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1

The Effect of 8Methoxypsoralen Plus Long-Wave Ultraviolet (PUVA) Radiation on Mast Cells: PUVA Suppresses Degranulation of Mouse Skin Mast Cells Induced by Compound 48\\/80 or Concanavalin A  

Microsoft Academic Search

In order to see whether 8-methoxypsoralen (8-MOP) plus long-wave ultraviolet (UVA) radiation (PUVA) has an influence on immediate-type skin reactions, we have undertaken an animal study. Ears of mice were treated with a 0.5% 8-MOP solution topically plus UVA radiation (1.5–2.5 J\\/cm2). After PUVA radiation, skin responses to intradermal injection with mast cell liberators, including compound 48\\/80 (2.5 mg\\/ml, 10

Kiichiro Danno; Kenichi Toda; Takeshi Horio

1985-01-01

2

Quercetin inhibits degranulation and superoxide generation in PMA stimulated neutrophils  

PubMed Central

Activated neutrophils represent the main source of myeloperoxidase (MPO), superoxide (SO) and subsequently derived oxygen metabolites. They have important microbicidal activities, however in inflammatory conditions they may secondarily attack surrounding tissues. Overproduction of reactive oxygen species, prolonged or excessive liberation of MPO and other effective yet also toxic substances from neutrophils may participate in disturbed apoptosis, intensify the inflammatory processes and result in serious human diseases. The inhibitory effect of quercetin on PMA stimulated SO generation in isolated human neutrophils was found to be dose-dependent, without affecting the activity of intact isolated neutrophils. At comparable conditions, quercetin was more potent in inhibiting MPO release than SO generation. Our results indicate that quercetin could support resolution of inflammation through decreased activity of neutrophils, i.e. respiratory burst and degranulation.

MacIckova, Tatiana; Svitekova, Klara; Nosal, Radomir

2012-01-01

3

Quercetin inhibits degranulation and superoxide generation in PMA stimulated neutrophils.  

PubMed

Activated neutrophils represent the main source of myeloperoxidase (MPO), superoxide (SO) and subsequently derived oxygen metabolites. They have important microbicidal activities, however in inflammatory conditions they may secondarily attack surrounding tissues. Overproduction of reactive oxygen species, prolonged or excessive liberation of MPO and other effective yet also toxic substances from neutrophils may participate in disturbed apoptosis, intensify the inflammatory processes and result in serious human diseases. The inhibitory effect of quercetin on PMA stimulated SO generation in isolated human neutrophils was found to be dose-dependent, without affecting the activity of intact isolated neutrophils. At comparable conditions, quercetin was more potent in inhibiting MPO release than SO generation. Our results indicate that quercetin could support resolution of inflammation through decreased activity of neutrophils, i.e. respiratory burst and degranulation. PMID:23118592

Pe?ivová, Jana; Ma?i?ková, Tatiana; Sviteková, Klára; Nosá?, Radomír

2012-06-01

4

Inhibition of human neutrophil degranulation by transforming growth factor-?1  

PubMed Central

Neutrophils enter tissues including the uterus and are found in the endometrium in increased numbers prior to menses. In this environment, they are exposed to transforming growth factor (TGF)-?1 produced by endometrial stromal and epithelial cells. We observed that incubation of neutrophils in vitro with TGF-?1 at 1 pg/ml significantly reduced their secretion of lactoferrin in response to lipopolysaccharide (LPS). This effect was achieved with as little as 15 min of pretreatment with TGF-?1. Inhibition of lactoferrin release by TGF-?1 was observed irrespective of whether neutrophils were stimulated by ligands for Toll-like receptor (TLR)-2, TLR-4 or FPR, the G protein-coupled receptor for formylated peptides. Inhibition by TGF-?1 was negated by SB-431542, a small molecule inhibitor that specifically blocks the kinase activity of the type I TGF-? receptor (ALK5) In contrast to lactoferrin release, another important neutrophil function, interleukin (IL)-8 driven chemotaxis, was not affected by TGF-?1 at 1 pg/ml or 100 pg/ml. We conclude that in tissues of the female reproductive tract, TGF-?1 inhibition of neutrophil degranulation may prevent these cells from initiating an inflammatory response or releasing degradative enzymes that could potentially damage the oocyte or fetus.

Shen, L; Smith, J M; Shen, Z; Eriksson, M; Sentman, C; Wira, C R

2007-01-01

5

Gangliosides inhibit bee venom melittin cytotoxicity but not phospholipase A(2)-induced degranulation in mast cells.  

PubMed

Sting accident by honeybee causes severe pain, inflammation and allergic reaction through IgE-mediated anaphylaxis. In addition to this hypersensitivity, an anaphylactoid reaction occurs by toxic effects even in a non-allergic person via cytolysis followed by similar clinical manifestations. Auto-injectable epinephrine might be effective for bee stings, but cannot inhibit mast cell lysis and degranulation by venom toxins. We used connective tissue type canine mast cell line (CM-MC) for finding an effective measure that might inhibit bee venom toxicity. We evaluated degranulation and cytotoxicity by measurement of ?-hexosaminidase release and MTT assay. Melittin and crude bee venom induced the degranulation and cytotoxicity, which were strongly inhibited by mono-sialoganglioside (G(M1)), di-sialoganglioside (G(D1a)) and tri-sialoganglioside (G(T1b)). In contrast, honeybee venom-derived phospholipase A(2) induced the net degranulation directly without cytotoxicity, which was not inhibited by G(M1), G(D1a) and G(T1b). For analysis of distribution of G?(q) and G?(i) protein by western blotting, lipid rafts were isolated by using discontinuous sucrose gradient centrifuge. Melittin disrupted the localization of G?(q) and G?(i) at lipid raft, but gangliosides stabilized the rafts. As a result from this cell-based study, bee venom-induced anaphylactoid reaction can be explained with melittin cytotoxicity and phospholipase A(2)-induced degranulation. Taken together, gangliosides inhibit the effect of melittin such as degranulation, cytotoxicity and lipid raft disruption but not phospholipase A(2)-induced degranulation in mast cells. Our study shows a potential of gangliosides as a therapeutic tool for anaphylactoid reaction by honeybee sting. PMID:21334356

Nishikawa, Hirofumi; Kitani, Seiichi

2011-02-18

6

Modeling pharmacological inhibition of mast cell degranulation as a therapy for insulinoma.  

PubMed

Myc, a pleiotropic transcription factor that is deregulated and/or overexpressed in most human cancers, instructs multiple extracellular programs that are required to sustain the complex microenvironment needed for tumor maintenance, including remodeling of tumor stroma, angiogenesis, and inflammation. We previously showed in a model of pancreatic ?-cell tumorigenesis that acute Myc activation in vivo triggers rapid recruitment of mast cells to the tumor site and that this is absolutely required for angiogenesis and macroscopic tumor expansion. Moreover, systemic inhibition of mast cell degranulation with sodium cromoglycate induced death of tumor and endothelial cells in established tumors. Hence, mast cells are required both to establish and to maintain the tumors. Whereas this intimates that selective inhibition of mast cell function could be therapeutically efficacious, cromoglycate is not a practical drug for systemic delivery in humans, and no other systemic inhibitor of mast cell degranulation has hitherto been available. PCI-32765 is a novel inhibitor of Bruton tyrosine kinase (Btk) that blocks mast cell degranulation and is currently in clinical trial as a therapy for B-cell non-Hodgkin lymphoma. Here, we show that systemic treatment of insulinoma-bearing mice with PCI-32765 efficiently inhibits Btk, blocks mast cell degranulation, and triggers collapse of tumor vasculature and tumor regression. These data reinforce the notion that mast cell function is required for maintenance of certain tumor types and indicate that the Btk inhibitor PCI-32765 may be useful in treating such diseases. PMID:22131884

Soucek, Laura; Buggy, Joseph J; Kortlever, Roderik; Adimoolam, Shanthi; Monclús, Helena Allende; Allende, Maria Teresa Salcedo; Swigart, Lamorna Brown; Evan, Gerard I

2011-11-01

7

Modeling Pharmacological Inhibition of Mast Cell Degranulation as a Therapy for Insulinoma12  

PubMed Central

Myc, a pleiotropic transcription factor that is deregulated and/or overexpressed in most human cancers, instructs multiple extracellular programs that are required to sustain the complex microenvironment needed for tumor maintenance, including remodeling of tumor stroma, angiogenesis, and inflammation. We previously showed in a model of pancreatic ?-cell tumorigenesis that acute Myc activation in vivo triggers rapid recruitment of mast cells to the tumor site and that this is absolutely required for angiogenesis and macroscopic tumor expansion. Moreover, systemic inhibition of mast cell degranulation with sodium cromoglycate induced death of tumor and endothelial cells in established tumors. Hence, mast cells are required both to establish and to maintain the tumors. Whereas this intimates that selective inhibition of mast cell function could be therapeutically efficacious, cromoglycate is not a practical drug for systemic delivery in humans, and no other systemic inhibitor of mast cell degranulation has hitherto been available. PCI-32765 is a novel inhibitor of Bruton tyrosine kinase (Btk) that blocks mast cell degranulation and is currently in clinical trial as a therapy for B-cell non-Hodgkin lymphoma. Here, we show that systemic treatment of insulinoma-bearing mice with PCI-32765 efficiently inhibits Btk, blocks mast cell degranulation, and triggers collapse of tumor vasculature and tumor regression. These data reinforce the notion that mast cell function is required for maintenance of certain tumor types and indicate that the Btk inhibitor PCI-32765 may be useful in treating such diseases.

Soucek, Laura; Buggy, Joseph J; Kortlever, Roderik; Adimoolam, Shanthi; Monclus, Helena Allende; Allende, Maria Teresa Salcedo; Swigart, Lamorna Brown; Evan, Gerard I

2011-01-01

8

Gangliosides inhibit bee venom melittin cytotoxicity but not phospholipase A{sub 2}-induced degranulation in mast cells  

SciTech Connect

Sting accident by honeybee causes severe pain, inflammation and allergic reaction through IgE-mediated anaphylaxis. In addition to this hypersensitivity, an anaphylactoid reaction occurs by toxic effects even in a non-allergic person via cytolysis followed by similar clinical manifestations. Auto-injectable epinephrine might be effective for bee stings, but cannot inhibit mast cell lysis and degranulation by venom toxins. We used connective tissue type canine mast cell line (CM-MC) for finding an effective measure that might inhibit bee venom toxicity. We evaluated degranulation and cytotoxicity by measurement of {beta}-hexosaminidase release and MTT assay. Melittin and crude bee venom induced the degranulation and cytotoxicity, which were strongly inhibited by mono-sialoganglioside (G{sub M1}), di-sialoganglioside (G{sub D1a}) and tri-sialoganglioside (G{sub T1b}). In contrast, honeybee venom-derived phospholipase A{sub 2} induced the net degranulation directly without cytotoxicity, which was not inhibited by G{sub M1}, G{sub D1a} and G{sub T1b}. For analysis of distribution of G{alpha}{sub q} and G{alpha}{sub i} protein by western blotting, lipid rafts were isolated by using discontinuous sucrose gradient centrifuge. Melittin disrupted the localization of G{alpha}{sub q} and G{alpha}{sub i} at lipid raft, but gangliosides stabilized the rafts. As a result from this cell-based study, bee venom-induced anaphylactoid reaction can be explained with melittin cytotoxicity and phospholipase A{sub 2}-induced degranulation. Taken together, gangliosides inhibit the effect of melittin such as degranulation, cytotoxicity and lipid raft disruption but not phospholipase A{sub 2}-induced degranulation in mast cells. Our study shows a potential of gangliosides as a therapeutic tool for anaphylactoid reaction by honeybee sting.

Nishikawa, Hirofumi; Kitani, Seiichi, E-mail: drkitani@kaiyodai.ac.jp

2011-05-01

9

Hyperglycemia enhances coagulation and reduces neutrophil degranulation, whereas hyperinsulinemia inhibits fibrinolysis during human endotoxemia.  

PubMed

Type 2 diabetes is associated with altered immune and hemostatic responses. We investigated the selective effects of hyperglycemia and hyperinsulinemia on innate immune, coagulation, and fibrinolytic responses during systemic inflammation. Twenty-four healthy humans were studied for 8 hours during clamp experiments in which either plasma glucose, insulin, both, or none was increased, depending on randomization. Target plasma concentrations were 5 versus 12 mM for glucose, and 100 versus 400 pmol/L for insulin. After 3 hours, 4 ng/kg Escherichia coli endotoxin was injected intravenously to induce a systemic inflammatory and procoagulant response. Endotoxin administration induced cytokine release, activation of neutrophils, endothelium and coagulation, and inhibition of fibrinolysis. Hyperglycemia reduced neutrophil degranulation (plasma elastase levels, P < .001) and exaggerated coagulation (plasma concentrations of thrombin-antithrombin complexes and soluble tissue factor, both P < .001). Hyperinsulinemia attenuated fibrinolytic activity due to elevated plasminogen activator-inhibitor-1 levels (P < .001). Endothelial cell activation markers and cytokine concentrations did not differ between clamps. We conclude that in humans with systemic inflammation induced by intravenous endotoxin administration hyperglycemia impairs neutrophil degranulation and potentiates coagulation, whereas hyperinsulinemia inhibits fibrinolysis. These data suggest that type 2 diabetes patients may be especially vulnerable to prothrombotic events during inflammatory states. PMID:18316629

Stegenga, Michiel E; van der Crabben, Saskia N; Blümer, Regje M E; Levi, Marcel; Meijers, Joost C M; Serlie, Mireille J; Tanck, Michael W T; Sauerwein, Hans P; van der Poll, Tom

2008-03-03

10

Resveratrol inhibits IgE-mediated basophilic mast cell degranulation and passive cutaneous anaphylaxis in mice.  

PubMed

Resveratrol is a phytoalexin abundantly found in red grape skin and is effective in antitumor and antiinflammation associated with immune responses. This study investigated whether resveratrol suppressed immunoglobulin (Ig)E-mediated allergic responses and passive cutaneous anaphylaxis (PCA) in rat RBL-2H3 mast cells and in BALB/c mice. The release of ?-hexosaminidase and histamine was enhanced in mast cells sensitized with anti-dinitrophenyl (DNP)-IgE and subsequently stimulated by DNP-human serum albumin (HSA), indicative of mast cell degranulation. When mast cells were pretreated with nontoxic resveratrol at 1-25 ?mol/L, such induction was dose dependently diminished. Spleen tyrosine kinase (Syk) and phospholipase C? (PLC?) of sensitized mast cells were activated by stimulation with DNP-HSA antigen, which was dampened by ?5 ?mol/L resveratrol. The phosphorylation of protein kinase C (PKC)? and PKC? was attenuated by administering resveratrol to DNP-HSA-exposed mast cells, whereas quiescent PKC?/? in sensitized cells was dose-dependently activated by resveratrol. Male BALB/c mice were sensitized for 24 h with DNP-IgE and orally administered with resveratrol 1 h before the DNP-HSA challenge. The histamine concentration was enhanced in sensitized mice challenged to DNP-HSA, which was reversed by administration of 10 mg/kg resveratrol. Additionally, it encumbered the tissue activation of Syk, PLC?, and PKC? in antigen-exposed mice. Resveratrol decreased IgE-mediated PCA and alleviated allergic edema of mouse ear and dorsal skin. Mast cell degranulation and allergic inflammation, accompanying the induction of monocyte chemotactic protein-1 and macrophage inflammatory protein-2, were inhibited by supplementing resveratrol to antigen-challenged mice. Resveratrol inhibited mast cell-derived, immediate-type allergic reactions, and these responses of resveratrol suggest possible therapeutic strategies in preventing allergic inflammatory diseases. PMID:23514766

Han, Seon-Young; Bae, Ji-Young; Park, Sin-Hye; Kim, Yun-Ho; Park, Jung Han Yoon; Kang, Young-Hee

2013-03-20

11

Toxoplasma gondii inhibits mast cell degranulation by suppressing phospholipase C?-mediated Ca(2+) mobilization.  

PubMed

Toxoplasma gondii is well-known to subvert normal immune responses, however, mechanisms are incompletely understood. In particular, its capacity to alter receptor-activated Ca(2+)-mediated signaling processes has not been well-characterized. In initial experiments, we found evidence that T. gondii infection inhibits Ca(2+) responses to fMetLeuPhe in murine macrophages. To further characterize the mechanism of inhibition of Ca(2+) mobilization by T. gondii, we used the well-studied RBL mast cell model to probe the capacity of T. gondii to modulate IgE receptor-activated signaling within the first hour of infection. Ca(2+) mobilization that occurs via IgE/Fc?RI signaling leads to granule exocytosis in mast cells. We found that T. gondii inhibits antigen-stimulated degranulation in infected cells in a strain-independent manner. Under these conditions, we found that cytoplasmic Ca(2+) mobilization, particularly antigen-mediated Ca(2+) release from intracellular stores, is significantly reduced. Furthermore, stimulation-dependent activation of Syk kinase leading to tyrosine phosphorylation and activation of phospholipase C? is inhibited by infection. Therefore, we conclude that inhibitory effects of infection are likely due to parasite-mediated inhibition of the tyrosine kinase signaling cascade that results in reduced hydrolysis of phosphatidylinositol 4,5-bisphosphate. Interestingly, inhibition of IgE/Fc?RI signaling persists when tachyzoite invasion is arrested via cytochalasin D treatment, suggesting inhibition is mediated by a parasite-derived factor secreted into the cells during the invasion process. Our study provides direct evidence that immune subversion by T. gondii is initiated concurrently with invasion. PMID:23847603

Smith, Norah L; Abi Abdallah, Delbert S; Butcher, Barbara A; Denkers, Eric Y; Baird, Barbara; Holowka, David

2013-07-04

12

Systemic effects of ingested Lactobacillus rhamnosus: inhibition of mast cell membrane potassium (IKCa) current and degranulation.  

PubMed

Exposure of the intestine to certain strains lactobacillus can have systemic immune effects that include the attenuation of allergic responses. Despite the central role of mast cells in allergic disease little is known about the effect of lactobacilli on the function of these cells. To address this we assessed changes in rat mast cell activation following oral treatment with a strain of Lactobacillus known to attenuate allergic responses in animal models. Sprague Dawley rats were fed with L. rhamnosus JB-1 (1×10(9)) or vehicle control for 9 days. Mediator release from peritoneal mast cells (RPMC) was determined in response to a range of stimuli. Passive cutaneous anaphylaxis (PCA) was used to assess mast cell responses in vivo. The Ca(2+) activated K(+) channel (KCa3.1) current, identified as critical to mast cell degranulation, was monitored by whole cell patch-clamp. L. rhamnosus JB-1 treatment lead to significant inhibition of mast cell mediator release in response to a range of stimuli including IgE mediated activation. Furthermore, the PCA response was significantly reduced in treated rats. Patch-clamp studies revealed that RPMC from treated animals were much less responsive to the KCa3.1 opener, DCEBIO. These studies demonstrate that Ingestion of L. rhamnosus JB-1 leads to mast cell stabilization in rats and identify KCa3.1 as an immunomodulatory target for certain lactobacilli. Thus the systemic effects of certain candidate probiotics may include mast cell stabilization and such actions could contribute to the beneficial effect of these organisms in allergic and other inflammatory disorders. PMID:22815978

Forsythe, Paul; Wang, Binxiang; Khambati, Ibrahim; Kunze, Wolfgang A

2012-07-17

13

Solanum trilobatum in the management of atopy: Through inhibition of mast cell degranulation and moderation of release of interleukins.  

PubMed

Solanum trilobatum is a widely used plant in the Indian indigenous systems of medicine. It is mainly used in the treatment of respiratory diseases like bronchial asthma. In our present study, we report that the aqueous and alcoholic extracts of S. trilobatum exhibited inhibition of mast cell degranulation. Further, aqueous and alcoholic extracts of S. trilobatum significantly decreased the release of IL1? and increased the release of IL8 from the cultured keratinocytes. Oral administration of the aqueous and alcoholic extracts of S. trilobatum stabilized mast cells in experimental rats. PMID:21808531

Ranjith, M S; Ranjitsingh, A J A; Shankar, S Gokul; Vijayalaksmi, G S; Deepa, K; Babu, K; Sidhu, Harcharan Singh

2010-01-01

14

Citreorosein inhibits degranulation and leukotriene C? generation through suppression of Syk pathway in mast cells.  

PubMed

The aim of this study was to evaluate whether citreorosein (CIT), a naturally occurring anthraquinone isolated from Polygoni cuspidati (P. cuspidati) radix, modulates degranulation and 5-lipoxygenase (5-LO)-dependent leukotriene C(4) (LTC(4)) generation in mast cells. Cit suppresses both degranulation and the generation of LTC(4) in a dose-dependent manner in stem cell factor (SCF)-mediated mouse bone marrow-derived mast cells (BMMCs). With regard to its molecular mechanism of action, we investigated the effects of CIT on intracellular signaling and mast cell activation employing BMMCs. Binding of SCF to c-Kit on mast cell membranes induced increases in intrinsic tyrosine kinase Syk activity and activation of multiple downstream events including phosphorylation of phospholipase C? (PLC?), mobilization of intracellular Ca(2+), phosphatidylinositol 3-kinase (PI3K), Akt, MAP kinases (MAPKs), translocation of phospho-phospholipase A(2) (PLA(2)) and 5-LO. The results from the biochemical analysis demonstrate that CIT attenuates degranulation and LTC(4) generation through the suppression of multiple step signaling and would be beneficial for the prevention of allergic inflammation. PMID:22395859

Lu, Yue; Li, Ying; Jahng, Yurndong; Son, Jong-Keun; Chang, Hyeun Wook

2012-03-01

15

Saucerneol F, a New Lignan Isolated from Saururus chinensis, Attenuates Degranulation via Phospholipase C? 1 Inhibition and Eicosanoid Generation by Suppressing MAP Kinases in Mast Cells.  

PubMed

During our on-going studies to identify bioactive compounds in medicinal herbs, we found that saucerneol F (SF), a naturally occurring sesquilignan isolated from Saururus chinensis (S. chinensis), showed in vitro anti-inflammatory activity. In this study, we examined the effects of SF on the generation of 5-lipoxygenase (5-LO) dependent leukotriene C4 (LTC4), cyclooxygenase-2 (COX-2) dependent prostaglandin D2 (PGD2), and on phospholipase C?1 (PLC?1)-mediated degranulation in SCF-induced mouse bone marrow-derived mast cells (BMMCs). SF inhibited eicosanoid (PGD2 and LTC4) generation and degranulation dose-dependently. To identify the molecular mechanisms underlying the inhibition of eicosanoid generation and degranulation by SF, we examined the effects of SF on the phosphorylation of PLC?1, intracellular Ca(2+) influx, the translocation of cytosolic phospholipase A2 (cPLA2) and 5-LO, and on the phosphorylation of MAP kinases (MAPKs). SF was found to reduce intracellular Ca(2+) influx by inhibiting PLC?1 phosphorylation and suppressing the nuclear translocations of cPLA2 and 5-LO via the phosphorylations of MAPKs, including extracellular signal-regulated protein kinase-1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38. Taken together, these results suggest that SF may be useful for regulating mast cell-mediated inflammatory responses by inhibiting degranulation and eicosanoid generation. PMID:24009845

Lu, Yue; Son, Jong-Keun; Chang, Hyeun Wook

2012-11-01

16

Saucerneol F, a New Lignan Isolated from Saururus chinensis, Attenuates Degranulation via Phospholipase C? 1 Inhibition and Eicosanoid Generation by Suppressing MAP Kinases in Mast Cells  

PubMed Central

During our on-going studies to identify bioactive compounds in medicinal herbs, we found that saucerneol F (SF), a naturally occurring sesquilignan isolated from Saururus chinensis (S. chinensis), showed in vitro anti-inflammatory activity. In this study, we examined the effects of SF on the generation of 5-lipoxygenase (5-LO) dependent leukotriene C4 (LTC4), cyclooxygenase-2 (COX-2) dependent prostaglandin D2 (PGD2), and on phospholipase C?1 (PLC?1)-mediated degranulation in SCF-induced mouse bone marrow-derived mast cells (BMMCs). SF inhibited eicosanoid (PGD2 and LTC4) generation and degranulation dose-dependently. To identify the molecular mechanisms underlying the inhibition of eicosanoid generation and degranulation by SF, we examined the effects of SF on the phosphorylation of PLC?1, intracellular Ca2+ influx, the translocation of cytosolic phospholipase A2 (cPLA2) and 5-LO, and on the phosphorylation of MAP kinases (MAPKs). SF was found to reduce intracellular Ca2+ influx by inhibiting PLC?1 phosphorylation and suppressing the nuclear translocations of cPLA2 and 5-LO via the phosphorylations of MAPKs, including extracellular signal-regulated protein kinase-1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38. Taken together, these results suggest that SF may be useful for regulating mast cell-mediated inflammatory responses by inhibiting degranulation and eicosanoid generation.

Lu, Yue; Son, Jong-Keun; Chang, Hyeun Wook

2012-01-01

17

Sequestration of phosphoinositides by mutated MARCKS effector domain inhibits stimulated Ca2+ mobilization and degranulation in mast cells  

PubMed Central

Protein kinase C ? (PKC?) participates in antigen-stimulated mast cell degranulation mediated by the high-affinity receptor for immunoglobulin E, Fc?RI, but the molecular basis is unclear. We investigated the hypothesis that the polybasic effector domain (ED) of the abundant intracellular substrate for protein kinase C known as myristoylated alanine-rich protein kinase C substrate (MARCKS) sequesters phosphoinositides at the inner leaflet of the plasma membrane until MARCKS dissociates after phosphorylation by activated PKC. Real-time fluorescence imaging confirms synchronization between stimulated oscillations of intracellular Ca2+ concentrations and oscillatory association of PKC?–enhanced green fluorescent protein with the plasma membrane. Similarly, MARCKS-ED tagged with monomeric red fluorescent protein undergoes antigen-stimulated oscillatory dissociation and rebinding to the plasma membrane with a time course that is synchronized with reversible plasma membrane association of PKC?. We find that MARCKS-ED dissociation is prevented by mutation of four serine residues that are potential sites of phosphorylation by PKC. Cells expressing this mutated MARCKS-ED SA4 show delayed onset of antigen-stimulated Ca2+ mobilization and substantial inhibition of granule exocytosis. Stimulation of degranulation by thapsigargin, which bypasses inositol 1,4,5-trisphosphate production, is also substantially reduced in the presence of MARCKS-ED SA4, but store-operated Ca2+ entry is not inhibited. These results show the capacity of MARCKS-ED to regulate granule exocytosis in a PKC-dependent manner, consistent with regulated sequestration of phosphoinositides that mediate granule fusion at the plasma membrane.

Gadi, Deepti; Wagenknecht-Wiesner, Alice; Holowka, David; Baird, Barbara

2011-01-01

18

Simultaneous initiation of degranulation and inhibition of leukotriene release by soman in human basophils  

SciTech Connect

Previous studies noted that the serine esterase inhibitor, soman, could induce histamine release from human basophils. To investigate the mechanisms by which soman causes histamine release (a preformed mediator), we also examined its ability to induce leukotriene release (a newly synthesized mediator) from basophils. We found that no leukotriene release followed activation with soman, while histamine release was usually greater than 70%. In addition, soman and diisopropyl-fluorophosphate were found actively to suppress low level spontaneous leukotriene release as well as ongoing leukotriene release induced by anti-IgE antibody. Soman (0.3 mM) was able to stop leukotriene release as rapidly as the calcium chelator, EDTA. In a series of control experiments, it was noted that soman did not influence the metabolism of LTC4 to LTD4 or LTE4 (for which little metabolism occurred), eliminating the possibility that reduced LTC4 release could have resulted from its enhanced metabolism. Therefore, using one compound (soman), basophils could be simultaneously activated to degranulate while having the pathway leading to leukotriene release actively suppressed. These results provide further evidence that histamine and leukotriene release are independent pathways resulting from the activation of basophils.

