in rigidity of activated mast cells reflect changes in intermediate filaments build up from vimentin. This review offers a critical appraisal of current knowledge on the role of cytoskeleton in mast cells signaling. PMID:22654883

  2. Preliminary effects of water hardness on triactinomyxon production and development from eastern tubifex worms infected with Myxobolus cerebralis

    USGS Publications Warehouse

    Waldrop, Thomas B.; Densmore, Christine; Blazer, Vicki; Smith, Dave; Schill, Bane

    1999-01-01

    Whirling disease is caused by Myxobolus cerebralis and requires an intermediate oligochaete host identified as Tubifex tubifex (Wolf, Markiw, and Hiltunen, 1986). M. cerebralis spores ingested by the tubifex worms develop into triactinomyxons (tams) that are eventually released into the water column to infect salmonid fish. There may be many environmental parameters, biotic or abiotic, that may affect the development of waterborne tams in eastern tubifex worms. This study will focus on one of those environmental parameters, total water hardness. Total water hardness is defined as the concentration of calcium and magnesium in a water sample expressed in milligrams per liter of equivalent CACO3 (Boyd, 1990). This study will address whether different levels of water hardness affect the development and production of tams released by infected tubifex worms.

  3. Influence of Physicochemical Properties of Silver Nanoparticles on Mast Cell Activation and Degranulation

    PubMed Central

    Aldossari, Abdullah A.; Shannahan, Jonathan H.; Podila, Ramakrishna; Brown, Jared M.

    2014-01-01

    Silver nanoparticles (AgNPs) are increasingly being incorporated into products for their antimicrobial properties. This has resulted in increased human exposures and the possibility of adverse health effects. Mast cells orchestrate allergic immune responses through degranulation and release of pre-formed mediators. Little data exists on understanding interactions of AgNPs with mast cells and the properties that influence activation and degranulation. Using bone marrow-derived mast cells and AgNPs of varying physicochemical properties we tested the hypothesis that AgNP physicochemical properties influence mast cell degranulation and osteopontin production. AgNPs evaluated included spherical 20 nm and 110 nm suspended in either polyvinylpyrrolidone (PVP) or citrate, Ag plates suspended in PVP of diameters between 40–60 nm or 100–130 nm, and Ag nanowires suspended in PVP with thicknesses <100 nm and length up to 2 microns. Mast cell responses were found to be dependent on the physicochemical properties of the AgNP. Further, we determined a role for scavenger receptor B1 in AgNP-induced mast cell responses. Mast cell degranulation was not dependent on AgNP dissolution but was prevented by tyrosine kinsase inhibitor pretreatment. This study suggests that exposure to AgNPs may elicit adverse mast cell responses that could contribute to the initiation or exacerbation of allergic disease. PMID:25458489

  4. Modulation of mast cell and basophil functions by benzene metabolites.

    PubMed

    Triggiani, Massimo; Loffredo, Stefania; Granata, Francescopaolo; Staiano, Rosaria I; Marone, Gianni

    2011-11-01

    Benzene is a carcinogenic compound used in industrial manufacturing and a common environmental pollutant mostly derived from vehicle emissions and cigarette smoke. Benzene exposure is associated with a variety of clinical conditions ranging from hematologic diseases to chronic lung disorders. Beside its direct toxicity, benzene exerts multiple effects after being converted to reactive metabolites such as hydroquinone and benzoquinone. Mast cells and basophils are primary effector cells involved in the development of respiratory allergies such as rhinitis and bronchial asthma and they play an important role in innate immunity. Benzene and its metabolites can influence mast cell and basophil responses either directly or by interfering with other cells, such as T cells, macrophages and monocytes, which are functionally connected to mast cells and basophils. Hydroquinone and benzoquinone inhibit the release of preformed mediators, leukotriene synthesis and cytokine production in human basophils stimulated by IgE- and non IgE-mediated agonists. Furthermore, these metabolites reduce IgE-mediated degranulation of mast cells and the development of allergic lung inflammation in rats. Both in vitro and in vivo studies indicate that benzene metabolites alter biochemical and functional activities of other immunocompetent cells and may impair immune responses in the lung. These inhibitory effects of benzene metabolites are primarily mediated by interference with early transduction signals such as PI3 kinase. Together, currently available studies indicate that benzene metabolites interfere by multiple mechanisms with the role of basophils and mast cells in innate immunity and in chronic inflammation in the lung. PMID:22103854

  5. Targeting Cardiac Mast Cells: Pharmacological Modulation of the Local Renin-Angiotensin System

    PubMed Central

    Reid, Alicia C.; Brazin, Jacqueline A.; Morrey, Christopher; Silver, Randi B.; Levi, Roberto

    2012-01-01

    Enhanced production of angiotensin II and excessive release of norepinephrine in the ischemic heart are major causes of arrhythmias and sudden cardiac death. Mast cell-dependent mechanisms are pivotal in the local formation of angiotensin II and modulation of norepinephrine release in cardiac pathophysiology. Cardiac mast cells increase in number in myocardial ischemia and are located in close proximity to sympathetic neurons expressing angiotensin AT1- and histamine H3-receptors. Once activated, cardiac mast cells release a host of potent pro-inflammatory and pro-fibrotic cytokines, chemokines, preformed mediators (e.g., histamine) and proteases (e.g., renin). In myocardial ischemia, angiotensin II (formed locally from mast cell-derived renin) and histamine (also released from local mast cells) respectively activate AT1- and H3-receptors on sympathetic nerve endings. Stimulation of angiotensin AT1-receptors is arrhythmogenic whereas H3-receptor activation is cardioprotective. It is likely that in ischemia/reperfusion the balance may be tipped toward the deleterious effects of mast cell renin, as demonstrated in mast cell-deficient mice, lacking mast cell renin and histamine in the heart. In these mice, no ventricular fibrillation occurs at reperfusion following ischemia, as opposed to wild-type hearts which all fibrillate. Preventing mast cell degranulation in the heart and inhibiting the activation of a local reninangiotensin system, hence abolishing its detrimental effects on cardiac rhythmicity, appears to be more significant than the loss of histamine-induced cardioprotection. This suggests that therapeutic targets in the treatment of myocardial ischemia, and potentially congestive heart failure and hypertension, should include prevention of mast cell degranulation, mast cell renin inhibition, local ACE inhibition, ANG II antagonism and H3-receptor activation. PMID:22103845

  6. 30 CFR 56.7004 - Drill mast.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Drill mast. 56.7004 Section 56.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling § 56.7004 Drill mast. Persons shall not be on a mast while the drill-bit is in operation...

  7. 30 CFR 57.7004 - Drill mast.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Drill mast. 57.7004 Section 57.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling-Surface Only § 57.7004 Drill mast. Persons shall not be on a mast while the drill-bit is...

  8. 30 CFR 57.7004 - Drill mast.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Drill mast. 57.7004 Section 57.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling-Surface Only § 57.7004 Drill mast. Persons shall not be on a mast while the drill-bit is...

  9. 30 CFR 56.7004 - Drill mast.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Drill mast. 56.7004 Section 56.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling § 56.7004 Drill mast. Persons shall not be on a mast while the drill-bit is in operation...

  10. 30 CFR 56.7004 - Drill mast.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Drill mast. 56.7004 Section 56.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling § 56.7004 Drill mast. Persons shall not be on a mast while the drill-bit is in operation...

  11. 30 CFR 57.7004 - Drill mast.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Drill mast. 57.7004 Section 57.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling-Surface Only § 57.7004 Drill mast. Persons shall not be on a mast while the drill-bit is...

  12. 30 CFR 57.7004 - Drill mast.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Drill mast. 57.7004 Section 57.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling-Surface Only § 57.7004 Drill mast. Persons shall not be on a mast while the drill-bit is...

  13. 30 CFR 56.7004 - Drill mast.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Drill mast. 56.7004 Section 56.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling § 56.7004 Drill mast. Persons shall not be on a mast while the drill-bit is in operation...

  14. 30 CFR 56.7004 - Drill mast.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Drill mast. 56.7004 Section 56.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling § 56.7004 Drill mast. Persons shall not be on a mast while the drill-bit is in operation...

  15. 30 CFR 57.7004 - Drill mast.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Drill mast. 57.7004 Section 57.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling-Surface Only § 57.7004 Drill mast. Persons shall not be on a mast while the drill-bit is...

  16. Automatic Erection System for Antenna Masts

    NASA Technical Reports Server (NTRS)

    Dotson, R. D.; Jacquemin, G. G.

    1985-01-01

    A telescoping mast does not require the payout of guy wires under tension. Erection system is built into stack of telescoping mast elements and is thereby protected from the weather. Concept is based on a telescoping tube mast, it is also applicable to an open truss with only minor modifications.

  17. Signal transduction pathways in mast cell granule-mediated endothelial cell activation.

    PubMed Central

    Chi, Luqi; Stehno-Bittel, Lisa; Smirnova, Irina; Stechschulte, Daniel J; Dileepan, Kottarappat N

    2003-01-01

    BACKGROUND: We have previously shown that incubation of human endothelial cells with mast cell granules results in potentiation of lipopolysaccharide-induced production of interleukin-6 and interleukin-8. AIMS: The objective of the present study was to identify candidate molecules and signal transduction pathways involved in the synergy between mast cell granules and lipopolysaccharide on endothelial cell activation. METHODS: Human umbilical vein endothelial cells were incubated with rat mast cell granules in the presence and absence of lipopolysaccharide, and IL-6 production was quantified. The status of c-Jun amino-terminal kinase and extracellular signal-regulated kinase 1/2 activation, nuclear factor-kappaB translocation and intracellular calcium levels were determined to identify the mechanism of synergy between mast cell granules and lipopolysaccaride. RESULTS: Mast cell granules induced low levels of interleukin-6 production by endothelial cells, and this effect was markedly enhanced by lipopolysaccharide. The results revealed that both serine proteases and histamine present in mast cell granules were involved in this activation process. Mast cell granules increased intracellular calcium, and activated c-Jun amino-terminal kinase and extracellular signal-regulated kinase 1/2. The combination of lipopolysaccharide and mast cell granules prolonged c-Jun amino-terminal kinase activity beyond the duration of induction by either stimulant alone and was entirely due to active proteases. However, both proteases and histamine contributed to calcium mobilization and extracellular signal-regulated kinase 1/2 activation. The nuclear translocation of nuclear factor-kappaB proteins was of greater magnitude in endothelial cells treated with the combination of mast cell granules and lipopolysaccharide. CONCLUSIONS:Mast cell granule serine proteases and histamine can amplify lipopolysaccharide-induced endothelial cell activation, which involves calcium mobilization, mitogen

  18. PTEN deficiency in mast cells causes a mastocytosis-like proliferative disease that heightens allergic responses and vascular permeability

    PubMed Central

    Furumoto, Yasuko; Charles, Nicolas; Olivera, Ana; Leung, Wai Hang; Dillahunt, Sandra; Sargent, Jennifer L.; Tinsley, Kevin; Odom, Sandra; Scott, Eric; Wilson, Todd M.; Ghoreschi, Kamran; Kneilling, Manfred; Chen, Mei; Lee, David M.; Bolland, Silvia

    2011-01-01

    Kit regulation of mast cell proliferation and differentiation has been intimately linked to the activation of phosphatidylinositol 3-OH kinase (PI3K). The activating D816V mutation of Kit, seen in the majority of mastocytosis patients, causes a robust activation of PI3K signals. However, whether increased PI3K signaling in mast cells is a key element for their in vivo hyperplasia remains unknown. Here we report that dysregulation of PI3K signaling in mice by deletion of the phosphatase and tensin homolog (Pten) gene (which regulates the levels of the PI3K product, phosphatidylinositol 3,4,5-trisphosphate) caused mast cell hyperplasia and increased numbers in various organs. Selective deletion of Pten in the mast cell compartment revealed that the hyperplasia was intrinsic to the mast cell. Enhanced STAT5 phosphorylation and increased expression of survival factors, such as Bcl-XL, were observed in PTEN-deficient mast cells, and these were further enhanced by stem cell factor stimulation. Mice carrying PTEN-deficient mast cells also showed increased hypersensitivity as well as increased vascular permeability. Thus, Pten deletion in the mast cell compartment results in a mast cell proliferative phenotype in mice, demonstrating that dysregulation of PI3K signals is vital to the observed mast cell hyperplasia. PMID:21926349

  19. Live Staphylococcus aureus Induces Expression and Release of Vascular Endothelial Growth Factor in Terminally Differentiated Mouse Mast Cells

    PubMed Central

    Johnzon, Carl-Fredrik; Rönnberg, Elin; Guss, Bengt; Pejler, Gunnar

    2016-01-01

    Mast cells have been shown to express vascular endothelial growth factor (VEGF), thereby implicating mast cells in pro-angiogenic processes. However, the mechanism of VEGF induction in mast cells and the possible expression of VEGF in fully mature mast cells have not been extensively studied. Here, we report that terminally differentiated peritoneal cell-derived mast cells can be induced to express VEGF in response to challenge with Staphylococcus aureus, thus identifying a mast cell–bacteria axis as a novel mechanism leading to VEGF release. Whereas live bacteria produced a robust upregulation of VEGF in mast cells, heat-inactivated bacteria failed to do so, and bacteria-conditioned media did not induce VEGF expression. The induction of VEGF was not critically dependent on direct cell–cell contact between bacteria and mast cells. Hence, these findings suggest that VEGF can be induced by soluble factors released during the co-culture conditions. Neither of a panel of bacterial cell-wall products known to activate toll-like receptor (TLR) signaling promoted VEGF expression in mast cells. In agreement with the latter, VEGF induction occurred independently of Myd88, an adaptor molecule that mediates the downstream events following TLR engagement. The VEGF induction was insensitive to nuclear factor of activated T-cells inhibition but was partly dependent on the nuclear factor kappa light-chain enhancer of activated B cells signaling pathway. Together, these findings identify bacterial challenge as a novel mechanism by which VEGF is induced in mast cells. PMID:27446077

  20. Deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice

    PubMed Central

    Liu, Jian; Divoux, Adeline; Sun, Jiusong; Zhang, Jie; Clément, Karine; Glickman, Jonathan N.; Sukhova, Galina K.; Wolters, Paul J.; Du, Juan; Gorgun, Cem Z.; Doria, Alessandro; Libby, Peter; Blumberg, Richard S.; Kahn, Barbara B.; Hotamisligil, Gokhan S.; Shi, Guo-Ping

    2009-01-01

    Although mast cell functions classically relate to allergic responses1–3, recent studies indicate that these cells contribute to other common diseases such as multiple sclerosis, rheumatoid arthritis, atherosclerosis, aortic aneurysm, and cancer4–8. This study presents evidence that mast cells contribute importantly to diet-induced obesity and diabetes. White adipose tissues (WAT) from obese humans and mice contain more mast cells than WAT from their lean counterparts. Genetically determined mast cell deficiency and pharmacological stabilization of mast cells in mice reduce body weight gain and levels of inflammatory cytokines, chemokines, and proteases in serum and WAT, in concert with improved glucose homeostasis and energy expenditure. Mechanistic studies reveal that mast cells contribute to WAT and muscle angiogenesis and associated cell apoptosis and cathepsin activity. Adoptive transfer of cytokine-deficient mast cells established that these cells contribute to mice adipose tissue cysteine protease cathepsin expression, apoptosis, and angiogenesis, thereby promoting diet-induced obesity and glucose intolerance by production of IL6 and IFN-γ. Mast cell stabilizing agents in clinical use reduced obesity and diabetes in mice, suggesting the potential of developing novel therapies for these common human metabolic disorders. PMID:19633655

  1. Archiving Community Contributed Data in MAST

    NASA Astrophysics Data System (ADS)

    Levay, K.; Kamp, I.; Thompson, R.; Smith, M.; White, R. L.

    2007-10-01

    High-Level Science Products (HLSPs) are community contributed, fully processed (reduced, co-added, cosmic-ray cleaned etc.) images and spectra that are ready for scientific analysis. HLSPs also include files such as object catalogs, spectral atlases, and README files describing a given set of data. The Multi-mission Archive at the Space Telescope Science Institute (MAST) solicits HLSPs from the community by (a) sending letters to the PIs of approved Treasury, Archival Legacy and Large proposals on HST, (b) discussing with scientists and distributing flyers at conferences and meetings, (c) newsletter articles, and (d) communicating with authors after reading pertinent journal papers. We work with the scientist to ensure a proper data format (e.g. by using a FITS verifier), a proper description of the data reduction process and the entire data product in the form of an ASCII file (README), and (if necessary) web pages. The HLSPs are kept separate from the original MAST data, although information is preserved to indicate how one is related to the other. Several image-based HLSPs are already provided through the Virtual Observatory (VO) Simple Image Access Protocol (SIAP), and spectral data will eventually be available using the Simple Spectral Access Protocol.

  2. IL-9 production by regulatory T cells recruits mast cells that are essential for regulatory T cell-induced immune suppression.

    PubMed

    Eller, Kathrin; Wolf, Dominik; Huber, Julia M; Metz, Martin; Mayer, Gert; McKenzie, Andrew N J; Maurer, Marcus; Rosenkranz, Alexander R; Wolf, Anna M

    2011-01-01

    Both mast cells (MCs) and regulatory T cells (Tregs) have gained attention as immunosuppressive cell populations. To investigate a possible interaction, we used the Th1- and Th17-dependent model of nephrotoxic serum nephritis (NTS), in which both MCs and Tregs have been shown to play a protective role. Transfer of wild-type (wt) Tregs into wt recipients almost completely prevents development of NTS and leads to a profound increase of MCs in the renal draining lymph nodes (LNs). By contrast, transfer of wt Tregs into animals deficient in MCs, which are characterized by an exaggerated susceptibility to NTS, no longer exhibited protective effects. Blocking the pleiotropic cytokine IL-9, known to be involved in MC recruitment and proliferation, by means of a mAb in mice receiving Tregs abrogated protection from NTS. Moreover, transfer of IL-9-deficient Tregs also failed to protect from NTS. In the absence of Treg-derived IL-9, MCs fail to accumulate in the LNs, despite the fact that IL-9 deficiency does not alter the general suppressive activity of Tregs. In summary, to our knowledge, we provide the first direct in vivo evidence that the nephroprotective, anti-inflammatory effects of Tregs critically depend on IL-9-mediated attraction of MCs into kidney-draining LNs. PMID:21115728

  3. Mast cell secretory granules: armed for battle.

    PubMed

    Wernersson, Sara; Pejler, Gunnar

    2014-07-01

    Mast cells are important effector cells of the immune system and recent studies show that they have immunomodulatory roles in diverse processes in both health and disease. Mast cells are distinguished by their high content of electron-dense secretory granules, which are filled with large amounts of preformed and pre-activated immunomodulatory compounds. When appropriately activated, mast cells undergo degranulation, a process by which these preformed granule compounds are rapidly released into the surroundings. In many cases, the effects that mast cells have on an immune response are closely associated with the biological actions of the granule compounds that they release, as exemplified by the recent studies showing that mast cell granule proteases account for many of the protective and detrimental effects of mast cells in various inflammatory settings. In this Review, we discuss the current knowledge of mast cell secretory granules. PMID:24903914

  4. Lipid Rafts in Mast Cell Biology

    PubMed Central

    Silveira e Souza, Adriana Maria Mariano; Mazucato, Vivian Marino; Jamur, Maria Célia; Oliver, Constance

    2011-01-01

    Mast cells have long been recognized to have a direct and critical role in allergic and inflammatory reactions. In allergic diseases, these cells exert both local and systemic responses, including allergic rhinitis and anaphylaxis. Mast cell mediators are also related to many chronic inflammatory conditions. Besides the roles in pathological conditions, the biological functions of mast cells include roles in innate immunity, involvement in host defense mechanisms against parasites, immunomodulation of the immune system, tissue repair, and angiogenesis. Despite their growing significance in physiological and pathological conditions, much still remains to be learned about mast cell biology. This paper presents evidence that lipid rafts or raft components modulate many of the biological processes in mast cells, such as degranulation and endocytosis, play a role in mast cell development and recruitment, and contribute to the overall preservation of mast cell structure and organization. PMID:21490812

  5. Mast Cells in Allergic Diseases and Mastocytosis

    PubMed Central

    Marquardt, Diana L.; Wasserman, Stephen I.

    1982-01-01

    Mast cells with their stores of vasoactive and chemotactic mediators are central to the pathogenesis of allergic diseases. The cross-linking of receptorbound IgE molecules on the surface of mast cells initiates a complex chain of events, including calcium ion influx, phospholipid methylation and turnover and cyclic nucleotide metabolism, ultimately resulting in the release of mediators of immediate hypersensitivity. These mast cell mediators are important in smooth muscle reactivity, in the recruitment of eosinophilic and neutrophilic leukocytes and in the generation of secondary chemical mediators. Histologic evidence of mast cell degranulation, biochemical evidence of mast cell mediators in blood and tissues and clinical evidence of signs and symptoms reproducible by these mediators have strongly supported the crucial role of mast cells in asthma, urticaria, anaphylaxis, rhinitis and mastocytosis. Because of their unique location at host environment interfaces, mast cells may both participate in allergic diseases and promote homeostasis. ImagesFigure 1.Figure 2.Figure 3. PMID:6293204

  6. Mast cells mediate acute inflammatory responses to implanted biomaterials

    PubMed Central

    Tang, Liping; Jennings, Timothy A.; Eaton, John W.

    1998-01-01

    Implanted biomaterials trigger acute and chronic inflammatory responses. The mechanisms involved in such acute inflammatory responses can be arbitrarily divided into phagocyte transmigration, chemotaxis, and adhesion to implant surfaces. We earlier observed that two chemokines—macrophage inflammatory protein 1α/monocyte chemoattractant protein 1—and the phagocyte integrin Mac-1 (CD11b/CD18)/surface fibrinogen interaction are, respectively, required for phagocyte chemotaxis and adherence to biomaterial surfaces. However, it is still not clear how the initial transmigration of phagocytes through the endothelial barrier into the area of the implant is triggered. Because implanted biomaterials elicit histaminic responses in the surrounding tissue, and histamine release is known to promote rapid diapedesis of inflammatory cells, we evaluated the possible role of histamine and mast cells in the recruitment of phagocytes to biomaterial implants. Using i.p. and s.c. implantation of polyethylene terephthalate disks in mice we find: (i) Extensive degranulation of mast cells, accompanied by histamine release, occurs adjacent to short-term i.p. implants. (ii) Simultaneous administration of H1 and H2 histamine receptor antagonists (pyrilamine and famotidine, respectively) greatly diminishes recruitment and adhesion of both neutrophils (<20% of control) and monocytes/macrophages (<30% of control) to implants. (iii) Congenitally mast cell-deficient mice also exhibit markedly reduced accumulation of phagocytes on both i.p. and s.c implants. (iv) Finally, mast cell reconstitution of mast cell-deficient mice restores “normal” inflammatory responses to biomaterial implants. We conclude that mast cells and their granular products, especially histamine, are important in recruitment of inflammatory cells to biomaterial implants. Improved knowledge of such responses may permit purposeful modulation of both acute and chronic inflammation affecting implanted biomaterials. PMID

  7. Mast cell-derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B.

    PubMed

    Grimbaldeston, Michele A; Nakae, Susumu; Kalesnikoff, Janet; Tsai, Mindy; Galli, Stephen J

    2007-10-01

    Allergic contact dermatitis, such as in response to poison ivy or poison oak, and chronic low-dose ultraviolet B irradiation can damage the skin. Mast cells produce proinflammatory mediators that are thought to exacerbate these prevalent acquired immune or innate responses. Here we found that, unexpectedly, mast cells substantially limited the pathology associated with these responses, including infiltrates of leukocytes, epidermal hyperplasia and epidermal necrosis. Production of interleukin 10 by mast cells contributed to the anti-inflammatory or immunosuppressive effects of mast cells in these conditions. Our findings identify a previously unrecognized function for mast cells and mast cell-derived interleukin 10 in limiting leukocyte infiltration, inflammation and tissue damage associated with immunological or innate responses that can injure the skin. PMID:17767162

  8. Nitrogen storage dynamics are affected by masting events in Fagus crenata.

    PubMed

    Han, Qingmin; Kabeya, Daisuke; Iio, Atsuhiro; Inagaki, Yoshiyuki; Kakubari, Yoshitaka

    2014-03-01

    It is generally assumed that the production of a large crop of seeds depletes stores of resources and that these take more than 1 year to replenish; this is accepted, theoretically, as the proximate mechanism of mast seeding (resource budget model). However, direct evidence of resource depletion in masting trees is very rare. Here, we trace seasonal and inter-annual variations in nitrogen (N) concentration and estimate the N storage pool of individuals after full masting of Fagus crenata in two stands. In 2005, a full masting year, the amount of N in fruit litter represented half of the N present in mature leaves in an old stand (age 190-260 years), and was about equivalent to the amount of N in mature leaves in a younger stand (age 83-84 years). Due to this additional burden, both tissue N concentration and individual N storage decreased in 2006; this was followed by significant replenishment in 2007, although a substantial N store remained even after full masting. These results indicate that internal storage may be important and that N may be the limiting factor for fruiting. In the 4 years following full masting, the old stand experienced two moderate masting events separated by 2 years, whilst trees in the younger stand did not fruit. This different fruiting behavior may be related to different "costs of reproduction" in the full masting year 2005, thus providing more evidence that N may limit fruiting. Compared to the non-fruiting stand, individuals in the fruiting stand exhibited an additional increase in N concentrations in roots early in the 2007 growing season, suggesting additional N uptake from the soil to supply resource demand. The enhanced uptake may alleviate the N storage depletion observed in the full masting year. This study suggests that masting affects N cycle dynamics in mature Fagus crenata and N may be one factor limiting fruiting. PMID:24221082

  9. Zipper mast for enhanced communications and surveillance

    NASA Astrophysics Data System (ADS)

    Woodruff, George; Muench, Paul; Witus, Gary

    2011-05-01

    In this project, we further developed and tested a "ZipperMast" for small robots and legacy manned vehicles. The ZipperMast knits three coiled bands of spring steel together to form a rigid mast. As the mast is extended, it draws up a cable connecting the host platform to the payload, typically antennas and sensors. Elevating the payload improves line of sight, and thus improves radio communication and surveillance situation awareness. When the mast is retracted, the interior cable slides into a horizontal tray. The ZipperMast is a scaleable design. We have made systems that elevate to 8 and 20 feet. The 8 foot ZipperMast collapses to less that 8 inches high and 8 inches wide. The 20 foot ZipperMast collapses to less that 12 inches high and 18 inches wide. In this paper we report on tests of the mechanical properties of the mast, specifically the strength and stiffness under quasi-static and impulsive loading. These properties are important for specifying constraints on height as a function of speed and payload and on speed as a function of height and payload in order to ensure that the mast will not fail in the event of sudden stop, as in the event of a collision.

  10. Tetraspanin CD151 Is a Negative Regulator of FcεRI-Mediated Mast Cell Activation

    PubMed Central

    Abdala-Valencia, Hiam; Bryce, Paul J.; Schleimer, Robert P.; Wechsler, Joshua B.; Loffredo, Lucas F.; Cook-Mills, Joan M.; Hsu, Chia-Lin; Berdnikovs, Sergejs

    2016-01-01

    Mast cells are critical in the pathogenesis of allergic disease due to the release of preformed and newly synthesized mediators, yet the mechanisms controlling mast cell activation are not well understood. Members of the tetraspanin family are recently emerging as modulators of FcεRI-mediated mast cell activation; however, mechanistic understanding of their function is currently lacking. The tetraspanin CD151 is a poorly understood member of this family and is specifically induced on mouse and human mast cells upon FcεRI aggregation but its functional effects are unknown. In this study, we show that CD151 deficiency significantly exacerbates the IgE-mediated late phase inflammation in a murine model of passive cutaneous anaphylaxis. Ex vivo, FcεRI stimulation of bone marrow–derived mast cells from CD151−/− mice resulted in significantly enhanced expression of proinflammatory cytokines IL-4, IL-13, and TNF-α compared with wild-type controls. However, FcεRI -induced mast cell degranulation was unaffected. At the molecular signaling level, CD151 selectively regulated IgE-induced activation of ERK1/2 and PI3K, associated with cytokine production, but had no effect on the phospholipase Cγ1 signaling, associated with degranulation. Collectively, our data indicate that CD151 exerts negative regulation over IgE-induced late phase responses and cytokine production in mast cells. PMID:26136426

  11. Tetraspanin CD151 Is a Negative Regulator of FcεRI-Mediated Mast Cell Activation.

    PubMed

    Abdala-Valencia, Hiam; Bryce, Paul J; Schleimer, Robert P; Wechsler, Joshua B; Loffredo, Lucas F; Cook-Mills, Joan M; Hsu, Chia-Lin; Berdnikovs, Sergejs

    2015-08-15

    Mast cells are critical in the pathogenesis of allergic disease due to the release of preformed and newly synthesized mediators, yet the mechanisms controlling mast cell activation are not well understood. Members of the tetraspanin family are recently emerging as modulators of FcεRI-mediated mast cell activation; however, mechanistic understanding of their function is currently lacking. The tetraspanin CD151 is a poorly understood member of this family and is specifically induced on mouse and human mast cells upon FcεRI aggregation but its functional effects are unknown. In this study, we show that CD151 deficiency significantly exacerbates the IgE-mediated late phase inflammation in a murine model of passive cutaneous anaphylaxis. Ex vivo, FcεRI stimulation of bone marrow-derived mast cells from CD151(-/-) mice resulted in significantly enhanced expression of proinflammatory cytokines IL-4, IL-13, and TNF-α compared with wild-type controls. However, FcεRI-induced mast cell degranulation was unaffected. At the molecular signaling level, CD151 selectively regulated IgE-induced activation of ERK1/2 and PI3K, associated with cytokine production, but had no effect on the phospholipase Cγ1 signaling, associated with degranulation. Collectively, our data indicate that CD151 exerts negative regulation over IgE-induced late phase responses and cytokine production in mast cells. PMID:26136426

  12. Asymmetric divertor biasing in MAST

    NASA Astrophysics Data System (ADS)

    Helander, P.; Cohen, R.; Counsell, G. C.; Ryutov, D. D.

    2002-11-01

    Experiments are being carried out on the Mega-Ampere Spherical Tokamak (MAST) where the divertor tiles are electrically biased in a toroidally alternating way. The aim is to induce convective cells in the divertor plasma, broaden the SOL and reduce the divertor heat load. This paper describes the underlying theory and experimental results. Criteria are presented for achieving strong broadening and exciting shear-flow turbulence in the SOL, and properties of the expected turbulence are derived. It is also shown that magnetic shear near the X-point is likely to confine the potential perturbations to the divertor region, leaving the part of the SOL that is in direct contact with the core plasma intact. Preliminary comparison of the theory with MAST data is encouraging: the distortion of the heat deposition pattern, its broadening, and the incremental heat load are qualitatively in agreement; quantitative comparisons are underway.

  13. Signaling through Toll-like receptors triggers HIV-1 replication in latently infected mast cells.

    PubMed

    Sundstrom, J Bruce; Little, Dawn M; Villinger, Francois; Ellis, Jane E; Ansari, Aftab A

    2004-04-01

    Evidence that human progenitor mast cells are susceptible to infection with CCR5-tropic strains of HIV-1 and that circulating HIV-1-infected FcepsilonRIalpha(+) cells with a similar progenitor phenotype have been isolated from AIDS patients has led to speculation that mast cells may serve as a potential reservoir for infectious HIV-1. In this study, progenitor mast cells, developed in vitro from CD34(+) cord blood stem cells, were experimentally infected with the CCR5-tropic strain HIV-1Bal after 28 days in culture as they reached their HIV-1-susceptible progenitor stage. HIV-1 p24 Ag levels were readily detectable by day 7 postinfection (PI), peaked at 2-3 wk PI as mature (tryptase/chymase-positive) HIV-1 infection-resistant mast cells emerged, and then steadily declined to below detectable limits by 10 wk PI, at which point integrated HIV-1 proviral DNA was confirmed by PCR quantitation in ( approximately 34% of) latently infected mast cells. Stimulation by ligands for Toll-like receptor (TLR) 2, TLR4, or TLR9 significantly enhanced viral replication in a dose- and time-dependent manner in both HIV-1-infected progenitor and latently infected mature mast cells, without promoting degranulation, apoptosis, cellular proliferation, or dysregulation of TLR agonist-induced cytokine production in infected mast cells. Limiting dilution analysis of TLR activated, latently infected mature mast cells indicated that one in four was capable of establishing productive infections in A301 sentinel cells. Taken together, these results indicate that mast cells may serve both as a viral reservoir and as a model for studying mechanisms of postintegration latency in HIV infection. PMID:15034054

  14. Mast material test program (MAMATEP)

    NASA Technical Reports Server (NTRS)

    Ciancone, Michael L.; Rutledge, Sharon K.

    1988-01-01

    The Mast Material Test Program (MAMATEP) at NASA Lewis is discussed. Objectives include verifying the need for, and evaluating the performance of, various protection techniques for the Solar Array Assembly mast of the Space Station Photovoltaic Power Module. Mast material samples were evaluated in terms of mass and bending modulus, measured before and after environmental exposure. Test environments included atomic oxygen exposure (RF plasma asher), thermal cycling, and mechanical flexing. Protective coatings included CV-1144 silicon, a Ni/Au/InSn eutectic, and an open weave, Al braid. Results indicate that unprotected samples degrade in an atomic oxygen environment at a steady rate. Open weave, Al braid offers little protection for the fiberglass-epoxy sample in an asher environment. Ni/Au/InSn eutectic offers excellent protection in an asher environment prior to thermal cycling and mechanical flexing. Long duration asher results from unprotected samples indicate that, even though the fiberglass-epoxy degrades, a protection technique may not be necessary to ensure structural integrity. However, a protection technique may be desirable to limit or contain the amount of debris generated by the degradation of the fiberglass-epoxy.

  15. IL-10 Enhances IgE-Mediated Mast Cell Responses and Is Essential for the Development of Experimental Food Allergy in IL-10-Deficient Mice.

    PubMed

    Polukort, Stephanie H; Rovatti, Jeffrey; Carlson, Logan; Thompson, Chelsea; Ser-Dolansky, Jennifer; Kinney, Shannon R M; Schneider, Sallie S; Mathias, Clinton B

    2016-06-15

    IL-10 is a key pleiotropic cytokine that can both promote and curb Th2-dependent allergic responses. In this study, we demonstrate a novel role for IL-10 in promoting mast cell expansion and the development of IgE-mediated food allergy. Oral OVA challenge in sensitized BALB/c mice resulted in a robust intestinal mast cell response accompanied by allergic diarrhea, mast cell activation, and a predominance of Th2 cytokines, including enhanced IL-10 expression. In contrast, the development of intestinal anaphylaxis, including diarrhea, mast cell activation, and Th2 cytokine production, was significantly attenuated in IL-10(-/-) mice compared with wild-type (WT) controls. IL-10 also directly promoted the expansion, survival, and activation of mast cells; increased FcεRI expression on mast cells; and enhanced the production of mast cell cytokines. IL-10(-/-) mast cells had reduced functional capacity, which could be restored by exogenous IL-10. Similarly, attenuated passive anaphylaxis in IL-10(-/-) mice could be restored by IL-10 administration. The adoptive transfer of WT mast cells restored allergic symptoms in IL-10(-/-) mice, suggesting that the attenuated phenotype observed in these animals is due to a deficiency in IL-10-responding mast cells. Lastly, transfer of WT CD4 T cells also restored allergic diarrhea and intestinal mast cell numbers in IL-10(-/-) mice, suggesting that the regulation of IL-10-mediated intestinal mast cell expansion is T cell dependent. Our observations demonstrate a critical role for IL-10 in driving mucosal mast cell expansion and activation, suggesting that, in its absence, mast cell function is impaired, leading to attenuated food allergy symptoms. PMID:27183617

  16. Atherosclerosis: a chronic inflammatory disease mediated by mast cells.

    PubMed

    Conti, Pio; Shaik-Dasthagirisaeb, Yazdami

    2015-01-01

    Inflammation is a process that plays an important role in the initiation and progression of atherosclerosis and immune disease, involving multiple cell types, including macrophages, T-lymphocytes, endothelial cells, smooth muscle cells and mast cells. The fundamental damage of atherosclerosis is the atheromatous or fibro-fatty plaque which is a lesion that causes several diseases. In atherosclerosis the innate immune response, which involves macrophages, is initiated by the arterial endothelial cells which respond to modified lipoproteins and lead to Th1 cell subset activation and generation of inflammatory cytokines and chemoattractant chemokines. Other immune cells, such as CD4+ T inflammatory cells, which play a critical role in the development and progression of atherosclerosis, and regulatory T cells [Treg], which have a protective effect on the development of atherosclerosis are involved. Considerable evidence indicates that mast cells and their products play a key role in inflammation and atherosclerosis. Activated mast cells can have detrimental effects, provoking matrix degradation, apoptosis, and enhancement as well as recruitment of inflammatory cells, which actively contributes to atherosclerosis and plaque formation. Here we discuss the relationship between atherosclerosis, inflammation and mast cells. PMID:26648785

  17. Mast Cell Stabilizer Ketotifen Inhibits Gouty Inflammation in Rats.

    PubMed

    Hsu, Dur-Zong; Chu, Pei-Yi; Chen, Si-Jin; Liu, Ming-Yie

    2016-01-01

    Gout, an extremely painful arthritis with relapsing inflammatory attacks, is a common inflammatory joint disease in adults. We examined the therapeutic effect of ketotifen, a mast cell stabilizer, on monosodium urate (MSU) crystal-induced acute inflammation. Eight-week-old male Wistar rats were injected with MSU crystals (5 mg per rat) into air pouch. Ketotifen (0, 0.1, 03, and 1 mg/kg) was given 1 hour before MSU crystal injection. Lavage histamine, leukocyte counts, mast cell counts, nitric oxide, and proinflammatory mediator levels were assessed 12 hours after MSU injection. Ketotifen significantly inhibited MSU-induced mast cell activation and histamine concentration in air pouch lavage. Ketotifen dose-dependently inhibited MSU-initiated leukocyte infiltration into the air pouch. Furthermore, ketotifen significantly decreased proinflammatory mediators, including nitric oxide, interleukin-1β, and interleukin-6, production in MSU-treated rats. Ketotifen may attenuate MSU-induced acute inflammation by inhibiting mast cell activation and leukocyte infiltration in rats. Furthermore, ketotifen has the potential to be a new approach in managing patients with gouty inflammation in the future. PMID:23884077

  18. Atherosclerosis: a chronic inflammatory disease mediated by mast cells

    PubMed Central

    Shaik-Dasthagirisaeb, Yazdami

    2015-01-01

    Inflammation is a process that plays an important role in the initiation and progression of atherosclerosis and immune disease, involving multiple cell types, including macrophages, T-lymphocytes, endothelial cells, smooth muscle cells and mast cells. The fundamental damage of atherosclerosis is the atheromatous or fibro-fatty plaque which is a lesion that causes several diseases. In atherosclerosis the innate immune response, which involves macrophages, is initiated by the arterial endothelial cells which respond to modified lipoproteins and lead to Th1 cell subset activation and generation of inflammatory cytokines and chemoattractant chemokines. Other immune cells, such as CD4+ T inflammatory cells, which play a critical role in the development and progression of atherosclerosis, and regulatory T cells [Treg], which have a protective effect on the development of atherosclerosis are involved. Considerable evidence indicates that mast cells and their products play a key role in inflammation and atherosclerosis. Activated mast cells can have detrimental effects, provoking matrix degradation, apoptosis, and enhancement as well as recruitment of inflammatory cells, which actively contributes to atherosclerosis and plaque formation. Here we discuss the relationship between atherosclerosis, inflammation and mast cells. PMID:26648785

  19. Our perception of the mast cell from Paul Ehrlich to now

    PubMed Central

    Beaven, Michael A.