Meier, H.L.; Warner, J.; MacGlashan, D.W.

1995-12-31

19

Prostaglandin E2 activates EP2 receptors to inhibit human lung mast cell degranulation  

PubMed Central

The prostanoid, PGE2, is known to inhibit human lung mast cell activity. The aim of the present study was to characterize the EP receptor that mediates this effect. PGE2 (pEC50, 5.8±0.1) inhibited the IgE-mediated release of histamine from mast cells in a concentration-dependent manner. Alternative EP receptor agonists were studied. The EP2-selective agonist, butaprost (pEC50, 5.2±0.2), was an effective inhibitor of mediator release whereas the EP1/EP3 receptor agonist, sulprostone, and the EP1-selective agonist, 17-phenyl-trinor-PGE2, were ineffective. The DP agonist PGD2, the FP agonist PGF2?, the IP agonist iloprost and the TP agonist U-46619 were ineffective inhibitors of IgE-mediated histamine release from mast cells. PGE2 induced a concentration-dependent increase in intracellular cAMP levels in mast cells. The effects of the EP1/EP2 receptor antagonist, AH6809, and the EP4 receptor antagonist, AH23848, on the PGE2-mediated inhibition of histamine release were determined. AH6809 (pKB, 5.6±0.1) caused a modest rightward shift in the PGE2 concentration–response curve, whereas AH23848 was ineffective. Long-term (24?h) incubation of mast cells with either PGE2 or butaprost (EP2 agonist), but not sulprostone (EP1/EP3 agonist), caused a significant reduction in the subsequent ability of PGE2 to inhibit histamine release. Collectively, these data suggest that PGE2 mediates effects on human lung mast cells by interacting with EP2 receptors.

Kay, Linda J; Yeo, Wilfred W; Peachell, Peter T

2006-01-01

20

Long chain acyl coenzyme A and signaling in neutrophils. An inhibitor of acyl coenzyme A synthetase, triacsin C, inhibits superoxide anion generation and degranulation by human neutrophils.  

PubMed

Ligand-initiated activation of neutrophils triggers O2- generation, degranulation, phospholipid remodeling, and release of fatty acids such as arachidonate, oleate, and palmitate. Long chain acyl-CoA synthetase converts free fatty acids to acyl-CoA esters; a role for acyl-CoA esters as positive modulators of neutrophil functions is proposed. Physiologically relevant concentrations (1-10 microM) of acyl-CoA esters such as palmitoyl-CoA, enhanced O2- generation triggered by fMet-Leu-Phe or guanosine 5'-O-(thiotriphosphate) (GTP gamma S) but did not act as a trigger per se. Triacsin C, an inhibitor of acyl-CoA synthetase, inhibited fMet-Leu-Phe-elicited O2- generation and degranulation in a concentration-dependent manner. Triacsin C inhibited O2- generation elicited by fMet-Leu-Phe and GTP gamma S in electroporated neutrophils, indicating that acyl-CoA acted downstream from the receptor. Palmitoyl-CoA reversed the Triacsin C-induced inhibition of O2- generation. fMet-Leu-Phe elicited a prompt increase in total long chain acyl-CoA esters. Arachidonoyl-CoA and oleoyl-CoA were elevated 5 s after addition of fMet-Leu-Phe, while palmitoyl-CoA was not elevated until 60 s. Triacsin C inhibited fMet-Leu-Phe-initiated increases in arachidonoyl-CoA, oleoyl-CoA, and palmitoyl-CoA. These results suggest a role for acyl-CoA esters in regulating activation of O2- generation and degranulation at the G protein or subsequent step(s). PMID:7982939

Korchak, H M; Kane, L H; Rossi, M W; Corkey, B E

1994-12-01

21

[PUVA-induced acro-bullous dermatosis].  

PubMed

PUVA-induced acrobullous dermatosis is characterized by the occurrence of blisters on the acral extremities during PUVA therapy. The tense blisters apparently arise as a result of PUVA damage to the epidermodermal cohesion coupled with friction or trauma. They must be distinguished from phototoxic reactions induced either by UVA over-dosage or excessive psoralen uptake. We report on, two cases of acrobullous PUVA-induced dermatosis, discussing clinical features, pathophysiological aspects and differential diagnosis. PMID:8767664

Grabbe, S; Schütte, B; Bruckner-Tuderman, L; Schwarz, T

1996-06-01

22

Antiallergic principles from Alpinia galanga: structural requirements of phenylpropanoids for inhibition of degranulation and release of TNF-alpha and IL-4 in RBL-2H3 cells.  

PubMed

The 80% aqueous acetone extract of the rhizomes of Alpinia galanga was found to inhibit release of beta-hexosaminidase, as a marker of antigen-IgE-mediated degranulation in RBL-2H3 cells. Nine known phenylpropanoids and p-hydroxybenzaldehyde were isolated from the extract. Among them, 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate exhibited potent inhibitory activity with IC(50) values of 15 and 19 microM. From the effects of various related compounds, both the 1'- and 4-acetoxyl groups of 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate were essential for their strong activity, and the 2'-3' double bond enhanced the activity. In addition, 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate inhibited ear passive cutaneous anaphylaxis reactions in mice and the antigen-IgE-mediated TNF-alpha and IL-4 production, both of which participate in the late phase of type I allergic reactions, in RBL-2H3 cells. PMID:12951092

Matsuda, Hisashi; Morikawa, Toshio; Managi, Hiromi; Yoshikawa, Masayuki

2003-10-01

23

Anti-allergic activity of stilbenes from Korean rhubarb ( Rheum undulatum L.): structure requirements for inhibition of antigen-induced degranulation and their effects on the release of TNF-? and IL4 in RBL-2H3 cells  

Microsoft Academic Search

Stilbenes isolated from the rhizomes of Rheum undulatum (Korean rhubarb) and the related compounds were investigated on their anti-allergic activities. The results revealed that 3,5,4?-trimethylpiceatannol exhibited the most potent inhibition against ?-hexosaminidase release as a marker of degranulation in RBL-2H3 cells with IC50 of 2.1?M, followed by trimethylresveratrol (IC50=5.1?M). Structural requirements of stilbenes for the activity are as follows: (1)

Hisashi Matsuda; Supinya Tewtrakul; Toshio Morikawa; Masayuki Yoshikawa

2004-01-01

24

Cardiovascular stress of photochemotherapy (PUVA)  

SciTech Connect

The recently devised therapy for psoriasis and related skin diseases, consisting of long-wave ultraviolet light and oral 8-methoxypsoralen (PUVA), was investigated for its cardiovascular effects. In seventeen patients, long-wave ultraviolet light therapy in a treatment enclosure (mean duration, 19.3 minutes) resulted in ambient temperatures of 39.2 degrees C +/- 2.1 degrees C (SD) and skin temperatures of 38.2 degrees C +/- 1.4 degrees C. In upright subjects, heart rate rose 30.8% to 114.4 +/- 25.2 beats per minute (bpm). Intensive room air conditioning, outside of the treatment enclosure, although significantly lowering skin and ambient temperatures, did not affect the heart rates significantly. PUVA therapy is associated with a definite cardiovascular stress when the box type of therapeutic unit is used. Possible modifications are discussed.

Ciafone, R.A.; Rhodes, A.R.; Audley, M.; Freedberg, I.M.; Abelmann, W.H.

1980-11-01

25

Cardiovascular stress of photochemotherapy (PUVA)  

Microsoft Academic Search

The recently devised therapy for psoriasis and related skin diseases, consisting of long-wave ultraviolet light and oral 8-methoxypsoralen (PUVA), was investigated for its cardiovascular effects. In seventeen patients, long-wave ultraviolet light therapy in a treatment enclosure (mean duration, 19.3 minutes) resulted in ambient temperatures of 39.2 degrees C +\\/- 2.1 degrees C (SD) and skin temperatures of 38.2 degrees C

Russell A. Ciafone; Arthur R. Rhodes; Mary Audley; Irwin M. Freedberg; Walter H. Abelmann

1980-01-01

26

Anti-allergic principles from Thai zedoary: structural requirements of curcuminoids for inhibition of degranulation and effect on the release of TNF-alpha and IL-4 in RBL-2H3 cells.  

PubMed

The 80% aqueous acetone extract of the rhizomes of Curcuma zedoaria cultivated in Thailand (Thai zedoary) was found to inhibit release of beta-hexosaminidase, as a marker of antigen-IgE-mediated degranulation, in RBL-2H3 cells and passive cutaneous anaphylaxis reaction in mice. From the active fraction, four curcuminoids (curcumin, dihydrocurcumin, tetrahydrodemethoxycurcumin, and tetrahydrobisdemethoxycurcumin) were isolated together with two bisabolane-type sesquiterpenes, and the effects of four curcuminoids from Thai zedoary and several related compounds on the degranulation were examined. Among them, curcumin showed the highest activity against beta-hexosaminidase release with IC(50) of 5.3 microM, followed by bisdemethoxycurcumin (IC(50) = 11 microM). With regard to the structural requirements of curcuminoids for the activity, the conjugated olefins at the 1-7 positions and the 4'- or 4''-hydroxyl groups of curcuminoids were suggested to be essential for the strong activity, whereas the 3'- or 3''-methoxyl group only enhanced the activity. Furthermore, effects of curcumin and bisdemethoxycurcumin on calcium ionophores (A23187 and ionomycin)-induced degranulation and antigen-induced release of TNF-alpha and IL-4 were examined. PMID:15498665

Matsuda, Hisashi; Tewtrakul, Supinya; Morikawa, Toshio; Nakamura, Akihiko; Yoshikawa, Masayuki

2004-11-15

27

Inhibition of beta-bungarotoxin binding to brain membranes by mast cell degranulating peptide, toxin I, and ethylene glycol bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid.  

PubMed

The presynaptically active snake venom neurotoxin beta-bungarotoxin (beta-Butx) is known to affect neurotransmitter release by binding to a subtype of voltage-activated K+ channels. Here we show that mast cell degranulating (MCD) peptide from bee venom inhibits the binding of 125I-labeled beta-Butx to chick and rat brain membranes with apparent Ki values of 180 nM and 1100 nM, respectively. The mechanism of inhibition by MCD peptide is noncompetitive, as is inhibition of 125I-beta-Butx binding by the protease inhibitor homologue from mamba venom, toxin I. Beta-Butx and its binding antagonists thus bind to different sites of the same membrane protein. Removal of Ca2+ by ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid inhibits the binding of 125I-beta-Butx by lowering its affinity to brain membranes. PMID:3130091

Schmidt, R R; Betz, H; Rehm, H

1988-02-01

28

Effects of PUVA on the eye  

SciTech Connect

Psoriasis is a common skin disease which may be treated with 8-methoxy psoralen and long-wave ultraviolet light (PUVA). Eye protection is provided during and after treatment to prevent the development of photokeratitis and cataracts. Fifteen patients, treated with medication and ultraviolet A (UVA) had an initial complete eye examination and a repeat examination after each treatment. No patients developed cataracts but almost one-half of the patients had a mild form of photokeratoconjunctivitis. The ocular manifestations included photophobia, conjunctivitis, keratitis, and dry eyes. Tear break-up time was reduced significantly immediately after treatment for two patients but returned to normal 8 hr later. Dermatologists who employ PUVA treatments should be concerned about photokeratoconjunctivitis and the dry-eye ocular manifestations included photophobia, conjunctivitis, keratitis, and dry eyes. Tear break-up time was reduced significantly immediately after treatment for two patients but returned to normal 8 hr later. Dermatologists who employ PUVA treatments should be concerned about photokeratoconjunctivitis and the dry-eye ocular manifestations included photophobia, conjunctivitis, keratitis, and dry eyes. Tear break-up time was reduced significantly immediately after treatment for two patients but returned to normal 8 hr later. Dermatologists who employ PUVA treatments should be concerned about photokeratoconjunctivitis and the dry-eye syndrome.

Backman, H.A.

1982-01-01

29

A possible role of arachidonic acid in human neutrophil aggregation and degranulation.  

PubMed Central

Chemotactic factors stimulate neutrophils to aggregate and, in the presence of cytochalasin B, to degranulate. Recently, the authors found that arachidonic acid also stimulates human neutrophils to aggregate but does not stimulate cytochalasin-B-treated or untreated cells to degranulate. In this report the authors examined the effect of three blockers of arachidonic acid metabolism on these cellular responses. It was found that the arachidonic acid analog 5,8,11,14-eicosatetraynoic acid and indomethacin, but not aspirin, inhibited no only the arachidonic-acid-induced aggregation response but also the degranulation responses evoked by C5a or a synthetic oligopeptide chemotactic factor. These results suggest that arachidonic acid may be a precursor of bioactive metabolites that stimulate the aggregation and foster the degranulation responses of neutrophils. Thus, these metabolites may be mediators of neutrophil function. Agents that block their formation may thereby inhibit aggregation and degranulation.

O'Flaherty, J. T.; Showell, H. J.; Ward, P. A.; Becker, E. L.

1979-01-01

30

Cytochrome P450 CYP1B1 Interacts with 8-Methoxypsoralen (8-MOP) and Influences Psoralen-Ultraviolet A (PUVA) Sensitivity  

PubMed Central

Background There are unpredictable inter-individual differences in sensitivity to psoralen-UVA (PUVA) photochemotherapy, used to treat skin diseases including psoriasis. Psoralens are metabolised by cytochrome P450 enzymes (P450), and we hypothesised that variability in cutaneous P450 expression may influence PUVA sensitivity. We previously showed that P450 CYP1B1 was abundantly expressed in human skin and regulated by PUVA, and described marked inter-individual differences in cutaneous CYP1B1 expression. Objectives We investigated whether CYP1B1 made a significant contribution to 8-methoxypsoralen (8-MOP) metabolism, and whether individuality in CYP1B1 activity influenced PUVA sensitivity. Methods We used E. coli membranes co-expressing various P450s and cytochrome P450 reductase (CPR) to study 8-MOP metabolism and cytotoxicity assays in CYP1B1-expressing mammalian cells to assess PUVA sensitivity. Results We showed that P450s CYP1A1, CYP1A2, CYP1B1, CYP2A6 and CYP2E1 influence 8-MOP metabolism. As CYP1B1 is the most abundant P450 in human skin, we further demonstrated that: (i) CYP1B1 interacts with 8-MOP (ii) metabolism of the CYP1B1 substrates 7-ethoxyresorufin and 17-?-estradiol showed concentration-dependent inhibition by 8-MOP and (iii) inhibition of 7-ethoxyresorufin metabolism by 8-MOP was influenced by CYP1B1 genotype. The influence of CYP1B1 on PUVA cytotoxicity was further investigated in a Chinese hamster ovary cell line, stably expressing CYP1B1 and CPR, which was more sensitive to PUVA than control cells, suggesting that CYP1B1 metabolises 8-MOP to a more phototoxic metabolite(s). Conclusion Our data therefore suggest that CYP1B1 significantly contributes to cutaneous 8-MOP metabolism, and that individuality in CYP1B1 expression may influence PUVA sensitivity.

Deeni, Yusuf Y.; Ibbotson, Sally H.; Woods, Julie A.; Wolf, C. Roland; Smith, Gillian

2013-01-01

31

Inhibitory effect of aqueous spinach extract on degranulation of RBL-2H3 cells.  

PubMed

The inhibitory effect of an aqueous extract from spinach on degranulation of RBL-2H3 cells is herein reported. The extract significantly suppressed antigen-induced degranulation in a dose-dependent manner without affecting cell viability. Active substances in the extract were heat-stable and trypsin-resistant with molecular weights ranging from 500 Da to 14 kDa. The extract inhibited elevation of the intracellular Ca(2+) concentration caused by stimulation by antigen, while not suppressing degranulation induced by a calcium ionophore A23187. Immunoblot analysis revealed that the inhibitory effect results from downregulation of phosphorylation of both Syk kinase and phosphatidylinositol 3-kinase in the signalling pathways involved in degranulation caused by the antigen-antibody interaction. Taken together, these findings suggest that aqueous spinach extract has an anti-allergic activity that controls degranulation. PMID:23122065

Ishida, Momoko; Nishi, Kosuke; Watanabe, Hisashi; Sugahara, Takuya

2012-09-08

32

Treatment of stable vitiligo with autologous epidermal grafting and PUVA  

Microsoft Academic Search

Background: Previous reports have shown the benefits of epidermal grafting for vitiligo.Objective: Our purpose was to evaluate the effectiveness and complications of epidermal grafting in combination with PUVA on stable vitiligo refractory to conventional treatments.Methods: In 100 patients with stable refractory vitiligo we performed epidermal grafting with suction blisters followed by PUVA treatment. The grafted sites were examined for repigmentation

Seung Kyung Hann; Sungbin Im; Ha Wook Bong; Yoon-Kee Park

1995-01-01

33

Comparison of efficacy and side-effect profile of oral PUVA vs. oral PUVA sol in the treatment of vitiligo: a 36-week prospective study.  

PubMed

Background? Both Oral PUVA and PUVA sol have been successfully used in vitiligo treatment. However, there is paucity of studies comparing the two therapies, especially under subtropical conditions of abundant sunlight where PUVA sol is more feasible. Objectives? To compare the efficacy and side effects of oral PUVA versus oral PUVA sol therapy in generalized vitiligo. Methods? Comparative prospective clinical trial conducted on consecutive patients of generalized vitiligo. Response to treatment was assessed using change in Lund & Browder (L & B) score for assessment of reduction in body surface area of involvement, patient global assessment (PGA) of improvement in vitiligo, investigator's global assessment (IGA) of extent of repigmentation, and quality of life (QOL) assessment using Tjioe et al questionnaire. Results? Thirty five patients were recruited- 18 in PUVA and 17 in PUVA sol group. Mean percentage change in L & B score at 36?weeks was 46.4% in PUVA and 26.1% in PUVA sol group (P?=?0.06), mean PGA score in PUVA was 4.58?±?2.23 and in PUVA sol group was 6?±?2.08 (P?=?0.13), mean IGA score was 3.08?±?1.68 in PUVA and 1.79?±?0.57 in PUVA sol group (P?=?0.11). QOL scores were significantly higher in PUVA group as compared to the PUVA sol group (P?=?0.04). Side effects were comparable in two groups except for phototoxic side effects which were significantly more in PUVA group. Conclusions? PUVA is more efficacious than PUVA sol and also provides greater psychological benefit in treatment of generalized vitiligo but is associated with more phototoxic adverse effects. PMID:23066663

Singh, S; Khandpur, S; Sharma, V K; Ramam, M

2012-10-16

34

Anaplasma phagocytophilum Infection Induces Protracted Neutrophil Degranulation  

PubMed Central

Anaplasma phagocytophilum-infected neutrophil degranulation could exacerbate inflammation. Thus, the degranulation of infected neutrophils was assayed. Infected neutrophils expressed CD11b and CD66b, and supernatants of infected neutrophils showed more proMMP-9 and MMP-9 activity than controls and continued to do so for ?18 h. Degranulation-related inflammatory tissue injury may account for some clinical manifestations in human granulocytic anaplasmosis.

Choi, Kyoung-seong; Grab, Dennis J.; Dumler, J. Stephen

2004-01-01

35

Hemodialysis-Induced Degranulation of Polymorphonuclear Cells: No Correlation between Membrane Markers and Degranulation Products  

Microsoft Academic Search

Background\\/Aims: Degranulation of polymorphonuclear leukocytes (PMN) during hemodialysis (HD) is usually assessed by measuring degranulation products. However, this process might also be estimated by the assessment of cell surface markers. In this study, the relationship between the expression of PMN degranulation markers (CD63 and CD66b) and the release of degranulation products [myeloperoxidase (MPO) and lactoferrin (LF)] was investigated during clinical

M. P. C. Grooteman; A. van Tellingen; A. J. van Houte; J. C. Bos; M. Schoorl; J. van Limbeek; M. J. Nubé

2000-01-01

36

Microvascular leakage of plasma proteins after PUVA and UVA  

SciTech Connect

The transcapillary escape rate of albumin (TERalb), is a parameter of the leakage of macromolecules from the total microvasculature. In patients with psoriasis short-term PUVA treatment induces an increase in TERalb. In this study TERalb was measured in 3 groups of normal humans treated with PUVA, UVA and 8-methoxypsoralen. Treatment with PUVA and UVA caused a statistically significant increase in TERalb, whereas treatment with 8-methoxypsoralen did not induce any measurable changes. It is concluded that the UVA irradiation causes the abnormal leakage of macromolecules, whereas psoralen is not the responsible component. Furthermore the phenomenon can be elicited in normals and is not based on a preexisting psoriasis.

Staberg, B.; Worm, A.M.; Rossing, N.; Brodthagen, H.

1982-04-01

37

Antiangiogenic Effect of Methotrexate and PUVA on Psoriasis.  

PubMed

Vascular endothelial growth factor (VEGF) is important factor for angiogenesis in psoriasis. Methotrexate and psoralen and ultraviolet light A (PUVA) mainly target the T cell-mediated immunopathology of psoriasis. Our work aimed at estimating VEGF mRNA in psoriatic patients and investigating whether the standard therapeutic modalities (methotrexate and PUVA) exert their antiangiogenic activity through altering VEGF levels. Twenty-four chronic plaque psoriasis patients were enrolled. Patients were divided into two groups (12 patients each); group A received intramuscular methotrexate and group B was treated by PUVA three times/week in a PUVA 1000 cabin for 10 weeks each. Twelve healthy volunteers served as controls. A skin biopsy was taken from lesional skin before and after treatment for RT-PCR detection of VEGF mRNA. Capillary perfusion scanning using LASER Doppler perfusion imaging was performed on the same psoriatic plaque before and after treatment and was also done for the controls. Following both methotrexate and PUVA, a significant reduction in the amount of VEGF mRNA (P < 0.001 and P = 0.002, respectively) and capillary perfusion (P = 0.002) occurred. These reductions were significantly higher in the methotrexate group (P < 0.001 and  P = 0.001, respectively) than in the PUVA group. The percentage of clinical improvement in the examined psoriatic plaque was significantly positively correlated with the percentage of reduction in the amount of VEGF mRNA (r = 0.850, P < 0.001) and the percentage of reduction in the capillary perfusion (r = 0.684, P < 0.001). Both modalities may exert an antiangiogenic effect. Methotrexate appears to have possibly a more potent antiangiogenic effect than PUVA. PMID:23504632

Shaker, Olfat G; Khairallah, Mongy; Rasheed, Hoda M; Abdel-Halim, Mona R; Abuzeid, Ola M; El Tawdi, Amira M; El Hadidi, Heba H; Ashmaui, Ali

2013-11-01

38

PUVA: A Monte Carlo code for intra-articular PUVA treatment of arthritis  

SciTech Connect

Current rheumatoid arthritis treatments are only partially successful. Intra-articular psoralen-ultraviolet light (PUVA) phototherapy appears to be a new and valid alternative. Ultraviolet laser light (UVA) delivered in the knee joint through a fiber optic is used in combination with 8-methoxypsoralen (8-MOP), a light-sensitive chemical administered orally. A few hours after ingestion, the psoralen has diffused in all body cells. Once activated by UVA light, it binds to biological molecules, inhabiting cell division and ultimately causing local control of the arthritis. The magnitude of the response is proportional to the number of photoproducts delivered to tissues (i.e., the number of absorbed photons): the PUVA treatment will only be effective if a sufficient and relatively uniform dose is delivered to the diseased synovial tissues, while sparing other tissues such as cartilage. An application is being developed, based on analog Monte Carlo methods, to predict photon densities in tissues and the minimum number of intra-articular catheter positions necessary to ensure proper treatment of the diseased zone. Other interesting aspects of the problem deal with the compexity of the joint geometry, the physics of light scattering in tissues (a relatively new field of research that is not fully understood because of the variety of tissues and tissue components), and, finally, the need to include optic laws (reflection and refraction) at interfaces.

Descalle, M.A.; Laing, T.J.; Martin, W.R. [Univ. of Michigan, Ann Arbor, MI (United States)

1996-12-31

39

Livedo reticularis and livedoid vasculitis responding to PUVA therapy.  

PubMed

Livedo reticularis is a mottled blue discoloration of the skin, which occurs in a netlike pattern. Livedoid vasculitis is a chronic disorder clinically manifested by recurrent painful ulcerations of the lower extremities and is characterized by the presence of smooth or depressed ivory-white lesions surrounded by hyperpigmentation and telangiectasia. We describe two patients with livedo reticularis and livedoid vasculitis who responded to PUVA therapy and propose that systemic PUVA with methoxsalen undergo further investigation as an alternative therapy for drug-resistant patients with livedo reticularis and livedoid vasculitis. PMID:10025746

Choi, H J; Hann, S K

1999-02-01

40

Mathematical modeling for laser PUVA treatment of psoriasis  

NASA Astrophysics Data System (ADS)

We used the Monte Carlo method to evaluate UV-A radiation penetration through human skin (epidermis and dermis). Calculations were performed for multilayered medium, refractive indices mismatch on boundaries of the sample and finite width of incident beam. The fluence rate distributions of UV-A radiation (wavelength 337 nm) within tissue are presented. In order to optimize the laser PUVA treatment of psoriasis were have developed the mathematical model of the dynamics of cell processed within epidermis. The task of optimal control for PUVA treatment is formulated.

Medvedev, Boris A.; Tuchin, Valery V.; Yaroslavsky, Ilya V.

1991-06-01

41

Accidental PUVA burns, vitiligo and atopic diathesis resulting in prurigo nodularis: a logical but undocumented rarity.  