    2010-01-01

    Just over a century ago Paul Ehrlich received the Nobel Prize for his studies of immunity. This review describes one of his legacies, the histochemical description of the mast cell, and the research that has ensued since then. After a long period of largely descriptive studies, which revealed little about the biological role of the mast cell, the field was galvanized in the 1950s by the recognition that the mast cell was the main repository of histamine and a key participant in anaphylactic reactions. Although the mast cell was long-viewed in these terms, recent research has now shown that the mast cell also plays a key role in innate and adaptive immune responses, autoimmune disease, and possibly tissue homeostasis by virtue of its expression of a diverse array of receptors and biologically active products. In addition, the responsiveness of mast cells to immunological and pathological stimulants is highly modulated by the tissue cytokine environment and by synergistic, or inhibitory, interactions among the various mast cell receptor systems. This once enigmatic cell of Paul Ehrlich has proved to be both adaptable and multifunctional. PMID:19130582

  20. Probing the Small-x Gluon Tomography in Correlated Hard Diffractive Dijet Production in Deep Inelastic Scattering.

    PubMed

    Hatta, Yoshitaka; Xiao, Bo-Wen; Yuan, Feng

    2016-05-20

    We investigate the close connection between the quantum phase space Wigner distribution of small-x gluons and the color dipole scattering amplitude, and we propose studying it experimentally in the hard diffractive dijet production at the planned electron-ion collider. The angular correlation between the nucleon recoiled momentum and the dijet transverse momentum probes the nontrivial correlation in the phase space Wigner distribution. This experimental study not only provides us with three-dimensional tomographic pictures of gluons inside high energy protons-it gives a unique and interesting signal for the small-x dynamics with QCD evolution effects. PMID:27258865

  1. Hard x-ray production from high intensity laser solid interactions

    SciTech Connect

    Sefcik, J. A., LLNL

    1998-06-03

    Intense laser (> 10{sup 21} W/cm{sup 2}) driven hard x-ray sources offer a new alternative to conventional electron accelerator bremsstrahlung sources. These laser driven sources offer considerable simplicity in design and cost advantage for multiple axis views and have the potential for much higher spatial and temporal resolution than is achievable with accelerator sources We have begun a series of experiments using the Petawatt Laser system at LLNL to determine the potential of these sources for radiography applications Absolutely calibrated spectra extending to 20 MeV and high resolution radiographs through a {rho}r{>=}150 gm/cm{sup 2} have been obtained The physics of these sources and the scaling relationships and laser technology required to provide the dose levels necessary for radiography applications will be discussed Diagnostics of the laser produced electrons and photons will be addressed

  2. Directed spray mast

    DOEpatents

    Nance, Thomas A.; Siddall, Alvin A.; Cheng, William Y.; Counts, Kevin T.

    2005-05-10

    Disclosed is an elongated, tubular, compact high pressure sprayer apparatus for insertion into an access port of vessels having contaminated interior areas that require cleaning by high pressure water spray. The invention includes a spray nozzle and a camera adjacent thereto with means for rotating and raising and lowering the nozzle so that areas identified through the camera may be cleaned with a minimum production of waste water to be removed.

  3. The role of the mast cell in the pathophysiology of asthma.

    PubMed

    Bradding, Peter; Walls, Andrew F; Holgate, Stephen T

    2006-06-01

    There is compelling evidence that human mast cells contribute to the pathophysiology of asthma. Mast cells, but not T cells or eosinophils, localize within the bronchial smooth muscle bundles in patients with asthma but not in normal subjects or those with eosinophilic bronchitis, a factor likely to be important in determining the asthmatic phenotype. The mechanism of mast cell recruitment by asthmatic airway smooth muscle involves the CXCL10/CXCR3 axis, and several mast cell mediators have profound effects on airway smooth muscle function. The autacoids are established as potent bronchoconstrictors, whereas the proteases tryptase and chymase are being demonstrated to have a range of actions consistent with key roles in inflammation, tissue remodeling, and bronchial hyperresponsiveness. IL-4 and IL-13, known mast cell products, also induce bronchial hyperresponsiveness in the mouse independent of the inflammatory response and enhance the magnitude of agonist-induced intracellular Ca2+ responses in cultured human airway smooth muscle. There are therefore many pathways by which the close approximation of mast cells with airway smooth muscle cells might lead to disordered airway smooth muscle function. Mast cells also infiltrate the airway mucous glands in subjects with asthma, showing features of degranulation, and a positive correlation with the degree of mucus obstructing the airway lumen, suggesting that mast cells play an important role in regulating mucous gland secretion. The development of potent and specific inhibitors of mast cell secretion, which remain active when administered long-term to asthmatic airways, should offer a novel approach to the treatment of asthma. PMID:16750987

  4. Mast pulses shape trophic interactions between fluctuating rodent populations in a primeval forest.

    PubMed

    Selva, Nuria; Hobson, Keith A; Cortés-Avizanda, Ainara; Zalewski, Andrzej; Donázar, José Antonio

    2012-01-01

    How different functional responses of consumers exploiting pulsed resources affect community dynamics is an ongoing question in ecology. Tree masting is a common resource pulse in terrestrial ecosystems that can drive rodent population cycles. Using stable isotope (δ(13)C, δ(15)N) analyses, we investigated the dietary response of two fluctuating rodent species, the yellow-necked mouse Apodemus flavicollis and the bank vole Myodes glareolus, to mast events in Białowieża Forest (NE Poland). Rodent hair samples were obtained non-invasively from faeces of their predators for an 11-year period that encompassed two mast events. Spectacular seed crops of deciduous trees, namely oak Quercus robur and hornbeam Carpinus betulus, occur after several intermediate years of moderate seed production, with a post-mast year characterised by a nil crop. While a Bayesian isotopic (SIAR) mixing model showed a variety of potential vegetation inputs to rodent diets, the isotopic niche of the yellow-necked mouse was strongly associated with mast of deciduous trees (>80% of diet), showing no variation among years of different seed crop. However, bank voles showed a strong functional response; in mast years the vole shifted its diet from herbs in deciduous forest (~66% of diet) to mast (~74%). Only in mast years did the isotopic niche of both rodent species overlap. Previous research showed that bank voles, subordinate and more generalist than mice, showed higher fluctuations in numbers in response to masting. This study provides unique data on the functional response of key pulse consumers in forest food webs, and contributes to our understanding of rodent population fluctuations and the mechanisms governing pulse-consumer interactions. PMID:23251475

  5. Mast Pulses Shape Trophic Interactions between Fluctuating Rodent Populations in a Primeval Forest

    PubMed Central

    Selva, Nuria; Hobson, Keith A.; Cortés-Avizanda, Ainara; Zalewski, Andrzej; Donázar, José Antonio

    2012-01-01

    How different functional responses of consumers exploiting pulsed resources affect community dynamics is an ongoing question in ecology. Tree masting is a common resource pulse in terrestrial ecosystems that can drive rodent population cycles. Using stable isotope (δ13C, δ15N) analyses, we investigated the dietary response of two fluctuating rodent species, the yellow-necked mouse Apodemus flavicollis and the bank vole Myodes glareolus, to mast events in Białowieża Forest (NE Poland). Rodent hair samples were obtained non-invasively from faeces of their predators for an 11-year period that encompassed two mast events. Spectacular seed crops of deciduous trees, namely oak Quercus robur and hornbeam Carpinus betulus, occur after several intermediate years of moderate seed production, with a post-mast year characterised by a nil crop. While a Bayesian isotopic (SIAR) mixing model showed a variety of potential vegetation inputs to rodent diets, the isotopic niche of the yellow-necked mouse was strongly associated with mast of deciduous trees (>80% of diet), showing no variation among years of different seed crop. However, bank voles showed a strong functional response; in mast years the vole shifted its diet from herbs in deciduous forest (∼66% of diet) to mast (∼74%). Only in mast years did the isotopic niche of both rodent species overlap. Previous research showed that bank voles, subordinate and more generalist than mice, showed higher fluctuations in numbers in response to masting. This study provides unique data on the functional response of key pulse consumers in forest food webs, and contributes to our understanding of rodent population fluctuations and the mechanisms governing pulse–consumer interactions. PMID:23251475

  6. Schistosoma mansoni infection in mice augments the capacity for interleukin 3 (IL-3) and IL-9 production and concurrently enlarges progenitor pools for mast cells and granulocytes-macrophages.

    PubMed Central

    Khalil, R M; Luz, A; Mailhammer, R; Moeller, J; Mohamed, A A; Omran, S; Dörmer, P; Hültner, L

    1996-01-01

    Mast cells and granulocytes-macrophages (GM) are components of the host defense system against worm infections, including schistosomiasis. Here we report the kinetics of changes in the number of colony-forming cells (CFC) for mast cells and GM during the course of a primary experimental infection of mice with Schistosoma mansoni cercariae over a period of 24 weeks postinfection (p.i.). Concurrently, we measured known myelopoietic and/or mast cell-stimulating cytokines (i.e., interleukin 3 [IL-3] and IL-9) in pokeweed mitogen-activated spleen cell-conditioned medium. Our results show that during the acute phase of the hepatic granulomatous reaction, the numbers of both mast-CFC and GM-CFC were significantly elevated in bone marrow. However, while femoral GM-CFC numbers had returned to normal control values at week 16 p.i., femoral and splenic mast-CFC numbers remained significantly elevated until week 20 p.i., which corresponds to the chronic fibrotic phase of hepatic granulomatous inflammation. Increased GM-CFC numbers correlated with elevated IL-3 levels, while increased mast-CFC numbers paralleled the increased IL-9 concentrations in spleen cell-conditioned medium. By the reverse transcription-PCR method, enhanced expression of IL-3 and IL-9 transcripts was found in RNA samples obtained from livers and spleens of infected mice. Our data demonstrate that during the course of infection of mice with S. mansoni, the coordinate need for mast cells and GM is at least partly regulated at the stage of progenitor cell commitment in the bone marrow and spleen. It appears that IL-3 and IL-9 help to promote at this stage the ultimate generation of mature effector cells. PMID:8945533

  7. Mast Fruiting Is a Frequent Strategy in Woody Species of Eastern South America

    PubMed Central

    Norden, Natalia; Chave, Jérôme; Belbenoit, Pierre; Caubère, Adeline; Châtelet, Patrick; Forget, Pierre-Michel; Thébaud, Christophe

    2007-01-01

    Background It is thought that mast seeding is a rare reproductive strategy in the tropics, since tropical climates are less variable, and fruit consumers tend to be more generalist in these regions. However, previous tests of this hypothesis were based on only few tropical datasets, and none from tropical South America. Moreover, reproductive strategies have been quantified based on the coefficient of variation of interannual seed production, an index that potentially confounds masting and high interannual variability in seed production. Methodology/Principal Findings We developed a new approach to model the monthly variability in seed production for 28 tree species, and 20 liana species monitored during 5 years in a tropical forest of Central French Guiana. We found that 23% of the species showed a masting pattern, 54% an annual fruiting pattern, and 23% an irregular fruiting pattern. The majority of masting species were trees (8 out of 11), most of them animal-dispersed. The classification into reproductive strategies based on the coefficient of variation was inconsistent with our results in nearly half of the cases. Conclusions/Significance Our study is the first to clearly evidence the frequency of the masting strategy in a tropical forest community of Eastern South America. The commonness of the masting strategy in tropical plants may promote species coexistence through storage dynamics. PMID:17957261

  8. Variable-Tilt Helicopter Rotor Mast

    NASA Technical Reports Server (NTRS)

    Kelley, Henry L.

    1995-01-01

    Variable-tilt helicopter rotor mast proposed to improve helicopter performance and reduce vibration, especially at upper end of forward-speed range of helicopters. Achieved by use of universal coupling in main rotor mast or by tilting entire engine-and-transmission platform. Performance, energy efficiency, and safety enhanced.

  9. The role of mast cells in cancers

    PubMed Central

    Maciel, Thiago T.; Moura, Ivan C.

    2015-01-01

    Mast cells are immune cells that accumulate in the tumors and their microenvironment during disease progression. Mast cells are armed with a wide array of receptors that sense environment modifications and, upon stimulation, they are able to secrete several biologically active factors involved in the modulation of tumor growth. For example, mast cells are able to secrete pro-angiogenic and growth factors but also pro- and anti-inflammatory mediators. Recent studies have allowed substantial progress in understanding the role of mast cells in tumorigenesis/disease progression but further studies are necessary to completely elucidate their impact in the pathophysiology of cancer. Here we review observations suggesting that mast cells could modulate tumor growth in humans. We also discuss the drawbacks related to observations from mast cell-deficient mouse models, which could have consequences in the determination of a potential causative relationship between mast cells and cancer. We believe that the understanding of the precise role of mast cells in tumor development and progression will be of critical importance for the development of new targeted therapies in human cancers. PMID:25705392

  10. Evidence questioning cromolyn’s effectiveness and selectivity as a “mast cell stabilizer” in mice

    PubMed Central

    Oka, Tatsuya; Kalesnikoff, Janet; Starkl, Philipp; Tsai, Mindy; Galli, Stephen J.

    2013-01-01

    Cromolyn, widely characterized as a “mast cell stabilizer”, has been used in mice to investigate the biological roles of mast cells in vivo. However, it is not clear to what extent cromolyn can either limit the function of mouse mast cells or influence biological processes in mice independently of effects on mast cells. We confirmed that cromolyn (at 10 mg/kg in vivo or 10 – 100 μM in vitro) can inhibit IgE-dependent mast cell activation in rats in vivo (measuring Evans blue extravasation in passive cutaneous anaphylaxis and increases in plasma histamine in passive systemic anaphylaxis) and in vitro (measuring peritoneal mast cell β-hexosaminidase release and prostaglandin D2 synthesis). However, under the conditions tested, cromolyn did not inhibit those mast cell-dependent responses in mice. In mice, cromolyn also failed to inhibit the ear swelling or leukocyte infiltration at sites of passive cutaneous anaphylaxis. Nor did cromolyn inhibit IgE-independent degranulation of mouse peritoneal mast cells induced by various stimulators in vitro. At 100 mg/kg, a concentration ten times higher than that which inhibited passive systemic anaphylaxis in rats, cromolyn significantly inhibited the increases in plasma concentrations of mouse mast cell protease-1 (but not of histamine) during passive systemic anaphylaxis, but had no effect on the reduction in body temperature in this setting. Moreover, this concentration of cromolyn (100 mg/kg) also inhibited LPS-induced TNF production in genetically mast cell-deficient C57BL/6-KitW-sh/W-sh mice in vivo. These results question cromolyn’s effectiveness and selectivity as an inhibitor of mast cell activation and mediator release in the mouse. PMID:22906983

  11. Human mast cells capture, store, and release bioactive, exogenous IL-17A.

    PubMed

    Noordenbos, Troy; Blijdorp, Iris; Chen, Sijia; Stap, Jan; Mul, Erik; Cañete, Juan D; Lubberts, Erik; Yeremenko, Nataliya; Baeten, Dominique

    2016-09-01

    IL-17A, a major proinflammatory cytokine, can be produced by a variety of leukocytes, but its exact cellular source in human inflammatory diseases remains incompletely understood. IL-17A protein is abundantly found in mast cells in human tissues, such as inflamed synovium, but surprisingly, mechanistic murine studies failed to demonstrate IL-17A production by mast cells. Here, we demonstrate that primary human tissue mast cells do not produce IL-17A themselves but actively capture exogenous IL-17A through receptor-mediated endocytosis. The exogenous IL-17A is stored in intracellular granules and can subsequently be released in a bioactive form. This novel mechanism confers to mast cells the capacity to steer IL-17A-mediated tissue inflammation by the rapid release of preformed cytokine. PMID:27034403

  12. Immunologic and Nonimmunologic Generation of Superoxide from Mast Cells and Basophils

    PubMed Central

    Henderson, William R.; Kaliner, Michael

    1978-01-01

    Mediator release from rat peritoneal and human lung mast cells as well as human leukemic basophils was examined to determine whether super-oxide (O−2) was concomitantly generated. Immunologic or nonimmunologic stimulation of each preparation induced parallel release of histamine and O−2 within 2 min. O−2 production was quantitated by superoxide dismutase (SOD)-inhibitable chemiluminescence and cytochrome c reduction. SOD was detected in basophil and mast cell lysates and was also released by rat mast cells stimulated by anti-IgE. Secretory granules isolated from purified rat mast cells released histamine, O−2, and SOD upon exposure to cations. Thus, both superoxide radicals and SOD may play a role in host defenses involved in immediate hypersensitivity reactions. Images PMID:73548

  13. Hard Surface Biocontrol in Hospitals Using Microbial-Based Cleaning Products

    PubMed Central

    Vandini, Alberta; Temmerman, Robin; Frabetti, Alessia; Caselli, Elisabetta; Antonioli, Paola; Balboni, Pier Giorgio; Platano, Daniela; Branchini, Alessio; Mazzacane, Sante

    2014-01-01

    Background Healthcare-Associated Infections (HAIs) are one of the most frequent complications occurring in healthcare facilities. Contaminated environmental surfaces provide an important potential source for transmission of many healthcare-associated pathogens, thus indicating the need for new and sustainable strategies. Aim This study aims to evaluate the effect of a novel cleaning procedure based on the mechanism of biocontrol, on the presence and survival of several microorganisms responsible for HAIs (i.e. coliforms, Staphyloccus aureus, Clostridium difficile, and Candida albicans) on hard surfaces in a hospital setting. Methods The effect of microbial cleaning, containing spores of food grade Bacillus subtilis, Bacillus pumilus and Bacillus megaterium, in comparison with conventional cleaning protocols, was evaluated for 24 weeks in three independent hospitals (one in Belgium and two in Italy) and approximately 20000 microbial surface samples were collected. Results Microbial cleaning, as part of the daily cleaning protocol, resulted in a reduction of HAI-related pathogens by 50 to 89%. This effect was achieved after 3–4 weeks and the reduction in the pathogen load was stable over time. Moreover, by using microbial or conventional cleaning alternatively, we found that this effect was directly related to the new procedure, as indicated by the raise in CFU/m2 when microbial cleaning was replaced by the conventional procedure. Although many questions remain regarding the actual mechanisms involved, this study demonstrates that microbial cleaning is a more effective and sustainable alternative to chemical cleaning and non-specific disinfection in healthcare facilities. Conclusions This study indicates microbial cleaning as an effective strategy in continuously lowering the number of HAI-related microorganisms on surfaces. The first indications on the actual level of HAIs in the trial hospitals monitored on a continuous basis are very promising, and may pave the

  14. Human dermal mast cells contain and release tumor necrosis factor alpha, which induces endothelial leukocyte adhesion molecule 1.

    PubMed Central

    Walsh, L J; Trinchieri, G; Waldorf, H A; Whitaker, D; Murphy, G F

    1991-01-01

    Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine that mediates endothelial leukocyte interactions by inducing expression of adhesion molecules. In this report, we demonstrate that human dermal mast cells contain sizeable stores of immunoreactive and biologically active TNF-alpha within granules, which can be released rapidly into the extracellular space upon degranulation. Among normal human dermal cells, mast cells are the predominant cell type that expresses both TNF-alpha protein and TNF-alpha mRNA. Moreover, induction of endothelial leukocyte adhesion molecule 1 expression is a direct consequence of release of mast cell-derived TNF-alpha. These findings establish a role for human mast cells as "gatekeepers" of the dermal microvasculature and indicate that mast cell products other than vasoactive amines influence endothelium in a proinflammatory fashion. Images PMID:1709737

  15. Tespa1 negatively regulates FcεRI-mediated signaling and the mast cell–mediated allergic response

    PubMed Central

    Zheng, Mingzhu; Qiu, Yuanjun; Guo, Chuansheng; Ji, Jian; Lei, Lei; Zhang, Xue; Liang, Jingjing; Lou, Jun; Huang, Wei; Dong, Bowen; Wu, Songquan; Wang, Jianli; Ke, Yuehai; Cao, Xuetao; Zhou, Yi Ting

    2014-01-01

    Antigen-mediated cross-linking of IgE on mast cells triggers a signaling cascade that results in their degranulation and proinflammatory cytokine production, which are key effectors in allergic reactions. We show that the activation of mast cells is negatively regulated by the newly identified adaptor protein Tespa1. Loss of Tespa1 in mouse mast cells led to hyper-responsiveness to stimulation via FcεRI. Mice lacking Tespa1 also displayed increased sensitivity to IgE-mediated allergic responses. The dysregulated signaling in KO mast cells was associated with increased activation of Grb2-PLC-γ1-SLP-76 signaling within the LAT1 (linker for activation of T cells family, member 1) signalosome versus the LAT2 signalosome. Collectively, these findings show that Tespa1 orchestrates mast cell activation by tuning the balance of LAT1 and LAT2 signalosome assembly. PMID:25422497

  16. The role of Lin28b in myeloid and mast cell differentiation and mast cell malignancy

    PubMed Central

    Wang, Leo D.; Rao, Tata Nageswara; Rowe, R. Grant; Nguyen, Phi T.; Sullivan, Jessica L.; Pearson, Daniel S.; Doulatov, Sergei; Wu, Linwei; Lindsley, R. Coleman; Zhu, Hao; DeAngelo, Daniel J.; Daley, George Q.; Wagers, Amy J.