PubMed

Vitiligo is a dreaded disease in India due to its social and cultural consequences. PUVA and PUVAsol are the main treatment modalities for vitiligo vulgaris. To the best of our knowledge, this is the first case of accidental PUVA burns eventuating in prurigo nodularis lesions to be reported in a female patient who was undergoing home PUVA therapy. The itch is so prominent and disabling that the focus of the patient has shifted from treating her vitiligo to ameliorating the pruritus. PMID:23197209

Verma, Shyam Bhanushankar; Wollina, Uwe

42

PUVA-Treatment for solar urticaria and persistent light reaction  

Microsoft Academic Search

A technique is described to successfully treat patients with extreme sensitivity to UV electromagnetic wave lengths with photochemotherapy. Representative data from a patient with solar urticaria and two patients with persistent light reaction are given. Prior to treatment the threshold doses for UV-C, UV-B, and UV-A were determined. Photochemotherapy was performed with standard 8-methoxypsoralen-UV-A (PUVA) schedules. Initial treatments were very

Erhard Hölzle; Cornelia Hofmann; Gerd Plewig

1980-01-01

43

Non-Melanoma Skin Cancer Occurring in Patients Treated With PUVA Five to Ten Years After First Treatment  

Microsoft Academic Search

Continued prospective study of the 1,380 patients enrolled in the PUVA study for 10 years after first exposure to PUVA demonstrates a strong association between cumulative exposure to PUVA and an increased risk of squamous cell carcinoma of the skin. For tumors occurring at least 58 months after first treatment, after adjustment for age, sex, and area of residence, we

Robert S. Stern; Rudee Lange

1988-01-01

44

Substance P Signaling Controls Mast Cell Activation, Degranulation, and Nociceptive Sensitization in a Rat Fracture Model of Complex Regional Pain Syndrome  

PubMed Central

Background Complex regional pain syndrome patients have increased tryptase in the skin of the affected extremity indicating mast cell (MC) accumulation and degranulation, processes known to be mediated by substance P (SP). The dysregulation of SP release from primary afferent neurons is characteristic of complex regional pain syndrome. We hypothesized that SP acting through the NK1 receptor results in mast cell accumulation, degranulation and nociceptive sensitization in a rat model of complex regional pain syndrome. Methods Groups of 6 to 10 rats underwent tibia fracture and hindlimb casting for 4 weeks, and the hindpaw skin was harvested for histological and immunohistochemical analysis. The effects of a selective NK1 receptor antagonist (LY303870) and of direct SP intraplantar injection were measured. Dermal MC degranulation induced by sciatic nerve stimulation and the effects of LY303870 on this process were investigated. Finally, the antinociceptive effects of acute and chronic treatment with a MC degranulator (48/80) were tested. Results We observed that 1) fracture caused MC accumulation, activation, and degranulation which were inhibited by LY303870, 2) the percentage of MCs in close proximity to peptidergic nerve fibers increased after fracture, 3) electrical stimulation caused MC activation and degranulation, which was blocked by LY303870, 4) intraplantar SP-induced MC degranulation, and 5) acute administration of 48/80 caused MC degranulation and enhanced postfracture nociception, but MCs depleted animals showed less sensitization. Conclusions These results indicate that facilitated peptidergic neuron-MC signaling after fracture can cause MC accumulation, activation and degranulation in the injured limb resulting in nociceptive sensitization.

Li, Wen-Wu; Guo, Tian-Zhi; Liang, De-yong; Sun, Yuan; Kingery, Wade S.; Clark, J. David

2012-01-01

45

Bath PUVA and Psoriasis: Is a Milder Treatment a Worse Treatment?  

Microsoft Academic Search

Background\\/Aim: The guidelines of the British Photodermatology Group for topical treatment with psoralen and ultraviolet light (PUVA) recommend starting UVA doses between 0.2 and 0.5 J\\/cm2, according to the phototype. Our purpose was to evaluate the therapeutic efficacy and tolerability of bath PUVA, with 8-methoxypsoralen (8-MOP), by using lower UVA doses, regardless of phototype. Methods: We compared 2 groups of

G. Delrosso; C. Bornacina; P. Farinelli; F. Bellinzona; G. Leigheb; E. Colombo

2008-01-01

46

Effects of stilbenes isolated from medicinal plants on arachidonate metabolism and degranulation in human polymorphonuclear leukocytes  

Microsoft Academic Search

Studies were made on the effects of stilbene derivatives isolated from medicinal plants on arachidonate metabolism and degranulation in human polymorphonuclear leukocytes (PMN-L). Resveratrol (3,4?,5-trihydroxystilbene) isolated from the roots of Reynoutria japonica was found to inhibit the 5-lipoxygenase products 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE), 5,12-dihydroxy-6,8,10,14-eicosatetraenoic acid (5,12-diHETE) and leukotriene C4(LTC4); its concentrations for 50% inhibition (IC50) were 8.90 × 10?6 M, 6.70

Yoshiyuki Kimura; Hiromichi Okuda; Michinori Kubo

1995-01-01

47

Lipopolysaccharide enhances Fc?RI-mediated mast cell degranulation by increasing Ca2+ entry through store-operated Ca2+ channels: implications for lipopolysaccharide exacerbating allergic asthma.  

PubMed

Lipopolysaccharide (LPS) can exacerbate asthma; however, the mechanisms are not fully understood. This study investigated the effect of LPS on antigen-stimulated mast cell degranulation and the underlying mechanisms. We found that LPS enhanced degranulation in RBL-2H3 cells and mouse peritoneal mast cells upon Fc?RI activation, in a dose- and time-dependent manner. Parallel to the alteration of degranulation, LPS increased Fc?RI-activated Ca(2+) mobilization, as well as Ca(2+) entry through store-operated calcium channels (SOCs) evoked by thapsigargin. Blocking Ca(2+) entry through SOCs completely abolished LPS enhancement of mast cell degranulation. Consistent with functional alteration of SOCs, LPS increased mRNA and protein levels of Orai1 and STIM1, two major subunits of SOCs, in a time-dependent manner. In addition, LPS increased the mRNA level of Toll-like receptor 4 (TLR4) in a time-dependent manner. Blocking TLR4 with Cli-095 inhibited LPS, increasing transcription and expression of SOC subunits. Concomitantly, the effect of LPS enhancement of Ca(2+) mobilization and mast cell degranulation was largely reduced by Cli-095. Administration of LPS (1 ?g) in vivo aggravated airway hyperreactivity and inflammatory reactions in allergic asthmatic mice. Histamine levels in serum and bronchoalveolar lavage fluid were increased by LPS treatment. In addition, Ca(2+) mobilization was enhanced in peritoneal mast cells isolated from LPS-treated asthmatic mice. Taken together, these results imply that LPS enhances mast cell degranulation, which potentially contributes to LPS exacerbating allergic asthma. Lipopolysaccharide increases Ca(2+) entry through SOCs by upregulating transcription and expression of SOC subunits, mainly through interacting with TLR4 in mast cells, resulting in enhancement of mast cell degranulation upon antigen stimulation. PMID:22581748

Yang, Chengbin; Mo, Xucheng; Lv, Jingzhang; Liu, Xiaoyu; Yuan, Meichun; Dong, Ming; Li, Li; Luo, Xinping; Fan, Xinmin; Jin, Zhe; Liu, Zhigang; Liu, Jie

2012-05-11

48

Microfilaments make mast cells migrate (rather than degranulate).  

PubMed

Expression of the high-affinity receptor for IgE (Fc?RI) provides mast cells with the ability to react in a proinflammatory manner to antigens (Ags). In particular, the immediate secretion of preformed mediators from secretory lysosomes (degranulation) is typical for Fc?RI-mediated mast cell activation. In addition to the Fc?RI, the stem cell factor receptor, KIT, is expressed at high levels on the surface of mast cells. KIT activation controls mast cell differentiation and survival in vivo and potently stimulates the chemotaxis of these cells. Although Fc?RI and KIT initiate many of the same early signaling events in mast cells, Fc?RI activation results in potent degranulation and a poor chemotactic response while KIT activation triggers very little degranulation and a strong chemotactic response. Novel data published in this issue of the European Journal of Immunology [Smrž et al. Eur. J. Immunol. 2013. 43: 1873-1882] demonstrate that actin de- and repolymerization, involved in both degranulation and chemotaxis, make all the difference: Pharmacological suppression of F-actin formation converts activated KIT into a strong degranulator. The possible implications for mast cell physiology and pathophysiology are discussed in this Commentary. PMID:23719840

Huber, Michael

2013-06-14

49

Human mast cell degranulation and preformed TNF secretion require mitochondrial translocation to exocytosis sites: Relevance to atopic dermatitis  

PubMed Central

Background Mast cells derive from hematopoietic cell precursors and participate in tissue allergic, immune, and inflammatory processes. They secrete many mediators, including preformed TNF, in response to allergic, neuropeptide, and environmental triggers. However, regulation of mast cell degranulation is not well understood. Objective We investigated the role of mitochondrial dynamics in degranulation of human cultured mast cells. Methods Human umbilical cord blood–derived mast cells (hCBMCs) and Laboratory of Allergic Diseases 2 (LAD2) mast cells were examined by confocal and differential interference contrast microscopy during activation by IgE/antigen and substance P (SP). Mast cells in control and atopic dermatitis (AD) skin were evaluated by transmission electron microscopy. LAD2 cells were pretreated with mitochondrial division inhibitor, a dynamin-related protein 1 (Drp1) inhibitor, and small interfering RNA for Drp1, which is necessary for mitochondrial fission and translocation. Calcineurin and Drp1 gene expression was analyzed in stimulated LAD2 cells and AD skin biopsies. Results Stimulation of hCBMCs with IgE/antigen or LAD2 cells with SP leads to rapid (30 minutes) secretion of preformed TNF. Degranulation is accompanied by mitochondrial translocation from a perinuclear location to exocytosis sites. Extracellular calcium depletion prevents these effects, indicating calcium requirement. The calcium-dependent calcineurin and Drp1 are activated 30 minutes after SP stimulation. Reduction of Drp1 activity by mitochondrial division inhibitor and decrease of Drp1 expression using small interfering RNA inhibit mitochondrial translocation, degranulation, and TNF secretion. Mitochondrial translocation is also evident by transmission electron microscopy in skin mast cells from AD biopsies, in which gene expression of calcineurin, Drp1, and SP is higher than in normal skin. Conclusion Human mast cell degranulation requires mitochondrial dynamics, also implicated in AD. (J Allergy Clin Immunol 2011;127:1522-31.)

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

2012-01-01

50

Sympathetic modulation of biochemical and physiological response to immune degranulation in canine bronchial airways in vivo.  

PubMed Central

The effect of sympathetic stimulation on bronchial smooth muscle contractile response after mast cell degranulation with Ascaris suum antigen was studied in 36 natively allergic dogs in situ. Bronchial smooth muscle response was measured isometrically in a single right middle lobe bronchus. A dose of antigen causing maximal release of mediator was administered to the bronchus through the bronchial arterial circulation. Serial plasma histamine concentrations were determined at 15-s intervals after intra-arterial (i.a.) administration of antigen. Samples of blood were obtained simultaneously from right heart and femoral artery, and arteriovenous difference (AVd) in histamine concentration across the bronchus was determined during mast cell degranulation. In nine dogs showing bronchial mast cell degranulation to antigen challenge, bronchial smooth muscle contraction was 22.3 +/- 2.95 g and the mean AVd in histamine concentration across the bronchus was 188 +/- 41.5 ng/ml. Six other dogs having muscarinic blockade with 0.75-1.0 mg/kg intravenous atropine were given i.a. antigen after 1 min of steady-state sympathetic stimulation with intravenous 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP). Sympathetic stimulation during Ascaris suum antigen challenge caused complete inhibition of bronchial smooth muscle contractile response to i.a. antigen (P less than 0.001), and a significant AVd in histamine concentration across the bronchus (9.8 +/- 16.0 ng/ml; P less than 0.01 vs. control) was not detected. Peak plasma histamine concentration in control dogs was 1,138 +/- 237 ng/ml vs. 310 +/- 135 ng/ml in animals receiving sympathetic stimulation (P less than 0.01). In four dogs undergoing systemic anaphylaxis to i.v. antigen, subsequent sympathetic stimulation with i.v. DMPP reduced bronchomotor tone to approximately 70% of base-line control. Exogenously induced sympathetic stimulation can substantially inhibit systemic mast cell degranulation to Ascaris suum antigen in allergic dogs. Maximal stimulation of the sympathetic nervous system causes substantial inhibition of respiratory mast cell secretion of histamine and bronchial smooth muscle contraction to circulating mediator. Images

Garrity, E R; Stimler, N P; Munoz, N M; Tallet, J; David, A C; Leff, A R

1985-01-01

51

PUVA-induced blisters, complement deposition, and damage to the dermoepidermal junction.  

PubMed

We followed the course of 56 patients receiving psoralen plus long-wave ultraviolet light (PUVA) therapy. Nonhemorrhagic blisters developed on clinically normal skin on the limbs of seven patients. Seeming to be related to friction and trauma, the blisters form as a result of damage to the basal and suprabasal layers. Perilesional skin specimens from all blistered patients contained granular deposits of C3 at the dermoepidermal junction, around the upper dermal blood vessels, or at both sites. The average time for initiation and complete formation of suction blisters was measured in 51 patients at different stages during the course of PUVA treatment. Blister separation was in the lamina lucida, with the pemphigoid antigen in the roof while the blister floor contained the lamina densa, laminin, and type IV collagen. This impaired dermoepidermal adhesion was a general phenomenon that occurred in all PUVA-treated patients. The mechanism remains to be determined. PMID:3314716

Friedmann, P S; Coburn, P; Dahl, M G; Diffey, B L; Ross, J; Ford, G P; Parker, S C; Bird, P

1987-11-01

52

Class I PI3K-mediated Akt and ERK signals play a critical role in Fc?RI-induced degranulation in mast cells.  

PubMed

Class IA and IB phosphoinositide 3-kinases (PI3Ks) have been shown to regulate mast cell functions such as proliferation, development, survival and degranulation, but the functional redundancy between these two PI3K signaling pathways in mast cells remains unclear. Here, we have generated mice deficient in both class IA regulatory subunit p85? and class IB catalytic subunit p110?, and show that p85?(-/-)p110?(-/-) mice exhibit a more severe defect in mast cell development than single-knockout mice. In addition, the in vivo passive cutaneous anaphylaxis reaction of p85?(-/-)p110?(-/-) mice was nearly completely abrogated, whereas single-knockout mice exhibit just marginal reduction. Pharmacological inactivation of Akt in wild-type bone marrow-derived mast cells (BMMCs) led to partial reduction of degranulation, while over-expression of a constitutively active Akt partially restored the impaired degranulation in p85?(-/-)p110?(-/-) BMMCs. We also found that the extracellular signal-regulated kinase (ERK) signaling pathway was activated in a PI3K-dependent manner upon Fc?RI stimulation and that simultaneous inhibition of Akt and ERK resulted in nearly complete blockade of Fc?RI-induced degranulation. Our data provide evidence that Akt and ERK pathways play redundant roles in Fc?RI-induced degranulation. PMID:23143475

Takayama, Gensuke; Ohtani, Masashi; Minowa, Akiko; Matsuda, Satoshi; Koyasu, Shigeo

2012-11-08

53

PUVA-induced Repigmentation of Vitiligo: Scanning Electron Microscopy of Hair Follicles  

Microsoft Academic Search

PUVA-induced repigmentation of vitiligo was studied using both the split-dopa reaction and scanning electron microscopy. Proliferation of hypertrophic, Dopa-positive melanocytes were observed in the lower portion of some hair follicles, whereas other giant melanocytes were observed along the middle portion. The existence of a melanocyte reservoir in human hair follicles is postulated.

J. P. Ortonne; D. Schmitt; J. Thivolet

1980-01-01

54

In situ screening of 3-arylcoumarin derivatives reveals new inhibitors of mast cell degranulation.  

PubMed

Due to the severity and high prevalence of allergic diseases, there is growing interest in the development of inhibitors of such conditions. 3-Arylcoumarin derivatives emerge as promising compounds for the treatment of allergic disorders, in particular due to their close structural similarity to flavonoids, whose anti-allergic activity has been extensively reported. The aim of this work was to perform a screening of a set of 3-arylcoumarins as potential inhibitors of mast cell degranulation, a key event for the development of allergic reactions. For that purpose, it was utilized a biosensor model based on mast cells, whose in vitro assay allows for such screening, in a high throughput fashion, and also permits bringing to attention some coumarin structural features that are important for their biological activity. The mast cell-based biosensor was shown to discriminate, with high sensitivity and reproducibility, between coumarins that did not affect or caused different degrees of inhibition of degranulation. Among active coumarins, some substituents could be accounted for their inhibitory activity, such as the hydroxylation of positions 6 and 2' of 3-phenylcoumarins, in addition to catechol, amino and thiophene moieties. In summary, 3-arylcoumarins could be suggested as potential candidates for the development of new anti-allergic drugs. PMID:23519647

de Souza Santos, Marcela; Freire de Morais Del Lama, Maria Perpétua; Deliberto, Laila Aparecida; da Silva Emery, Flávio; Tallarico Pupo, Mônica; Zumstein Georgetto Naal, Rose Mary

2013-06-01

55

Mechanical loading promotes mast cell degranulation via RGD-integrin dependent pathways.  

PubMed

Mast cells are known to respond to a number of stimuli, such as IgE antibody-antigen complexes, pathogens, chemical compounds, and physical stimulation, resulting in the activation of these cells and subsequent release of cytokines, inflammatory mediators and granules which can influence the pathophysiology of neighboring cells. Although different forms of physical stimulation (i.e. shear stress and acupuncture) have been investigated, the effect of cyclic tensile loading on mast cell activation has not. To characterize the response of mast cells to tensile loading, RBL-2H3 cells were embedded in a 3-dimensional fibrin construct and subjected to 24h of cyclic loading at 0%, 5% or 10% peak tensile strain. Mechanical loading significantly increased RBL-2H3 cell secretion of ?-hexosaminidase (2.1- to 2.3-fold, respectively) in a load- and time-dependent manner when compared to the controls. Furthermore, no evidence of load-induced cell death or alterations in cell proliferation was observed. To determine if RGD-dependent integrins mediated the degranulation of mast cells during mechanical loading, cell-matrix interactions were inhibited by treating the cells with echistatin, a disintegrin that binds RGD-dependent integrins. Treatment with echistatin significantly attenuated load-induced degranulation without compromising cell viability. These results suggest a novel mechanism through which mechanical loading induces mast cell activation via RGD binding integrins. PMID:23261248

Fowlkes, Vennece; Wilson, Christopher G; Carver, Wayne; Goldsmith, Edie C

2012-12-20

56

Silver nanoparticle-induced degranulation observed with quantitative phase microscopy  

NASA Astrophysics Data System (ADS)

The use of AgNP is becoming more and more widespread in biomedical field. But compared with the promising bactericidal function, other physiological effects of AgNP on cells are relatively scant. In this research, we propose quantitative phase microscopy (QPM) as a new method to study the degranulation, and AgNP-induced RBL-2H3 cell degranulation is studied as well. Firstly, HeLa cells as the cell control and PBS as the solvent control, we measured the cell volume and cross section profile (x-z plane) with QPM. The results showed that the volume and cross section profile changed only the RBL-2H3 cells exposed to calcium ionophore A23187, which demonstrates the validity of QPM in degranulation research. Secondly, 50?g/mL of AgNP was used instead of A23187, and the measurement of cell volume and cross section profile was carried out again. RBL-2H3 cell volume increased immediately after AgNP was added, and cross section profile showed that the cell surface became granulated, but HeLa cell was lack of that effect. Phase images obviously indicated the RBL-2H3 cell deformation. Thirdly, stained with Fluo-3/AM, intracellular calcium Ca2+]i of single RBL-2H3 cell treated with AgNP was observed with fluorescent microscopy; incubated with AgNP for 20min, the supernatant of RBL-2H3 cells was collected and reacted with o-phthalaldehyde (OPA), then the fluorescent intensity of histamine-OPA complex was assayed with spectrofluorometer. The results of Ca2+]i and histamine increase showed that degranulation of AgNP-induced RBL-2H3 cell occurred. So, the cell volume was used as a parameter of degranulation in our study and AgNP-induced RBL-2H3 cells degranulation was confirmed by the cell volume increment, cross section profile change, and [Ca2+]i and histamine in supernatant increase.

Yang, Wenzhong; Lee, Seungrag; Lee, Jiyong; Bae, Yoonsung; Kim, Dugyoung

2010-02-01

57

Quantifying psoralen in tissues by fluorescence: dosimetry for psoralen administration followed by ultraviolet A irradiation (PUVA) to block restenosis  

NASA Astrophysics Data System (ADS)

PUVA therapy may prove effective in preventing restenosis of vessels following balloon angioplasty to open vessels narrowed by atherosclerosis. The technique relies on the ability of PUVA (psoralen administration followed by ultraviolet A irradiation) to cause crosslinks and monoadducts that prevent cellular proliferation without causing cell death. Such PUVA treatment has been successful in controlling cutaneous cell proliferation of psoriasis. The efficacy of PUVA treatment depends on the drug concentration and the light dose. The amount of light delivered is easily modified to adapt to variations in the drug concentration if the drug levels in the vessel wall are known. This paper demonstrates the feasibility of assaying psoralen levels in tissues and in serum samples using psoralen fluorescence as an indictor.

Jacques, Steven L.; Buckley, Lisa A.; Prahl, Scott A.; Gregory, Kenton W.

1994-07-01

58

The Tetraspanin CD63 Is Required for Efficient IgE-Mediated Mast Cell Degranulation and Anaphylaxis.  

PubMed

Mast cell (MC) activation through the high-affinity IgE receptor Fc?RI leads to the release of mediators involved in immediate-type allergic reactions. Although Abs against the tetraspanins CD63 and CD81 inhibit Fc?RI-induced MC degranulation, the intrinsic role of these molecules in Fc?RI-induced MC activation is unknown. In MCs, CD63 is expressed at the cell surface and in lysosomes (particularly secretory lysosomes that contain allergic mediators). In this study, we investigated the role of CD63 in MC using a CD63 knockout mouse model. CD63-deficiency did not affect in vivo MC numbers and tissue distribution. Bone marrow-derived MC developed normally in the absence of CD63 protein. However, CD63-deficient bone marrow-derived MC showed a significant decrease in Fc?RI-mediated degranulation, but not PMA/ionomycin-induced degranulation, as shown by ?-hexosaminidase release assays. The secretion of TNF-?, which is both released from granules and synthesized de novo upon MC activation, was also decreased. IL-6 secretion and production of the lipid mediator leukotriene C4 were unaffected. There were no ultrastructural differences in granule content and morphology, late endosomal/lysosomal marker expression, Fc?RI-induced global tyrosine phosphorylation, and Akt phosphorylation. Finally, local reconstitution in genetically MC-deficient Kit(w/w-v) mice was unaffected by the absence of CD63. However, the sites reconstituted with CD63-deficient MC developed significantly attenuated cutaneous anaphylactic reactions. These findings demonstrate that the absence of CD63 results in a significant decrease of MC degranulation, which translates into a reduction of acute allergic reactions in vivo, thus identifying CD63 as an important component of allergic inflammation. PMID:23945142

Kraft, Stefan; Jouvin, Marie-Hélène; Kulkarni, Nitin; Kissing, Sandra; Morgan, Ellen S; Dvorak, Ann M; Schröder, Bernd; Saftig, Paul; Kinet, Jean-Pierre

2013-08-14

59

An Acidic Microenvironment Increases NK Cell Killing of Cryptococcus neoformans and Cryptococcus gattii by Enhancing Perforin Degranulation  

PubMed Central

Cryptococcus gattii and Cryptococcus neoformans are encapsulated yeasts that can produce a solid tumor-like mass or cryptococcoma. Analogous to malignant tumors, the microenvironment deep within a cryptococcoma is acidic, which presents unique challenges to host defense. Analogous to malignant cells, NK cells kill Cryptococcus. Thus, as in tumor defense, NK cells must kill yeast cells across a gradient from physiologic pH to less than 6 in the center of the cryptococcoma. As acidic pH inhibits anti-tumor activities of NK cells, we sought to determine if there was a similar reduction in the anticryptococcal activity of NK cells. Surprisingly, we found that both primary human NK cells and the human NK cell line, YT, have preserved or even enhanced killing of Cryptococcus in acidic, compared to physiological, pH. Studies to explore the mechanism of enhanced killing revealed that acidic pH does not increase the effector to target ratio, binding of cytolytic cells to Cryptococcus, or the active perforin content in effector cells. By contrast, perforin degranulation was greater at acidic pH, and increased degranulation was preceded by enhanced ERK1/2 phosphorylation, which is essential for killing. Moreover, using a replication defective ras1 knockout strain of Cryptococcus increased degranulation occurred during more rapid replication of the organisms. Finally, NK cells were found intimately associated with C. gattii within the cryptococcoma of a fatal infection. These results suggest that NK cells have amplified signaling, degranulation, and greater killing at low pH and when the organisms are replicating quickly, which would help maintain microbicidal host defense despite an acidic microenvironment.

Islam, Anowara; Li, Shu Shun; Oykhman, Paul; Timm-McCann, Martina; Huston, Shaunna M.; Stack, Danuta; Xiang, Richard F.; Kelly, Margaret M.; Mody, Christopher H.

2013-01-01

60

Thermal effects from degranulation of mastcells in cutaneous mastocytosis.  

PubMed

Small bipsies of the skin were taken from patients with papulo-cutaneous mastocytosis. The mast cell tumours were then degranulated with compound 48/80 (250 mug/ml in saline), and with a Sorption microcalorimeter, relatively strong exothermic reactions were measured, whereas normal skin showed only 1/10th the intensity. Disodium chromoglicate (1%) had no inhibitory effect on this thermal reaction. PMID:836433

Hellgren, L; Larsson, K

1977-01-15

61

Bullous pemphigoid. Occurrence in a patient with mycosis fungoides receiving PUVA and topical nitrogen mustard therapy  

SciTech Connect

A 57-year-old woman with mycosis fungoides developed blisters within cutaneous plaques while receiving PUVA therapy and topical nitrogen mustard. Direct and indirect immunofluorescence studies showed the findings of bullous pemphigoid. Her bullous disease was controlled after cessation of these therapies and institution of prednisone and methotrexate. During the 5 months following completion of a course of electron-beam therapy, she has been free of the cutaneous manifestations of both diseases. Previous instances of PUVA-related pemphigoid have occurred in psoriatics. The role of ultraviolet light in the induction of pemphigoid is discussed, particularly with regard to its possible interaction with the altered skin of psoriasis or mycosis fungoides. Some of the rare cases of bullous mycosis fungoides might actually have represented ultraviolet-unmasked bullous pemphigoid.

Patterson, J.W.; Ali, M.; Murray, J.C.; Hazra, T.A.

1985-04-01

62

Epidermal T lymphocytes and dendritic cells in chronic plaque psoriasis: the effects of PUVA treatment.  

PubMed Central

The numbers and HLA-DR expression of T cell subsets and dendritic cells in chronic psoriatic plaques were compared to previously reported findings in spontaneously resolving guttate lesions, and the effects of PUVA treatment on these cell populations studied. The chronic lesions showed a similar T helper/T suppressor (TH/TS) ratio (0.66 +/- 0.10) to resolving guttate lesions. However, in contrast to the resolving lesions which do not contain activated epidermal TH cells, a substantial proportion of the TH cells in the persistent plaques were DR+. Moreover, these persistent lesions contained markedly increased numbers of DR+ dendritic cells, approximately 20% of which were T6 negative. PUVA-induced resolution of chronic lesions was associated with depletion of epidermal TH and TS cells, and a subsequent reduction in DR+ dendritic cells. In each patient the rate of disappearance of both cell types correlated with the rate of resolution. Furthermore, the epidermal T cell depletion preceded the onset of clinical improvement. In contrast, significant reduction of the dendritic cells was generally not observed until the lesions were largely resolved. Dendritic cells decreased faster in uninvolved than in lesional skin and to a subnormal level. Dermal T cells also decreased during PUVA therapy but this did not show any obvious correlation with resolution of the lesions. Blood T cell levels were not significantly affected by the treatment. These findings support the concept that the initiation and maintenance of the psoriatic process requires activation of TH cells in the epidermis via interaction with antigen presenting cells. Furthermore PUVA treatment may clear psoriasis by interfering with such a mechanism through its effects on T lymphocytes. Images Fig. 1

Baker, B S; Swain, A F; Griffiths, C E; Leonard, J N; Fry, L; Valdimarsson, H

1985-01-01

63

DNA damage in human skin fibroblasts exposed to UVA light used in clinical PUVA treatment  

SciTech Connect

Human skin fibroblasts were irradiated with a clinically used UVA light source. The doses (1.1 and 3 J/cm2) were similar to those reaching the dermis during clinical PUVA treatment of psoriasis. DNA strand breaks, as determined by alkaline elution, were formed in a dose-dependent way and disappeared within 1 hr of postincubation at 37 degrees C. These findings have clinical implications since UVA-induced DNA damage may be accompanied by mutagenic and tumor promoting effects.

Bredberg, A.

1981-06-01

64

Quantitative analysis on PUVA-induced skin photodamages using optical coherence tomography  

NASA Astrophysics Data System (ADS)

Psoralen plus ultraviolet A radiation (PUVA) therapy is a very important clinical treatment of skin diseases such as vitiligo and psoriasis, but associated with an increased risk of skin photodamages especially photoaging. Since skin biopsy alters the original skin morphology and always requires an iatrogenic trauma, optical coherence tomography (OCT) appears to be a promising technique to study skin damage in vivo. In this study, the Balb/c mice had 8-methoxypsralen (8-MOP) treatment prior to UVA radiation was used as PUVA-induced photo-damaged modal. The OCT imaging of photo-damaged group (modal) and normal group (control) in vivo was obtained of mice dorsal skin at 0, 24, 48, 72 hours after irradiation respectively. And then the results were quantitatively analyzed combined with histological information. The experimental results showed that, PUVA-induced photo-damaged skin had an increase in epidermal thickness (ET), a reduction of attenuation coefficient in OCT images signal, and an increase in brightness of the epidermis layer compared with the control group. In conclusion, noninvasive high-resolution imaging techniques such as OCT may be a promising tool for photobiological studies aimed at assessing photo-damage and repair processes in vivo. It can be used to quantitative analysis of changes in photo-damaged skin, such as the ET and collagen in dermis, provides a theoretical basis for treatment and prevention of skin photodamages.

Zhai, Juan; Guo, Zhouyi; Liu, Zhiming; Xiong, Honglian; Zeng, Changchun; Jin, Ying

2009-08-01

65

Late phase bronchial obstruction following nonimmunologic mast cell degranulation.  

PubMed

Immunologic degranulation of airway mast cells after antigen inhalation produces early and late airway obstructions in allergic sheep. In this study we determined whether nonimmunologic degranulation of airway mast cells by inhalation of compound 48/80 had similar effects. In five sheep, pulmonary flow resistance (RL), thoracic gas volume (Vtg), and arterial O2 tension (Pao2) were determined prior to and at predetermined times after inhalation of 48/80 aerosol. Immediately after challenge mean specific lung resistance (sRL = RL X Vtg) increased by 259% and mean Pao2 decreased by 29%. All values returned to normal by 3 h. By 5-h postchallenge sRL again increased significantly; this second increase in sRL (92% above base line) was maximal at 7 h and was accompanied by a 17% drop in Pao2. In these same sheep inhalation of Ascaris suum antigen produced comparable early changes in sRL, but the onset of the late response was somewhat delayed and more pronounced. In a second group of sheep (n = 5), pretreatment with the mast cell stabilizer cromolyn sodium prevented both early and late responses by compound 48/80. Pretreatment with the histamine H1-antagonist chlorpheniramine had no significant effect on either response, whereas pretreatment with FPL 55712, an antagonist of slow-reacting substance of anaphylaxis (SRS-A), slightly but not significantly attenuated the early response and completely prevented the late response. We conclude that, like immunologic stimuli, nonimmunologic mast cell degranulation produces early and late bronchial obstructions in allergic sheep; that these responses are mediator dependent; and that while histamine and SRS-A contribute to the early response, it is the early appearance of SRS-A which is an important prerequisite for the late response. PMID:6209256

Russi, E W; Perruchoud, A P; Yerger, L D; Stevenson, J S; Tabak, J; Marchette, B; Abraham, W M

1984-10-01

66

Bifidobacterium suppresses IgE-mediated degranulation of rat basophilic leukemia (RBL-2H3) cells.  

PubMed

Sixteen heat-killed bifidobacteria isolated from human intestine and a probiotic strain Lactobacillus GG were tested for their ability to influence IgE-mediated degranulation of rat basophilic leukemia (RBL-2H3) cells in vitro. The bifidobacteria suppressed IgE-mediated degranulation of RBL-2H3 cells by 1.6-56.4% in a strain-dependent manner. Bifidobacteria from healthy infants expressed high inhibitory effects on IgE-mediated degranulation (41-55%), while those from allergic infants varied greatly in their effects against degranulation. Bifidobacteria taxonomically identified as Bifidobacterium bifidum exhibited much stronger inhibitory effects against IgE-mediated degranulation than those taxonomically identified as B. adolescentis (P < 0.05).These results indicate that the intestinal bifidobacteria might be one of factors influencing IgE-mediated allergic responses. PMID:20055943

Harata, Gaku; He, Fang; Takahashi, Kyoko; Hosono, Akira; Kawase, Manabu; Kubota, Akira; Hiramatsu, Masaru; Kaminogawa, Shuichi

2010-01-01

67

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

PubMed Central

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.

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

2005-01-01

68

Molecular Mechanisms of N-Formyl-Methionyl-Leucyl-Phenylalanine-Induced Superoxide Generation and Degranulation in Mouse Neutrophils: Phospholipase D Is Dispensable  

PubMed Central

Phospholipase D (PLD), which produces the lipid messenger phosphatidic acid (PA), has been implicated in superoxide generation and degranulation in neutrophils. The basis for this conclusion is the observation that primary alcohols, which interfere with PLD-catalyzed PA production, inhibit these neutrophil functions. However, off-target effects of primary alcohols cannot be totally excluded. Here, we generated PLD?/? mice in order to reevaluate the involvement of PLD in and investigate the molecular mechanisms of these neutrophil functions. Surprisingly, N-formyl-methionyl-leucyl-phenylalanine (fMLP) induced these functions in PLD?/? neutrophils, and these functions were suppressed by ethanol. These results indicate that PLD is dispensable for these neutrophil functions and that ethanol nonspecifically inhibits them, warning against the use of primary alcohols as specific inhibitors of PLD-mediated PA formation. The calcium ionophore ionomycin and the membrane-permeative compound 1-oleoyl-2-acetyl-sn-glycerol (OADG) synergistically induced superoxide generation. On the other hand, ionomycin alone induced degranulation, which was further augmented by OADG. These results demonstrate that conventional protein kinase C (cPKC) is crucial for superoxide generation, and a Ca2+-dependent signaling pathway(s) and cPKC are involved in degranulation in mouse neutrophils.

Sato, Takanobu; Hongu, Tsunaki; Sakamoto, Megumi; Funakoshi, Yuji

2013-01-01

69

Differential activation of signal transduction pathways mediating phagocytosis, oxidative burst, and degranulation by chicken heterophils in response to stimulation with opsonized Salmonella enteritidis.  

PubMed

The activation of signal transduction pathways is required for the expression of functional enhancement of cellular activities. In the present studies, initial attempts were made to identify the signal transduction factors involved in activating phagocytosis, generation of an oxidative burst, and degranulation by heterophils isolated from neonatal chickens in response to opsonized Salmonella enteritidis (opsonized SE). Peripheral blood heterophils were isolated and exposed to known inhibitors of signal transduction pathways for either 20 min (staurosporin, genistein, or verapamil) or 120 min (pertussis toxin) at 39 degrees C. The cells were then stimulated for 30 min at 39 degrees C with opsonized SE. Phagocytosis, luminol-dependent chemoluminescence (LDCL), and beta-D glucuronidase release were then evaluated in vitro. The G-protein inhibitor pertussin toxin markedly inhibited (>80%) phagocytosis of opsonized SE. Both the protein kinase inhibitor (staurosporin) and calcium channel inhibitor (verapamil) reduced phagocytosis in a dose response manner. Genistein, a tyrosine kinase inhibitor, had no effect on phagocytosis. Staurosporin had a marked inhibitory effect on LDCL (>90%) while genistein had a dose responsive inhibition on LDCL. Both verapamil (40-45%) and pertussin toxin (50-55%) had a statistically significant, but less biologically significant effect on LDCL. Genistein significantly reduced the degranulation (78-81%) of heterophils by opsonized SE. Staurosporin also reduced degranulation by 43-50%, but neither verapamil nor pertussis toxin had a significant effect on degranulation. These findings demonstrate that distinct signal transduction pathways differentially regulate the stimulation of the functional activities of avian heterophils. Pertussin toxin-sensitive, Ca++-dependent G-proteins appear to regulate phagocytosis of opsonized SE, protein kinase C-dependent, tyrosine kinase-dependent protein phosphorylation plays a major role in LDCL, and tyrosine kinase(s)-dependent phosphorylation regulates primary granule release. PMID:11293667

Kogut, M H; Genovese, K J; Lowry, V K

2001-02-01

70

E-prostanoid 2 receptors dampen mast cell degranulation via cAMP/PKA-mediated suppression of IgE-dependent signaling.  

PubMed

The experimental administration of PGE(2) for the treatment of asthma dampens clinical symptoms, and similar efficacy has been found in dust mite-induced hypersensitivity reactions in animal models. Here, we investigate the mechanism by which PGE(2) mediates suppression of MC degranulation. We find that the effect of PGE(2) on Fc?RI-dependent MC degranulation varies from activating to suppressing, depending on the relative ratio of EP(2) to EP(3) expression on these cells with suppression evident only in cells having increased EP(2) to EP(3) expression. Consistent with a role for EP(2) in suppressing MC responses in vitro, we found that a selective EP(2) agonist, Butaprost, inhibited MC-mediated Fc?RI-induced immediate hypersensitivity in a model of PCA. EP(2) engagement on MCs increased cAMP production and inhibited Fc?RI-mediated calcium influx. In addition, it also decreased the extent of Fc?RI-induced Fyn kinase activity, leading to decreased phosphorylation of key signaling molecules such as Gab2 and Akt. Treatment with an antagonist of cAMP or shRNA down-regulation of PKA (the principal intracellular target of cAMP) reversed the EP(2)-mediated inhibitory effect on MC degranulation and restored calcium influx and phosphorylation of Akt. Collectively, the findings demonstrate that EP(2) suppresses the Fyn-mediated signals that are central to Fc?RI-dependent MC degranulation, suggesting that engagement of the EP(2) on MCs may be beneficial in dampening allergic responses. PMID:22859831

Serra-Pages, Mariona; Olivera, Ana; Torres, Rosa; Picado, César; de Mora, Fernando; Rivera, Juan

2012-08-02

71

Technical Advance: Soluble OX40 molecule mimics regulatory T cell modulatory activity on Fc?RI-dependent mast cell degranulation  

PubMed Central

Tregs play a central role in modulating Fc?RI-dependent MC effector functions in the course of the allergic response. Cellular interaction depends on the constitutive expression of OX40 on Tregs and the OX40L counterpart on MCs. Study of OX40L signaling on MCs is hampered by the need of a highly purified molecule, which triggers OX40L specifically. We now report that sOX40 mimics the physiological activity of Treg interaction by binding to activated MCs. When treated with sOX40, activated MCs showed decreased degranulation and Ca++ influx, whereas PLC-?2 phosphorylation remained unaffected. Once injected into experimental animals, sOX40 not only located within the endothelium but also in parenchyma, where it could be found in close proximity and apparently bound to MCs. This soluble molecule triggers MC-OX40L without the requirement of Tregs, thus allowing study of OX40L signaling pathways in MCs and in other OX40L-expressing cell populations. Importantly, as sOX40 inhibits MC degranulation, it may provide an in vivo therapeutic tool in allergic disease.

Sibilano, Riccardo; Gri, Giorgia; Frossi, Barbara; Tripodo, Claudio; Suzuki, Ryo; Rivera, Juan; MacDonald, Andrew S.; Pucillo, Carlo E.

2011-01-01

72

Cutaneous and ocular side-effects of PUVA photochemotherapy--a 10-year follow-up study.  

PubMed

To record the potentially serious side-effects of melanoma and non-melanoma skin cancers and ocular damage following long-term PUVA chemotherapy, we re-examined 198 of 242 patients. These comprised: 90 with psoriasis, 27 with parapsoriasis, 19 with cutaneous T-cell lymphoma, 23 with vitiligo, eight with cutaneous mastocytosis, 16 with atopic dermatitis, three with prurigo nodularis, two with polymorphous light eruption and 10 with pruritus of chronic renal failure on dialysis, treated between 1977 and 1987 in our department. During the 10-year period, 11 patients died of unrelated disease. None of the patients reviewed had previous skin cancer or had been treated with arsenic, methotrexate or ionizing irradiation before PUVA treatment. None of the patients were children under 16 years of age. The mean age was 54.5 years, the sex ratio 102:96 (M:F). The mean cumulative dose of UVA for the whole group was 169.5 J/cm2. One patient with psoriasis, psoriatic arhropathy, ankylosing spondylitis and Crohn's disease, who was on azathioprine for 6 years, developed squamous-cell carcinoma on the left lower leg. Another patient with pustular psoriasis, who received PUVA treatment to her palms and soles only, developed malignant lentigo of Hutchinson on the right lower leg. PUVA lentigines were found in about 20% of patients. All patients had a yearly ophthalmological examination. None of them developed cataracts, lens opacities or had impairment of their visual acuity. PMID:2691134

Abdullah, A N; Keczkes, K

1989-11-01

73

Dissociation of the 47-Kilodalton Protein Phosphorylation From Degranulation and Superoxide Production in Neutrophils  

Microsoft Academic Search

The aim for the present studies is to examine the relationship between the phosphory- lation of the 47-kDa protein and some neutrophil responses such as degranulation, the synergistic effect of PMA on calcium lonophore-induced degranulation, superoxide generation, and the priming of the oxidative burst produced by the chemotactic factor fMet-Leu-Phe and phorbol 12-myristate 13-acetate (PMA). incubation of neutrophils with the

T. F. P. Molski; J. Gomez-Cambronero; C.-K. Huang

1988-01-01

74

The src Homology 2-Containing Inositol Phosphatase (SHIP) is the Gatekeeper of Mast Cell Degranulation  

Microsoft Academic Search

To clarify the role that the src homology 2-containing inositol phosphatase (SHIP) plays in mast cell degranulation, the gene for SHIP was disrupted by homologous recombination in embryonic stem cells. Bone-marrow-derived mast cells from SHIP+\\/+, +\\/-, and -\\/- F2 littermates were compared. SHIP-\\/- mast cells were found to be far more prone to degranulation, after the crosslinking of IgE preloaded

Michael Huber; Cheryl D. Helgason; Jacqueline E. Damen; Ling Liu; R. Keith Humphries; Gerald Krystal

1998-01-01

75

Mast cell degranulation requires N-ethylmaleimide-sensitive factor-mediated SNARE disassembly.  

PubMed

Mast cells possess specialized granules that, upon stimulation of surface FcR with IgE, fuse with the plasma membrane, thereby releasing inflammatory mediators. A family of membrane fusion proteins called SNAREs, which are present on both the granule and the plasma membrane, plays a role in the fusion of these granules with the plasma membrane of mast cells. In addition to the SNAREs themselves, it is likely that the SNARE accessory protein, N-ethylmaleimide-sensitive factor (NSF), affects the composition and structure of the SNARE complex. NSF is a cytoplasmic ATPase that disassembles the SNARE complexes. To investigate the role of NSF in mast cell degranulation, we developed an assay to measure secretion from transiently transfected RBL (rat basophilic leukemia)-2H3 mast cells (a tumor analog of mucosal mast cells). RBL-2H3 cells were cotransfected with a plasmid encoding a human growth hormone secretion reporter along with either wild-type NSF or an NSF mutant that lacks ATPase activity. Human growth hormone was targeted to and released from secretory granules in RBL-2H3 cells, and coexpression with mutant NSF dramatically inhibited regulated exocytosis from the transfected cells. Biochemical analysis of SNARE complexes in these cells revealed that overexpression of the NSF mutant decreased disassembly and resulted in an accumulation of SNARE complexes. These data reveal a role for NSF in mast cell exocytosis and highlight the importance of SNARE disassembly, or priming, in regulated exocytosis from mast cells. PMID:14607937

Puri, Niti; Kruhlak, Michael J; Whiteheart, Sidney W; Roche, Paul A

2003-11-15

76

Measurement of 5-methoxypsoralen and 8-methoxypsoralen in saliva of PUVA patients as a noninvasive, clinically relevant alternative to monitoring in blood  

Microsoft Academic Search

\\u000a Abstract\\u000a Background: Monitoring of psoralen concentration and time-course in PUVA patients is vital for efficient PUVA therapy. Blood sampling\\u000a is invasive and labour-intensive and thus unsuited for routine use and repeat measurements over the course of therapy. Objective: Psoralen pharmacokinetics in saliva were investigated and validated as a noninvasive, simple and biologically relevant alternative\\u000a to measurements in blood. Methods: The

Sarah E. Shephard; Marianne Zogg; Günter Burg; Renato G. Panizzon

1999-01-01

77

Luminol-dependent photoemission from single neutrophil stimulated by phorbol ester and calcium ionophore--role of degranulation and myeloperoxidase  

SciTech Connect

Luminol-dependent photonic burst from phorbol ester-treated single neutrophil was visually investigated by using an ultrasensitive photonic image intensifier microscope. Neutrophils stimulated by phorbol myristate acetate (0.1 microgram/ml) alone produced a negligible level of photonic activities in the presence of luminol (10 micrograms/ml). The additional application of 0.1 microM Ca2+ ionophore A23187 induced explosive changes of photonic burst corresponding to the distribution of neutrophils, and these photonic activities were gradually spread to extracellular space. Sodium azide, which prevents myeloperoxidase activity, inhibited Ca2+ ionophore-induced photonic burst from phorbol ester-treated neutrophil. These findings suggest a prerequisite role of degranulation and myeloperoxidase release in luminol-dependent photoemission from stimulated neutrophils.

Suematsu, M.; Oshio, C.; Miura, S.; Suzuki, M.; Houzawa, S.; Tsuchiya, M.

1988-08-30

78

Mast cell degranulation - a mechanism for the anti-arrhythmic effect of endothelin-1?  

PubMed Central

Background and purpose: The aim of this study was to investigate whether the previously reported anti-arrhythmic effect of endothelin-1 (ET-1) is mediated by degranulation of cardiac mast cells prior to myocardial ischaemia. Experimental approach: Male Sprague-Dawley rats received either ET-1 (1.6 nmol·kg?1) in the presence or absence of disodium cromoglycate (DSCG; 20 mg·kg?1·h?1) prior to coronary artery occlusion (CAO). In separate experiments rats were given compound 48/80 (50 µg·kg?1) to compare the effects of ET-1 with those of a known mast cell degranulator. Ischaemia-induced ventricular arrhythmias were detected through continuous monitoring of a lead I electrocardiogram. After 30 min of CAO, the hearts were removed and mast cell degranulation determined by histological analysis. A parallel series of sham groups were performed to determine the direct effects of ET-1 and compound 48/80 on mast cell degranulation in the absence of ischaemia. Key results: ET-1 and compound 48/80 both exerted profound anti-arrhythmic effects, significantly reducing the total number of ventricular ectopic beats (P < 0.001) and the incidence of ventricular fibrillation (P < 0.05). These anti-arrhythmic effects were abolished by concomitant DSCG infusion prior to CAO. In sham animals ET-1 and compound 48/80 both induced mast cell degranulation (P < 0.001), an effect which was abolished by DSCG, confirming their ability to induce degranulation of mast cells. Conclusions and implications: These results demonstrate for the first time that when given prior to ischaemia ET-1 mediates its anti-arrhythmic effects, at least in part, via cardiac mast cell degranulation.

Walsh, SK; Kane, KA; Wainwright, CL

2009-01-01

79

Modulation of human neutrophil oxidative metabolism and degranulation by extract of Tamarindus indica L. fruit pulp.  

PubMed

The tamarind (Tamarindus indica L.) is indigenous to Asian countries and widely cultivated in the American continents. The tamarind fruit pulp extract (ExT), traditionally used in spices, food components and juices, is rich in polyphenols that have demonstrated anti-atherosclerotic, antioxidant and immunomodulatory activities. This study evaluated the modulator effect of a crude hydroalcoholic ExT on some peripheral human neutrophil functions. The neutrophil reactive oxygen species generation, triggered by opsonized zymosan (OZ), n-formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol myristate acetate (PMA), and assessed by luminol- and lucigenin-enhanced chemiluminescence (LumCL and LucCL, respectively), was inhibited by ExT in a concentration-dependent manner. ExT was a more effective inhibitor of the PMA-stimulated neutrophil function [IC50 (in microg/10(6)cells)=115.7+/-9.7 (LumCL) and 174.5+/-25.9 (LucCL)], than the OZ- [IC50=248.5+/-23.1 (LumCL) and 324.1+/-34.6 (LucCL)] or fMLP-stimulated cells [IC50=178.5+/-12.2 (LumCL)]. The ExT also inhibited neutrophil NADPH oxidase activity (evaluated by O2 consumption), degranulation and elastase activity (evaluated by spectrophotometric methods) at concentrations higher than 200 microg/10(6)cells, without being toxic to the cells, under the conditions assessed. Together, these results indicate the potential of ExT as a source of compounds that can modulate the neutrophil-mediated inflammatory diseases. PMID:19022329

Paula, Fabiana S; Kabeya, Luciana M; Kanashiro, Alexandre; de Figueiredo, Andréa S G; Azzolini, Ana Elisa C S; Uyemura, Sérgio A; Lucisano-Valim, Yara Maria

2008-11-03

80

Structures of new flavonoids and benzofuran-type stilbene and degranulation inhibitors of rat basophilic leukemia cells from the Brazilian herbal medicine Cissus sicyoides.  

PubMed

Three new flavonoid glycosides (cissosides I, II, and III) and a new benzofuran-type stilbene (cissusin) were isolated from the methanolic extract of the aerial parts of Cissus sicyoides cultivated in Brazil. Their structures were elucidated on the basis of chemical and physicochemical evidence. The inhibitory effects of the isolated constituents on the release of beta-hexosaminidase as a marker of degranulation in rat basophilic leukemia (RBL-2H3) cells were examined. Cissusin, flavonols (kaempferol, quercetin), flavones (7,3',4'-trihydroxyflavone, lanceolatin B), pterocarpanes (homopterocarpin), chalcones (isoliquiritigenin, E-7-O-methylpongamol), and tryptanthrin markedly inhibited the release of beta-hexosaminidase. PMID:19801863

Xu, Fengming; Matsuda, Hisashi; Hata, Hiroki; Sugawara, Kaoru; Nakamura, Seikou; Yoshikawa, Masayuki

2009-10-01

81

Systemic mast cell degranulation increases mortality during polymicrobial septic peritonitis in mice.  

PubMed

MCs are required for an effective host response during septic peritonitis. Local MC degranulation facilitates neutrophil recruitment, activation, and bacterial killing. However, the role of MCs located distant from the site of infection is unknown. We studied the temporal and spacial degranulation of MCs following CLP-induced septic peritonitis. The functional importance of systemic MC degranulation during infection was evaluated by compartment-specific MC reconstitution. Serum histamine, reflecting MC degranulation, was elevated 4 h after onset of septic peritonitis. Histologic examination revealed progressive MC degranulation in select tissues during the first 24 h of infection. MC-deficient Wsh mice, reconstituted only in the peritoneal compartment, had improved survival after CLP compared with controls. However, reconstitution in peritoneal plus systemic compartments worsened survival after CLP. IL-6 contributed to the detrimental effects of systemic MCs on survival, as mice systemically reconstituted with IL-6(-/-) MCs were more likely to survive than control mice. These results indicate that in contrast to the benefits of local MC activation during infection, systemic MC activation worsens survival during CLP-induced sepsis. PMID:21653231

Seeley, Eric J; Sutherland, Rachel E; Kim, Sophia S; Wolters, Paul J

2011-06-07

82

Fibronectin degradation products containing the cytoadhesive tetrapeptide stimulate human neutrophil degranulation.  

PubMed Central

We investigated whether adhesive glycoproteins, such as fibronectin or fibrinogen, could function to provide a nidus for neutrophil degranulation. Elastase release in recalcified plasma was normal in afibrinogenemic plasma, but 73% less in plasma depleted of fibronectin. Proteolytic digests of fibronectin, but not intact fibronectin (50-1,000 micrograms/ml), induced a concentration-dependent release of neutrophil elastase and lactoferrin. MAbs N293, which recognized the mid-molecule of fibronectin, N294, which was directed toward the 11-kD cell adhesive fragment, and N295, generated against the amino terminal of the 11-kD fragment, inhibited the release of elastase by 7, 24, and 60%, respectively. The cytoadhesive tetrapeptide portion of fibronectin, Arg-Gly-Asp-Ser (250-1,000 micrograms/ml), released 1.94 +/- 0.10 micrograms/ml of elastase from 10(7) neutrophils, in contrast to the lack of release by the control hexapeptide, Arg-Gly-Tyr-Ser-Leu-Gly. Plasmin appeared to be the enzyme responsible for fibronectin cleavage, since neutrophil elastase release in plasma that had been depleted of plasminogen was decreased and reconstitution of plasminogen-deficient plasma with purified plasminogen corrected the abnormal release. Plasmin cleaved fibronectin to multiple degradation products, each less than 200 kD. This fibronectin digest released 1.05 microgram/ml of elastase from 10(7) neutrophils. We suggest that the activation of plasminogen leads to the formation of fibronectin degradation products capable of functioning as agonists for neutrophils. Images

Wachtfogel, Y T; Abrams, W; Kucich, U; Weinbaum, G; Schapira, M; Colman, R W

1988-01-01

83

Effects of in vitro UVA irradiation and PUVA treatment on membrane fatty acids and activities of antioxidant enzymes in human keratinocytes  

SciTech Connect

Human Keratinocytes (NCTC 2544) in culture were exposed to either plain ultraviolet A (UVA) irradiation or to 8-methoxypsoralen plus UVA (PUVA) treatment. Lipid peroxidation, activities of antioxidant enzymes, and percentage amounts of 14C-arachidonic acid in various cellular lipid subclasses and in the culture medium were measured. Both UVA irradiation and PUVA treatment induced significant changes in the distribution of arachidonic acid and increased the liberation of arachidonic acid from membrane phospholipids. At 24 h after either UVA irradiation or PUVA treatment the formation of thiobarbituric acid reactive material was significantly increased, whereas the amount of conjugated dienes was unaffected. The activities of the antioxidant enzymes, catalase and superoxide dismutase, were already significantly decreased at 0.5 h after UVA irradiation or PUVA treatment. The enzyme activities were partially restored during the following 24 h incubation. From the present study, we suggest that in keratinocytes both plain UVA irradiation and PUVA treatment induce changes in the distribution of membrane fatty acids and cause an impairment in the enzymic defense system against oxidative stress.

Punnonen, K.; Jansen, C.T.; Puntala, A.; Ahotupa, M. (Univ. of Turku (Finland))

1991-02-01

84

Sulfur mustard primes human neutrophils for increased degranulation and stimulates cytokine release via TRPM2/p38 MAPK signaling.  