    2015-01-01

    Mast cells are critical components of the innate immune system and important for host defense, allergy, autoimmunity, tissue regeneration, and tumor progression. Dysregulated mast cell development leads to systemic mastocytosis, a clinically variable but often devastating family of hematologic disorders. Here we report that induced expression of Lin28, a heterochronic gene and pluripotency factor implicated in driving a fetal hematopoietic program, caused mast cell accumulation in adult mice in target organs such as the skin and peritoneal cavity. In vitro assays revealed a skewing of myeloid commitment in LIN28B-expressing hematopoietic progenitors, with increased levels of LIN28B in common myeloid and basophil-mast cell progenitors altering gene expression patterns to favor cell fate choices that enhanced mast cell specification. In addition, LIN28B-induced mast cells appeared phenotypically and functionally immature, and in vitro assays suggested a slowing of mast cell terminal differentiation in the context of LIN28B upregulation. Finally, interrogation of human mast cell leukemia samples revealed upregulation of LIN28B in abnormal mast cells from patients with systemic mastocytosis (SM). This work identifies Lin28 as a novel regulator of innate immune function and a new protein of interest in mast cell disease. PMID:25655194

  17. Accumulation of intraepithelial mast cells with a unique protease phenotype in TH2-high asthma

    PubMed Central

    Dougherty, Ryan H.; Sidhu, Sukhvinder S.; Raman, Kavita; Solon, Margaret; Solberg, Owen D.; Caughey, George H.; Woodruff, Prescott G.; Fahy, John V.

    2010-01-01

    Background Previously, we found that mast cell tryptases and carboxypeptidase A3 (CPA3) are differentially expressed in the airway epithelium in asthmatic subjects. We also found that asthmatic subjects can be divided into 2 subgroups (“TH2 high” and “TH2 low” asthma) based on epithelial cell gene signatures for the activity of TH2 cytokines. Objectives We sought to characterize intraepithelial mast cells (IEMCs) in asthma. Methods We performed gene expression profiling in epithelial brushings and stereology-based quantification of mast cell numbers in endobronchial biopsy specimens from healthy control and asthmatic subjects before and after treatment with inhaled corticosteroids (ICSs). We also performed gene expression and protein quantification studies in cultured airway epithelial cells and mast cells. Results By means of unsupervised clustering, mast cell gene expression in the airway epithelium related closely to the expression of IL-13 signature genes. The levels of expression of mast cell genes correlate positively with lung function improvements with ICSs. IEMC density was 2-fold higher than normal in subjects with TH2-high asthma compared with that seen in subjects with TH2-low asthma or healthy control subjects (P = .015 for both comparisons), and these cells were characterized by expression of tryptases and CPA3 but not chymase. IL-13 induced expression of stem cell factor in cultured airway epithelial cells, and mast cells exposed to conditioned media from IL-13–activated epithelial cells showed downregulation of chymase but no change in tryptase or CPA3 expression. Conclusion IEMC numbers are increased in subjects with TH2-high asthma, have an unusual protease phenotype (tryptase and CPA3 high and chymase low), and predict responsiveness to ICSs. IL-13–stimulated production of stem cell factor by epithelial cells potentially explains mast cell accumulation in TH2-high asthmatic epithelium. PMID:20451039

  18. Mast cells modulate the pathogenesis of elastase-induced abdominal aortic aneurysms in mice

    PubMed Central

    Sun, Jiusong; Sukhova, Galina K.; Yang, Min; Wolters, Paul J.; MacFarlane, Lindsey A.; Libby, Peter; Sun, Chongxiu; Zhang, Yadong; Liu, Jian; Ennis, Terri L.; Knispel, Rebecca; Xiong, Wanfen; Thompson, Robert W.; Baxter, B. Timothy; Shi, Guo-Ping

    2007-01-01

    Abdominal aortic aneurysm (AAA), an inflammatory disease, involves leukocyte recruitment, immune responses, inflammatory cytokine production, vascular remodeling, neovascularization, and vascular cell apoptosis, all of which contribute to aortic dilatation. This study demonstrates that mast cells, key participants in human allergic immunity, participate in AAA pathogenesis in mice. Mast cells were found to accumulate in murine AAA lesions. Mast cell–deficient KitW-sh/KitW-sh mice failed to develop AAA elicited by elastase perfusion or periaortic chemical injury. KitW-sh/KitW-sh mice had reduced aortic expansion and internal elastic lamina degradation; decreased numbers of macrophages, CD3+ T lymphocytes, SMCs, apoptotic cells, and CD31+ microvessels; and decreased levels of aortic tissue IL-6 and IFN-γ. Activation of mast cells in WT mice via C48/80 injection resulted in enhanced AAA growth while mast cell stabilization with disodium cromoglycate diminished AAA formation. Mechanistic studies demonstrated that mast cells participated in angiogenesis, aortic SMC apoptosis, and matrix-degrading protease expression. Reconstitution of KitW-sh/KitW-sh mice with bone marrow–derived mast cells from WT or TNF-α–/– mice, but not from IL-6–/– or IFN-γ–/– mice, caused susceptibility to AAA formation to be regained. These results demonstrate that mast cells participate in AAA pathogenesis in mice by releasing proinflammatory cytokines IL-6 and IFN-γ, which may induce aortic SMC apoptosis, matrix-degrading protease expression, and vascular wall remodeling, important hallmarks of arterial aneurysms. PMID:17932568

  19. Critical role of tissue mast cells in controlling long-term glucose sensor function in vivo.

    PubMed

    Klueh, Ulrike; Kaur, Manjot; Qiao, Yi; Kreutzer, Donald L

    2010-06-01

    Little is known about the specific cells, mediators and mechanisms involved in the loss of glucose sensor function (GSF) in vivo. Since mast cells (MC) are known to be key effector cells in inflammation and wound healing, we hypothesized that MC and their products are major contributors to the skin inflammation and wound healing that controls GSF at sites of sensor implantation. To test this hypothesis we utilized a murine model of continuous glucose monitoring (CGM) in vivo in both normal C57BL/6 mice (mast cell sufficient), as well as mast cell deficient B6.Cg-Kit(W-sh)/HNihrJaeBsmJ (Sash) mice over a 28 day CGM period. As expected, both strains of mice displayed excellent CGM for the first 7 days post sensor implantation (PSI). CGM in the mast cell sufficient C57BL/6 mice was erratic over the remaining 21 days PSI. CGM in the mast cell deficient Sash mice displayed excellent sensor function for the entire 28 day of CGM. Histopathologic evaluation of implantation sites demonstrated that tissue reactions in Sash mice were dramatically less compared to the reactions in normal C57BL/6 mice. Additionally, mast cells were also seen to be consistently associated with the margins of sensor tissue reactions in normal C57BL/6 mice. Finally, direct injection of bone marrow derived mast cells at sites of sensor implantation induced an acute and dramatic loss of sensor function in both C57BL/6 and Sash mice. These results demonstrate the key role of mast cells in controlling glucose sensor function in vivo. PMID:20226521

  20. Ripe fruit of Rubus coreanus inhibits mast cell-mediated allergic inflammation.

    PubMed

    Kim, Hui-Hun; Choi, Phil Hyung; Yoo, Jin-Su; Jeon, Hoon; Chae, Byeong-Suk; Park, Jeong-Suk; Kim, Sang-Hyun; Shin, Tae-Yong

    2012-02-01

    In this study, we investigated the effect of a water extract of the ripe fruits of Rubus coreanus Miq. (Rosaceae) (RFRC) on mast cell-mediated allergic inflammation and studied the possible mechanism of action. Mast cell-mediated allergic disease is involved in many diseases such as anaphylaxis, rhinitis, asthma and atopic dermatitis. RFRC dose-dependently inhibited compound 48/80-induced systemic anaphylaxis and serum histamine release in mice. RFRC reduced the immunoglobulin E (IgE)-mediated local allergic reaction, passive cutaneous anaphylaxis. RFRC attenuated histamine release from rat peritoneal mast cells and human mast cells by the reduction of intracellular calcium. RFRC decreased the phorbol 12-myristate 13-acetate (PMA) and the calcium ionophore A23187 (PMACI)-stimulated expression and secretion of pro-inflammatory cytokines in human mast cells. The inhibitory effect of RFRC on cytokine production was nuclear factor (NF)-κB- and mitogen-activated protein kinase (MAPK)-dependent. In addition, RFRC suppressed the activation of caspase-1. Our findings provide evidence that RFRC inhibits mast cell-derived allergic inflammatory reactions, and for the involvement of calcium, NF-κB, MAPKs and caspase-1 in these effects. Furthermore, in vivo and in vitro anti-allergic inflammatory effects of RFRC provide affirmative proof of a possible therapeutic application of this agent in allergic inflammatory diseases. PMID:22075758

  1. Impaired expression of the mitochondrial calcium uniporter suppresses mast cell degranulation.

    PubMed

    Furuno, Tadahide; Shinkai, Narumi; Inoh, Yoshikazu; Nakanishi, Mamoru

    2015-12-01

    Calcium ion (Ca(2+)) uptake into the mitochondrial matrix influences ATP production, Ca(2+) homeostasis, and apoptosis regulation. Ca(2+) uptake across the ion-impermeable inner mitochondrial membrane is mediated by the mitochondrial Ca(2+) uniporter (MCU) complex. The MCU complex forms a pore structure composed of several proteins. MCU is a Ca(2+)-selective channel in the inner-mitochondrial membrane that allows electrophoretic Ca(2+) entry into the matrix. Mitochondrial Ca(2+) uptake 1 (MICU1) functions as a Ca(2+)-sensing regulator of the MCU complex. Previously, by microscopic analysis at the single-cell level, we found that during mast cell activation, mitochondria capture cytosolic Ca(2+) in two steps. Consequently, mitochondrial Ca(2+) uptake likely plays a role in cellular function through cytosolic Ca(2+) buffering. Here, we investigate the role of MCU and MICU1 in mitochondrial Ca(2+) uptake and mast cell degranulation using MCU- and MICU1-knockdown (KD) mast cells. Whereas MCU- and MICU1-KD mast cells show normal proliferation rates and mitochondrial membrane potential, they exhibit slow and reduced cytosolic and mitochondrial Ca(2+) elevation after antigen stimulation. Moreover, β-hexosaminidase release induced by antigen was significantly suppressed in MCU-KD cells but not MICU1-KD cells. This suggests that both MCU and MICU1 are involved in mitochondrial Ca(2+) uptake in mast cells, while MCU plays a role in mast cell degranulation. PMID:26350567

  2. 4-Chlorotetrazolo[1,5-a]quinoxaline inhibits activation of Syk kinase to suppress mast cells in vitro and mast cell-mediated passive cutaneous anaphylaxis in mice

    SciTech Connect

    Park, Kui Lea; Ko, Na Young; Lee, Jun Ho; Kim, Do Kyun; Kim, Hyuk Soon; Kim, A-Ram; Her, Erk; Kim, Bokyung; Kim, Hyung Sik; Moon, Eun-Yi; Kim, Young Mi; Kim, Hang-Rae; Choi, Wahn Soo

    2011-12-15

    4-Chlorotetrazolo[1,5-a]quinoxaline is a quinoxaline derivative. We aimed to study the effects of 4-chlorotetrazolo[1,5-a]quinoxaline on activation of mast cells in vitro and in mice. 4-Chlorotetrazolo[1,5-a]quinoxaline reversibly inhibited degranulation of mast cells in a dose-dependent manner, and also suppressed the expression and secretion of TNF-{alpha} and IL-4 in mast cells. Mechanistically, 4-chlorotetrazolo[1,5-a]quinoxaline inhibited activating phosphorylation of Syk and LAT, which are crucial for early Fc{epsilon}RI-mediated signaling events, as well as Akt and MAP kinases, which play essential roles in the production of various pro-inflammatory cytokines in mast cells. Notably, although 4-chlorotetrazolo[1,5-a]quinoxaline inhibited the activation of Fyn and Syk, minimal inhibition was observed in mast cells in the case of Lyn. Furthermore, consistent with its in vitro activity, 4-chlorotetrazolo[1,5-a]quinoxaline significantly suppressed mast cell-mediated passive cutaneous anaphylaxis in mice. In summary, the results from this study demonstrate that 4-chlorotetrazolo[1,5-a]quinoxaline shows an inhibitory effect on mast cells in vitro and in vivo, and that this is mediated by inhibiting the activation of Syk in mast cells. Therefore, 4-chlorotetrazolo[1,5-a]quinoxaline could be useful in the treatment of mast cell-mediated allergic diseases. -- Highlights: Black-Right-Pointing-Pointer 4-chlorotetrazolo[1,5-a]quinoxaline is a quinoxaline derivative. Black-Right-Pointing-Pointer The effect of 4-chlorotetrazolo[1,5-a]quinoxaline on mast cells was investigated. Black-Right-Pointing-Pointer 4-chlorotetrazolo[1,5-a]quinoxaline reversibly inhibited Syk activation. Black-Right-Pointing-Pointer 4-chlorotetrazolo[1,5-a]quinoxaline could be useful for IgE-mediated allergy.

  3. 44. VIEW OF UMBILICAL MAST AND LAUNCH PAD FROM SOUTHWEST. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    44. VIEW OF UMBILICAL MAST AND LAUNCH PAD FROM SOUTHWEST. DOORS FOR THE UMBILICAL MAST TRENCH RAISED FOR MAINTENANCE POSITION OF 10 DEGREES. LAUNCHER IS RIGHT OF MAST; RAILS PARALLEL TO MAST. CONTROL PANELS LEFT TO RIGHT: ELECTRICAL PANEL, COMMUNICATIONS PANEL, AND MAST CONTROL PANEL. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  4. Heavy ion precompound phenomena: A glance at hard gamma and subthreshold pion production

    SciTech Connect

    Blann, M.; Remington, B.A.

    1987-08-01

    We test a relaxation model based on two body nucleon-nucleon scattering processes to interpret phenomena observed in heavy ion reactions. We use the Boltzmann master equation to accomplish this. By assuming that the projectile nucleons share the total excitation with equal a-priori probability of all configurations, we are able to reproduce several sets of neutron spectra from /sup 20/Ne and /sup 12/C induced reactions on /sup 165/Ho. With no additional free parameters our model successfully reproduces subthreshold pion production cross sections, high energy ..gamma..-ray spectra, and angular distributions of high energy ..gamma..-rays. 40 refs., 12 figs., 2 tabs.

  5. Benign mast cell hyperplasia and atypical mast cell infiltrates in penile lichen planus in adult men.

    PubMed

    Regauer, Sigrid; Beham-Schmid, Christine

    2014-08-01

    Introduction. Lichen planus (LP) is a chronic cytokine-mediated disease of possible auto-immune etiology. 25% of men have anogenital manifestations. Erosive penile LP causes a scarring phimosis of the foreskin in uncircumcised men. Mast cells as potent immune modulators have been implicated in a number of autoimmune and chronic inflammatory diseases, but have not been investigated in LP. Material and Methods. Formalin-fixed tissues of 117 circumcision specimens of adult men affected by LP were evaluated for the extent of mast cell and lymphocyte infiltrates, characterized immunohistochemically with antibodies to CD 3, 4, 8, 20, 21, 25, 30, 117c and human mast cell tryptase. Specimens with dense mast cell infiltrates were analyzed for point mutations of the c-kit gene (D816V). Results. Unaffected skin and modified mucosa of foreskins contained ⟨5 mast cells/mm². The inflammatory infiltrate of LP-lesions displayed ⟨15 mast cells/mm² in 33/117 foreskins, 16-40 mast cells/mm² in 22/117 and ⟩40 mast cells/mm² (average 70, range 40-100) in 62/117 foreskins. Lesional mast cells of 29/117 (24%) foreskins showed aberrant CD25-expression and/or spindled morphology, with 11/29 men having erosive LP, 13/29 a lymphocytic vasculitis and 1/28 a systemic mastocytosis. Neither CD30-expression nor c-kit mutations were identified. Atypical mast cell infiltrates in LP correlated with high disease activity, erosive LP and presence of lymphocytic vasculitis Conclusions. Increased mast cells in penile LP, mostly representing a benign hyperplasia/activation syndrome, suggests them as targets for innovative therapy options for symptomatic LP-patients not responding to corticosteroid therapy. Presently, the biological implications of atypical mast cell infiltrates in penile LP are unknown. PMID:24402730

  6. Mast cells, angiogenesis and cancer.

    PubMed

    Ribatti, Domenico; Crivellato, Enrico

    2011-01-01

    Mast cells (MCs) were first described by Paul Ehrlich 1 in his doctoral thesis. MCs have long been implicated in the pathogenesis of allergic reactions and certain protective responses to parasites. As most tumors contain inflammatory cell infiltrates, which often include plentiful MCs, the question as to the possible contribution of MCs to tumor development has progressively been emerging. In this chapter, the specific involvement of MCs in tumor biology and tumor fate will be considered, with particular emphasis on the capacity of these cells to stimulate tumor growth by promoting angiogenesis and lymphangiogenesis. Data from experimental carcinogenesis and from different tumor settings in human pathology will be summarized. Information to be presented will suggest that MCs may serve as a novel therapeutic target for cancer treatment. PMID:21713661

  7. A mast-seeding desert shrub regulates population dynamics and behavior of its heteromyid dispersers.

    PubMed

    Auger, Janene; Meyer, Susan E; Jenkins, Stephen H

    2016-04-01

    Granivorous rodent populations in deserts are primarily regulated through precipitation-driven resource pulses rather than pulses associated with mast-seeding, a pattern more common in mesic habitats. We studied heteromyid responses to mast-seeding in the desert shrub blackbrush (Coleogyne ramosissima), a regionally dominant species in the Mojave-Great Basin Desert transition zone. In a 5-year study at Arches National Park, Utah, USA, we quantified spatiotemporal variation in seed resources in mast and intermast years in blackbrush-dominated and mixed desert vegetation and measured responses of Dipodomys ordii (Ord's kangaroo rat) and Perognathus flavescens (plains pocket mouse). In blackbrush-dominated vegetation, blackbrush seeds comprised >79% of seed production in a mast year, but 0% in the first postmast year. Kangaroo rat abundance in blackbrush-dominated vegetation was highest in the mast year, declined sharply at the end of the first postmast summer, and then remained at low levels for 3 years. Pocket mouse abundance was not as strongly associated with blackbrush seed production. In mixed desert vegetation, kangaroo rat abundance was higher and more uniform through time. Kangaroo rats excluded the smaller pocket mice from resource-rich patches including a pipeline disturbance and also moved their home range centers closer to this disturbance in a year of low blackbrush seed production. Home range size for kangaroo rats was unrelated to seed resource density in the mast year, but resource-poor home ranges were larger (P < 0.001) in the first postmast year, when resources were limiting. Blackbrush seeds are higher in protein and fat but lower in carbohydrates than the more highly preferred seeds of Indian ricegrass (Achnatherum hymenoides) and have similar energy value per unit of handling time. Kangaroo rats cached seeds of these two species in similar spatial configurations, implying that they were equally valued as stored food resources. Blackbrush mast

  8. Sphingosine-1-phosphate synthesis and functions in mast cells

    PubMed Central

    Price, Megan M; Oskeritzian, Carole A; Milstien, Sheldon; Spiegel, Sarah

    2009-01-01

    Sphingolipids are not only major lipid components of all eukaryotic cell membranes, but they also comprise an important family of bioactive signaling molecules that regulate a diverse array of biological responses. The sphingolipid metabolite sphingosine-1-phosphate (S1P), is a key regulator of immune responses. Cellular levels of S1P are determined by the balance between its synthesis, involving two sphingosine kinases (SphK1 and SphK2), and its degradation, involving S1P lyase and S1P phosphatases. S1P mainly signals through its cell-surface receptors and may also have intracellular functions. S1P has important functions in mast cells – the major effectors of allergic responses. Antigen triggering of IgE receptors on mast cells activates both SphKs resulting in the production of S1P that is released and regulates and amplifies mast cell functions, including degranulation as well as cytokine and chemokine release. PMID:19802381

  9. Amarogentin Displays Immunomodulatory Effects in Human Mast Cells and Keratinocytes

    PubMed Central

    Wölfle, Ute; Haarhaus, Birgit; Schempp, Christoph M.

    2015-01-01

    Keratinocytes express the bitter taste receptors TAS2R1 and TAS2R38. Amarogentin as an agonist for TAS2R1 and other TAS2Rs promotes keratinocyte differentiation. Similarly, mast cells are known to express bitter taste receptors. The aim of this study was to assess whether bitter compounds display immunomodulatory effects on these immunocompetent cells in the skin, so that they might be a target in chronic inflammatory diseases such as atopic dermatitis and psoriasis. Here, we investigated the impact of amarogentin on substance P-induced release of histamine and TNF-α from the human mast cell line LAD-2. Furthermore, the effect of amarogentin on HaCaT keratinocytes costimulated with TNF-α and histamine was investigated. Amarogentin inhibited in LAD-2 cells substance P-induced production of newly synthesized TNF-α, but the degranulation and release of stored histamine were not affected. In HaCaT keratinocytes histamine and TNF-α induced IL-8 and MMP-1 expression was reduced by amarogentin to a similar extent as with azelastine. In conclusion amarogentin displays immunomodulatory effects in the skin by interacting with mast cells and keratinocytes. PMID:26600671

  10. Acrolein induction of oxidative stress and degranulation in mast cells.

    PubMed

    Hochman, Daniel J; Collaco, Christopher R; Brooks, Edward G

    2014-08-01

    Increases in asthma worldwide have been associated epidemiologically with expanding urban air pollution. The mechanistic relationship between airway hyper-responsiveness, inflammation, and ambient airborne triggers remains ambiguous. Acrolein, a ubiquitous aldehyde pollutant, is a product of incomplete combustion reactions. Acrolein is abundant in cigarette smoke, effluent from industrial smokestacks, diesel exhaust, and even hot oil cooking vapors. Acrolein is a potent airway irritant and can induce airway hyper-responsiveness and inflammation in the lungs of animal models. In the present study, we utilized the mast cell analog, RBL-2H3, to interrogate the responses of cells relevant to airway inflammation and allergic responses as a model for the induction of asthma-like conditions upon exposure to acrolein. We hypothesized that acrolein would induce oxidative stress and degranulation in airway mast cells. Our results indicate that acrolein at 1 ppm initiated degranulation and promoted the generation of reactive oxygen species (ROS). Introduction of antioxidants to the system significantly reduced both ROS generation and degranulation. At higher levels of exposure (above 100 ppm), RBL-2H3 cells displayed signs of severe toxicity. This experimental data indicates acrolein can induce an allergic inflammation in mast cell lines, and the initiation of degranulation was moderated by the application of antioxidants. PMID:23047665

  11. Singular Values for Products of Complex Ginibre Matrices with a Source: Hard Edge Limit and Phase Transition

    NASA Astrophysics Data System (ADS)

    Forrester, Peter J.; Liu, Dang-Zheng

    2016-05-01

    The singular values squared of the random matrix product {Y = {Gr G_{r-1}} ldots G1 (G0 + A)}, where each {Gj} is a rectangular standard complex Gaussian matrix while A is non-random, are shown to be a determinantal point process with the correlation kernel given by a double contour integral. When all but finitely many eigenvalues of A* A are equal to bN, the kernel is shown to admit a well-defined hard edge scaling, in which case a critical value is established and a phase transition phenomenon is observed. More specifically, the limiting kernel in the subcritical regime of {0 < b < 1} is independent of b, and is in fact the same as that known for the case b = 0 due to Kuijlaars and Zhang. The critical regime of b = 1 allows for a double scaling limit by choosing {{b = (1 - τ/√{N})^{-1}}}, and for this the critical kernel and outlier phenomenon are established. In the simplest case r = 0, which is closely related to non-intersecting squared Bessel paths, a distribution corresponding to the finite shifted mean LUE is proven to be the scaling limit in the supercritical regime of {b > 1} with two distinct scaling rates. Similar results also hold true for the random matrix product {Tr T_{r-1} ldots T1 (G0 + A)}, with each {Tj} being a truncated unitary matrix.

  12. Further characterization of protein kinase C in mouse mast cells

    SciTech Connect

    White, J.R.; Ishizaka, T.

    1986-03-01

    Bridging of cell-bound IgE antibody molecules on colony stimulating factor dependent mouse mast cell line (PT-18) cells by multivalent antigen induces the mobilization and uptake of Ca/sup 2 +/ monitored by Quin-2 and the production of diacylglycerol. Exposure of the sensitized cells to antigen also induces a substantial increase in protein kinase C (PKC) activity in the plasma membrane (340 units to 1375 units: 1 unit = 1 pmol of /sup 32/P incorporated into Histone H-1/min/10/sup 7/ cells), within 30 seconds. There is also an increase in /sup 3/H phorbol-12, 13-dibutyrate (/sup 3/H-PDB) binding which parallels the increase in PKC activity both in kinetics and antigen dose dependency. Determination of K/sub m/ and V/sub max/ for PKC revealed no difference between the cytosolic and membranous forms of PKC. Partial purification of PKC from the membrane of sensitized mast cells which had been labeled with /sup 32/P and stimulated with DNP-HSA revealed a protein of 80-84,000 molecular weight, which migrated on polyacrylamide gel electrophoresis just above an authentic standard of PKC purified from rat brain. Treatment of the PKC from mouse mast cell membrane with alkaline phosphatase resulted in a reduction of phosphorylating activity and bindability of /sup 3/H-PDB. In conclusion, the authors speculate that activation of mouse mast cells by cross-linking IgE results in the phosphorylation of a silent-pool of PKC converting it from an inactive state to an activated form.

  13. Mast cells in laser and surgical wounds.

    PubMed

    Pinheiro, A L; Browne, R M; Frame, J W; Matthews, J B

    1995-01-01

    Precooling of tissues was investigated as a possible means of reducing thermal damage during CO2 laser surgery of the oral mucosa. The changes in mast cells in scalpel, and in non-cooled and precooled (tissue temperature lowered to approximately 10 degrees C) CO2 laser wounds were studied. Standard wounds five mm in length were created with the CO2 laser or scalpel on the dorsum of the tongues of 32 Sprague-Dawley rats under general anesthesia with fentanyl/fluanisone and midazolam. Animals were killed with excess anesthetic immediately or six hours after surgery, their tongues were removed, trimmed, fixed in neutral formalin and processed to paraffin wax. Acid (pH 1.4) toluidine blue stained sections were used to count normal and degranulated mast cells in five fields (0.1 mm2) located at defined positions immediately adjacent to the wound site. At both 0 and 6 hours normal mast cell numbers were significantly different between treatment groups (P<0.045; ANOVA) with mean numbers highest in scalpel wounds and lowest in uncooled laser wounds. Similarly, at 0 time, there were significant differences in degranulated mast cells between treatment groups (P=0.004; ANOVA) but highest numbers were detected in uncooled laser wounds and lowest in scalpel wounds. There were no significant differences in degranulated mast cell counts at six hours although there was a similar distribution in numbers between groups. Total numbers of mast cells (normal + degranulated) did not differ between treatment groups. These results demonstrated that i) laser wounds are associated with greater levels of mast cell degranulation than scalpel wounds and ii) precooling of tissues prior to laser treatment decreases the level of mast cell degranulation. It is concluded that tissue damage in CO2 laser surgery may be reduced by precooling of tissue. PMID:8688643

  14. Mast cell leukemia: an extremely rare disease.

    PubMed

    Lu, Dai-Yin; Gau, Jyh-Pyng; Hong, Ying-Chung; Liu, Chun-Yu; Yu, Yuan-Bin; Hsiao, Liang-Tsai; Liu, Jin-Hwang; Chen, Po-Min; Chiou, Tzeon-Jye; Tzeng, Cheng-Hwai

    2014-08-01

    Systemic mastocytosis is characterized by pathologic proliferation and accumulation of mast cells in at least one extracutaneous organ such as liver, spleen, bone marrow, or lymph nodes. The clinical features are highly variable depending on impairment of the involved organ systems. It often raises diagnostic challenges. Here we report a case of a 78-year-old patient with mast cell leukemia. The literature is reviewed regarding the diagnosis and updated management of this rare disease. PMID:25028296

  15. Mast cells as targets of pimecrolimus.

    PubMed

    Ma, Zhongcai; Jiao, Zongjiu

    2011-11-01

    Mast cells, the multi-functional secretory cells, are the pivotal effector cells in immune response, and contribute to the pathogenesis of many diverse diseases, like asthma and mastocytosis, by releasing numerous proinflammatory mediators. Pimecrolimus (SDZ ASM 981) is a derivative of the macrolactam ascomycin and is a member of the calcineurin inhibitor class of immunosuppressors. It inhibits the calcineurin-dependent activation of nuclear factor of activated T cells and the expression of a number of proinflammatory cytokines in turn. Pimecrolimus has high and selective anti-inflammatory activity within the skin, and with much lower potential to affect local and systemic immune responses. Therefore it has been widely used for treatment of various inflammatory skin diseases. It has a cellselective mode of action, and mast cells are its specific target cells. Pimecrolimus inhibits the release of both preformed and de novo synthesized mediators from activated mast cells and inhibits accumulation of mast cells by inducing apoptosis. Several experimental and clinical reports have demonstrated the successful application of pimecrolimus and other calcineurin inhibitors, such as tacrolimus and cyclosporine A, to treat mastocytosis, a spectrum of disorders characterized by mast cell hyperplasia, especially cutaneous mastocytosis. These new findings suggest that pimecrolimus and other calcineurin inhibitors may be a novel and effective therapeutic approach for mast cell-associated diseases such as asthma and mastocytosis. PMID:22114844

  16. Role(s) of IL-2 inducible T cell kinase and Bruton's tyrosine kinase in mast cell response to lipopolysaccharide.

    PubMed

    Huang, Weishan; August, Avery

    2016-06-01

    Mast cells play critical roles during immune responses to the bacterial endotoxin lipopolysaccharide (LPS) that can lead to fatal septic hypothermia [1], [2], [3]. IL-2 inducible T cell kinase (ITK) and Bruton's tyrosine kinase (BTK) are non-receptor tyrosine kinases that act downstream of numerous receptors, and have been shown to modulate mast cell responses downstream of FcεRIα [4], however, their roles in regulating mast cell responses to endotoxic stimuli were unclear. We found that the absence of ITK and BTK alters the mast cell response to LPS, and leads to enhanced pro-inflammatory cytokine production by mast cells and more severe LPS-induced hypothermia in mice [5]. Here, we detail our investigation using microarray analysis to study the transcriptomic profiles of mast cell responses to LPS, and the roles of ITK and/or BTK expression in this process. Mouse whole genome array data of WT, Itk (-/-) , Btk (-/-) , and Itk (-/-)  Btk (-/-) bone marrow-derived mast cells (BMMCs) stimulated by PBS (control) or LPS for 1 h were used in our latest research article [5] and is available in the Gene Expression Omnibus under accession number GSE64287. PMID:27081634

  17. Effect of fruits of Opuntia elatior Mill on mast cell degranulation

    PubMed Central

    Chauhan, Sanjay P.; Sheth, N. R.; Suhagia, B. N.

    2015-01-01

    Background: The presence of potentially active nutrients and their multifunctional properties make prickly pear a perfect candidate for the production of phytopharmaceutical products. Among the numerous Opuntia species, bioactive compounds have been isolated and characterized primarily from Opuntia ficus-indica, Opuntia polycantha, Opuntia stricta, Opuntia dilleni for various medicinal properties. Objective: Based on the traditional use of prickly pear for enhancement of immune function, the objective of the present study to evaluate the effect of prickly pear on mast cell degranulation function. Materials and Methods: The Opuntia fruit juice (OFJ) (10-200 μl/ml) were studied for the effect on sensitized rat peritoneal mast cell degranulation induced by immunological (egg albumin), and nonimmunological (compound 48/80) stimuli and compared with that of the reference standard, sodium cromoglycate and ketotifen (10 μg/ml). Results and Conclusion: The OFJ exhibited significantly (P < 0.001) concentration dependent inhibition of mast cell degranulation. The IC50 value of OFJ was found 12.24 and 18 μl/ml for immunological and nonimmunological induced mast cell degranulation, respectively. The betacyanin is an active principle compound in prickly pear that may responsible for mast cell stabilizing action. PMID:25883521

  18. Hard-pan soils - Management

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hard pans, hard layers, or compacted horizons, either surface or subsurface, are universal problems that limit crop production. Hard layers can be caused by traffic or soil genetic properties that result in horizons with high density or cemented soil particles; these horizons have elevated penetrati...

  19. The hard metal diseases.

    PubMed

    Cugell, D W

    1992-06-01

    Hard metal is a mixture of tungsten carbide and cobalt, to which small amounts of other metals may be added. It is widely used for industrial purposes whenever extreme hardness and high temperature resistance are needed, such as for cutting tools, oil well drilling bits, and jet engine exhaust ports. Cobalt is the component of hard metal that can be a health hazard. Respiratory diseases occur in workers exposed to cobalt--either in the production of hard metal, from machining hard metal parts, or from other sources. Adverse pulmonary reactions include asthma, hypersensitivity pneumonitis, and interstitial fibrosis. A peculiar, almost unique form of lung fibrosis, giant cell interstitial pneumonia, is closely linked with cobalt exposure. PMID:1511554

  20. Ancient origin of mast cells.

    PubMed

    Wong, G William; Zhuo, Lisheng; Kimata, Koji; Lam, Bing K; Satoh, Nori; Stevens, Richard L

    2014-08-22

    The sentinel roles of mammalian mast cells (MCs) in varied infections raised the question of their evolutionary origin. We discovered that the test cells in the sea squirt Ciona intestinalis morphologically and histochemically resembled cutaneous human MCs. Like the latter, C. intestinalis test cells stored histamine and varied heparin·serine protease complexes in their granules. Moreover, they exocytosed these preformed mediators when exposed to compound 48/80. In support of the histamine data, a C. intestinalis-derived cDNA was isolated that resembled that which encodes histidine decarboxylase in human MCs. Like heparin-expressing mammalian MCs, activated test cells produced prostaglandin D2 and contained cDNAs that encode a protein that resembles the synthase needed for its biosynthesis in human MCs. The accumulated morphological, histochemical, biochemical, and molecular biology data suggest that the test cells in C. intestinalis are the counterparts of mammalian MCs that reside in varied connective tissues. The accumulated data point to an ancient origin of MCs that predates the emergence of the chordates >500million years ago, well before the development of adaptive immunity. The remarkable conservation of MCs throughout evolution is consistent with their importance in innate immunity. PMID:25094046

  1. Inhibitory effect of putranjivain A on allergic inflammation through suppression of mast cell activation

    SciTech Connect

    Kim, Hui-Hun; Park, Seung-Bin; Lee, Soyoung; Kwon, Taeg Kyu; Shin, Tae-Yong; Park, Pil-Hoon; Lee, Seung-Ho; Kim, Sang-Hyun

    2014-02-01

    A great number of people are suffering from allergic inflammatory disease such as asthma, atopic dermatitis, and sinusitis. Therefore discovery of drugs for the treatment of these diseases is an important subject in human health. Putranjivain A (PJA), member of ellagitannin, is known to possess beneficial effects including anti-cancer and anti-viral activities. The aim of the present study was to elucidate whether PJA modulates the allergic inflammatory reaction and to study its possible mechanisms of action using mast cell-based in vitro and in vivo models. The study was performed in anaphylaxis mouse model and cultured mast cells. PJA inhibited the expression of pro-inflammatory cytokines in immunoglobulin E-stimulated mast cells. PJA reduced this expression by inhibiting nuclear factor (NF)-κB and nuclear factor of activated T cell. The oral administration of PJA reduced systemic and cutaneous anaphylaxis, the release of serum histamine, and the expression of the histamine H{sub 1} receptor. In addition, PJA attenuated the activation of mast cells. PJA inhibited the release of histamine from various types of mast cells by the suppression of intracellular calcium. The inhibitory activity of PJA on the allergic reaction was similar to that of disodium cromoglycate, a known anti-allergic drug. These results suggest that PJA can facilitate the prevention or treatment of allergic inflammatory diseases mediated by mast cells. - Highlights: • PJA reduced the degranulation of mast cells. • PJA inhibited the production of inflammatory cytokines. • The effect of PJA on allergic reaction was comparable to the DSCG. • PJA might be a candidate for the treatment of allergic inflammatory diseases.

  2. The Tec family kinase Itk differentially controls mast cell responses*

    PubMed Central

    Iyer, Archana S.; August, Avery

    2008-01-01

    The Tec family tyrosine kinase Itk is expressed in T cells and mast cells. Mice lacking Itk exhibit impaired TH2 cytokine secretion; however, they have increased circulating serum IgE but exhibit few immunological symptoms of allergic airway responses. We have examined the role of Itk in mast cell function and FcεRI signaling. We report here that Itk null mice have reduced allergen/IgE induced histamine release as well as early airway hyperresponsiveness in vivo. This is due to the increased levels of IgE in the serum of these mice, since the transfer of Itk null BMMC into mast cell deficient W/Wv animals is able to fully rescue histamine release in the W/Wv mice. Further analysis of Itk null BMMC in vitro revealed that while they have normal degranulation responses, they secrete elevated levels of cytokines, including IL-13 and TNF-α, particularly in response to unliganded IgE. Analysis of biochemical events downstream of the FcεRI revealed little difference in overall tyrosine phosphorylation of specific substrates or calcium responses, however, these cells express elevated levels of NFAT which was largely nuclear. Our results suggest that the reduced mast cell response in vivo in Itk null mice is due to elevated levels of IgE in these mice. Our results also suggest that Itk differentially modulates mast cell degranulation and cytokine production in part by regulating expression and activation of NFAT proteins in these cells. “This is an author-produced version of a manuscript accepted for publication in The Journal of Immunology (The JI). The American Association of Immunologists, Inc. (AAI), publisher of The JI, holds the copyright to this manuscript. This version of the manuscript has not yet been copyedited or subjected to editorial proofreading by The JI; hence, it may differ from the final version published in The JI (online and in print). AAI (The JI) is not liable for errors or omissions in this author-produced version of the manuscript or in any

  3. Analysis of the components of hard resin in hops (Humulus lupulus L.) and structural elucidation of their transformation products formed during the brewing process.

    PubMed

    Taniguchi, Yoshimasa; Taniguchi, Harumi; Yamada, Makiko; Matsukura, Yasuko; Koizumi, Hideki; Furihata, Kazuo; Shindo, Kazutoshi

    2014-11-26

    The resins from hops (Humulus lupulus L.), which add the bitter taste to beer, are classified into two main sub-fractions, namely, soft and hard resins. α- and β-Acids in soft resin and their transformation during the wort boiling process are well-studied; however, other constituents in resins, especially hard resin, have been unidentified. In this study, we identified humulinones and hulupones as soft-resin components, in addition to 4'-hydroxyallohumulinones and tricyclooxyisohumulones A and B as hard-resin components. These compounds are all oxidation products derived from α- or β-acids. We also investigated compositional changes in the hard resin during the wort boiling process, which has a significant effect on the taste of the beer, by using model boiling experiments. The major changes were identified to be isomerization of 4'-hydroxyallohumulinones into 4'-hydroxyallo-cis-humulinones, followed by decomposition into cis-oxyhumulinic acids. These findings will be helpful in systematically evaluating and optimizing the effect of the hard resin on beer quality. PMID:25354357

  4. Signal transduction and chemotaxis in mast cells.

    PubMed

    Draber, Petr; Halova, Ivana; Polakovicova, Iva; Kawakami, Toshiaki

    2016-05-01

    Mast cells play crucial roles in both innate and adaptive arms of the immune system. Along with basophils, mast cells are essential effector cells for allergic inflammation that causes asthma, allergic rhinitis, food allergy and atopic dermatitis. Mast cells are usually increased in inflammatory sites of allergy and, upon activation, release various chemical, lipid, peptide and protein mediators of allergic reactions. Since antigen/immunoglobulin E (IgE)-mediated activation of these cells is a central event to trigger allergic reactions, innumerable studies have been conducted on how these cells are activated through cross-linking of the high-affinity IgE receptor (FcεRI). Development of mature mast cells from their progenitor cells is under the influence of several growth factors, of which the stem cell factor (SCF) seems to be the most important. Therefore, how SCF induces mast cell development and activation via its receptor, KIT, has been studied extensively, including a cross-talk between KIT and FcεRI signaling pathways. Although our understanding of the signaling mechanisms of the FcεRI and KIT pathways is far from complete, pharmaceutical applications of the knowledge about these pathways are underway. This review will focus on recent progresses in FcεRI and KIT signaling and chemotaxis. PMID:25941081

  5. Do mast cells link obesity and asthma?

    PubMed Central

    Sismanopoulos, Nikolaos; Delivanis, Danae-Anastasia; Mavrommati, Despina; Hatziangelaki, Erifille; Conti, Pio; Theoharides, Theoharis C.