PubMed

Sulfur mustard (2,2'-bis-chloroethyl-sulfide; SM) has been a military threat since the World War I. The emerging threat of bioterrorism makes SM a major threat not only to military but also to civilian world. SM injury elicits an inflammatory response characterized by infiltration of neutrophils. Although SM was reported to prime neutrophils, the mechanism has not been identified yet. In the present study, we investigated the mechanism of SM-induced priming in human neutrophils. SM increased [Ca(2+)](i) in human neutrophils in a concentration-dependent fashion. Transient receptor potential melastatin (TRPM) 2 inhibitors (clotrimazole, econazole and flufenamic acid) and silencing of TRPM2 by shRNA attenuated SM-induced [Ca(2+)](i) increase. SM primed degranulation of azurophil and specific granules in response to activation by fMLP as previously reported. SB203580, an inhibitor of p38 MAPK, inhibited SM-induced priming. Neither PD98057, an ERK inhibitor, nor SP600215, a JNK inhibitor, inhibited SM-induced priming. In addition, SM enhanced phosphorylation of NF-kB p65 and release of TNF-?, interleukin (IL)-6 and IL-8. SB203580 inhibited SM-induced NF-kB phosphorylation and cytokine release. These results suggest the involvement of TRPM2/p38 MAPK pathway in SM-induced priming and cytokines release in neutrophils. PMID:22036725

Ham, Hwa-Yong; Hong, Chang-Won; Lee, Si-Nae; Kwon, Min-Soo; Kim, Yeon-Ja; Song, Dong-Keun

2011-10-18

85

Degranulating mast cells in fibrotic regions of human tumors and evidence that mast cell heparin interferes with the growth of tumor cells through a mechanism involving fibroblasts  

PubMed Central

Background The purpose of this study was to test the hypothesis that mast cells that are present in fibrotic regions of cancer can suppress the growth of tumor cells through an indirect mechanism involving peri-tumoral fibroblasts. Methods We first immunostained a wide variety of human cancers for the presence of degranulated mast cells. In a subsequent series of controlled in vitro experiments, we then co-cultured UACC-812 human breast cancer cells with normal fibroblasts in the presence or absence of different combinations and doses of mast cell tryptase, mast cell heparin, a lysate of the human mast cell line HMC-1, and fibroblast growth factor-7 (FGF-7), a powerful, heparin-binding growth factor for breast epithelial cells. Results Degranulating mast cells were localized predominantly in the fibrous tissue of every case of breast cancer, head and neck cancer, lung cancer, ovarian cancer, non-Hodgkin's lymphoma, and Hodgkin's disease that we examined. Mast cell tryptase and HMC-1 lysate had no significant effect on the clonogenic growth of cancer cells co-cultured with fibroblasts. By contrast, mast cell heparin at multiple doses significantly reduced the size and number of colonies of tumor cells co-cultured with fibroblasts, especially in the presence of FGF-7. Neither heparin nor FGF-7, individually or in combination, produced any significant effect on the clonogenic growth of breast cancer cells cultured without fibroblasts. Conclusion Degranulating mast cells are restricted to peri-tumoral fibrous tissue, and mast cell heparin is a powerful inhibitor of clonogenic growth of tumor cells co-cultured with fibroblasts. These results may help to explain the well-known ability of heparin to inhibit the growth of primary and metastatic tumors.

Samoszuk, Michael; Kanakubo, Emi; Chan, John K

2005-01-01

86

Atypical mast cell degranulation and focal hydropic degeneration of venular endothelium in diffuse fibrosing alveolitis  

Microsoft Academic Search

Summary Atypical scroll-like and tubular degranulation of mast cells closely associated with focal endothelial hydropic degeneration is reported in human lung from 4 patients with diffuse fibrosing alveolitis in which the predominant abnormality was hyperplasia and desquamation of type 2 pneumocytes.

A. W. J. Lykke; M. E. Schonell; B. W. Stewart

1979-01-01

87

Neutrophil degranulation and cell lysis is associated with clinical severity in virus-induced asthma  

Microsoft Academic Search

Acute exacerbations of asthma are frequently caused by viral infections, but the inflammatory mechanisms in virus-induced asthma are poorly understood. The aim of the present study was to determine whether viral infection in acute asthma was associated with increased sputum neutrophil degranulation and increased cellular lysis and whether these changes are related to clinical severity. Adults (n=49) presenting to the

P. A. B. Wark; S. L. Johnston; I. Moric; J. L. Simpson; M. J. Hensley; P. G. Gibson

2002-01-01

88

Citrate anticoagulation abolishes degranulation of polymorphonuclear cells and platelets and reduces oxidative stress during haemodialysis  

Microsoft Academic Search

Background. During haemodialysis (HD), polymor- phonuclear cells (PMNs) and platelets are activated and release various granule products, including myeloperoxidase (MPO) and platelet factor 4 (PF4). MPO triggers the generation of reactive oxygen species, leading to irreversible protein, carbohydrate and lipid modification. PF4 probably also contributes to oxidative stress. As previously shown, HD-induced PMN degranulation is almost completely abolished during citrate

Mareille Gritters; Muriel P. C. Grooteman; Margreet Schoorl; Marianne Schoorl; Piet C. M. Bartels; Peter G. Scheffer; Tom Teerlink; Casper G. Schalkwijk; Marieke Spreeuwenberg; Menso J. Nube

2005-01-01

89

Diesel exhaust particulates enhance eosinophil adhesion to nasal epithelial cells and cause degranulation.  

PubMed

Diesel exhaust particulates (DEP) are a common air pollutant from diesel-engine-powered car exhaust and are thought to cause chronic airway diseases. On the other hand, eosinophils are major components of allergic inflammatory disorders such as asthma, nasal allergy and atopic dermatitis. We examined the effects of DEP and DEP extract (extract of polyaromatic hydrocarbons) on eosinophil adhesion, survival rate and degranulation. Eosinophils, human mucosal microvascular endothelial cells (HMMECs) and human nasal epithelial cells (HNECs) were preincubated in the presence or absence of DEP and DEP extract. 35S-labeled eosinophils were allowed to adhere to monolayers of HMMECs and HNECs. After washing, 35S radioactivity was determined and numbers of adherent eosinophils were calculated using each standard curve. The effects of DEP and DEP extract on eosinophil survival rate and degranulation were also determined. Although neither DEP nor DEP extract affected the adhesiveness of HMMECs and HNECs to eosinophils, 5 ng/ml of DEP extract and 50 ng/ml of DEP extract each significancy increased eosinophil adhesiveness to HNECs (134+/-9 and 143+/-8%, respectively; p<0.01 vs. control), but neither effected eosinophil adhesiveness to HMMECs. DEP extract also induced eosinophil degranulation without changing the eosinophil survival rate. Given that eosinophil-derived lipid mediators and toxic proteins play important roles in the development of nasal allergy, the above findings strongly suggest that DEP plays an important role in promoting the nasal hypersensitivity induced by enhanced eosinophil infiltration of epithelium and eosinophil degranulation. PMID:9338611

Terada, N; Maesako, K; Hiruma, K; Hamano, N; Houki, G; Konno, A; Ikeda, T; Sai, M

1997-10-01

90

Mast cell function: Regulation of degranulation by serine\\/threonine phosphatases  

Microsoft Academic Search

Mast cells play both effector and modulatory roles in a range of allergic and immune responses. The principal function of these cells is the release of inflammatory mediators from mast cells by degranulation, which involves a complex interplay of signalling molecules. Understanding the molecular architecture underlying mast cell signalling has attracted renewed interest as the capacity for therapeutic intervention through

Alistair T. R. Sim; Russell I. Ludowyke; Nicole M. Verrills

2006-01-01

91

Replication study concerning the effects of homeopathic dilutions of histamine on human basophil degranulation in vitro  

Microsoft Academic Search

Summary Background: Various investigators have observed significant effects of highly diluted histamine on human basophil degranulation in vitro, compared to corresponding water controls. However, active and inactive dilution levels differed in most studies. Objective: We aimed to reproduce former studies with flow-cytometry usingrig or- ously controlled experimental conditions to minimise confoundingfactors. Methods: In seven independent experiments, basophils of the same

Adrian G. Guggisberg; Stephan M. Baumgartner; Cornelia M. Tschoppb; Peter Heusser

2005-01-01

92

CPG-OLIGODEOXYNUCLEOTIDE-STIMULATED CHICKEN HETEROPHIL DEGRANULATION IS SERUM COFACTOR- AND CELL SURFACE RECEPTOR-DEPENDENT  

Technology Transfer Automated Retrieval System (TEKTRAN)

Synthetic oligodeoxynucleotide containing unmethylated CpG motif (CpG-ODN) is immune stimulatory to chicken heterophils. Recognition of CpG-ODN by chicken heterophils leads to the mobilization and release of granules. This CpG-ODN-induced heterophil degranulation was chicken serum (CS)-dependent. ...

93

CPG-OLIGODEOXYNUCLEOTIDE-STIMULATED CHICKEN HETEROPHIL DEGRANULATION IS SERUM COFACTOR AND CELL SURFACE RECEPTOR DEPENDENT  

Technology Transfer Automated Retrieval System (TEKTRAN)

Synthetic oligodeoxynucleotide containing unmethylated CpG motif (CpG-ODN) is stimulatory to chicken heterophils. Recognition of CpG-ODN by chicken heterophils leads to the mobilization and release of granules. This CpG-ODN-induced heterophil degranulation was serum-dependent. Removal of chicken ...

94

Ultraviolet B irradiation of skin induces mast cell degranulation and release of tumour necrosis factor-?  

Microsoft Academic Search

In the ‘sunburn’ response in skin, dermal blood vessels are activated and traffic of dendritic Langerhans' cells altered. While these changes have been attributed to the cytokine TNF-?, the source of this acutely released TNF has not been identified. This report demonstrates that the ‘sunburn’ response, both in vivo and in vitro, is accompanied by rapid degranulation of cutaneous mast

Laurence J Walsh

1995-01-01

95

Immature DC isolated after co-culture with PUVA-treated peripheral blood mononuclear cells downregulate graft-versus-host reactions in the human skin explant model.  

PubMed

Graft-versus-host disease (GvHD) remains the major barrier to successful allogeneic hematopoietic stem cell transplantation (HSCT). Extracorporeal photopheresis (ECP) is a potent immunomodulatory treatment option for GvHD. In contrast to conventional immunosuppressants, ECP is considered not to increase relapse and infection rates resulting from generalised immunosuppression. ECP involves the mechanical separation of 5-10% of patient peripheral blood mononuclear cells, which are then exposed to psoralen and UVA light (PUVA) before they are returned to the patient. ECP has been shown to induce apoptosis in various cell types, in particular lymphocytes. Several studies describe downregulation of pro-inflammatory cytokines as well as promotion of peripheral tolerance through enhanced production of T regulatory cells in the course of ECP-treatment. Modulation of antigen-presenting cells such as dendritic cells (DC) by PUVA-treated lymphocytes might be implicated in these regulatory processes. We evaluated the impact of PUVA-treated lymphocytes on immature DC and further demonstrated the functional capacity of such modified DC to modulate GVH reactions using a well-established human skin-explant model of GvHD. Addition of immature DC isolated after co-culture with PUVA-treated but not untreated MLR cells significantly downregulated skin-GvH reactions (p=0.023, Mann-Whitney-Test). IFN-gamma levels were non-significantly decreased in MLR and skin supernatants. We observed a non-significant increase in PD-L1 expression in iDC after co-culture with PUVA-treated MLR cells whereas expression levels of IDO and ILT-3 were not affected. We conclude that iDC modulated by PUVA-induced apoptotic cells potently downregulate allogeneic immune responses possibly through PD-L1- dependent signaling. PMID:23363467

Holtick, Udo; Wang, Xiao N; Marshall, Scott R; Scheid, Christof; von Bergwelt-Baildon, Michael; Dickinson, Anne M

2013-07-01

96

Defective degranulation and calcium mobilization of bone-marrow derived mast cells from Xid and Btk-deficient mice  

Microsoft Academic Search

Regulation of adhesion and degranulation of mast cells plays an important role in allergy and inflammation. We investigated a possible role of Bruton's tyrosine kinase (Btk) in the regulation of adhesion and degranulation by using bone marrow-derived mast cells from X-linked immunodeficiency (Xid) and Btk-deficient mice. Cross-linking of the high affinity IgE receptor (Fc?RI) and steel factor (SLF) induced indistinguishable

Ruri Setoguchi; Tatsuo Kinashi; Hiroshi Sagara; Kazushige Hirosawa; Kiyoshi Takatsu

1998-01-01

97

Role of Complement Activation and Mast Cell Degranulation in the Pathogenesis of Rapid Intestinal Ischemia\\/Reperfusion Injury in Rats  

Microsoft Academic Search

The aim of this study is to define the putative role of complement activation and mucosal mast cell (MMC) degranulation in the pathogenesis of rapid ischemia-reperfusion (I\\/R) injury. We prepared complement activity-depleted rats by the administration of the anti-complementary agent K-76COONa. To assess the role of MMC degranulation, we used the MMC stabilizer MAR-99 and genetically mast cell-deficient Ws\\/Ws rats.

Akira Andoh; Yoshihide Fujiyama; Yoshio Araki; Toshio Kimura; Tomoyuki Tsujikawa; Tadao Bamba

2001-01-01

98

UVA/UVA1 phototherapy and PUVA photochemotherapy in connective tissue diseases and related disorders: a research based review  

PubMed Central

Background Broad-band UVA, long-wave UVA1 and PUVA treatment have been described as an alternative/adjunct therapeutic option in a number of inflammatory and malignant skin diseases. Nevertheless, controlled studies investigating the efficacy of UVA irradiation in connective tissue diseases and related disorders are rare. Methods Searching the PubMed database the current article systematically reviews established and innovative therapeutic approaches of broad-band UVA irradiation, UVA1 phototherapy and PUVA photochemotherapy in a variety of different connective tissue disorders. Results Potential pathways include immunomodulation of inflammation, induction of collagenases and initiation of apoptosis. Even though holding the risk of carcinogenesis, photoaging or UV-induced exacerbation, UVA phototherapy seems to exhibit a tolerable risk/benefit ratio at least in systemic sclerosis, localized scleroderma, extragenital lichen sclerosus et atrophicus, sclerodermoid graft-versus-host disease, lupus erythematosus and a number of sclerotic rarities. Conclusions Based on the data retrieved from the literature, therapeutic UVA exposure seems to be effective in connective tissue diseases and related disorders. However, more controlled investigations are needed in order to establish a clear-cut catalogue of indications.

Breuckmann, Frank; Gambichler, Thilo; Altmeyer, Peter; Kreuter, Alexander

2004-01-01

99

c-kit receptor signaling through its phosphatidylinositide-3'-kinase-binding site and protein kinase C: role in mast cell enhancement of degranulation, adhesion, and membrane ruffling.  

PubMed Central

In bone marrow-derived mast cells (BMMCs), the Kit receptor tyrosine kinase mediates diverse responses including proliferation, survival, chemotaxis, migration, differentiation, and adhesion to extracellular matrix. In connective tissue mast cells, a role for Kit in the secretion of inflammatory mediators has been demonstrated as well. We recently demonstrated a role for phosphatidylinositide-3' (PI 3)-kinase in Kit-ligand (KL)-induced adhesion of BMMCs to fibronectin. Herein, we investigated the mechanism by which Kit mediates enhancement of Fc epsilon RI-mediated degranulation, cytoskeletal rearrangements, and adhesion in BMMCs. Wsh/Wsh BMMCs lacking endogenous Kit expression, were transduced to express normal and mutant Kit receptors containing Tyr-->Phe substitution at residues 719 and 821. Although the normal Kit receptor fully restored KL-induced responses in Wsh/Wsh BMMCs, Kit gamma 719F, which fails to bind and activate PI 3-kinase, failed to potentiate degranulation and is impaired in mediating membrane ruffling and actin assembly. Inhibition of PI 3-kinase with wortmannin or LY294002 also inhibited secretory enhancement and cytoskeletal rearrangements mediated by Kit. In contrast, secretory enhancement and adhesion stimulated directly through protein kinase C (PKC) do not require PI 3-kinase. Calphostin C, an inhibitor of PKC, blocked Kit-mediated adhesion to fibronectin, secretory enhancement, membrane ruffling, and filamentous actin assembly. Although cytochalasin D inhibited Kit-mediated filamentous actin assembly and membrane ruffling, secretory enhancement and adhesion to fibronectin were not affected by this drug. Therefore, Kit-mediated cytoskeletal rearrangements that are dependent on actin polymerization can be uncoupled from the Kit-mediated secretory and adhesive responses. Our results implicate receptor-proximal PI 3-kinase activation and activation of a PKC isoform in Kit-mediated secretory enhancement, adhesion, and cytoskeletal reorganization. Images

Vosseller, K; Stella, G; Yee, N S; Besmer, P

1997-01-01

100

Suction Blister Formation in Skin after Acute and Repeated Mast Cell Degranulation  

Microsoft Academic Search

Mast cells and their proteases are thought to participate in the development of skin blisters in various pathological condi- tions. In this study, suction blistering was used as an experi- mental model to evaluate the signi¢cance of mast cells in blister formation after pre-treatment of normal skin with intradermal injections of 100 mg\\/ml compound 48\\/80 (a mast cell degranulator) or

RENATA KAMINSKA; ANITA NAUKKARINEN; MAIJA HORSMANHEIMO; ILKKA T. HARVIMA

101

The Role of the Extracorporeal Circuit in the Trapping and Degranulation of Platelets  

Microsoft Academic Search

Background: Although platelet (PLT) activation and degranulation are well-known phenomena during hemodialysis (HD), controversies still exist about their nature and origin. Methods: PLT characteristics [PLT numbers, mean PLT volume (MPV), PLT distribution width (PDW), PLT large cell ratio (p-LCR), immature PLT fraction] and activation status [CD62p expression, platelet factor 4 (PF4) and ?-thromboglobulin (BTG) plasma levels] were estimated in 19

Mareille Gritters-van den Oever; Marianne Schoorl; Margreet Schoorl; Piet C. M. Bartels; Muriel P. C. Grooteman; Menso J. Nubé

2009-01-01

102

The effect of cutaneous mast cell degranulation on sensitivity to heat  

Microsoft Academic Search

Objective:To determine whether depletion of inflammatory mediators from cutaneous mast cells influences cutaneous sensitivity to heat or the thermal hyperalgesia provoked by capsaicin or noradrenaline. Subjects:Ten healthy men. Methods and results:Compound 48\\/80 was introduced by iontophoresis into the forearm. Wheals at the site of compound 48\\/80 iontophoresis subsided over four pre-treatments, consistent with mast cell degranulation. Flares in the skin

P. D. Drummond

2004-01-01

103

Membrane-bound IgE receptor complexes fused with rat basophilic leukemia cells mediate degranulation  

Microsoft Academic Search

The high affinity receptor for IgE on rat basophilic leukemia (RBL) cells mediates antigen- triggered cellular degranulation. Polyethylene glycol- induced membrane fusion methods were used to in- troduce exogenous IgE receptors into living RBL cells, and these were tested for normal activities. In cell- cell fusion experiments, RBL cells with fluorescein- labeled rat IgE bound to receptors and containing (5-1,2-3H(N))hydroxytryptamine

Katherine Estes; Laura L. Monfalcone; Stephen R. Hammes; David Holowka; Barbara Baird

1987-01-01

104

Prevention of F-actin assembly switches the response to SCF from chemotaxis to degranulation in human mast cells.  

PubMed

Following antigen/IgE-mediated aggregation of high affinity IgE-receptors (Fc?RI), mast cells (MCs) degranulate and release inflammatory mediators leading to the induction of allergic reactions including anaphylaxis. Migration of MCs to resident tissues and sites of inflammation is regulated by tissue chemotactic factors such as stem cell factor (SCF (KIT ligand)). Despite inducing similar early signaling events to antigen, chemotactic factors, including SCF, produce minimal degranulation in the absence of other stimuli. We therefore investigated whether processes regulating MC chemotaxis are rate limiting for MC mediator release. To investigate this issue, we disrupted actin polymerization, a requirement for MC chemotaxis, with latrunculin B and cytochalasin B, then examined chemotaxis and mediator release in human (hu)MCs induced by antigen or SCF. As expected, such disruption minimally affected early signaling pathways, but attenuated SCF-induced human mast cell chemotaxis. In contrast, SCF, in the absence of other stimuli, induced substantial degranulation in a concentration-dependent manner following actin disassembly. It also moderately enhanced antigen-mediated human mast cell degranulation which was further enhanced in the presence of SCF. These observations suggest that processes regulating cell migration limit MC degranulation as a consequence of cytoskeletal reorganization. PMID:23616175

Smrž, Daniel; Bandara, Geethani; Beaven, Michael A; Metcalfe, Dean D; Gilfillan, Alasdair M

2013-06-04

105

Mecanismos implicados en la reparacion de las lesiones inducidas en pBR322 por tratamiento Puva (8-metoxipsoraleno + luz ultravioleta A). (Mechanisms involved in repairing the lesions induced in pBR 322 by PUVA treatment (8-Methoxypsoralen + ultraviolet A light)).  

National Technical Information Service (NTIS)

This work deals with the genotoxic effects derived from damaging pBR322 DNA through PUVA treatment (8-Methoxypsoralen plus UVA light), both with respect to the lethality and mutagenicity of the lesions produced by the treatment. The mechanisms involved in...

C. Bauluz

1988-01-01

106

Disaggregation of HeLa-Cx43- and HeLa-spheroids induced by PUVA and photo-oxidized psoralen (POP)  

NASA Astrophysics Data System (ADS)

To investigate the effects of PUVA (psoralen + UVA-irradiation) and photooxidized psoralen (POP) on cell-cell junctions, two kinds of multicellular spheroids, which were grown from HeLa cells of epithelioid human cervix carcinoma, were used as a model systems: i) defective in intercellular communication through gap junctions (HeLa-spheroids) and ii) transfected with coding sequences of murine connexin Cx43 with restored gap-junction coupling (HeLa-Cx43-spheroids). It was been found that both PUVA and POP induced disaggregation of HeLa-spheroids as well as HeLa-Cx43-spheroids. It implies that gap-junction plaques are not, apparently, critical targets in psoralen-photosensitized disaggregation. The rate of disaggregation was estimated as inverse time of disaggregation of 50% or 100% spheroids in suspensions (1/t50 or 1/t100, respectively). The rate of PUVA-induced disaggregation was found to increase with the increase of UVA-fluence up to 85 kJ/m2. Photosensitization coefficient was highest at low UVA-fluences (4-6 kJ/m2) and significantly decreased with increase in UVA-fluence. The viability of cells in spheroids was estimated with the use of trypan blue stain. At low UVA-fluences, the process of disaggregation was found to occur without the formation of trypan positive cells in spheroids. Results obtained evidence that PUVA-induced disaggregation of spheroids may occur, at least partially, through the action of POP-products.

Lysenko, Eugene P.; Pliquett, Fritz; Wunderlich, Siegfried; Potapenko, Alexander Y.

2003-10-01

107

Effect of dietary omega-3 and omega-6 fatty acid sources on PUVA-induced cutaneous toxicity and tumorigenesis in the hairless mouse  

Microsoft Academic Search

Because of concern about psoralen-induced phototoxicity and photocarcinogenesis, we investigated the effects of dietary lipids in a mouse model in which 8-methoxypsoralen (8-MOP) and UVA (PUVA) therapy has been shown to be carcinogenic. SKH-Hr-1 hairless albino mice were fed diets containing either omega-3 or omega-6 fatty-acid sources (menhaden oil and corn oil, respectively). After 2 weeks on the diets, the

A. Yen; H. S. Black; J. Tschen

1994-01-01

108

New insights on how nucleotide excision repair could remove DNA adducts induced by chemotherapeutic agents and psoralens plus UVA (PUVA) in Escherichia coli cells  

Microsoft Academic Search

Chemotherapeutic agents such as mitomycin C or nitrogen mustards induce DNA inter-strand cross-links (ICL) and are highly toxic, thus constituting an useful tool to treat some human degenerative diseases, such as cancer. Additionally, psoralens plus UV-A (PUVA), which also induce ICL, find use in treatment of patients afflicted with psoriasis and vitiligo. The repair of DNA ICL generated by different

Claudia Lage; Marcelo de Pádula; Tatiana Amorim Muniz de Alencar; Silvia Regina da Fonseca Gonçalves; Leonardo da Silva Vidal; Januário Cabral-Neto; Alvaro Costa Leitão

2003-01-01

109

Influence of a mindfulness meditation-based stress reduction intervention on rates of skin clearing in patients with moderate to severe psoriasis undergoing phototherapy (UVB) and photochemotherapy (PUVA)  

Microsoft Academic Search

OBJECTIVE: This study tests the hypothesis that stress reduction methods based on mindfulness meditation can positively influence the rate at which psoriasis clears in patients undergoing phototherapy or photochemotherapy treatment.\\u000aMETHODS: Thirty-seven patients with psoriasis about to undergo ultraviolet phototherapy (UVB) or photochemotherapy (PUVA) were randomly assigned to one of two conditions: a mindfulness meditation-based stress reduction intervention guided by

Jon Kabat-Zinn; Elizabeth V. Wheeler; Timothy Light; Anne Skillings; Mark J. Scharf; Thomas G. Cropley; David W. Hosmer; Jeffrey D. Bernhard

1998-01-01

110

Paeonol inhibits anaphylactic reaction by regulating histamine and TNF-?  

Microsoft Academic Search

Paeonol, a major phenolic component of Moutan Cortex, was known to have antiaggregatory, antioxidant and antiinflammatory activities. In the present study, we tried to elucidate the effects of paeonol on anaphylactic reaction and its mode of action. Paeonol significantly inhibited histamine release from the rat peritoneal mast cells (RPMCs) treated with compound 48\\/80, a mast cell degranulator. The release of

Sung Hoon Kim; Seung-Ae Kim; Mi-Kyung Park; Seung-Hyung Kim; Young-Doo Park; Ho-Jeong Na; Hyung-Min Kim; Min-Kyu Shin; Kyoo-Seok Ahn

2004-01-01

111

Effect of dialkyl phthalates on the degranulation and Ca 2+ response of RBL-2H3 mast cells  

Microsoft Academic Search

We examined the effect of three dialkyl phthalates, di-n-butylphthalate (DBP), di-isobutylphthalate (DIBP) and di(2-ethylhexyl)phthalate (DEHP), on antigen-induced degranulation of RBL-2H3 mast cells. Exposure to 50–500 ?M DBP, 50–500 ?M DIBP, and 500 ?M DEHP significantly potentiated antigen-induced ?-hexosaminidase release. Without antigen stimulation, the phthalates did not cause any significant increase in degranulation. Next, we examined the Ca2+ response of RBL-2H3

Ryosuke Nakamura; Reiko Teshima; Jun-ichi Sawada

2002-01-01

112

Crucial role of the hydrophobic pocket region of Munc18 protein in mast cell degranulation.  