    2012-01-01

    Asthma is a chronic inflammatory disease of the lungs. Both the number of cases and severity of asthma have been increasing without a clear explanation. Recent evidence suggests that obesity, which has also been increasing alarmingly, may worsen or precipitate asthma, but there is little evidence of how obesity may contribute to lung inflammation. We propose that mast cells are involved in both asthma and obesity by being the target and source of adipocytokines, “alarmins” such as interleukin-9 (IL-9) and interleukin-33 (IL-33), and stress molecules including corticotropin-releasing hormone (CRH) and neurotensin (NT), secreted in response to the metabolic burden. In particular, CRH and NT have synergistic effects on mast cell secretion of vascular endothelial growth factor (VEGF). IL-33 augments VEGF release induced by substance P (SP) and tumor necrosis factor (TNF) release induced by NT. Both IL-9 and IL-33 also promote lung mast cell infiltration and augment allergic inflammation. These molecules are also expressed in human mast cells leading to autocrine effects. Obese patients are also less sensitive to glucocorticoids and bronchodilators. Development of effective mast cell inhibitors may be a novel approach for the management of both asthma and obesity. Certain flavonoid combinations may be a promising new treatment approach. PMID:23066905

  6. 107. UMBILICAL MAST HYDRAULIC CONTROL PANEL IN CENTER OF ROOM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    107. UMBILICAL MAST HYDRAULIC CONTROL PANEL IN CENTER OF ROOM UMBILICAL MAST PUMP ROOM (109), LSB (BDLG. 770), FACING WEST - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  7. Vaccine adjuvants: Tailor-made mast-cell granules

    NASA Astrophysics Data System (ADS)

    Gunzer, Matthias

    2012-03-01

    Mast cells induce protective immune responses through secretion of stimulatory granules. Microparticles modelled after mast-cell granules are now shown to replicate and enhance the functions of their natural counterparts and to direct the character of the resulting immunity.

  8. Mast Cell-Mediated Mechanisms of Nociception

    PubMed Central

    Aich, Anupam; Afrin, Lawrence B.; Gupta, Kalpna

    2015-01-01

    Mast cells are tissue-resident immune cells that release immuno-modulators, chemo-attractants, vasoactive compounds, neuropeptides and growth factors in response to allergens and pathogens constituting a first line of host defense. The neuroimmune interface of immune cells modulating synaptic responses has been of increasing interest, and mast cells have been proposed as key players in orchestrating inflammation-associated pain pathobiology due to their proximity to both vasculature and nerve fibers. Molecular underpinnings of mast cell-mediated pain can be disease-specific. Understanding such mechanisms is critical for developing disease-specific targeted therapeutics to improve analgesic outcomes. We review molecular mechanisms that may contribute to nociception in a disease-specific manner. PMID:26690128

  9. MAST YAG Thomson scattering upgrade alignment system

    SciTech Connect

    Figueiredo, J.; Serra, F.; Naylor, G.; Walsh, M.; Dunstan, M.; Scannell, R.

    2010-10-15

    The recent upgrade to the MAST YAG Thomson scattering while enhancing the diagnostic capabilities increased the complexity of the system. There are eight YAG lasers now operational, doubling the number from the previous setup. This means alignment between each laser individually and reference points is essential to guarantee data quality and diagnostic reliability. To address this issue an alignment system was recently installed. It mimics the beams alignment in MAST by sampling 1% of the laser beam that is sent into a telescope which demagnifies by a factor of 8. The demagnified beam is viewed with a CCD camera. By scanning the camera the profile and position of the beams in the scattering zone and in a range of several meters inside MAST can be determined. Therefore alignment is checked along the beam path without having to sample it inside the vessel. The experimental apparatus and test procedures are described.

  10. 43. TOP PART OF UMBILICAL MAST, NORTH AND WEST SIDES. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    43. TOP PART OF UMBILICAL MAST, NORTH AND WEST SIDES. AIR CONDITIONING DUCTING IS VISIBLE ON INTERIOR OF MAST. RAIL IS VISIBLE LEFT OF THE MAST. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  11. 42. VIEW OF UMBILICAL MAST AND LAUNCH PAD FROM MST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    42. VIEW OF UMBILICAL MAST AND LAUNCH PAD FROM MST BASE. LAUNCHER IS BEHIND UMBILICAL MAST AND RAIL SYSTEM IS PARALLEL TO MAST ON RIGHT AND LEFT. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  12. The Michigan Alcoholism Screening Test (MAST): A Statistical Validation Analysis

    ERIC Educational Resources Information Center

    Laux, John M.; Newman, Isadore; Brown, Russ

    2004-01-01

    This study extends the Michigan Alcoholism Screening Test (MAST; M. L. Selzer, 1971) literature base by examining 4 issues related to the validity of the MAST scores. Specifically, the authors examine the validity of the MAST scores in light of the presence of impression management, participant demographic variables, and item endorsement…

  13. Perivascular mast cells regulate vein graft neointimal formation and remodeling

    PubMed Central

    Grassia, Gianluca; Cambrook, Helen; Ialenti, Armando; MacRitchie, Neil; Carberry, Jaclyn; Lawrence, Catherine

    2015-01-01

    Objective. Emerging evidence suggests an important role for mast cells in vein graft failure. This study addressed the hypothesis that perivascular mast cells regulate in situ vascular inflammatory and proliferative responses and subsequent vein graft neointimal lesion formation, using an optimized local mast cell reconstitution method. Methods and Results. Neointimal hyperplasia was induced by insertion of a vein graft into the right carotid artery in wild type and mast cell deficient KitW−sh/W−sh mice. In some experiments, mast cells were reconstituted systemically (tail vein injection of bone marrow-derived mast cells) or locally (directly into the right neck area) prior to vein grafting. Vein graft neointimal lesion formation was significantly (P < 0.05) reduced in KitW−sh/W−sh mice. Mast cell deficiency reduced the number of proliferating cells, and inhibited L-selectin, CCL2, M-CSF and MIP-3α expression in the vein grafts. Local but not systemic mast cell reconstitution restored a perivascular mast cell population that subsequently promoted neointimal formation in mast cell deficient mice. Conclusion. Our data demonstrate that perivascular mast cells play a key role in promoting neointima formation by inducing local acute inflammatory and proliferative responses. These results suggest that ex vivo intraoperative targeting of mast cells may have therapeutic potential for the prevention of pathological vein graft remodeling. PMID:26312183

  14. 53. VIEW FROM FLOOR OF MAST TRENCH SHOWING BASE OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    53. VIEW FROM FLOOR OF MAST TRENCH SHOWING BASE OF ERECT UMBILICAL MAST. AIR-CONDITIONING DUCTS VISIBLE ON RIGHT SIDE OF MAST. HYDRAULIC ACTUATOR ARMS FOR OPENING TRENCH DOORS VISIBLE ON LEFT SIDE OF PHOTO. 'DOOR STOP' PEDESTAL IN FOREGROUND. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  15. Effect of disodium cromoglycate on mast cell-mediated immediate-type allergic reactions.

    PubMed

    Shin, Hye-Young; Kim, Jung-Sook; An, Nyeon-Hyoung; Park, Rae-Kil; Kim, Hyung-Min

    2004-04-23

    We investigated the effect of disodium cromoglycate (DSCG) on mast cell-mediated immediate-type hypersensitivity. DSCG inhibited systemic allergic reaction induced by compound 48/80 dose-dependently. Passive cutaneous anaphylaxis was inhibited by 71.6% by oral administration of DSCG (1 g/kg). When DSCG was pretreated at concentration rang from 0.01-1000 g/kg, the serum histamine levels were reduced in a dose dependent manner. DSCG also significantly inhibited histamine release from rat peritoneal mast cell (RPMC) by compound 48/80. We confirmed that DSCG inhibited compound 48/80-induced degranulation of RPMC by alcian blue/nuclear fast red staining. In addition, DSCG showed a significant inhibitory effect on anti-dinitrophenyl IgE-mediated tumor necrosis factor-alpha production. These results indicate that DSCG inhibits mast cell-mediated immediate-type allergic reaction. PMID:15050425

  16. Association of mast cells with calcification in the human pineal gland.

    PubMed

    Maślińska, Danuta; Laure-Kamionowska, Milena; Deręgowski, Krzysztof; Maśliński, Sławomir

    2010-01-01

    advanced stages of calcification. Our results lead to the conclusion that the tryptase mast cells play a major role in the pineal calcification process as sites where this process starts and as a source of production of numerous biologically active substances including tryptase that participate in calcification. PMID:21225510

  17. Fruiting Strategies of Perennial Plants: A Resource Budget Model to Couple Mast Seeding to Pollination Efficiency and Resource Allocation Strategies.

    PubMed

    Venner, Samuel; Siberchicot, Aurélie; Pélisson, Pierre-François; Schermer, Eliane; Bel-Venner, Marie-Claude; Nicolas, Manuel; Débias, François; Miele, Vincent; Sauzet, Sandrine; Boulanger, Vincent; Delzon, Sylvain

    2016-07-01

    Masting, a breeding strategy common in perennial plants, is defined by seed production that is highly variable over years and synchronized at the population level. Resource budget models (RBMs) proposed that masting relies on two processes: (i) the depletion of plant reserves following high fruiting levels, which leads to marked temporal fluctuations in fruiting; and (ii) outcross pollination that synchronizes seed crops among neighboring trees. We revisited the RBM approach to examine the extent to which masting could be impacted by the degree of pollination efficiency, by taking into account various logistic relationships between pollination success and pollen availability. To link masting to other reproductive traits, we split the reserve depletion coefficient into three biological parameters related to resource allocation strategies for flowering and fruiting. While outcross pollination is considered to be the key mechanism that synchronizes fruiting in RBMs, our model counterintuitively showed that intense masting should arise under low-efficiency pollination. When pollination is very efficient, medium-level masting may occur, provided that the costs of female flowering (relative to pollen production) and of fruiting (maximum fruit set and fruit size) are both very high. Our work highlights the powerful framework of RBMs, which include explicit biological parameters, to link fruiting dynamics to various reproductive traits and to provide new insights into the reproductive strategies of perennial plants. PMID:27322122

  18. VEGF secretion during hypoxia depends on free radicals-induced Fyn kinase activity in mast cells

    SciTech Connect

    Garcia-Roman, Jonathan; Ibarra-Sanchez, Alfredo; Lamas, Monica; Gonzalez Espinosa, Claudia

    2010-10-15

    Research highlights: {yields} Bone marrow-derived mast cells (BMMCs) secrete functional VEGF but do not degranulate after Cobalt chloride-induced hypoxia. {yields} CoCl{sub 2}-induced VEGF secretion in mast cells occurs by a Ca{sup 2+}-insensitive but brefeldin A and Tetanus toxin-sensitive mechanism. {yields} Trolox and N-acetylcysteine inhibit hypoxia-induced VEGF secretion but only Trolox inhibits Fc{epsilon}RI-dependent anaphylactic degranulation in mast cells. {yields} Src family kinase Fyn activation after free radical production is necessary for hypoxia-induced VEGF secretion in mast cells. -- Abstract: Mast cells (MC) have an important role in pathologic conditions such as asthma and chronic obstructive pulmonary disease (COPD), where hypoxia conduce to deleterious inflammatory response. MC contribute to hypoxia-induced angiogenesis producing factors such as vascular endothelial growth factor (VEGF), but the mechanisms behind the control of hypoxia-induced VEGF secretion in this cell type is poorly understood. We used the hypoxia-mimicking agent cobalt chloride (CoCl{sub 2}) to analyze VEGF secretion in murine bone marrow-derived mast cells (BMMCs). We found that CoCl{sub 2} promotes a sustained production of functional VEGF, able to induce proliferation of endothelial cells in vitro. CoCl{sub 2}-induced VEGF secretion was independent of calcium rise but dependent on tetanus toxin-sensitive vesicle-associated membrane proteins (VAMPs). VEGF exocytosis required free radicals formation and the activation of Src family kinases. Interestingly, an important deficiency on CoCl{sub 2}-induced VEGF secretion was observed in Fyn kinase-deficient BMMCs. Moreover, Fyn kinase was activated by CoCl{sub 2} in WT cells and this activation was prevented by treatment with antioxidants such as Trolox and N-acetylcysteine. Our results show that BMMCs are able to release VEGF under hypoxic conditions through a tetanus toxin-sensitive mechanism, promoted by free radicals

  19. Mast cells in airway diseases and interstitial lung disease.

    PubMed

    Cruse, Glenn; Bradding, Peter

    2016-05-01

    Mast cells are major effector cells of inflammation and there is strong evidence that mast cells play a significant role in asthma pathophysiology. There is also a growing body of evidence that mast cells contribute to other inflammatory and fibrotic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. This review discusses the role that mast cells play in airway diseases and highlights how mast cell microlocalisation within specific lung compartments and their cellular interactions are likely to be critical for their effector function in disease. PMID:25959386

  20. Mast Cell: A Multi-Functional Master Cell

    PubMed Central

    Krystel-Whittemore, Melissa; Dileepan, Kottarappat N.; Wood, John G.

    2016-01-01

    Mast cells are immune cells of the myeloid lineage and are present in connective tissues throughout the body. The activation and degranulation of mast cells significantly modulates many aspects of physiological and pathological conditions in various settings. With respect to normal physiological functions, mast cells are known to regulate vasodilation, vascular homeostasis, innate and adaptive immune responses, angiogenesis, and venom detoxification. On the other hand, mast cells have also been implicated in the pathophysiology of many diseases, including allergy, asthma, anaphylaxis, gastrointestinal disorders, many types of malignancies, and cardiovascular diseases. This review summarizes the current understanding of the role of mast cells in many pathophysiological conditions. PMID:26779180

  1. Molecular markers linked to genes important for Hard Winter Wheat production and marketing in the U.S. Great Plains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Biotic stresses including diseases [leaf, stem and stripe rusts, and wheat streak mosaic virus (WSMV)] and insects [greenbug (GB), Hessian fly (Hf), Russian wheat aphid (RWA) and wheat curl mite (WCM)] significantly affect grain yield and end-use quality of hard winter wheat (HWW, Triticum aestivum ...

  2. National Survey on Telephone Services and Products: The Views of Deaf and Hard-of-Hearing People.

    ERIC Educational Resources Information Center

    Bowe, Frank G.

    1991-01-01

    A national survey of 128 deaf and hard-of-hearing adults aged 18 to 70 years found a willingness to pay as much as $15 per month for new telephone-based information services. The most desired services were "enhanced 911," fire, police, and other life/safety services. Subjects also wanted such a network equipped with speech recognition…

  3. A protective role of mast cells in intestinal tumorigenesis.

    PubMed

    Sinnamon, Mark J; Carter, Kathy J; Sims, Lauren P; Lafleur, Bonnie; Fingleton, Barbara; Matrisian, Lynn M

    2008-04-01

    Mast cells have been observed in numerous types of tumors; however, their role in carcinogenesis remains poorly understood. The majority of epidemiological evidence suggests a negative association between the presence of mast cells and tumor progression in breast, lung and colonic neoplasms. Intestinal adenomas in the multiple intestinal neoplasia (Min, APC(Min/+)) mouse displayed increased numbers of mast cells and increased abundance of mast cell-associated proteinases as determined by transcriptional profiling with the Hu/Mu ProtIn microarray. To examine the role of mast cells in intestinal tumorigenesis, a mutant mouse line deficient in mast cells, Sash mice (c-kit(W-sh/W-sh)), was crossed with the Min mouse, a genetic model of intestinal neoplasia. The resulting mast cell-deficient Min-Sash mice developed 50% more adenomas than littermate controls and the tumors were 33% larger in Min-Sash mice. Mast cell deficiency did not affect tumor cell proliferation; however, apoptosis was significantly inhibited in mast cell-deficient mice. Mast cells have been shown to act as critical upstream regulators of numerous inflammatory cells. Neutrophil, macrophage and T cell populations were similar between Min and Min-Sash mice; however, eosinophils were significantly less abundant in tumors obtained from Min-Sash animals. These results indicate a protective, antitumor role of mast cells in a genetic model of early-stage intestinal tumorigenesis. PMID:18258601

  4. Mast Cells Synthesize, Store, and Release Nerve Growth Factor

    NASA Astrophysics Data System (ADS)

    Leon, A.; Buriani, A.; dal Toso, R.; Fabris, M.; Romanello, S.; Aloe, L.; Levi-Montalcini, R.

    1994-04-01

    Mast cells and nerve growth factor (NGF) have both been reported to be involved in neuroimmune interactions and tissue inflammation. In many peripheral tissues, mast cells interact with the innervating fibers. Changes in the behaviors of both of these elements occur after tissue injury/inflammation. As such conditions are typically associated with rapid mast cell activation and NGF accumulation in inflammatory exudates, we hypothesized that mast cells may be capable of producing NGF. Here we report that (i) NGF mRNA is expressed in adult rat peritoneal mast cells; (ii) anti-NGF antibodies clearly stain vesicular compartments of purified mast cells and mast cells in histological sections of adult rodent mesenchymal tissues; and (iii) medium conditioned by peritoneal mast cells contains biologically active NGF. Mast cells thus represent a newly recognized source of NGF. The known actions of NGF on peripheral nerve fibers and immune cells suggest that mast cell-derived NGF may control adaptive/reactive responses of the nervous and immune systems toward noxious tissue perturbations. Conversely, alterations in normal mast cell behaviors may provoke maladaptive neuroimmune tissue responses whose consequences could have profound implications in inflammatory disease states, including those of an autoimmune nature.

  5. Platelet activating factor: regulation by mast cells and aspirin.

    PubMed

    Denburg, J A; Williams, D B; Kinlough-Rathbone, R L; Cazenave, J P; Bienenstock, J

    1984-02-01

    We have investigated some aspects of the regulation of production of rat platelet activating factor (PAF)2 in vitro. Suspensions of unseparated (PLC1), mast cell-depleted (PLC2), or mast cell (MC)-enriched rat peritoneal lavage cells (PLC) were analyzed for PAF content by extraction at alkaline pH. PAF activity extracted from PLC1 varied inversely with viable cell concentration: at 1 X 10(6) cells/ml, 32 +/- 9.3 PAF units, decreasing to 11.2 +/- 9.5 units at 10 X 10(6) cells/ml, and no activity at higher concentrations. Incubation of PLC1 in Tyrode's buffer or acetylsalicylic acid (ASA), but not salicylate, resulted in a time-dependent loss of PAF activity. Mean PAF activity of PLC2 was similar to that in PLC1, while no PAF activity was extractable from MC. Co-incubation with MC extracts inhibited PAF activity of PLC1 extracts in a dose-dependent fashion. Ultracentrifugation of PAF-containing samples led to a loss of all PAF activity in PLC1 extracts, suggesting the association of PAF activity with subcellular components. PAF appears to be derived from a non-MC population of rat PLC, is not extractable from rat PLC in the presence of ASA and is inhibited by MC extracts. These studies suggest that ASA regulates PAF availability unrelated to its effect on cyclooxygenase and that MC membrane products directly inhibit PAF activity from rat PLC. PMID:6711391

  6. 46 CFR 111.05-9 - Masts.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Masts. 111.05-9 Section 111.05-9 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS... reference; see 46 CFR 110.10-1). System Grounding...

  7. Mast fruiting and seedling survival of the ectomycorrhizal, monodominant Dicymbe corymbosa (Caesalpiniaceae) in Guyana.

    PubMed

    Henkel, Terry W; Mayor, Jordan R; Woolley, Lance P

    2005-08-01

    In Guyana, we investigated seed output, and resulting seedling establishment and survival, during a 'mast' year, by the ectomycorrhizal, monodominant rainforest canopy tree Dicymbe corymbosa (Caesalpiniaceae), a species with high, synchronous seed production at intermittent years. By utilizing seed traps, the mast seed output, predation, carbon and mineral investment, and masting synchrony were quantified in 2003 in primary D. corymbosa forests. Establishment of seedling cohorts was monitored, and climatic conditions associated with masting were assessed. During 2003, D. corymbosa in the Pakaraima Mountains exhibited high, synchronous seed production with low dispersal and predation. Investment in reproductive biomass was large relative to that in other tropical forests. Recent D. corymbosa reproductive events followed El Nino-induced droughts, with little intervening seed production. Over 12 months, 40% of the 2003 seedling cohort survived. Our results suggest that D. corymbosa has a strongly bimodal fruiting pattern that allows the establishment of a large seedling bank, facilitating persistent monodominance. Resource investment in large seed crops may depend on mineral recycling via ectomycorrhizas, coupled with the reallocation of carbon from vegetative maintenance. PMID:15998405

  8. Further studies on the effect of nitrogen dioxide on mast cells: The effect of the metabolite, nitrite

    SciTech Connect

    Fujimaki, Hidekazu ); Ozawa, Masashi ); Bissonnette, E.; Befus, A.D. )

    1993-05-01

    To evaluate the relationship between atmospheric nitrogen dioxide exposure and the development of allergic diseases, the effects of nitrite as a chemical product of inhaled nitrogen dioxide on mast cell functions were investigated. We have studied nitride-induced histamine release from two functionally distinct mast cell populations, namely peritoneal mast cells (PMC) and intestinal mucosal mast cells (IMMC) of Nippostrongylus brasiliensis-infected rats. High concentrations of nitrite alone (10, 20, and 50 mM) induced histamine release from IMMC, but not from PMC. Moreover, histamine release from PMC and IMMC stimulated with sensitizing antigen was significantly enhanced by pretreatment with 50 mM nitrite or nitrate. No differences in histamine release from nitrite-treated and control PMC were seen below 1 mM. To investigate the effect of nitrite on tumor cell cytotoxic activity, PMC were incubated with various concentrations of nitrite. Pretreatment with 5 and 50 mM nitrite markedly depressed tumor necrosis factor (TNF)-[alpha]-dependent natural cytotoxicity of PMC for the tumor target WEHI-164. Thus, high concentrations of nitrite enhanced mast cell histamine release, but depressed TNF-[alpha]-dependent cytotoxicity. However, low concentrations of nitrite (<1 mM) that would normally be produced by short-term atmospheric exposure to nitrogen dioxide may have no significant effects on mast cell functions. 27 refs., 3 figs., 1 tab.

  9. Must "Hard Problems" Be Hard?

    ERIC Educational Resources Information Center

    Kolata, Gina

    1985-01-01

    To determine how hard it is for computers to solve problems, researchers have classified groups of problems (polynomial hierarchy) according to how much time they seem to require for their solutions. A difficult and complex proof is offered which shows that a combinatorial approach (using Boolean circuits) may resolve the problem. (JN)

  10. A Microplate Assay to Assess Chemical Effects on RBL-2H3 Mast Cell Degranulation: Effects of Triclosan without Use of an Organic Solvent

    PubMed Central

    Shim, Juyoung; Gosse, Julie A.

    2013-01-01

    Mast cells play important roles in allergic disease and immune defense against parasites. Once activated (e.g. by an allergen), they degranulate, a process that results in the exocytosis of allergic mediators. Modulation of mast cell degranulation by drugs and toxicants may have positive or adverse effects on human health. Mast cell function has been dissected in detail with the use of rat basophilic leukemia mast cells (RBL-2H3), a widely accepted model of human mucosal mast cells3-5. Mast cell granule component and the allergic mediator β-hexosaminidase, which is released linearly in tandem with histamine from mast cells6, can easily and reliably be measured through reaction with a fluorogenic substrate, yielding measurable fluorescence intensity in a microplate assay that is amenable to high-throughput studies1. Originally published by Naal et al.1, we have adapted this degranulation assay for the screening of drugs and toxicants and demonstrate its use here. Triclosan is a broad-spectrum antibacterial agent that is present in many consumer products and has been found to be a therapeutic aid in human allergic skin disease7-11, although the mechanism for this effect is unknown. Here we demonstrate an assay for the effect of triclosan on mast cell degranulation. We recently showed that triclosan strongly affects mast cell function2. In an effort to avoid use of an organic solvent, triclosan is dissolved directly into aqueous buffer with heat and stirring, and resultant concentration is confirmed using UV-Vis spectrophotometry (using ε280 = 4,200 L/M/cm)12. This protocol has the potential to be used with a variety of chemicals to determine their effects on mast cell degranulation, and more broadly, their allergic potential. PMID:24300285

  11. A microplate assay to assess chemical effects on RBL-2H3 mast cell degranulation: effects of triclosan without use of an organic solvent.

    PubMed

    Weatherly, Lisa M; Kennedy, Rachel H; Shim, Juyoung; Gosse, Julie A

    2013-01-01

    Mast cells play important roles in allergic disease and immune defense against parasites. Once activated (e.g. by an allergen), they degranulate, a process that results in the exocytosis of allergic mediators. Modulation of mast cell degranulation by drugs and toxicants may have positive or adverse effects on human health. Mast cell function has been dissected in detail with the use of rat basophilic leukemia mast cells (RBL-2H3), a widely accepted model of human mucosal mast cells(3-5). Mast cell granule component and the allergic mediator β-hexosaminidase, which is released linearly in tandem with histamine from mast cells(6), can easily and reliably be measured through reaction with a fluorogenic substrate, yielding measurable fluorescence intensity in a microplate assay that is amenable to high-throughput studies(1). Originally published by Naal et al.(1), we have adapted this degranulation assay for the screening of drugs and toxicants and demonstrate its use here. Triclosan is a broad-spectrum antibacterial agent that is present in many consumer products and has been found to be a therapeutic aid in human allergic skin disease(7-11), although the mechanism for this effect is unknown. Here we demonstrate an assay for the effect of triclosan on mast cell degranulation. We recently showed that triclosan strongly affects mast cell function(2). In an effort to avoid use of an organic solvent, triclosan is dissolved directly into aqueous buffer with heat and stirring, and resultant concentration is confirmed using UV-Vis spectrophotometry (using ε280 = 4,200 L/M/cm)(12). This protocol has the potential to be used with a variety of chemicals to determine their effects on mast cell degranulation, and more broadly, their allergic potential. PMID:24300285

  12. Hard π0 and η production in S+Au nuclear collisions at SPS energies and possible signature of quark-gluon plasma

    NASA Astrophysics Data System (ADS)

    Tarasov, Yu. A.

    1998-11-01

    Hard π0 and η production is investigated in Landau and Bjorken hydrodynamical models taking into account great number of hadronic resonances (16 and 42) in hadronic phase. We consider two different scenario: with quark-gluon plasma (QGP) formation and with only hadronic gas one without QGP. The Cronin effect and hard direct pions emission are taken into account. It is shown that these two scenario give similar p⊥ spectra which agrees with experimental data obtained by WA80 collaboration. Therefore we conclude that from hadronic spectra it is difficult to extract the proof of QGP formation. However we calculate also the η/π0 ratio. We show that this value agrees with experiment only for scenario with QGP and phase transition to hadrons. The hadronic gas scenario without QGP disagrees with experimental data.

  13. The natural compound nujiangexanthone A suppresses mast cell activation and allergic asthma.

    PubMed

    Lu, Yue; Cai, Shuangfan; Nie, Jia; Li, Yangyang; Shi, Guochao; Hao, Jimin; Fu, Wenwei; Tan, Hongsheng; Chen, Shilin; Li, Bin; Xu, Hongxi

    2016-01-15

    Mast cells play an important role in allergic diseases such as asthma, allergic rhinitis and atopic dermatitis. The genus Garcinia of the family Guttiferae is well known as a prolific source of polycyclic polyprenylated acylphloroglucinols and bioactive prenylated xanthones, which exhibit various biological activities including antibacterial, antifungal, anti-inflammatory, antioxidant, and cytotoxic effects. Nujiangexanthone A (N7) is a novel compound isolated from the leaves of Garcinia nujiangensis. In this paper, we sought to determine the anti-allergic and anti-inflammation activity of N7 in vivo and its mechanism in vitro. We found N7 suppressed IgE/Ag induced mast cell activiation, including degranulation and production of cytokines and eicosanoids, through inhibiting Src kinase activity and Syk dependent pathways. N7 inhibited histamine release, prostaglandin D2 and leukotriene C4 generation in mast cell dependent passive cutaneous anaphylaxis animal model. We also found N7 inhibited the IL-4, IL-5, IL-13 and IgE levels in ovalbumin-induced asthma model. Histological studies demonstrated that N7 substantially inhibited OVA-induced cellular infiltration and increased mucus production in the lung tissue. Our study reveals the anti-allergic function of N7, thereby suggesting the utility of this compound as a possible novel agent for preventing mast cell-related immediate and delayed allergic diseases. PMID:26571438

  14. Propagation by Cutting of Grewia coriacea Mast. (Malvaceae).

    PubMed

    Mercier, Bita Alain; Attibayéba; Pierre, Kampé Jean; Léon, Ngantsoué; Fidèle, Mialoundama

    2016-01-01

    Congolese forests contain important spontaneous food plants. Among these plants, there is the Grewia coriacea Mast., called in the national language "Tsui-téké", which is a tree of 4-25 m high and of 12-40 cm in diameter. Its fruits are used in several drinks making (juice, sparkling wine, syrup) and lollipops. Grewia's barks are used in pharmacopoeia to cure of stomach aches, syphilis. However, the fruits harvesting method based on branches or trees cutting as well as swidden agriculture by local people dangerously threatens the Grewia in the natural ecosystems of Congo. To insure the longevity of this species, we undertook trials of vegetative reproduction of the plant by means of propagation by cuttings for its domestication. Less woody leafless cuttings of 30 cm in length provided best results with a resumption rate of 63.3%, a good rooting production and an average duration of the apparent plastochrone of three days from the second to the fifth leaf. The study shows that domestication of the Grewia coriacea Mast. is possible today by cuttings. Its culture might allow the diversification of species which can be used in orchards. PMID:26930798

  15. New models for analyzing mast cell functions in vivo.

    PubMed

    Reber, Laurent L; Marichal, Thomas; Galli, Stephen J

    2012-12-01

    In addition to their well-accepted role as critical effector cells in anaphylaxis and other acute IgE-mediated allergic reactions, mast cells (MCs) have been implicated in a wide variety of processes that contribute to disease or help to maintain health. Although some of these roles were first suggested by analyses of MC products or functions in vitro, it is critical to determine whether, and under which circumstances, such potential roles actually can be performed by MCs in vivo. This review discusses recent advances in the development and analysis of mouse models to investigate the roles of MCs and MC-associated products during biological responses in vivo, and comments on some of the similarities and differences in the results obtained with these newer versus older models of MC deficiency. PMID:23127755

  16. Resource limitation underlying multiple masting models makes mast seeding sensitive to future climate change.

    PubMed

    Monks, Adrian; Monks, Joanne M; Tanentzap, Andrew J

    2016-04-01

    Mechanistic models can help resolve controversy over the responses of mast seeding plants to future environmental change. We evaluate drivers of mast seeding by: developing and validating a new mechanistic resource-based model of mast seeding using four 40-yr Chionochloa (snow tussock) datasets; and comparing the performance of competing empirically-based statistical models, that aim to approximate the mechanisms underlying mast seeding, in explaining simulated and observed data. Our mechanistic model explained 90-99% of the variation in Chionochloa flowering, with higher rates of stored resource mobilisation and lower probability of climatic induction of flowering occurring at lower fertility sites. Inter-annual variation in floral induction and the degree to which seeding is resource-limited explained shifts in the relative performance of different empirical models fitted to data simulated from the mechanistic model. Empirical models explicitly capturing the interaction between the floral induction cue and internal resource state underlying the resource-limited induction mechanism had > 8.7× the statistical support of alternatives when fitted to Chionochloa datasets. We find support for resource-limited floral induction with multiple empirical models consistent with this same mechanism. As both resource acquisition and flowering cues are climate sensitive, we expect climate change to impact upon patterns of mast seeding. PMID:26725252

  17. A Numerical Study of Material Parameter Sensitivity in the Production of Hard Metal Components Using Powder Compaction

    NASA Astrophysics Data System (ADS)

    Andersson, Daniel C.; Lindskog, Per; Staf, Hjalmar; Larsson, Per-Lennart

    2014-06-01

    Modeling of hard metal powder inserts is analyzed based on a continuum mechanics approach. In particular, one commonly used cutting insert geometry is studied. For a given advanced constitutive description of the powder material, the material parameter space required to accurately model the mechanical behavior is determined. These findings are then compared with the corresponding parameter space that can possibly be determined from a combined numerical/experimental analysis of uniaxial die powder compaction utilizing inverse modeling. The analysis is pertinent to a particular WC/Co powder and the finite element method is used in the numerical investigations of the mechanical behavior of the cutting insert.

  18. Hymenoptera Allergy and Mast Cell Activation Syndromes.

    PubMed

    Bonadonna, Patrizia; Bonifacio, Massimiliano; Lombardo, Carla; Zanotti, Roberta

    2016-01-01

    Mast cell activation syndrome (MCAS) can be diagnosed in patients with recurrent, severe symptoms from mast cell (MC)-derived mediators, which are transiently increased in serum and are attenuated by mediator-targeting drugs. When KIT-mutated, clonal MC are detected in these patients, a diagnosis of primary MCAS can be made. Severe systemic reactions to hymenoptera venom (HV) represent the most common form of anaphylaxis in patients with mastocytosis. Patients with primary MCAS and HV anaphylaxis are predominantly males and do not have skin lesions in the majority of cases, and anaphylaxis is characterized by hypotension and syncope in the absence of urticaria and angioedema. A normal value of tryptase (≤11.4 ng/ml) in these patients does not exclude a diagnosis of mastocytosis. Patients with primary MCAS and HV anaphylaxis have to undergo lifelong venom immunotherapy, in order to prevent further potentially fatal severe reactions. PMID:26714690

  19. MAST Propellant and Delivery System Design Methods

    NASA Technical Reports Server (NTRS)

    Nadeem, Uzair; Mc Cleskey, Carey M.

    2015-01-01

    A Mars Aerospace Taxi (MAST) concept and propellant storage and delivery case study is undergoing investigation by NASA's Element Design and Architectural Impact (EDAI) design and analysis forum. The MAST lander concept envisions landing with its ascent propellant storage tanks empty and supplying these reusable Mars landers with propellant that is generated and transferred while on the Mars surface. The report provides an overview of the data derived from modeling between different methods of propellant line routing (or "lining") and differentiate the resulting design and operations complexity of fluid and gaseous paths based on a given set of fluid sources and destinations. The EDAI team desires a rough-order-magnitude algorithm for estimating the lining characteristics (i.e., the plumbing mass and complexity) associated different numbers of vehicle propellant sources and destinations. This paper explored the feasibility of preparing a mathematically sound algorithm for this purpose, and offers a method for the EDAI team to implement.

  20. The SNARE Machinery in Mast Cell Secretion

    PubMed Central

    Lorentz, Axel; Baumann, Anja; Vitte, Joana; Blank, Ulrich

    2012-01-01

    Mast cells are known as inflammatory cells which exert their functions in allergic and anaphylactic reactions by secretion of numerous inflammatory mediators. During an allergic response, the high-affinity IgE receptor, FcεRI, becomes cross-linked by receptor-bound IgE and antigen resulting in immediate release of pre-synthesized mediators – stored in granules – as well as in de novo synthesis of various mediators like cytokines and chemokines. Soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptors (SNARE) proteins were found to play a central role in regulating membrane fusion events during exocytosis. In addition, several accessory regulators like Munc13, Munc18, Rab GTPases, secretory carrier membrane proteins, complexins, or synaptotagmins were found to be involved in membrane fusion. In this review we summarize our current knowledge about the SNARE machinery and its mechanism of action in mast cell secretion. PMID:22679448

  1. Characterization of Mast Cell Secretory Granules and Their Cell Biology

    PubMed Central

    Azouz, Nurit Pereg; Hammel, Ilan

    2014-01-01

    Exocytosis and secretion of secretory granule (SG) contained inflammatory mediators is the primary mechanism by which mast cells exert their protective immune responses in host defense, as well as their pathological functions in allergic reactions and anaphylaxis. Despite their central role in mast cell function, the molecular mechanisms underlying the biogenesis and secretion of mast cell SGs remain largely unresolved. Early studies have established the lysosomal nature of the mast cell SGs and implicated SG homotypic fusion as an important step occurring during both their biogenesis and compound secretion. However, the molecular mechanisms that account for key features of this process largely remain to be defined. A novel high-resolution imaging based methodology allowed us to screen Rab GTPases for their phenotypic and functional impact and identify Rab networks that regulate mast cell secretion. This screen has identified Rab5 as a novel regulator of homotypic fusion of the mast cell SGs that thereby regulates their size and cargo composition. PMID:24988214

  2. Mast cells and their activation in lung disease.

    PubMed

    Virk, Harvinder; Arthur, Greer; Bradding, Peter

    2016-08-01

    Mast cells and their activation contribute to lung health via innate and adaptive immune responses to respiratory pathogens. They are also involved in the normal response to tissue injury. However, mast cells are involved in disease processes characterized by inflammation and remodeling of tissue structure. In these diseases mast cells are often inappropriately and chronically activated. There is evidence for activation of mast cells contributing to the pathophysiology of asthma, pulmonary fibrosis, and pulmonary hypertension. They may also play a role in chronic obstructive pulmonary disease, acute respiratory distress syndrome, and lung cancer. The diverse mechanisms through which mast cells sense and interact with the external and internal microenvironment account for their role in these diseases. Newly discovered mechanisms of redistribution and interaction between mast cells, airway structural cells, and other inflammatory cells may offer novel therapeutic targets in these disease processes. PMID:26845625

  3. A20-Deficient Mast Cells Exacerbate Inflammatory Responses In Vivo

    PubMed Central

    Vahl, J. Christoph; Aszodi, Attila; Peschke, Katrin; Schenten, Dominik; Hammad, Hamida; Beyaert, Rudi; Saur, Dieter; van Loo, Geert; Roers, Axel; Lambrecht, Bart N.; Kool, Mirjam; Schmidt-Supprian, Marc

    2014-01-01

    Mast cells are implicated in the pathogenesis of inflammatory and autoimmune diseases. However, this notion based on studies in mast cell-deficient mice is controversial. We therefore established an in vivo model for hyperactive mast cells by specifically ablating the NF-κB negative feedback regulator A20. While A20 deficiency did not affect mast cell degranulation, it resulted in amplified pro-inflammatory responses downstream of IgE/FcεRI, TLRs, IL-1R, and IL-33R. As a consequence house dust mite- and IL-33-driven lung inflammation, late phase cutaneous anaphylaxis, and collagen-induced arthritis were aggravated, in contrast to experimental autoimmune encephalomyelitis and immediate anaphylaxis. Our results provide in vivo evidence that hyperactive mast cells can exacerbate inflammatory disorders and define diseases that might benefit from therapeutic intervention with mast cell function. PMID:24453940

  4. Creatine phosphokinase in rat mast cells.

    PubMed Central

    Magro, A M

    1980-01-01

    The soluble cytoplasmic fraction of an homogenate from peritoneal rat mast cells, demonstrated a considerable amount of catalytic activity which promotes the transfer of phosphate from creatine phosphate to ADP. The plasma membrane, mitochondrial and microsomal fractions show negligible amounts of the catalyst. Enzyme activity is maximal at 37 degrees showing little activity below 17 degrees or above 45 degrees. The enzyme is strongly Mg2+-dependent, whereas it is only slightly activated by Ca2+. pH values between 7 and 8 are optimal and the enzyme is irreversibly inactivated below pH 4. The overall behaviour of the catalyst indicates it to be a creatine phosphokinase (CPK), an enzyme considered important to muscle and nerve tissues. The CPK is probably not encapsulated within the mast cells' perigranular membranes and is retained in the soluble cytoplasm during exocytosis. The possible role of CPK, as to whether it is assisting in maintaining proper levels of intracellular ATP during exocytosis, and/or whether it is associated with components of the mast cells' contractile apparatus, is discussed. PMID:6160090

  5. Mast cell activation syndrome masquerading as agranulocytosis.

    PubMed

    Afrin, Lawrence B

    2012-01-01

    Acquired agranulocytosis is a rare, life-threatening disorder. The few known causes/associations usually are readily identifiable (e.g., drug reaction, Felty syndrome, megaloblastosis, large granular lymphocytic leukemia, etc.). We report a novel association with mast cell disease. A 61-year-old morbidly obese man developed rheumatoid arthritis unresponsive to several medications. Agranulocytosis developed shortly after sulfasalazine was started but did not improve when the drug was soon stopped. Other symptoms across many systems developed including hives and presyncope. Marrow aspiration and biopsy showed only neutropenia. Serum tryptase was mildly elevated; urinary prostaglandin D2 was markedly elevated. Other causes were not found. Mast cell activation syndrome (MCAS) was diagnosed. Oral antihistamines, montelukast, and cromolyn were unhelpful; aspirin was initially felt contraindicated. Imatinib immediately increased neutrophils from 0% to 25% but did not help symptoms; subsequent addition of aspirin increased neutrophils further and abated symptoms. Different presentations of different MCAS patients reflect elaboration of different mediators likely consequent to different Kit mutations. Mast cells (MCs) help regulate adipocytes, and adipocytes can inhibit granulopoiesis; thus, a Kit-mutated MC clone may have directly and/or indirectly driven agranulocytosis. MCAS should be considered in otherwise idiopathic agranulocytosis presenting with comorbidities best explained by MC mediator release. PMID:22338992

  6. Inhibition of mast cells by algae.

    PubMed

    Price, Joseph A; Sanny, Charles; Shevlin, Dennis

    2002-01-01

    There is a history of use of algae as foods and as food additives, or nutraceuticals. Although algae are a safe component of human foods and animal feeds, the effects of the algae other than as a source of protein are not clear. We examined the prevalence of an antiinflammatory activity in selected algae using, as an assay system, the inhibition of histamine release from mast cells. Methanolic extracts of eleven algae were examined for activity to inhibit the release of histamine from mast cells in vitro. This activity was found widely among the samples tested. The activities of these extracts were not uniformly stable in acid methanol. Selected extracts studied further did not separate with the use of size-exclusion filtration filters. LH-20 chromatography suggested at least two main elution areas of activity of the Chlorella extract. In summary, we saw wide phylogenetic dispersion of mast cell inhibition activity, suggesting that this antiinflammatory property is common in algae. This effect was apparently due to multiple activities within the algal extracts. PMID:12639395

  7. Evidence that Meningeal Mast Cells Can Worsen Stroke Pathology in Mice

    PubMed Central

    Arac, Ahmet; Grimbaldeston, Michele A.; Nepomuceno, Andrew R.B.; Olayiwola, Oluwatobi; Pereira, Marta P.; Nishiyama, Yasuhiro; Tsykin, Anna; Goodall, Gregory J.; Schlecht, Ulrich; Vogel, Hannes; Tsai, Mindy; Galli, Stephen J.; Bliss, Tonya M.; Steinberg, Gary K.