PubMed

The function of the Munc18-1 protein hydrophobic pocket, which interacts with the syntaxin-1 N-terminal peptide, has been highly controversial in neurosecretion. Recent analysis of patients with familial hemophagocytic lymphohistiocytosis type 5 has identified the E132A mutation in the hydrophobic pocket of Munc18-2, prompting us to examine the role of this region in the context of immune cell secretion. Double knockdown of Munc18-1 and Munc18-2 in RBL-2H3 mast cells eliminates both IgE-dependent and ionomycin-induced degranulation and causes a significant reduction in syntaxin-11 without altering expressions of the other syntaxin isoforms examined. These phenotypes were effectively rescued on reexpression of wild-type Munc18-1 or Munc18-2 but not the mutants (F115E, E132A, and F115E/E132A) in the hydrophobic pocket of Munc18. In addition, these mutants show that they are unable to directly interact with syntaxin-11, as tested through protein interaction experiments. Our results demonstrate the crucial roles of the hydrophobic pocket of Munc18 in mast cell degranulation, which include the regulation of syntaxin-11. We also suggest that the functional importance of this region is significantly different between neuronal and immune cell exocytosis. PMID:23487749

Bin, Na-Ryum; Jung, Chang Hun; Piggott, Christopher; Sugita, Shuzo

2013-03-04

113

Crucial role of the hydrophobic pocket region of Munc18 protein in mast cell degranulation  

PubMed Central

The function of the Munc18-1 protein hydrophobic pocket, which interacts with the syntaxin-1 N-terminal peptide, has been highly controversial in neurosecretion. Recent analysis of patients with familial hemophagocytic lymphohistiocytosis type 5 has identified the E132A mutation in the hydrophobic pocket of Munc18-2, prompting us to examine the role of this region in the context of immune cell secretion. Double knockdown of Munc18-1 and Munc18-2 in RBL-2H3 mast cells eliminates both IgE-dependent and ionomycin-induced degranulation and causes a significant reduction in syntaxin-11 without altering expressions of the other syntaxin isoforms examined. These phenotypes were effectively rescued on reexpression of wild-type Munc18-1 or Munc18-2 but not the mutants (F115E, E132A, and F115E/E132A) in the hydrophobic pocket of Munc18. In addition, these mutants show that they are unable to directly interact with syntaxin-11, as tested through protein interaction experiments. Our results demonstrate the crucial roles of the hydrophobic pocket of Munc18 in mast cell degranulation, which include the regulation of syntaxin-11. We also suggest that the functional importance of this region is significantly different between neuronal and immune cell exocytosis.

Bin, Na-Ryum; Jung, Chang Hun; Piggott, Christopher; Sugita, Shuzo

2013-01-01

114

Respiratory Syncytial Virus-Infected Pulmonary Epithelial Cells Induce Eosinophil Degranulation by a CD18-Mediated Mechanism1  

Microsoft Academic Search

Respiratory syncytial virus (RSV)-induced bronchiolitis in infants is characterized by wheezing, respiratory distress, and the histologic findings of necrosis and sloughing of airway epithelium. High concentrations of eosinophil cationic protein (ECP), a cytotoxic protein contained in the granules of eosinophils, have been found in the airways of RSV-infected infants. The mechanisms of eosinophil degranulation in vivo remain largely unknown. Since

Barbara Olszewska-Pazdrak; Konrad Pazdrak; Pearay L. Ogra; Roberto P. Garofalo

115

Activated T lymphocytes induce degranulation and cytokine production by human mast cells following cell-to-cell contact  

Microsoft Academic Search

Activated mast cells reside in close appo- sition to T cells in some inflammatory processes. In this study, we analyzed whether this close physical proximity affects human mast cell degranulation and cytokine release. Thus HMC-1 human mast cells or primary bone marrow-derived human mast cells were cocultured with activated and with rest- ing T cells. Mast cells cocultured with activated

Siba P. Bhattacharyya; Ilana Drucker; Tamar Reshef; Arnold S. Kirshenbaum; Dean D. Metcalfe; Yoseph A. Mekori

116

Degranulated eosinophils, eosinophil granule basic proteins and humoral factors in Nigerians with endomyocardial fibrosis.  

PubMed

The frequency of eosinophilia, degranulated eosinophils, and raised serum levels of eosinophil granule basic proteins was determined in ten Nigerians with EMF and fifteen normal controls matched for age and sex, and from the same environment and social background as the patients. Sera from the patients and control subjects were also examined for auto-antibodies, immune complexes, filaria antibodies and immunoglobulins. A mild eosinophilia was observed in four of the patients. The mean direct eosinophil count in the patients (0.407 +/- 0.14 X 10(9)/l) was, however, not significantly different from that of the control subjects (0.399 +/- 0.07 x 10(9)/l). Degranulated eosinophils were absent in the blood and bone marrow aspirates of the patients, and peripheral blood of the controls. It was also found that the mean concentration of eosinophil granule basic proteins (ECP/EPX) in the patients (0.278 +/- 0.1 micrograms/ml) was not significantly different from the mean value for the control subjects (0.371 +/- 0.1 micrograms/ml, P greater than 0.5). Serological studies using Brugia pahangi antigens failed to demonstrate filaria antibodies in the patients and the control subjects. Microfilaria were also absent in their peripheral blood films. Using the indirect immunofluorescent technique, anti-heart antibodies were not demonstrated in the sera of the EMF patients and control subjects. Five (50%) of the patients and four (30.7%) of the normal controls had immune complexes levels far in excess of the upper limit of normal. However, the mean concentration of immune complexes in the patients (16.35%) was not significantly different from the value for control subjects (12.13%, P greater than 0.5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2829606

Urhoghide, G E; Falase, A O

1987-09-01

117

Hydrogen sulfide regulates cAMP homeostasis and renin degranulation in As4.1 and rat renin-rich kidney cells.  

PubMed

The present study aims to investigate the regulatory effect of hydrogen sulfide (H(2)S) on cAMP homeostasis and renin degranulation in As4.1 and rat renin-rich kidney cells. It was found in the present study that NaHS at 0.1-10 ?M significantly decreased cAMP production in As4.1 cells treated with isoproterenol (a ?-adrenoceptor agonist), forskolin (an adenylyl cyclase activator), or 3-isobutyl-1-methylxanthine (IBMX, a phosphodiesterase inhibitor). NaHS at 10 ?M suppressed adenylate cyclase activity but stimulated phosphodiesterase activity. We continued to study whether H(2)S may mediate cAMP-dependent renin degranulaion in As4.1 cells. It was found that NaHS at 0.1-10 ?M significantly increased intracellular renin protein level. Moreover, NaHS reversed the declined renin content within As4.1 cells and normalized the upregulated renin activity in the culture medium of As4.1 cells treated with the above three stimuli. RT-PCR showed that cystathionine-?-lyase is the main enzyme to produce endogenous H(2)S in As4.1 cells. Overexpression of cystathionine-?-lyase increased endogenous H(2)S production and suppressed isoproterenol-induced renin release, suggesting that endogenous H(2)S may also inhibit renin release from As4.1 cells. We also tested whether H(2)S has a similar effect in renin-rich kidney cells. It was found that isoproterenol elevated intracellular cAMP level and extracellular renin activity but decreased renin protein level in the renin-rich kidney cells. Pretreatment with NaHS abolished these effects. In conclusion, H(2)S regulates cAMP homeostasis via inhibition of adenylate cyclase and stimulation of phosphodiesterase. Our findings suggest that H(2)S plays a critical role in regulation of renin degranulation in As4.1 and rat renin-rich kidney cells. PMID:21940660

Lu, Ming; Liu, Yi-Hong; Ho, Chui Ying; Tiong, Chi Xin; Bian, Jin-Song

2011-09-21

118

Platelet activation by endogenous 5-hydroxytryptamine and histamine released by mast cell degranulation with compound 48\\/80 in the rat  

Microsoft Academic Search

The intravenous injection of the mast cell degranulator C 48\\/80 (1 mg\\/kg) in rats did not produce thrombocytopenia nor circulating platelet aggregates but sensitized the platelets to aggregate upon turbulence challenge. Such turbulence-induced platelet aggregation was not accompanied by formation of thromboxane B2. Electron microscopy revealed absence of platelet degranulation. Turbulence-induced platelet aggregation was completely prevented by pre-treatment of the

F. De Clerck; Y. Somers; L. Van Gorp; B. Xhonneux

1983-01-01

119

Loss of TRPC1-mediated Ca2+ influx contributes to impaired degranulation in Fyn-deficient mouse bone marrow-derived mast cells  

PubMed Central

MC degranulation requires the influx of calcium from the extracellular environment. Orai1/STIM1 is essential to MC SOCE, as shown in rat peritoneal MCs, the rat MC lines (RBL-2H3), or in Orai1 null embryo liver-derived, cultured MCs. However, minimal information exists about the role of other calcium channels expressed on these cells. Here, we demonstrate that the nonselective TRPC1 participates in Fc?RI-mediated calcium entry in mouse BMMCs. We found that Fyn null MCs, which have an impaired degranulation response, expressed reduced levels of TRPC1, had normal depletion of intracellular calcium stores but an impaired calcium influx, and failed to depolymerize cortical F-actin (a key step for granule-plasma membrane fusion). Partial RNAi silencing of TRPC1 expression in WT MCs (to the level of Fyn null MCs) mimicked the Fyn null defect in calcium influx, cortical F-actin depolymerization, and MC degranulation. Ectopic expression of Fyn or TRPC1 in Fyn null MCs restored calcium responses and cortical F-actin depolymerization and increased MC degranulation. Together with our findings that expression of Orai1 is not altered in Fyn null MCs, our findings suggest that TRPC1 participates in calcium influx and other key events required for MC degranulation. This demonstrates that in addition to a role described previously for Orai1 in promoting MC degranulation, nonselective cation channels participate in promoting the exocytotic response.

Suzuki, Ryo; Liu, Xibao; Olivera, Ana; Aguiniga, Lizath; Yamashita, Yumi; Blank, Ulrich; Ambudkar, Indu; Rivera, Juan

2010-01-01

120

Lesional skin chemokine CTACK/CCL27 expression in mycosis fungoides and disease control by IFN-? and PUVA therapy  

PubMed Central

Recruitment of neoplastic T cells to skin is a critical step in the pathogenesis of mycosis fungoides (MF) lesions. Cutaneous T-cell attracting chemokine (CTACK)/CCL27 attracts memory T cells to skin, resulting in increased cutaneous expression. The interactions between neoplastic cells and skin immune system require further elucidation. CTACK/CCL27 expression and density of dendritic cells (DC), CD8+ and CD4+ lymphocytes were investigated in skin lesions of 52 early-stage MF patients treated by interferon (IFN)-? in combination with photochemotherapy (psoralen plus ultraviolet A, PUVA). Skin lesion biopsies obtained at diagnosis and after treatment were studied by immunohistochemistry. Initial CTACK/CCL27 expression was abnormal/suprabasal in 36 patients. Normal/basal CTACK/CCL27 expression tended to correlate with a high DC density and low CD4+ cell density in the neoplastic infiltrate. Treatment induced a significant increase in CTACK/CCL27 expression (?2 test: P=0.004). Overall, 33 patients relapsed [median event-free survival (EFS), 46 months] during follow-up (median, 92.5 months, range, 43–165). Normal/basal CTACK/CCL27 expression at the end of treatment correlated with lower rates of recurrence and a longer median EFS (111 months vs. 39 months with suprabasal expression; log rank test: P=0.031). CTACK/CCL27 overexpression in early-stage MF might thus be related to a balance between neoplastic cells and immunomodulant DC. Normal CTACK/CCL27 expression after treatment designates a subset of patients with favorable disease behavior. The mechanisms underpinning CTACK/CCL27 overexpression after therapy in the remaining patients, who are at greater risk of recurrence, warrant further investigation.

Goteri, Gaia; Rupoli, Serena; Campanati, Anna; Costagliola, Antonello; Sabato, Simona; Stramazzotti, Daniela; Picardi, Paola; Canafoglia, Lucia; Pulini, Stefano; Ganzetti, Giulia; Offidani, Anna Maria; Leoni, Pietro

2009-01-01

121

Patients with allergic rhinitis and allergic asthma share the same pattern of eosinophil and neutrophil degranulation after allergen challenge  

PubMed Central

Background Patients with allergic rhinitis and allergic asthma demonstrate comparable local and systemic eosinophil inflammation, and yet they present with different clinical pictures. Less is even known about the contribution of neutrophil inflammation in allergic diseases. The aim of the study was to examine the propensity and selectivity of granule release from primed systemic eosinophils and neutrophils in allergic rhinitis and allergic asthma after seasonal and experimental allergen exposure. We hypothesize that the dissimilar clinical manifestations are due to diverse eosinophil and neutrophil degranulation. Methods Nine birch pollen allergic patients with rhinitis, eight with asthma and four controls were studied during pollen season and after nasal and bronchial allergen challenge. Eosinophils and neutrophils were incubated in vitro with assay buffer and opsonized Sephadex particles for spontaneous and C3b-induced granule protein release. The released amount of eosinophil cationic protein (ECP), eosinophil peroxidase (EPO) and myeloperoxidase (MPO) was measured by specific radioimmunoassay. Results C3b-induced degranulation resulted in increased release of ECP and MPO from primed blood eosinophils and neutrophils in both allergic rhinitis and allergic asthma during pollen season and after both nasal and bronchial challenge (p-values 0.008 to 0.043). After bronchial challenge, the ECP release was significantly higher in the rhinitic group compared to the asthmatic group [19.8 vs. 13.2%, (p = 0.010)]. The propensity for EPO release was weak in all challenge models but followed the same pattern in both allergic groups. Conclusions Systemically activated eosinophils and neutrophils have similar patterns of degranulation after allergen exposure in allergic rhinitis and allergic asthma. The released amount of ECP, EPO and MPO was similar in all allergen challenge models in both allergic groups. Our results indicate that other mechanisms than the magnitude of eosinophil and neutrophil inflammation or the degranulation pattern of the inflammatory cells determines whether or not an allergic patient develops asthma.

2011-01-01

122

A Pak1-PP2A-ERM signaling axis mediates F-actin rearrangement and degranulation in mast cells.  

PubMed

Mast cells coordinate allergy and allergic asthma and are crucial cellular targets in therapeutic approaches to inflammatory disease. Allergens cross-link immunoglobulin E bound at high-affinity receptors on the mast cell's surface, causing release of preformed cytoplasmic granules containing inflammatory molecules, including histamine, a principal effector of fatal septic shock. Both p21 activated kinase 1 (Pak1) and protein phosphatase 2A (PP2A) modulate mast cell degranulation, but the molecular mechanisms underpinning these observations and their potential interactions in common or disparate pathways are unknown. In this study, we use genetic and other approaches to show that Pak1's kinase-dependent interaction with PP2A potentiates PP2A's subunit assembly and activation. PP2A then dephosphorylates threonine 567 of Ezrin/Radixin/Moesin (ERM) molecules that have been shown to couple F-actin to the plasma membrane in other cell systems. In our study, the activity of this Pak1-PP2A-ERM axis correlates with impaired systemic histamine release in Pak1(-/-) mice and defective F-actin rearrangement and impaired degranulation in Ezrin disrupted (Mx1Cre(+)Ezrin(flox/flox)) primary mast cells. This heretofore unknown mechanism of mast cell degranulation provides novel therapeutic targets in allergy and asthma and may inform studies of kinase regulation of cytoskeletal dynamics in other cell lineages. PMID:23063725

Staser, Karl; Shew, Matthew A; Michels, Elizabeth G; Mwanthi, Muithi M; Yang, Feng-Chun; Clapp, D Wade; Park, Su-Jung

2012-10-11

123

A Pak1-PP2A-ERM signaling axis mediates F-actin rearrangement and degranulation in mast cells  

PubMed Central

Mast cells coordinate allergy and allergic asthma and are crucial cellular targets in therapeutic approaches to inflammatory disease. Allergens cross-link IgE bound at high-affinity receptors on the mast cell's surface, causing release of pre-formed cytoplasmic granules containing inflammatory molecules, including histamine, a principal effector of fatal septic shock. Both p21 activated kinase 1 (Pak1) and protein phosphatase 2A (PP2A) modulate mast cell degranulation, but the molecular mechanisms underpinning these observations and their potential interactions in common or disparate pathways are unknown. Here, we use genetic and other approaches to show that Pak1's kinase-dependent interaction with PP2A potentiates PP2A's subunit assembly and activation. PP2A then dephosphorylates threonine 567 of Ezrin/Radixin/Moesin (ERM), molecules that have been shown to couple F-actin to the plasma membrane in other cell systems. In our study, the activity of this Pak1-PP2A-ERM axis correlates with impaired systemic histamine release in Pak1?/? mice and defective F-actin rearrangement and impaired degranulation in Ezrin disrupted (Mx1Cre+Ezrinflox/flox) primary mast cells. This heretofore unknown mechanism of mast cell degranulation provides novel therapeutic targets in allergy and asthma and may inform studies of kinase regulation of cytoskeletal dynamics in other cell lineages.

Staser, Karl; Shew, Matthew A; Michels, Elizabeth G; Mwanthi, Muithi M; Yang, Feng-Chun; Clapp, D Wade; Park, Su-Jung

2013-01-01

124

A novel PKC regulates ERK activation and degranulation of cytotoxic T lymphocytes: Plasticity in PKC regulation of ERK.  

PubMed

Stimulation of cytotoxic T lymphocyte (CTL) degranulation with plate-bound anti-CD3 Ab leads to two phases of ERK activation: an early PKC-independent phase followed by a later sustained PKC-dependent phase. Herein, we show that a novel PKC (nPKC) mediates the late phase of ERK activation, upstream of Ras in murine T cells. In contrast, when CTL are activated with cross-linked anti-CD3 Ab, which does not trigger CTL degranulation, there is a requirement for conventional PKC (cPKC) for ERK activation. We detect increased novel PKCtheta activation only when CTL are stimulated with plate-bound Ab and not cross-linked Ab. Interestingly, in T cells from mice lacking PKCtheta, sustained ERK activation requires the activity of cPKC, implying that PKCtheta is required for the nPKC pathway that normally mediates sustained ERK activation. CTL lines derived from PKCtheta-deficient mice degranulate and activate ERK normally, and exhibit altered expression of PKC isozymes, which may compensate for the loss of PKCtheta. Taken together, these data demonstrate that normally an nPKC participates in the sustained activation of ERK. However, if the nPKC pathway is compromised, alternate PKC pathways can compensate, suggesting that considerable plasticity exists with respect to PKC regulation of ERK activation in T cells. PMID:16552708

Puente, Lawrence G; He, Jin-Shu; Ostergaard, Hanne L

2006-04-01

125

Effect of dialkyl phthalates on the degranulation and Ca2+ response of RBL-2H3 mast cells.  

PubMed

We examined the effect of three dialkyl phthalates, di-n-butylphthalate (DBP), di-isobutylphthalate (DIBP) and di(2-ethylhexyl)phthalate (DEHP), on antigen-induced degranulation of RBL-2H3 mast cells. Exposure to 50-500 microM DBP, 50-500 microM DIBP, and 500 microM DEHP significantly potentiated antigen-induced beta-hexosaminidase release. Without antigen stimulation, the phthalates did not cause any significant increase in degranulation. Next, we examined the Ca2+ response of RBL-2H3 cells after exposure to these phthalates. The cytosolic calcium ion concentration ([Ca2+]i) of the cells clearly increased when the cells were stimulated with 50-500 microM and 50-500 microM DIBP, and increased slightly when stimulated with 50-500 microM DEHP. Digital imaging fluorescence microscope analysis showed that the addition of DBP evoked Ca2+ oscillation in individual mast cells. Finally, we investigated the relationship between the DBP-sensitive Ca2+ stores and thapsigargin (TG)-sensitive Ca2+ stores. A rise in [Ca2+](i) following challenge with DBP after TG was observed, and thus the DBP-sensitive and TG-sensitive Ca2+ stores in RBL-2H3 cells seem to be different. In conclusion, some dialkyl phthalates increase antigen-induced degranulation in RBL-2H3 cells dependent on the increase of [Ca2+]i. PMID:11750043

Nakamura, Ryosuke; Teshima, Reiko; Sawada, Jun ichi

2002-02-01

126

A worm's best friend: recruitment of neutrophils by Wolbachia confounds eosinophil degranulation against the filarial nematode Onchocerca ochengi.  

PubMed

Onchocerca ochengi, a filarial parasite of cattle, represents the closest relative of the human pathogen, Onchocerca volvulus. Both species harbour Wolbachia endosymbionts and are remarkable in that adult female worms remain viable but sessile for many years while surrounded by host cells and antibodies. The basis of the symbiosis between filariae and Wolbachia is thought to be metabolic, although a role for Wolbachia in immune evasion has received little attention. Neutrophils are attracted to Wolbachia, but following antibiotic chemotherapy they are replaced by eosinophils that degranulate on the worm cuticle. However, it is unclear whether the eosinophils are involved in parasite killing or if they are attracted secondarily to dying worms. In this study, cattle infected with Onchocerca ochengi received adulticidal regimens of oxytetracycline or melarsomine. In contrast to oxytetracycline, melarsomine did not directly affect Wolbachia viability. Eosinophil degranulation increased significantly only in the oxytetracycline group; whereas nodular gene expression of bovine neutrophilic chemokines was lowest in this group. Moreover, intense eosinophil degranulation was initially associated with worm vitality, not degeneration. Taken together, these data offer strong support for the hypothesis that Wolbachia confers longevity on O. ochengi through a defensive mutualism, which diverts a potentially lethal effector cell response. PMID:21177682

Hansen, Rowena D E; Trees, Alexander J; Bah, Germanus S; Hetzel, Udo; Martin, Coralie; Bain, Odile; Tanya, Vincent N; Makepeace, Benjamin L

2010-12-22

127

Enhanced innate immune responses in a brood parasitic cowbird species: degranulation and oxidative burst  

USGS Publications Warehouse

We examined the relative effectiveness of two innate immune responses in two species of New World blackbirds (Passeriformes, Icteridae) that differ in resistance to West Nile virus (WNV). We measured degranulation and oxidative burst, two fundamental components of phagocytosis, and we predicted that the functional effectiveness of these innate immune responses would correspond to the species' relative resistance to WNV. The brown-headed cowbird (Molothrus ater), an obligate brood parasite, had previously shown greater resistance to infection with WNV, lower viremia and faster recovery when infected, and lower subsequent antibody titers than the red-winged blackbird (Agelaius phoeniceus), a close relative that is not a brood parasite. We found that cowbird leukocytes were significantly more functionally efficient than those of the blackbird leukocytes and 50% more effective at killing the challenge bacteria. These results suggest that further examination of innate immunity in the cowbird may provide insight into adaptations that underlie its greater resistance to WNV. These results support an eco-immunological interpretation that species like the cowbird, which inhabit ecological niches with heightened exposure to parasites, experience evolutionary selection for more effective immune responses.

Hahn, D. Caldwell; Summers, Scott G.; Genovese, Kenneth J.; He, Haiqi; Kogut, Michael H.

2013-01-01

128

Cyclical mechanical stretch enhances degranulation and IL-4 secretion in RBL-2H3 mast cells.  

PubMed

Mast cells are widely distributed in the body and affect their surrounding environment through degranulation and secretion of cytokines. Conversely, mast cells are influenced by environmental stimuli such as cyclical mechanical stretch (CMS), such as that induced by heartbeat and respiration. Peripherally distributed mast cells are surrounded by extracellular matrix, where they bind IgE on their surface by expressing the high-affinity Fc receptor for IgE (Fc?RI), and they release mediators after cross-linking of surface-bound IgE by allergen. To analyse how CMS affects mast cell responses, we examined the effect of applying CMS on the behaviour of IgE-bound mast cells (RBL-2H3 cell line) adhering to fibronectin as a substitute for extracellular matrix. We found that CMS enhanced Fc?RI-mediated secretion in the presence of antigen (2,4-dinitrophenol-bovine serum albumin). CMS increased expression of IL-4 mRNA and secretion of IL-4 protein. Western blot analysis showed that CMS changes the signal transduction in mitogen-activated protein kinases and AKT, which in turn alters the regulation of IL-4 and increases the secretion of IL-4. These results suggest that CMS modulates the effect of mast cells on inflammation and resultant tissue remodelling. Understanding how CMS affects mast cell responses is crucial for developing therapies to treat mast cell-related diseases. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23584980

Komiyama, Hidenori; Miyake, Koichi; Asai, Kuniya; Mizuno, Kyoichi; Shimada, Takashi

2013-04-15

129

Regional citrate anticoagulation reduces polymorphonuclear cell degranulation in critically ill patients treated with continuous venovenous hemofiltration.  

PubMed

Citrate which chelates ionized calcium can be used as regional anticoagulation in continuous venovenous hemofiltration (CVVH). This is the first study conducted to examine the potentially additive benefit effect of regional citrate anticoagulation (RCA) on polymorphonuclear (PMN) cell degranulation of myeloperoxidase (MPO) and cytokines production in patients with critically acute kidney injury (AKI) undergoing CVVH treatment. This prospective randomized controlled trial was conducted in 20 critically ill patients with AKI who underwent CVVH. The patients were randomized into regional citrate group (n=10) and heparin group (n=10). The pre-dilution CVVH with polyethersulfone dialyzers were utilized in both groups. The levels of pre-filter and post-filter MPO as well as inflammatory and anti-inflammatory cytokines were measured at baseline, 6h, and 24 h after initiating CVVH. In the heparin group, the post-filter serum MPO levels were significantly higher than the pre-filter (median 49.0 vs. 60.5 ng/mL, P<0.05) at 6 h. There were no significant differences between pre- and post-dialyzer MPO levels in the citrate group. Citrate could significantly decrease systemic pre-filter serum MPO levels from baseline at 6 h (median 43.5 vs. 17.3 ng/mL, P<0.01) as well as IL-8 levels (P<0.05) whereas heparin provided only significant TNF-? reduction (P<0.05). The CVVH circuit survival in the citrate group was longer than the heparin group. In conclusion, citrate, utilized as a regional anticoagulant in CVVH, can reduce both membrane bioincompatibility-induced and systemic oxidative stress and inflammation, and can prolong CVVH circuit survival time. PMID:22107692

Tiranathanagul, Khajohn; Jearnsujitwimol, Onanong; Susantitaphong, Paweena; Kijkriengkraikul, Narin; Leelahavanichkul, Asada; Srisawat, Nattachai; Praditpornsilpa, Kearkiat; Eiam-Ong, Somchai

2011-12-01

130

Retrovirally induced CTL degranulation mediated by IL-15 expression and infection of mononuclear phagocytes in patients with HTLV-I-associated neurologic disease  

PubMed Central

CD8+ T cells contribute to central nervous system inflammation in human T-cell lymphotropic virus type I (HTLV-I)–associated myelopathy/tropical spastic paraparesis (HAM/TSP). We analyzed CD8+ T-cell dysfunction (degranulation and IFN-? production) and have demonstrated that CD8+ T cells of patients with HAM/TSP (HAM/TSP patients) spontaneously degranulate and express IFN-? in ex vivo unstimulated culture. CD8+ T cells of HTLV-I asymptomatic carriers and healthy donors did not. Spontaneous degranulation was detected in Tax11-19/HLA-A*201 tetramer+ cells, but not in CMV pp65 tetramer+ cells. Interestingly, degranulation and IFN-? production in CD8+ T cells was induced by coculture with autologous CD14+ cells, but not CD4+ T cells, of HAM/TSP patients, which correlated with proviral DNA load in CD14+ cells of infected patients. Moreover, the expression of IL-15, which induced degranulation and IFN-? production in infected patients, was enhanced on surface of CD14+ cells in HAM/TSP patients. Blockade of MHC class I and IL-15 confirmed these results. Thus, CD8+ T-cell dysregulation was mediated by both virus infection and enhanced IL-15 on CD14+ cells in HAM/TSP patients. Despite lower viral expression than in CD4+ T cells, HTLV-I–infected or –activated CD14+ cells may be a heretofore important but under recognized reservoir particularly in HAM/TSP patients.