    2015-01-01

    Stroke is the leading cause of adult disability and the fourth most common cause of death in the United States. Inflammation is thought to play an important role in stroke pathology, but the factors that promote inflammation in this setting remain to be fully defined. An understudied but important factor is the role of meningeal-located immune cells in modulating brain pathology. Although different immune cells traffic through meningeal vessels en route to the brain, mature mast cells do not circulate but are resident in the meninges. With the use of genetic and cell transfer approaches in mice, we identified evidence that meningeal mast cells can importantly contribute to the key features of stroke pathology, including infiltration of granulocytes and activated macrophages, brain swelling, and infarct size. We also obtained evidence that two mast cell-derived products, interleukin-6 and, to a lesser extent, chemokine (C-C motif) ligand 7, can contribute to stroke pathology. These findings indicate a novel role for mast cells in the meninges, the membranes that envelop the brain, as potential gatekeepers for modulating brain inflammation and pathology after stroke. PMID:25134760

  8. Rat Embryonic Mast Cells Originate in the AGM

    PubMed Central

    Guiraldelli, Michel Farchi; França, Carolina Nunes; de Souza, Devandir Antonio; da Silva, Elaine Zayas Marcelino; Toso, Vanina Danuza; Carvalho, Celiane Cardoso; Jamur, Maria Célia; Oliver, Constance

    2013-01-01

    Mast cells originate from pluripotent hematopoietic stem cells. Two mast cell specific antibodies, mAbsAA4 and BGD6, have previously been used to identify and study committed mast cell precursors (MCcps) in the bone marrow of adult mice and rats. However, the embryonic origin of MCcps is still not known. In the present study, we identified MCcps in rat embryos using these previously characterized mast cell specific antibodies. The MCcps were found in the AGM (aorta-gonad-mesonephros) region of rat embryos at E11.5. These cells were BGD6+, CD34+, c-kit+, CD13+, FcεRI−, AA4− CD40−, and Thy-1−. By PCR the cells contained message for the α and β subunits of FcεRI and mast cell specific proteases. In vitro, the MCcps differentiated into metachromatic mast cells. With age of gestation the percent of MCcps diminished while the percent of mast cell progenitors increased. An increased knowledge of the biology and embryonic origin of mast cells may contribute to a greater understanding of allergy, asthma, and other mast cell related diseases. PMID:23505443

  9. Mast cells in the sheep, hedgehog and rat forebrain

    PubMed Central

    MICHALOUDI, HELEN C.; PAPADOPOULOS, GEORGIOS C.

    1999-01-01

    The study was designed to reveal the distribution of various mast cell types in the forebrain of the adult sheep, hedgehog and rat. Based on their histochemical and immunocytochemical characteristics, mast cells were categorised as (1) connective tissue-type mast cells, staining metachromatically purple with the toluidine blue method, or pale red with the Alcian blue/safranin method, (2) mucosal-type or immature mast cells staining blue with the Alcian blue/safranin method and (3) serotonin immunopositive mast cells. All 3 types of brain mast cells in all species studied were located in both white and grey matter, often associated with intraparenchymal blood vessels. Their distribution pattern exhibited interspecies differences, while their number varied considerably not only between species but also between individuals of each species. A distributional left-right asymmetry, with more cells present on the left side, was observed in all species studied but it was most prominent in the sheep brain. In the sheep, mast cells were abundantly distributed in forebrain areas, while in the hedgehog and the rat forebrain, mast cells were less widely distributed and were relatively or substantially fewer in number respectively. A limited number of brain mast cells, in all 3 species, but primarily in the rat, were found to react both immunocytochemically to 5-HT antibody and histochemically with Alcian blue/safranin staining. PMID:10634696

  10. Augmentation of reverse arthus reaction by mast cells in mice.

    PubMed Central

    Zhang, Y; Ramos, B F; Jakschik, B A

    1991-01-01

    Immune complex-induced injury is an important pathogenic factor in antibody-mediated nephritis, systemic lupus erythematosus, rheumatoid arthritis, and other diseases. In this study we investigated the role mast cells in immune complex-mediated injury in mouse skin. Reverse Arthus reaction was induced in mast cell-deficient WBB6F1-W/Wv mice and their congenic controls (WBB6F1(-)+/+). Serial skin sections were evaluated for neutrophil infiltration, edema, and hemorrhage. In WBB6F1-W/Wv mice the neutrophil influx was only 40% and edema 60% of that in congenic controls. Hemorrhage was also significantly reduced in the mast cell-deficient mice. After mast cell reconstitution, the magnitude of the reaction in WBB6F1-W/Wv was equivalent to that in WBB6F1(-)+/+ mice. Mast cell release in reverse Arthus reaction was evaluated by measuring fluorescence intensity after avidin-FITC staining of mast cell granules. There was a 70% decrease in fluorescence intensity. The 5-lipoxygenase inhibitor A-63162 significantly decreased neutrophil accumulation (40%), edema (60%), and hemorrhage in WBB6F1(-)+/+, but not in mast cell-deficient mice. Mast cell reconstitution of WBB6F1-W/Wv mice restored the effect of A-63162. The results indicate that mast cells and their mediators, including leukotrienes, make an important contribution to reverse Arthus reaction. Images PMID:1832174

  11. Mast Cells Can Enhance Resistance to Snake and Honeybee Venoms

    NASA Astrophysics Data System (ADS)

    Metz, Martin; Piliponsky, Adrian M.; Chen, Ching-Cheng; Lammel, Verena; Åbrink, Magnus; Pejler, Gunnar; Tsai, Mindy; Galli, Stephen J.

    2006-07-01

    Snake or honeybee envenomation can cause substantial morbidity and mortality, and it has been proposed that the activation of mast cells by snake or insect venoms can contribute to these effects. We show, in contrast, that mast cells can significantly reduce snake-venom-induced pathology in mice, at least in part by releasing carboxypeptidase A and possibly other proteases, which can degrade venom components. Mast cells also significantly reduced the morbidity and mortality induced by honeybee venom. These findings identify a new biological function for mast cells in enhancing resistance to the morbidity and mortality induced by animal venoms.

  12. Tick Salivary Sialostatin L Represses the Initiation of Immune Responses by Targeting IRF4-Dependent Transcription in Murine Mast Cells.

    PubMed

    Klein, Matthias; Brühl, Till-Julius; Staudt, Valérie; Reuter, Sebastian; Grebe, Nadine; Gerlitzki, Bastian; Hoffmann, Markus; Bohn, Toszka; Ulges, Alexander; Stergiou, Natascha; de Graaf, Jos; Löwer, Martin; Taube, Christian; Becker, Marc; Hain, Tobias; Dietzen, Sarah; Stassen, Michael; Huber, Magdalena; Lohoff, Michael; Campos Chagas, Andrezza; Andersen, John; Kotál, Jan; Langhansová, Helena; Kopecký, Jan; Schild, Hansjörg; Kotsyfakis, Michalis; Schmitt, Edgar; Bopp, Tobias

    2015-07-15

    Coevolution of ticks and the vertebrate immune system has led to the development of immunosuppressive molecules that prevent immediate response of skin-resident immune cells to quickly fend off the parasite. In this article, we demonstrate that the tick-derived immunosuppressor sialostatin L restrains IL-9 production by mast cells, whereas degranulation and IL-6 expression are both unaffected. In addition, the expression of IL-1β and IRF4 is strongly reduced in the presence of sialostatin L. Correspondingly, IRF4- or IL-1R-deficient mast cells exhibit a strong impairment in IL-9 production, demonstrating the importance of IRF4 and IL-1 in the regulation of the Il9 locus in mast cells. Furthermore, IRF4 binds to the promoters of Il1b and Il9, suggesting that sialostatin L suppresses mast cell-derived IL-9 preferentially by inhibiting IRF4. In an experimental asthma model, mast cell-specific deficiency in IRF4 or administration of sialostatin L results in a strong reduction in asthma symptoms, demonstrating the immunosuppressive potency of tick-derived molecules. PMID:26078269

  13. Tick salivary Sialostatin L represses the initiation of immune responses by targeting IRF4-dependent transcription in murine mast cells

    PubMed Central

    Klein, Matthias; Brühl, Till-Julius; Staudt, Valérie; Reuter, Sebastian; Grebe, Nadine; Gerlitzki, Bastian; Hoffmann, Markus; Bohn, Toszka; Ulges, Alexander; Stergiou, Natascha; de Graaf, Jos; Löwer, Martin; Taube, Christian; Becker, Marc; Hain, Tobias; Dietzen, Sarah; Stassen, Michael; Huber, Magdalena; Lohoff, Michael; Chagas, Andrezza Campos; Andersen, John; Kotál, Jan; Langhansová, Helena; Kopecký, Jan; Schild, Hansjörg; Kotsyfakis, Michalis; Schmitt, Edgar; Bopp, Tobias

    2015-01-01

    Co-evolution of ticks and the vertebrate immune system has led to the development of immunosuppressive molecules that prevent immediate response of skin-resident immune cells to quickly fend off the parasite. Herein, we demonstrate that the tick-derived immunosuppressor sialostatin L restrains IL-9 production by mast cells while degranulation and IL-6 expression are both unaffected. In addition, the expression of IL-1β and IRF4 is strongly reduced in the presence of sialostatin L. Correspondingly, IRF4- or IL-1 receptor-deficient mast cells exhibit strong impairment in IL-9 production demonstrating the importance of IRF4 and IL-1 in the regulation of the Il9 locus in mast cells. Furthermore, IRF4 binds to the promoters of Il1b and Il9 suggesting that sialostatin L suppresses mast cell-derived IL-9 preferentially by inhibiting IRF4. In an experimental asthma model, mast cell-specific deficiency in IRF4 or administration of sialostatin L results in a strong reduction of asthma symptoms demonstrating the immunosuppressive potency of tick-derived molecules. PMID:26078269

  14. Microjet formation and hard x-ray production from a liquid metal target irradiated by intense femtosecond laser pulses

    NASA Astrophysics Data System (ADS)

    Lar'kin, A.; Uryupina, D.; Ivanov, K.; Savel'ev, A.; Bonnet, T.; Gobet, F.; Hannachi, F.; Tarisien, M.; Versteegen, M.; Spohr, K.; Breil, J.; Chimier, B.; Dorchies, F.; Fourment, C.; Leguay, P.-M.; Tikhonchuk, V. T.

    2014-09-01

    By using a liquid metal as a target one may significantly enhance the yield of hard x-rays with a sequence of two intense femtosecond laser pulses. The influence of the time delay between the two pulses is studied experimentally and interpreted with numerical simulations. It was suggested that the first arbitrary weak pulse produces microjets from the target surface, while the second intense pulse provides an efficient electron heating and acceleration along the jet surface. These energetic electrons are the source of x-ray emission while striking the target surface. The microjet formation is explained based on the results given by both optical diagnostics and hydrodynamic modeling by a collision of shocks originated from two distinct zones of laser energy deposition.

  15. Microjet formation and hard x-ray production from a liquid metal target irradiated by intense femtosecond laser pulses

    SciTech Connect

    Lar'kin, A. Uryupina, D.; Ivanov, K.; Savel'ev, A.; Bonnet, T.; Gobet, F.; Hannachi, F.; Tarisien, M.; Versteegen, M.; Spohr, K.; Breil, J.; Chimier, B.; Dorchies, F.; Fourment, C.; Leguay, P.-M.; Tikhonchuk, V. T.

    2014-09-15

    By using a liquid metal as a target one may significantly enhance the yield of hard x-rays with a sequence of two intense femtosecond laser pulses. The influence of the time delay between the two pulses is studied experimentally and interpreted with numerical simulations. It was suggested that the first arbitrary weak pulse produces microjets from the target surface, while the second intense pulse provides an efficient electron heating and acceleration along the jet surface. These energetic electrons are the source of x-ray emission while striking the target surface. The microjet formation is explained based on the results given by both optical diagnostics and hydrodynamic modeling by a collision of shocks originated from two distinct zones of laser energy deposition.

  16. Human mast cell tryptase: Multiple cDNAs and genes reveal a multigene serine protease family

    SciTech Connect

    Vanderslice, P.; Ballinger, S.M., Tam, E.K.; Goldstein, S.M.; Craik, C.S.; Caughey, G.H. )

    1990-05-01

    Three different cDNAs and a gene encoding human skin mast cell tryptase have been cloned and sequenced in their entirety. The deduced amino acid sequences reveal a 30-amino acid prepropeptide followed by a 245-amino acid catalytic domain. The C-terminal undecapeptide of the human preprosequence is identical in dog tryptase and appears to be part of a prosequence unique among serine proteases. The differences among the three human tryptase catalytic domains include the loss of a consensus N-glycosylation site in one cDNA, which may explain some of the heterogeneity in size and susceptibility to deglycosylation seen in tryptase preparations. All three tryptase cDNAs are distinct from a recently reported cDNA obtained from a human lung mast cell library. A skin tryptase cDNA was used to isolate a human tryptase gene, the exons of which match one of the skin-derived cDNAs. The organization of the {approx}1.8-kilobase-pair tryptase gene is unique and is not closely related to that of any other mast cell or leukocyte serine protease. The 5{prime} regulatory regions of the gene share features with those of other serine proteases, including mast cell chymase, but are unusual in being separated from the protein-coding sequence by an intron. High-stringency hybridization of a human genomic DNA blot with a fragment of the tryptase gene confirms the presence of multiple tryptase genes. These findings provide genetic evidence that human mast cell tryptases are the products of a multigene family.

  17. Kalanchoe pinnata inhibits mast cell activation and prevents allergic airway disease.

    PubMed

    Cruz, E A; Reuter, S; Martin, H; Dehzad, N; Muzitano, M F; Costa, S S; Rossi-Bergmann, B; Buhl, R; Stassen, M; Taube, C

    2012-01-15

    Aqueous extract of Kalanchoe pinnata (Kp) have been found effective in models to reduce acute anaphylactic reactions. In the present study, we investigate the effect of Kp and the flavonoid quercetin (QE) and quercitrin (QI) on mast cell activation in vitro and in a model of allergic airway disease in vivo. Treatment with Kp and QE in vitro inhibited degranulation and cytokine production of bone marrow-derived mast cells following IgE/FcɛRI crosslinking, whereas treatment with QI had no effect. Similarly, in vivo treatment with Kp and QE decreased development of airway hyperresponsiveness, airway inflammation, goblet cell metaplasia and production of IL-5, IL-13 and TNF. In contrast, treatment with QI had no effect on these parameters. These findings demonstrate that treatment with Kp or QE is effective in treatment of allergic airway disease, providing new insights to the immunomodulatory functions of this plant. PMID:21802918

  18. Masting in whitebark pine (Pinus albicaulis) depletes stored nutrients.

    PubMed

    Sala, Anna; Hopping, Kelly; McIntire, Eliot J B; Delzon, Sylvain; Crone, Elizabeth E

    2012-10-01

    • In masting trees, synchronized, heavy reproductive events are thought to deplete stored resources and to impose a replenishment period before subsequent masting. However, direct evidence of resource depletion in wild, masting trees is very rare. Here, we examined the timing and magnitude (local vs individual-level) of stored nutrient depletion after a heavy mast event in Pinus albicaulis. • In 2005, the mast year, we compared seasonal changes in leaf and sapwood nitrogen (N) and phosphorus (P) concentrations and leaf photosynthetic rates in cone-bearing branches, branches that never produced cones, and branches with experimentally removed cones. We also compared nutrient concentrations in cone branches and branches that had never had cones between 2005 and 2006, and measured tree ring width and new shoot growth during 2005. • During the mast year, N or P depletion occurred only in tissue fractions of reproductive branches, where photosynthetic rates were reduced. However, by the end of the following year, nutrients were depleted in all branches, indicating individual-level resource depletion. New shoot and radial growth were not affected by masting. • We provide direct evidence that mast events in wild trees deplete stored nutrients. Our results highlight the importance of evaluating reproductive costs over time and at the individual level. PMID:22889129

  19. 109. REDUNDANCY SYSTEM CONTROLS FOR UMBILICAL MAST RETRACTION AT LOWER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    109. REDUNDANCY SYSTEM CONTROLS FOR UMBILICAL MAST RETRACTION AT LOWER LEFT SIDE OF HYDRAULIC CONTROL PANEL IN UMBILICAL MAST PUMP ROOM (109), LSB (BLDG. 770) - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  20. 127. HYDRAULIC CONTROLS AND GAUGES FOR THE UMBILICAL MAST ON ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    127. HYDRAULIC CONTROLS AND GAUGES FOR THE UMBILICAL MAST ON UPPER RIGHT SIDE OF HYDRAULIC CONTROL PANEL IN UMBILICAL MAST PUMP ROOM (209), LSB (BLDG. 751) - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  1. 125. HYDRAULIC CONTROLS FOR MAST TRENCH DOORS ON LEFT SIDE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    125. HYDRAULIC CONTROLS FOR MAST TRENCH DOORS ON LEFT SIDE OF HYDRAULIC CONTROL PANEL IN UMBILICAL MAST PUMP ROOM (209), LSB (BLDG. 751) - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  2. 126. REDUNDANCY SYSTEM CONTROLS FOR UMBILICAL MAST RETRACTION AT LOWER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    126. REDUNDANCY SYSTEM CONTROLS FOR UMBILICAL MAST RETRACTION AT LOWER LEFT SIDE OF HYDRAULIC CONTROL PANEL IN UMBILICAL MAST PUMP ROOM (209), LSB (BLDG. 751) - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  3. 41. VIEW OF UMBILICAL MAST AND LAUNCH PAD FROM LAUNCHER; ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    41. VIEW OF UMBILICAL MAST AND LAUNCH PAD FROM LAUNCHER; SOUTH FACE OF MST IN BACKGROUND. RAIL SYSTEM FROM BASE OF MST PARALLEL TO MAST. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  4. Malignant mast cell tumor in an African hedgehog (Atelerix albiventris).

    PubMed

    Raymond, J T; White, M R; Janovitz, E B

    1997-01-01

    In November 1995, a malignant mast cell tumor (mastocytoma) was diagnosed in an adult African hedgehog (Atelerix albiventris) from a zoological park (West Lafayette, Indiana, USA). The primary mast cell tumor presented as a firm subcutaneous mass along the ventrum of the neck. Metastasis to the right submandibular lymph node occurred. PMID:9027702

  5. Machine Tool Advanced Skills Technology Program (MAST). Overview and Methodology.

    ERIC Educational Resources Information Center

    Texas State Technical Coll., Waco.

    The Machine Tool Advanced Skills Technology Program (MAST) is a geographical partnership of six of the nation's best two-year colleges located in the six states that have about one-third of the density of metals-related industries in the United States. The purpose of the MAST grant is to develop and implement a national training model to overcome…

  6. 33 CFR 401.82 - Reporting mast height.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 3 2012-07-01 2012-07-01 false Reporting mast height. 401.82... mast height. A vessel, any part of which extends more than 33.5 m above water level, shall not transit any part of the Seaway until precise information concerning the height of the vessel has...

  7. 33 CFR 401.82 - Reporting mast height.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 3 2014-07-01 2014-07-01 false Reporting mast height. 401.82... mast height. A vessel, any part of which extends more than 33.5 m above water level, shall not transit any part of the Seaway until precise information concerning the height of the vessel has...

  8. 33 CFR 401.82 - Reporting mast height.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Reporting mast height. 401.82... mast height. A vessel, any part of which extends more than 33.5 m above water level, shall not transit any part of the Seaway until precise information concerning the height of the vessel has...

  9. 33 CFR 401.82 - Reporting mast height.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Reporting mast height. 401.82... mast height. A vessel, any part of which extends more than 33.5 m above water level, shall not transit any part of the Seaway until precise information concerning the height of the vessel has...

  10. 33 CFR 401.82 - Reporting mast height.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 3 2013-07-01 2013-07-01 false Reporting mast height. 401.82... mast height. A vessel, any part of which extends more than 33.5 m above water level, shall not transit any part of the Seaway until precise information concerning the height of the vessel has...