Enose-Akahata, Yoshimi; Oh, Unsong; Grant, Christian

2008-01-01

131

Structure and biological activities of eumenine mastoparan-AF (EMP-AF), a new mast cell degranulating peptide in the venom of the solitary wasp ( Anterhynchium flavomarginatum micado)  

Microsoft Academic Search

A new mast cell degranulating peptide, eumenine mastoparan-AF (EMP-AF), was isolated from the venom of the solitary wasp Anterhynchium flavomarginatum micado, the most common eumenine wasp found in Japan. The structure was analyzed by FAB-MS\\/MS together with Edman degradation, which was corroborated by solid-phase synthesis. The sequence of EMP-AF, Ile–Asn–Leu–Leu–Lys–Ile–Ala–Lys–Gly–Ile–Ile–Lys–Ser–Leu–NH2, was similar to that of mastoparan, a mast cell degranulating

Katsuhiro Konno; Miki Hisada; Hideo Naoki; Yasuhiro Itagaki; Nobufumi Kawai; Akiko Miwa; Tadashi Yasuhara; Yukiko Morimoto; Yoshihiro Nakata

2000-01-01

132

The antigen-induced degranulation of basophil leucocytes from atopic subjects, studied by phase-contrast microscopy  

PubMed Central

A type of microscopical chamber is described which enables monolayers of cells to be examined at 37°C by phase-contrast microscopy at high magnification and which can be perfused semi-automatically. Such chambers have been used to observe morphological changes in the basophil leucocytes of atopic subjects when challenged with an extract of Timothy grass pollen. The appearance of basophil leucocytes in monolayers prepared from both washed and defibrinated blood cell suspensions has been studied. Basophils taken from non-atopic subjects or atopic subjects who were not hypersensitive to grass pollen showed no reaction to Timothy grass pollen extract. By contrast, basophils taken from pollen sensitive atopic subjects reacted to Timothy grass pollen extract with an acute change in motility and many degranulated. The morphological changes observed are described and illustrated in detail. No significant changes were seen in other types of cell. Some immunological and cellular mechanisms which may underlie this degranulation of human basophil leucocytes are discussed. ImagesFIG. 2FIG. 3FIG. 4

Hastie, R.

1971-01-01

133

Differential survival of Escherichia coli uvrA, uvrB, and uvrC mutants to psoralen plus UVA (PUVA): Evidence for uncoupled action of nucleotide excision repair to process DNA adducts  

Microsoft Academic Search

The nucleotide excision repair mechanism (NER) of Escherichia coli is responsible for the recognition and elimination of more than twenty different DNA lesions. Herein, we evaluated the in vivo role of NER in the repair of DNA adducts generated by psoralens (mono- or bi-functional) and UV-A light (PUVA) in E. coli. Cultures of wild-type E. coli K12 and mutants for

Claudia Lage; Silvia R. F. Gonçalves; Luciana L. Souza; Marcelo de Pádula; Alvaro C. Leitão

2010-01-01

134

Cross-linking of IgE-receptor complexes by rigid bivalent antigens greater than 200 A in length triggers cellular degranulation  

PubMed Central

We have examined the effect of cross-linking IgE-receptor complexes with variable receptor-receptor distances on the transmembrane signaling that leads to degranulation of rat basophilic leukemia cells. Linear polymers of the biotin-binding protein avidin were generated with bis biotin-1,12-diamidododecane, and a dinitrophenyl-biotin conjugate was bound at each end of the polymers to form a series of rigid bivalent haptens of well-defined length. The polymers were fractionated by size with nondenaturing PAGE, electro-eluted, and tested for their ability to stimulate degranulation of rat basophilic leukemia cells sensitized with anti-DNP IgE. We found that hexamers of avidin (of length greater than or equal to 240 A) were as effective in triggering degranulation as dimers (of length approximately 80 A), while the monomeric avidin antigen (of length approximately 40 A) elicited a poorer degranulation response from the cells. The mechanism by which aggregation of cell surface receptors can initiate signal transduction is discussed in light of these results.

1988-01-01

135

NK cell lytic granules are highly motile at the immunological synapse and require F-actin for post-degranulation persistence.  

PubMed

The formation of a dynamic, actin-rich immunological synapse (IS) and the polarization of cytolytic granules toward target cells are essential to the cytotoxic function of NK cells. Following polarization, lytic granules navigate through the pervasive actin network at the IS to degranulate and secrete their toxic contents onto target cells. We examined lytic granule motility and persistence at the cell cortex of activated human NK cells, using high-resolution total internal reflection microscopy and highly quantitative analysis techniques. We illustrate that lytic granules are dynamic and observe substantial motility at the plane of the cell cortex prior to, but not after, degranulation. We also show that there is no significant change in granule motility in the presence of Latrunculin A (which induces actin depolymerization), when added after granule polarization, but that there is a significant decrease in lytic granule persistence subsequent to degranulation. Thus, we show that lytic granules are highly dynamic at the cytolytic human NK cell IS prior to degranulation and that the persistence of granules at the cortex following exocytosis requires the integrity of the synaptic actin network. PMID:23066148

Mace, Emily M; Wu, Winona W; Ho, Tina; Mann, Shaina S; Hsu, Hsiang-Ting; Orange, Jordan S

2012-10-12

136

Inhibitory effect of xanthones isolated from the pericarp of Garcinia mangostana L. on rat basophilic leukemia RBL-2H3 cell degranulation  

Microsoft Academic Search

Mangostin, Garcinia mangostana L. is used as a traditional medicine in southeast Asia for inflammatory and septic ailments. Hitherto we indicated the anticancer activity induced by xanthones such as ?-, ?-, and ?-mangostin which were major constituents of the pericarp of mangosteen fruits. In this study, we examined the effect of xanthones on cell degranulation in rat basophilic leukemia RBL-2H3

Tomohiro Itoh; Kenji Ohguchi; Munekazu Iinuma; Yoshinori Nozawa; Yukihiro Akao

2008-01-01

137

Differential regulation of mast cell degranulation versus cytokine secretion by the actin regulatory proteins Coronin1a and Coronin1b  

PubMed Central

Mast cell (MC) activation via aggregation of the high affinity IgE receptor (Fc?RI) causes degranulation and release of proinflammatory mediators in a process that involves the reorganization of the actin cytoskeleton. However, the regulatory pathways and the molecular links between cytoskeletal changes and MC function are incompletely understood. In this study, we provide genetic evidence for a critical role of the actin-regulatory proteins Coronin1a (Coro1a) and Coro1b on exocytic pathways in MCs: Coro1a?/? bone marrow–derived MCs exhibit increased Fc?RI-mediated degranulation of secretory lysosomes but significantly reduced secretion of cytokines. Hyperdegranulation of Coro1a?/? MCs is further augmented by the additional loss of Coro1b. In vivo, Coro1a?/?Coro1b?/? mice displayed enhanced passive cutaneous anaphylaxis. Functional reconstitution assays revealed that the inhibitory effect of Coro1a on MC degranulation strictly correlates with cortical localization of Coro1a, requires its filamentous actin–binding activity, and is regulated by phosphorylation of Ser2 of Coro1a. Thus, coronin proteins, and in turn the actin cytoskeleton, exhibit a functional dichotomy as differential regulators of degranulation versus cytokine secretion in MC biology.

Foger, Niko; Jenckel, Andre; Orinska, Zane; Lee, Kyeong-Hee; Chan, Andrew C.; Bulfone-Paus, Silvia

2011-01-01

138

Expression of CD203c and CD63 in Human Basophils: Relationship to Differential Regulation of Piecemeal and Anaphylactic Degranulation Processes  

PubMed Central

Background Activation of human basophils results in the release of many different mediators and the expression of new cell surface proteins. The markers CD63 and CD203c have been used in recent years to assess basophil activation but there have been many studies that demonstrate that expression of these markers can be dissociated from histamine release. Objective To determine the signal transduction requirements for CD203c and CD63 expression. Methods The current study began by exploring the dependency of CD203c and CD63 expression on protein kinase C (PKC) using known selective inhibitors of PKC. Results Between 30-300 nM, Ro-31-8220 and Bisindoylmaleimide II had no effect on FMLP- or anti-IgE-induced CD63 or CD203c but enhanced IgE-mediated expression of CD63 by an average of 15 fold at concentrations greater than 1 ?M. These results led to the suggestion that these inhibitors altered the normal pathways of degranulation (by a non-PKC dependent mechanism), shifting the normal presence of piecemeal degranulation (PMD) to the process termed anaphylactic degranulation (AND). Morphological studies demonstrated that concentrations of Ro-31-8220 and Bis II >1 ?M dramatically increased the presence of degranulation sacs, a morphological feature of AND. Conclusion It is proposed that CD63 expression results from only the AND form of histamine release.

MacGlashan, Donald

2010-01-01

139

Mast cell degranulation distinctly activates trigemino-cervical and lumbosacral pain pathways and elicits widespread tactile pain hypersensitivity  

PubMed Central

Mast cells (MCs) are tissue resident immune cells that participate in a variety of allergic and other inflammatory conditions. In most tissues, MCs are found in close proximity to nerve endings of primary afferent neurons that signal pain (i.e. nociceptors). Activation of MCs causes the release of a plethora of mediators that can activate these nociceptors and promote pain. Although MCs are ubiquitous, conditions associated with systemic MC activation give rise primarily to two major types of pain, headache and visceral pain. In this study we therefore examined the extent to which systemic MC degranulation induced by intraperitoneal administration of the MC secretagogue compound 48/80 activates pain pathways that originate in different parts of the body and studied whether this action can lead to development of behavioral pain hypersensitivity. Using c-fos expression as a marker of central nervous system neural activation, we found that intraperitoneal administration of 48/80 leads to the activation of dorsal horn neurons at two specific levels of the spinal cord; one responsible for processing cranial pain, at the medullary/C2 level, and one that processes pelvic visceral pain, at the caudal lumbar/rostral sacral level (L6-S2). Using behavioral sensory testing, we found that this nociceptive activation is associated with development of widespread tactile pain hypersensitivity within and outside the body regions corresponding to the activated spinal levels. Our data provide a neural basis for understanding the primacy of headache and visceral pain in conditions that involve systemic MC degranulation. Our data further suggest that MC activation may lead to widespread tactile pain hypersensitivity.

Levy, Dan; Kainz, Vanessa; Burstein, Rami; Strassman, Andrew M.

2011-01-01

140

Histochemical study of cardiac mast cells degranulation and collagen deposition: interaction with the cathecolaminergic system in the rat.  

PubMed

Although their role in the cardiovascular system is still largely unknown, mast cells are present in the myocardium of both experimental animals and humans. Interestingly, cathecolaminergic nerve fibres and mast cells are often described in close morphological and functional interactions in various organs. In the present study we investigated the effects of chronic interference with beta-adrenergic receptors (via either sympathectomy or beta-blockade) on cardiac mast cell morphology/activation and on interstitial collagen deposition. In rats subjected to chemical sympathectomizy with the neurotoxin 6-hydroxydopamine (6-OHDA) we observed a significant increase of mast cell density, and in particular of degranulating mast cells, suggesting a close relationship between the cardiac catecholaminergic system and mast cell activation. In parallel, chronic 6-OHDA treatment was associated with increased collagen deposition. The influence of the beta-adrenergic receptor component was investigated in rats subjected to chronic propranolol administration, that caused a further significant increase in mast cell activation associated with a lower extent of collagen deposition when compared to chemical sympathectomy. These data are the first demonstration of a close relationship between rat cardiac mast cell activation and the catecholaminergic system, with a complex interplay with cardiac collagen deposition. Specifically, abrogation of the cardiac sympathetic efferent drive by chemical sympathectomy causes mast cell activation and interstitial fibrosis, possibly due to the local effects of the neurotoxin 6-hydroxydopamine. In contrast, beta-adrenergic blockade is associated with enhanced mast cell degranulation and a lower extent of collagen deposition in the normal myocardium. In conclusion, cardiac mast cell activation is influenced by beta-adrenergic influences. PMID:16864125

Facoetti, A; Fallarini, S; Miserere, S; Bertolotti, A; Ferrero, I; Tozzi, R; Gatti, C; Palladini, G; Perlini, S; Nano, R

141

In vivo tracking of platelets: circulating degranulated platelets rapidly lose surface P-selectin but continue to circulate and function.  

PubMed Central

To examine the hypothesis that surface P-selectin-positive (degranulated) platelets are rapidly cleared from the circulation, we developed novel methods for tracking of platelets and measurement of platelet function in vivo. Washed platelets prepared from nonhuman primates (baboons) were labeled with PKH2 (a lipophilic fluorescent dye), thrombin-activated, washed, and reinfused into the same baboons. Three-color whole blood flow cytometry was used to simultaneously (i) identify platelets with a mAb directed against glycoprotein (GP)IIb-IIIa (integrin alpha 11b beta 3), (ii) distinguish infused platelets by their PKH2 fluorescence, and (iii) analyze platelet function with mAbs. Two hours after infusion of autologous thrombin-activated platelets (P-selectin-positive, PKH2-labeled), 95 +/- 1% (mean +/- SEM, n = 5) of the circulating PKH2-labeled platelets had become P-selectin-negative. Compared with platelets not activated with thrombin preinfusion, the recovery of these circulating PKH2-labeled, P-selectin-negative platelets was similar 24 h after infusion and only slightly less 48 h after infusion. The loss of platelet surface P-selectin was fully accounted for by a 67.1 +/- 16.7 ng/ml increase in the plasma concentration of soluble P-selectin. The circulating PKH2-labeled, P-selectin-negative platelets were still able to function in vivo, as determined by their (i) participation in platelet aggregates emerging from a bleeding time wound, (ii) binding to Dacron in an arteriovenous shunt, (iii) binding of mAb PAC1 (directed against the fibrinogen binding site on GPIIb-IIIa), and (iv) generation of procoagulant platelet-derived microparticles. In summary, (i) circulating degranulated platelets rapidly lose surface P-selectin to the plasma pool, but continue to circulate and function; and (ii) we have developed novel three-color whole blood flow cytometric methods for tracking of platelets and measurement of platelet function in vivo. Images Fig. 2 Fig. 5

Michelson, A D; Barnard, M R; Hechtman, H B; MacGregor, H; Connolly, R J; Loscalzo, J; Valeri, C R

1996-01-01

142

UDP-glucose acting at P2Y14 receptors is a mediator of mast cell degranulation  

PubMed Central

UDP-glucose (UDPG), a glycosyl donor in the biosynthesis of carbohydrates, is an endogenous agonist of the G protein-coupled P2Y14 receptor. RBL-2H3 mast cells endogenously express a P2Y14 receptor at which UDPG mediates degranulation as indicated by ?-hexosaminidase (HEX) release. Both UDPG and a more potent, selective 2-thio-modified UDPG analog, MRS2690 (diphosphoric acid 1-?-D-glucopyranosyl ester 2-(2-thiouridin-5’’-yl) ester), caused a substantial calcium transient in RBL-2H3 cells, which was blocked by pertussis toxin, indicating the presence of the Gi-coupled P2Y14 receptor, supported also by quantitative detection of abundant mRNA. Expression of the closely related P2Y6 receptor was over 100 times lower than the P2Y14 receptor, and the P2Y6 agonist 3-phenacyl-UDP was inactive in RBL-2H3 cells. P2Y14 receptor agonists also induced [35S]GTP?S binding to RBL-2H3 cell membranes, and phosphorylation of ERK1/2, P38 and JNK. UDPG and MRS2690 concentration-dependently enhanced HEX release with EC50 values of 1150 ± 320 and 103 ± 18 nM, respectively. The enhancement was completely blocked by pertussis toxin and significantly diminished by P2Y14 receptor-specific siRNA. Thus, mast cells express an endogenous P2Y14 receptor, which mediates Gi-dependent degranulation and is therefore a potential novel therapeutic target for allergic conditions.

Gao, Zhan-Guo; Ding, Yi; Jacobson, Kenneth A.

2009-01-01

143

G protein coupled receptor specificity for C3a and compound 48\\/80-induced degranulation in human mast cells: Roles of Mas-related genes MrgX1 and MrgX2  

Microsoft Academic Search

Although human mast cells express G protein coupled receptors for the anaphylatoxin C3a, previous studies indicated that C3a causes mast cell degranulation, at least in part, via a C3a receptor-independent mechanism similar to that proposed for polycationic molecules such as compound 48\\/80. The purpose of the present study was to delineate the receptor specificity of C3a-induced degranulation in human mast

Sakeen W. Kashem; Hariharan Subramanian; Sarah J. Collington; Paola Magotti; John D. Lambris; Hydar Ali

2011-01-01

144

The use of selective pharmacological inhibitors to delineate signal transduction pathways activated during complement receptor-mediated degranulation in chicken heterophils  

Microsoft Academic Search

Complement receptors (CRs), along with Fc receptors, play a primary role in the removal of bacterial pathogens in poultry. The binding of serum-opsonized bacteria to CR results in the secretion of both toxic oxygen metabolites and antibacterial granules. We have previously shown that the stimulation of chicken heterophils with serum-opsonized Salmonella enteritidis induced tyrosine kinase-dependent phosphorylation regulated degranulation. In the

Michael H. Kogut; Virginia K. Lowry; Morgan Farnell

2003-01-01

145

Spontaneous locomotor activity correlates with the degranulation of mast cells in the meninges rather than in the thalamus: Disruptive effect of cocaine  

PubMed Central

Mast cells are located in the central nervous system (CNS) of many mammals and stress induces their degranulation. We postulated that mast cells are associated with wakefulness and stimulatory tone in the CNS, as reflected by spontaneous motor activity. Because stress also precipitates drug-seeking behavior in cocaine addicts, we also postulated that cocaine manifests its effects through this relationship. We investigated the influence of single and repeated injections of cocaine on circulating corticosterone, motor activity and degranulation of mast cells in both the thalamus and meninges of mice. Mice were subjected to 5 consecutive days of cocaine or saline followed by a single injection of cocaine or saline 11 days later. Spontaneous locomotor activity was measure for one hour after the final injection before death. Neither a single injection nor prior treatment with cocaine increased motor activity compared to saline-injected controls, however, repeated administration of cocaine induced a significant sensitization to its behavioral effect when delivered 11 days later. In mice that received only saline, motor activity correlated positively with mast cell degranulation in the meninges but not in the thalamus. Cocaine, regardless of the treatment schedule, disrupted this correlation. The concentration of corticosterone did not differ amongst groups and did not correlate with either behavior or mast cell parameters in any group. The correlation between behavioral activity and the mast cell degranulation in the meninges suggests that these parameters are linked. The disruptive effect of cocaine on this relationship indicates a role downstream from mast cells in the regulation of motor activity.

Larson, Alice A.; Thomas, Mark J.; McElhose, Alex; Kovacs, Katalin J.

2011-01-01

146

TiO2, CeO2 and ZnO nanoparticles and modulation of the degranulation process in human neutrophils.  

PubMed

Inflammation is frequently associated with nanoparticle (NP) exposures. Given that excessive polymorphonuclear neutrophil cell degranulation is a common feature of inflammatory disorders, and since these cells are key players in inflammation, we decided to test the hypothesis that NPs could act as modulators of degranulation in human neutrophils. TiO2, CeO2 and ZnO NPs slightly down-regulated cell surface expression of the granule marker CD35, but increased CD66b and CD63 expression, as assessed by flow cytometry. In addition, expression of myeloperoxidase, MMP-9 and albumin stored in azurophil, specific/gelatinase and secretrory granules, respectively, was significantly increased in the supernatants of NPs-induced neutrophils when compared to untreated cells. Moreover, NPs were more potent than the classical bacterial tripeptide N-formyl-methionine-leucine-phenylalanine (fMLP) agonist. Finally, TiO2 and CeO2 markedly increased the enzymatic activity of MMP-9 released into the supernatant, as assessed by gelatin zymography, while ZnO exerted only a modest effect. We conclude that NPs can differentially affect all steps involved during neutrophil degranulation, namely, cell surface expression of granule markers, liberation of proteins in the supernatants and enzymatic activity. These results are expected to be helpful to understand the toxicity of TiO2, CeO2 and ZnO. PMID:23726862

Babin, Kim; Antoine, Francis; Goncalves, David Miguel; Girard, Denis

2013-05-30

147

A truncated splice-variant of the Fc?RI? receptor subunit is critical for microtubule formation and degranulation in mast cells.  

PubMed

Human linkage analyses have implicated the MS4A2-containing gene locus (encoding Fc?RI?) as a candidate for allergy susceptibility. We have identified a truncation of Fc?RI? (t-Fc?RI?) in humans that contains a putative calmodulin-binding domain and thus, we sought to identify the role of this variant in mast cell function. We determined that t-Fc?RI? is critical for microtubule formation and degranulation and that it may perform this function by trafficking adaptor molecules and kinases to the pericentrosomal and Golgi region in response to Ca2+ signals. Mutagenesis studies suggest that calmodulin binding to t-Fc?RI? in the presence of Ca2+ could be critical for t-Fc?RI? function. In addition, gene targeting of t-Fc?RI? attenuated microtubule formation, degranulation, and IL-8 production downstream of Ca2+ signals. Therefore, t-Fc?RI? mediates Ca2+ -dependent microtubule formation, which promotes degranulation and cytokine release. Because t-Fc?RI? has this critical function, it represents a therapeutic target for the downregulation of allergic inflammation. PMID:23643722

Cruse, Glenn; Beaven, Michael A; Ashmole, Ian; Bradding, Peter; Gilfillan, Alasdair M; Metcalfe, Dean D

2013-05-02

148

Setaria cervi dual specific phosphatase: characterization and its effect on eosinophil degranulation.  

PubMed

Setaria cervi, a bovine filarial parasite contains significant acid phosphatase (AcP) activity in its various life stages. Two forms of AcP were separated from somatic extract of adult female parasite using cation exchange, gel filtration and concavalin affinity chromatography. One form having a molecular mass of 79 kDa was characterized as dual specific protein tyrosine phosphatase (ScDSP) based on substrate specificity and inhibition studies. With various substrates tested, it showed significant activity in the order of phospho-L-tyrosine>pNPP>ADP>phospho-L-serine. Inhibition by orthovanadate, fluoride, molybdate, and zinc ions further confirms protein tyrosine phosphatase nature of the enzyme. Km and Vmax determined with various substrates were found to be 16.66 mM, 25.0 microM/ml/min with pNPP; 20.0 mM, 40.0 microM/ml/min with phospho-L-tyrosine and 27.0 mM, 25.0 microM/ml/min with phospho-L-serine. KI with pNPP and sodium orthovanadate (IC50 33.0 microM) was calculated to be 50.0 mM. Inhibition with pHMB, silver nitrate, DEPC and EDAC suggested the presence of cysteine, histidine and carboxylate residues at its active site. Cross-reactivity with W. bancrofti-infected sera was demonstrated by Western blotting. ScDSP showed elevated levels of IgE in chronic filarial sera using ELISA. Under in vitro conditions, ScDSP resulted in increased effector function of human eosinophils when stimulated by IgG, which showed a further decrease with increasing enzyme concentration. Results presented here suggest that S. cervi DSP should be further studied to determine its role in pathogenesis and the persistence of filarial parasite. PMID:19523248

Rathaur, S; Rai, R; Srikanth, E; Srivastava, S

2009-06-15

149

Sustained TCR signaling is required for mitogen-activated protein kinase activation and degranulation by cytotoxic T lymphocytes.  

PubMed

Requirements for T cell activation are not fully established. One model is that receptor occupancy and down-regulation are essential for activation, and another, not necessarily mutually exclusive, model is that sustained signals are important. Here we examine the importance of signal duration in T cell activation. First, we demonstrate that immobilized, but not soluble cross-linked, Abs to CD3 stimulate degranulation by CTL. The cross-linked Abs are not deficient in their ability to signal since they stimulate the same tyrosine phosphorylation pattern as immobilized Ab, but it is very transient relative to that stimulated by immobilized Ab. Furthermore, novel decreased migratory forms of Lck occur to a significant extent only after stimulation with immobilized Abs. A dramatic difference in the duration of signals is very evident when mitogen-activated protein kinase (MAPK) activity is examined. Immobilized anti-CD3 stimulates very high levels of MAPK activation that is still detectable 1 h after stimulation. In contrast, cross-linked Ab stimulates only transient and incomplete activation of MAPK. Taken together, these results suggest that TCR engagement and induction of tyrosine phosphorylation alone are not sufficient for T cell activation and that the duration of TCR-stimulated signals is critical to attain a functional response. PMID:9743353

Berg, N N; Puente, L G; Dawicki, W; Ostergaard, H L

1998-09-15

150

Lesional skin chemokine CTACK/CCL27 expression in mycosis fungoides and disease control by IFN-alpha and PUVA therapy.  

PubMed

Recruitment of neoplastic T cells to skin is a critical step in the pathogenesis of mycosis fungoides (MF) lesions. Cutaneous T-cell attracting chemokine (CTACK)/CCL27 attracts memory T cells to skin, resulting in increased cutaneous expression. The interactions between neoplastic cells and skin immune system require further elucidation. CTACK/CCL27 expression and density of dendritic cells (DC), CD8+ and CD4+ lymphocytes were investigated in skin lesions of 52 early-stage MF patients treated by interferon (IFN)-alpha in combination with photochemotherapy (psoralen plus ultraviolet A, PUVA). Skin lesion biopsies obtained at diagnosis and after treatment were studied by immunohistochemistry. Initial CTACK/CCL27 expression was abnormal/suprabasal in 36 patients. Normal/basal CTACK/CCL27 expression tended to correlate with a high DC density and low CD4+ cell density in the neoplastic infiltrate. Treatment induced a significant increase in CTACK/CCL27 expression (chi(2) test: P=0.004). Overall, 33 patients relapsed [median event-free survival (EFS), 46 months] during follow-up (median, 92.5 months, range, 43-165). Normal/basal CTACK/CCL27 expression at the end of treatment correlated with lower rates of recurrence and a longer median EFS (111 months vs. 39 months with suprabasal expression; log rank test: P=0.031). CTACK/CCL27 overexpression in early-stage MF might thus be related to a balance between neoplastic cells and immunomodulant DC. Normal CTACK/CCL27 expression after treatment designates a subset of patients with favorable disease behavior. The mechanisms underpinning CTACK/CCL27 overexpression after therapy in the remaining patients, who are at greater risk of recurrence, warrant further investigation. PMID:19956431

Goteri, Gaia; Rupoli, Serena; Campanati, Anna; Costagliola, Antonello; Sabato, Simona; Stramazzotti, Daniela; Picardi, Paola; Canafoglia, Lucia; Pulini, Stefano; Ganzetti, Giulia; Offidani, Anna Maria; Leoni, Pietro

2009-01-31

151

Altered expression of degranulation-related genes in CD8+ T cells in human T lymphotropic virus type I infection.  

PubMed

Human T lymphotropic virus type I (HTLV-1) is the etiological agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). CD8+ T cells may contribute to the protection or development of HAM/TSP. In this study we used SAGE methodology to screen for differentially expressed genes in CD8+ T cells isolated from HTLV-1 asymptomatic carriers (HAC) and from HAM/TSP patients to identify genes involved in HAM/TSP development. SAGE analysis was conducted by pooling samples according to clinical status. The comparison of gene expression profiles between HAC and HAM/TSP libraries identified 285 differentially expressed tags. We focus on cytotoxicity and cytokine-related genes due to their potential biological role in HTLV-1 infection. Our results showed that patients with HAM/TSP have high expression levels of degranulation-related genes, namely GZMH and PRF1, and of the cytoskeletal adaptor PXN. We found that GZMB and ZAP70 were overexpressed in HTLV-infected patients compared to the noninfected group. We also detected that CCL5 was higher in the HAM/TSP group compared to the HAC and CT groups. Our findings showed that CD8+ T cells of HAM/TSP patients have an inflammatory and active profile. PXN and ZAP70 overexpression in HTLV-1-infected patients was described for the first time here and reinforces this concept. However, although active and abundant, CD8+ T cells are not able to completely eliminate infected cells and prevent the development of HAM/TSP and, moreover, these cells might contribute to the pathogenesis of the disease by migrating to the central nervous system (CNS). These results should be further tested with biological functional assays to increase our understanding on the role of these molecules in the development of HTLV-1-related diseases. PMID:23301858

Malta, Tathiane M; Silva, Israel T; Pinheiro, Daniel G; Santos, Anemarie R D; Pinto, Mariana T; Panepucci, Rodrigo A; Takayanagui, Osvaldo M; Tanaka, Yuetsu; Covas, Dimas T; Kashima, Simone

2013-02-05

152

Catestatin, a neuroendocrine antimicrobial peptide, induces human mast cell migration, degranulation and production of cytokines and chemokines  

PubMed Central

Catestatin, a neuroendocrine peptide with effects on human autonomic function, has recently been found to be a cutaneous antimicrobial peptide. Human catestatin exhibits three single nucleotide polymorphisms: Gly364Ser, Pro370Leu and Arg374Gln. Given reports indicating that antimicrobial peptides and neuropeptides induce mast cell activation, we postulated that catestatin might stimulate numerous functions of human mast cells, thereby participating in the regulation of skin inflammatory responses. Catestatin and its naturally occurring variants caused the human mast cell line LAD2 and peripheral blood-derived mast cells to migrate, degranulate and release leukotriene C4 and prostaglandins D2 and E2. Moreover, catestatins increased intracellular Ca2+ mobilization in mast cells, and induced the production of pro-inflammatory cytokines/chemokines such as granulocyte–macrophage colony-stimulating factor, monocyte chemotactic protein-1/CCL2, macrophage inflammatory protein-1?/CCL3 and macrophage inflammatory protein-1?/CCL4. Our evaluation of possible cellular mechanisms suggested that G-proteins, phospholipase C and the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) are involved in catestatin-induced mast cell activation as evidenced by the inhibitory effects of pertussis toxin (G-protein inhibitor), U-73122 (phospholipase C inhibitor) and U0126 (ERK inhibitor), respectively. We also found that human mast cells express the ?7 subunit of the nicotinic acetylcholine receptor at both the mRNA and protein levels. Given that silencing the ?7 receptor mRNA and an ?7-specific inhibitor did not affect catestatin-mediated activation of mast cells, however, we concluded that this receptor is not likely to be functional in human mast cell stimulation by catestatins. Our finding that the neuroendocrine antimicrobial peptide catestatin activates human mast cells suggests that this peptide might have immunomodulatory functions, and provides a new link between neuroendocrine and cutaneous immune systems.

Aung, Gyi; Niyonsaba, Francois; Ushio, Hiroko; Kajiwara, Naoki; Saito, Hirohisa; Ikeda, Shigaku; Ogawa, Hideoki; Okumura, Ko

2011-01-01

153

Herbex-kid Inhibits Immediate Hypersensitivity Reactions in Mice and Rats  

PubMed Central

Herbex-kid (HK), a polyherbal formulation was evaluated in various experimental allergic models of Type I hypersensitivity reactions. Compound 48/80 (C 48/80) has been shown to induce rat mesentery mast cell degranulation and HK (1.07, 10.75 and 107.5?mg?ml?1) inhibited the mast cell degranulation in a dose dependent manner. HK (1.07, 10.75 and 107.5?mg?kg?1; p.o.) showed dose-dependent protection against C 48/80 induced systemic anaphylaxis in male Balb/C mice. In active anaphylaxis model, male Wistar rats orally administered with 10.75 and 107.5?mg?kg?1 of HK showed significant (P?degranulation, while in passive anaphylaxis model, only at 107.5?mg?kg?1 showed significant (P?degranulation. HK at all dose levels was able to significantly decrease the time spent in nasal rubbing in Wistar rats sensitized to ovalbumin, while only at 107.5?mg?kg?1 it showed significant (P?inhibition in histamine induced contraction in guinea pig ileum. From the above findings we conclude that the HK possesses antiallergic activity mediated by reducing of the release mediators from mast cells and also by 5-HT antagonism without the involvement of histamine (H1) receptors.

Prasad, Rawal; Jogge, Nanjan Mulla; Bhojraj, Suresh; Emerson, Solomon F.; Prabakar, S.

2008-01-01

154

Herbex-kid Inhibits Immediate Hypersensitivity Reactions in Mice and Rats.  

PubMed

Herbex-kid (HK), a polyherbal formulation was evaluated in various experimental allergic models of Type I hypersensitivity reactions. Compound 48/80 (C 48/80) has been shown to induce rat mesentery mast cell degranulation and HK (1.07, 10.75 and 107.5 mg ml(-1)) inhibited the mast cell degranulation in a dose dependent manner. HK (1.07, 10.75 and 107.5 mg kg(-1); p.o.) showed dose-dependent protection against C 48/80 induced systemic anaphylaxis in male Balb/C mice. In active anaphylaxis model, male Wistar rats orally administered with 10.75 and 107.5 mg kg(-1) of HK showed significant (P < 0.01) protection against mast cell degranulation, while in passive anaphylaxis model, only at 107.5 mg kg(-1) showed significant (P < 0.01) reduction in mast cell degranulation. HK at all dose levels was able to significantly decrease the time spent in nasal rubbing in Wistar rats sensitized to ovalbumin, while only at 107.5 mg kg(-1) it showed significant (P < 0.01) reduction in number of sneezes. In C 48/80-induced skin itch model, all dose levels of HK significantly (P < 0.001) decreased the time spent in itching and the number of itches. HK did not produce any significant inhibition in histamine induced contraction in guinea pig ileum. From the above findings we conclude that the HK possesses antiallergic activity mediated by reducing of the release mediators from mast cells and also by 5-HT antagonism without the involvement of histamine (H1) receptors. PMID:18830458

Kumar, Anil; Prasad, Rawal; Jogge, Nanjan Mulla; Bhojraj, Suresh; Emerson, Solomon F; Prabakar, S

2008-09-01

155

Inhibitory effects of sesquiterpene lactones isolated from Eupatorium chinense L. on IgE-mediated degranulation in rat basophilic leukemia RBL-2H3 cells and passive cutaneous anaphylaxis reaction in mice.  

PubMed

Sesquiterpene lactones (SQTLs) have been shown to suppress the degranulation as inferred by histamine release in rat basophilic leukemia RBL-2H3 cells. In this study, we isolated the 9 kinds of SQTLs from Eupatorium chinense L. and examined the effects of these SQTLs on the degranulation in RBL-2H3 cells. The chemical structures of two novel compounds (SQTL-3 and 8) were determined. All the SQTLs suppressed the degranulation from Ag-stimulated RBL-2H3 cells. To disclose the inhibitory mechanism of degranulation by SQTLs, we examined the activation of intracellular signaling molecules such as Lyn, Syk, and PLCgammas and intracellular free Ca(2+) concentration ([Ca(2+)]i). None of these SQTLs showed the activation of Syk and PLCgammas. The intracellular free Ca(2+) concentration ([Ca(2+)]i) was elevated by Fc epsilonRI activation, but SQTLs treatment reduced the elevation of [Ca(2+)]i by suppressing Ca(2+) influx. Thus, it was suggested that the suppression of Ag-stimulated degranulation by these SQTLs is mainly due to the decreased Ca(2+) influx. Furthermore, in order to clarify the in vivo effect of SQTL-rich extract, we administered SQTL-rich extract to the type I allergic model mice and measured the passive cutaneous anaphylaxis (PCA) reaction induced by IgE-antigen complex. The SQTLs remarkably suppressed PCA reaction in a dose-dependent manner. Thus, it was suggested that SQTLs would be a candidate as an anti-allergic agent. PMID:19318257

Itoh, Tomohiro; Oyama, Masayoshi; Takimoto, Norihiko; Kato, Chihiro; Nozawa, Yoshinori; Akao, Yukihiro; Iinuma, Munekazu

2009-03-05

156

IL-1 beta does not cause neutrophil degranulation but does lead to IL-6, IL-8, and nitrite/nitrate release when used in patients with cancer.  

PubMed

The use of IL-1 in humans is associated with dose-limiting toxicity which resembles that of TNF-alpha or IL-2. Activation of neutrophils is thought to contribute to the toxicity caused by these two cytokines. We studied the effect of IL-1 in vivo on changes in neutrophil numbers and neutrophil degranulation as well as on the formation of neutrophil agonists, such as complement activation products, and on levels of TNF, IL-6, IL-8, and nitrite/nitrate (as a measure of nitric oxide production). Six patients with metastatic melanoma were treated with 3 ng/kg recombinant human IL-1 beta daily. One hour after the start of the 30-min IL-1 infusion, which caused mild cardiovascular toxicity, plasma levels of IL-6 reached a peak of 25 +/- 9 ng/L (mean +/- SEM), IL-8 reached a peak of 311 +/- 100 ng/L at 2 h, and nitrite/nitrate peaked after 10 h to 89 +/- 27 mumol/L. IL-1 did not induce significant changes in plasma levels of TNF or of the complement activation products C3a and C4b/c. Although IL-1 induced neutrophilia, levels of elastase and lactoferrin did not change. The failure of IL-1 to degranulate neutrophils was confirmed in an ex vivo model with whole blood culture in which doses of up to 100 microgram/L IL-1 beta or IL-1 alpha failed to induce significant elastase or lactoferrin release, whereas TNF, tested as a positive control, was able to do so. These results demonstrate that, unlike TNF, IL-1 does not cause neutrophil degranulation in man, despite its ability to cause neutrophilia and the rapid release of IL-6, IL-8, and nitrite/nitrate. PMID:8598489

Ogilvie, A C; Hack, C E; Wagstaff, J; van Mierlo, G J; Erenberg, A J; Thomsen, L L; Hoekman, K; Rankin, E M

1996-01-01

157

Food allergen--induced mast cell degranulation is dependent on PI3K-mediated reactive oxygen species production and upregulation of store-operated calcium channel subunits.  

PubMed

The importance of Ca(2+) influx via store-operated calcium channels (SOCs) leading to mast cell degranulation is well known in allergic disease. However, the underlying mechanisms are not fully understood. With food-allergic rat model, the morphology of degranulated mast cell was analysed by toluidine blue stain and electron microscope. Ca(2+) influx via SOCs was checked by Ca(2+) imaging confocal microscope. Furthermore, the mRNA and protein expression of SOCs subunits were investigated using qPCR and Western blot. We found that ovalbumin (OVA) challenge significantly increased the levels of Th2 cytokines and OVA-specific IgE in allergic animals. Parallel to mast cell activation, the levels of histamine in serum and supernatant of rat peritoneal lavage solution were remarkably increased after OVA treatment. Moreover, the Ca(2+) entry through SOCs evoked by thapsigargin was increased in OVA-challenged group. The mRNA and protein expressions of SOC subunits, stromal interaction molecule 1 (STIM1) and Orail (calcium-release-activated calcium channel protein 1), were dramatically elevated under food-allergic condition. Administration of Ebselen, a scavenger of reactive oxygen species (ROS), significantly attenuated OVA sensitization-induced intracellular Ca(2+) rise and upregulation of SOCs subunit expressions. Intriguingly, pretreatment with PI3K-specific inhibitor (Wortmannin) partially abolished the production of ROS and subsequent elevation of SOCs activity and their subunit expressions. Taken together, these results imply that enhancement of SOC-mediated Ca(2+) influx induces mast cell activation, contributing to the pathogenesis of OVA-stimulated food allergy. PI3K-dependent ROS generation involves in modulating the activity of SOCs by increasing the expressions of their subunit. PMID:23672459

Yang, B; Yang, C; Wang, P; Li, J; Huang, H; Ji, Q; Liu, J; Liu, Z

2013-07-01

158

Inhibitory effect of xanthones isolated from the pericarp of Garcinia mangostana L. on rat basophilic leukemia RBL-2H3 cell degranulation.  

PubMed

Mangostin, Garcinia mangostana L. is used as a traditional medicine in southeast Asia for inflammatory and septic ailments. Hitherto we indicated the anticancer activity induced by xanthones such as alpha-, beta-, and gamma-mangostin which were major constituents of the pericarp of mangosteen fruits. In this study, we examined the effect of xanthones on cell degranulation in rat basophilic leukemia RBL-2H3 cells. Antigen (Ag)-mediated stimulation of high affinity IgE receptor (FcepsilonRI) activates intracellular signal transductions resulting in the release of biologically active mediators such as histamine. The release of histamine and other inflammatory mediators from mast cell or basophils is the primary event in several allergic responses. These xanthones suppressed the release of histamine from IgE-sensitized RBL-2H3 cells. In order to reveal the inhibitory mechanism of degranulation by xanthones, we examined the activation of intracellular signaling molecules such as Lyn, Syk, and PLCgammas. All the xanthones tested significantly suppressed the signaling involving Syk and PLCgammas. In Ag-mediated activation of FcepsilonRI on mast cells, three major subfamilies of mitogen-activated protein kinases were activated. The xanthones decreased the level of phospho-ERKs. Furthermore, the levels of phospho-ERKs were observed to be regulated by Syk/LAT/Ras/ERK pathway rather than PKC/Raf/ERK pathway, suggesting that the inhibitory mechanism of xanthones was mainly due to suppression of the Syk/PLCgammas/PKC pathway. Although intracellular free Ca(2+) concentration ([Ca(2+)](i)) was elevated by FcepsilonRI activation, it was found that alpha- or gamma-mangostin treatment was reduced the [Ca(2+)](i) elevation by suppressed Ca(2+) influx. PMID:18328716

Itoh, Tomohiro; Ohguchi, Kenji; Iinuma, Munekazu; Nozawa, Yoshinori; Akao, Yukihiro

2008-02-21

159

Pharmacologic inhibition of I?B kinase activates immediate hypersensitivity reactions in mice.  

PubMed

Pharmacologic inhibitors of I?B kinase (IKK), especially IKK-?, have been developed to treat inflammatory diseases. However, their interactions with components of the NF-?B pathways are not fully known in allergic diseases. To examine whether IKK is involved in immediate hypersensitivity reactions and to determine whether counterregulatory mechanisms in the NF-?B activation system were active, we examined the role played by IKK components on mast cell degranulation using a murine ocular immediate hypersensitivity reaction model. Pharmacologic inhibition of IKK in mice caused paradoxical aggravation of the mast cell-mediated immediate hypersensitivity reaction and up-regulation in the expression of inflammatory cytokines. Downstream analyses showed that B-cell deficiency or treatment by IL-1 receptor antagonist corrected the aberrant activation of tissue-resident mast cells, which would indicate contribution by activated B cells. Analyses of co-cultures of tissue-resident mast cells showed the contribution of activated B cells to activation of mast cells and secretion of inflammatory cytokines. Aberrant activation of the NF-?B promoter in isolated B cells was induced exclusively by IKK-? inhibition and was negated by ablating IKK-?. Aggravated mast cell degranulation by pharmacologic IKK inhibition in the murine immediate hypersensitivity reaction was corrected by B-cell-targeted inhibition of IKK-?. Thus, IKK-? limits B-cell-mediated mast cell activation and inflammatory cytokine induction in immediate hypersensitivity by counterbalancing the activity of IKK-?. PMID:23665348

Miyazaki, Dai; Mihara, Sachiko; Inata, Koudai; Sasaki, Shin-ichi; Tominaga, Takeshi; Yakura, Keiko; Ishida, Waka; Fukushima, Atsuki; Inoue, Yoshitsugu

2013-05-08

160

G Protein coupled Receptor Specificity for C3a and Compound 48/80-induced degranulation in human mast cells: Roles of Mas-related genes MrgX1 and MrgX2  

PubMed Central

Although human mast cells express G protein coupled receptors for the anaphylatoxin C3a, previous studies indicated that C3a causes mast cell degranulation, at least in part, via a C3a receptor-independent mechanism similar to that proposed for polycationic molecules such as compound 48/80. The purpose of the present study was to delineate the receptor specificity of C3a-induced degranulation in human mast cells. We found that C3a, a C3a receptor “superagonist” (E7) and compound 48/80 induced Ca2+ mobilization and degranulation in a differentiated human mast cell line, LAD2. However, C3a and E7 caused Ca2+ mobilization in an immature mast cell line, HMC-1 but compound 48/80 did not. We have previously shown that LAD2 cells express MrgX1 and MrgX2 but HMC-1 cells do not. To delineate the receptor specificity for C3a and compound 48/80 further, we generated stable transfectants expressing MrgX1 and MrgX2 in a rodent mast cell line, RBL-2H3 cells. We found that compound 48/80 caused degranulation in RBL-2H3 cells expressing MrgX1 and MrgX2 but C3a did not. By contrast, E7 activated RBL-2H3 cells expressing MrgX2 but not MrgX1. These findings demonstrate that in contrast to previous reports, C3a and compound 48/80 do not use a shared mechanism for mast cell degranulation. It shows that while compound 48/80 utilizes MrgX1 and MrgX2 for mast cell degranulation C3a does not. It further reveals the novel finding that the previously characterized synthetic peptide, C3a receptor “superagonist” E7 activates human mast cells via two mechanisms; one involving the C3a receptor and the other MrgX2.

Kashem, Sakeen W.; Subramanian, Hariharan; Collington, Sarah J.; Magotti, Paola; Lambris, John D.; Ali, Hydar

2011-01-01

161

G protein coupled receptor specificity for C3a and compound 48/80-induced degranulation in human mast cells: roles of Mas-related genes MrgX1 and MrgX2.  

PubMed

Although human mast cells express G protein coupled receptors for the anaphylatoxin C3a, previous studies indicated that C3a causes mast cell degranulation, at least in part, via a C3a receptor-independent mechanism similar to that proposed for polycationic molecules such as compound 48/80. The purpose of the present study was to delineate the receptor specificity of C3a-induced degranulation in human mast cells. We found that C3a, a C3a receptor "superagonist" (E7) and compound 48/80 induced Ca(2+) mobilization and degranulation in a differentiated human mast cell line, LAD2. However, C3a and E7 caused Ca(2+) mobilization in an immature mast cell line, HMC-1 but compound 48/80 did not. We have previously shown that LAD2 cells express MrgX1 and MrgX2 but HMC-1 cells do not. To delineate the receptor specificity for C3a and compound 48/80 further, we generated stable transfectants expressing MrgX1 and MrgX2 in a rodent mast cell line, RBL-2H3 cells. We found that compound 48/80 caused degranulation in RBL-2H3 cells expressing MrgX1 and MrgX2 but C3a did not. By contrast, E7 activated RBL-2H3 cells expressing MrgX2 but not MrgX1. These findings demonstrate that in contrast to previous reports, C3a and compound 48/80 do not use a shared mechanism for mast cell degranulation. It shows that while compound 48/80 utilizes MrgX1 and MrgX2 for mast cell degranulation C3a does not. It further reveals the novel finding that the previously characterized synthetic peptide, C3a receptor "superagonist" E7 activates human mast cells via two mechanisms; one involving the C3a receptor and the other MrgX2. PMID:21741965

Kashem, Sakeen W; Subramanian, Hariharan; Collington, Sarah J; Magotti, Paola; Lambris, John D; Ali, Hydar

2011-07-03

162

Selective pharmacological inhibitors reveal the role of Syk tyrosine kinase, phospholipase C, phosphatidylinositol-3?-kinase, and p38 mitogen-activated protein kinase in Fc receptor-mediated signaling of chicken heterophil degranulation  

Microsoft Academic Search

Fc receptors of avian heterophils play a primary role in the elimination of bacterial pathogens in poultry. The cross-linking of Fc receptors with IgG-bacteria complexes results in the secretion of toxic oxygen metabolites and anti-bacterial granules. We have been investigating the upstream signaling events that precede degranulation following crosslinkage of Fc receptors on heterophils. Previously when using the non-selective pharmacological

Michael Kogut; Virginia K. Lowry; Morgan Farnell

2002-01-01

163

Novel mast cell lines with enhanced proliferative and degranulative abilities established from temperature-sensitive SV40 large T antigen transgenic mice.  

PubMed

Mast cells (MCs) play crucial roles in innate immunity to parasitic and bacterial infections as well as in hypersensitivity, such as the induction and exacerbation of allergy and autoimmune diseases. The regulatory mechanisms for MC development and effector functions are of great interest for developing novel therapeutic strategies against such disorders. Here we report the establishment of novel, immortalized MC lines from bone marrow (BM) cells of a temperature-sensitive mutant of SV40 large T antigen-transgenic mice (termed SVMCs). BM cells from tsSV40LT mice were cultured in the presence of interleukin (IL)-3 for 3 weeks, and then subjected to limiting dilution and single-cell cloning, yielding 27 independent MC clones, three of which were subjected to further analysis. On culture with nerve growth factor, stem cell factor and IL-3, these SVMC clones showed morphologic and biochemical changes from mucosal MC-like to connective-tissue MC-like phenotypes. These SVMC lines exhibited a significantly enhanced proliferation rate, and a higher responsiveness to the high affinity Fc receptor for IgE-mediated intracellular calcium mobilization and degranulation than those of BM-derived cultured MCs. These cell lines should facilitate studies on the mechanisms for the development, differentiation and effector functions of MCs in health and diseases. PMID:16822814

Kanehira, Masahiko; Kaifu, Tomonori; Maya, Kozue; Kaji, Mitsuji; Nakamura, Akira; Obinata, Masuo; Takai, Toshiyuki

2006-07-05

164

Insulin-containing lipogenic stimuli suppress mast cell degranulation potential and up-regulate lipid body biogenesis and eicosanoid secretion in a PPAR?-independent manner  

PubMed Central

Lipid bodies are most studied in adipocytes, where the lipogenic action of insulin initiates their formation. Here, we test the hypothesis that insulin may regulate lipid body content in mast cells and hence, modify their proinflammatory potential. Our data show that insulin causes lipid body accumulation in RBL2H3 and BMMCs. Lipid body accumulation in mast cells is associated with enhanced levels of leukotriene-synthesizing enzymes (LTC4S and 5-LO). Increased basal and antigen-stimulated release of LTC4 is observed in insulin-treated mast cells. Concomitantly, the insulin-containing lipogenic stimulus induces a phenotypic change in mast cells, where this enhancement in leukotriene levels is accompanied by a marked down-regulation in secretory granule content and release in response to stimulus. Mast cells exposed to insulin exhibit altered scatter and fluorescence properties, accumulating in a SSCloFSChi population that exhibits decreased BS staining and degranulation responses and is enriched in NR-positive lipid bodies and eicosanoid synthesis enzymes. Lipid body accumulation in mast cells is mechanistically distinct from the process in adipocytes; for example, it is independent of PPAR? up-regulation and does not involve significant accumulation of conjugated glycerides. Thus, chronic exposure to metabolic stimuli, such as insulin, may be a determinant of the proinflammatory potential of the mast cell.

Greineisen, William E.; Shimoda, Lori M. N.; Maaetoft-Udsen, Kristina; Turner, Helen

2012-01-01

165

Probing the mystery of Chinese medicine meridian channels with special emphasis on the connective tissue interstitial fluid system, mechanotransduction, cells durotaxis and mast cell degranulation  

PubMed Central

This article hypothesizes that the Chinese medicine meridian system is a special channel network comprising of skin with abundant nerves and nociceptive receptors of various types, and deeper connective tissues inside the body with the flowing interstitial fluid system. These meridian channels provide efficient migratory tracks mainly due to durotaxis (also including chemotaxis) for mast cells, fibroblasts and other cells to migrate and carry out a number of physiological functions. Acupuncture acting on meridian channel causes cytoskeletal remodeling through mechanotransduction, leading to regulation of gene expression and the subsequent production of related proteins. Also, stimulation on cell surface can trigger Ca2+ activities, resulting in a cascade of intra- and inter-cellular signaling. Moreover, nerve endings in the meridian channels interact with mast cells and induce the degranulation of these cells, leading to the release of many specific biomolecules needed for homeostasis, immune surveillance, wound healing and tissue repair. Acupoint along a meridian channel is a functional site to trigger the above functions with specificity and high efficiency.

Fung, Peter Chin Wan

2009-01-01

166

Effect of Scrophularia buergeriana extract on the degranulation of mast cells and ear swelling induced by dinitrofluorobenzene in mice.  

PubMed

Scrophularia buergeriana Miquel (Scrophulariaceae, SB) is a biennial plant native to Korea, northern China, and Japan that plays an important role in traditional medicine. The dried root of SB has long been used in oriental medicine for treatment of fever, swelling, constipation, pharyngitis, neuritis, and laryngitis. In the present study, we evaluated the ethanol extract of SB (SBE) to determine if it exerted any anti-allergic effects that had not previously been demonstrated. SBE markedly inhibited ?-hexosaminidase and histamine release and suppressed the expression of tumor necrosis factor-? and interleukin-4 cytokines by RBL-2H3 mast cells. In addition, topical treatment with SBE effectively reduced allergic inflammation in a dinitrofluorobenzene-induced contact hypersensitivity mouse model. These results strongly suggest that SBE is a promising source of anti-allergic agents. PMID:21318391

Kim, Jin-Kyung; Kim, Yoon Hee; Lee, Hee Hwan; Lim, Soon Sung; Park, Kyung Woo

2012-02-01

167

Mountain cedar pollen induces IgE-independent mast cell degranulation, IL-4 production, and intracellular reactive oxygen species generation  

PubMed Central

Cedar pollens cause severe allergic disease throughout the world. We have previously characterized allergenic pollen glycoproteins from mountain cedar (Juniperus ashei) that bind to allergen-specific immunoglobulin E (IgE). In the present report, we investigated an alternative pathway of mast cell activation by mountain cedar pollen extract through IgE-independent mechanisms. We show that mountain cedar pollen directly induces mast cell serotonin and IL-4 release and enhances release induced by IgE cross-linking. Concomitant with mediator release, high levels of intracellular reactive oxygen species (ROS) were generated, and both ROS and serotonin release were inhibited by anti-oxidants. These findings suggest that alternative mechanisms exist whereby pollen exposure enhances allergic inflammatory mediator release through mechanisms that involve ROS. These mechanisms have the potential for enhancing the allergenic potency of pollens.

Endo, Shuichiro; Hochman, Daniel J.; Midoro-Horiuti, Terumi; Goldblum, Randall M.; Brooks, Edward G.

2011-01-01

168

Platelet Adhesion and Degranulation Induce Pro-Survival and Pro-Angiogenic Signalling in Ovarian Cancer Cells  

PubMed Central

Thrombosis is common in ovarian cancer. However, the interaction of platelets with ovarian cancer cells has not been critically examined. To address this, we investigated platelet interactions in a range of ovarian cancer cell lines with different metastatic potentials [HIO-80, 59M, SK-OV-3, A2780, A2780cis]. Platelets adhered to ovarian cancer cells with the most significant adhesion to the 59M cell line. Ovarian cancer cells induced platelet activation [P-selectin expression] in a dose dependent manner, with the most significant activation seen in response to the 59M cell line. The platelet antagonists [cangrelor, MRS2179, and apyrase] inhibited 59M cell induced activation suggesting a P2Y12 and P2Y1 receptor mediated mechanism of platelet activation dependent on the release of ADP by 59M cells. A2780 and 59M cells potentiated PAR-1, PAR-4, and TxA2 receptor mediated platelet activation, but had no effect on ADP, epinephrine, or collagen induced activation. Analysis of gene expression changes in ovarian cancer cells following treatment with washed platelets or platelet releasate showed a subtle but valid upregulation of anti-apoptotic, anti-autophagy pro-angiogenic, pro-cell cycle and metabolic genes. Thus, ovarian cancer cells with different metastatic potential adhere and activate platelets differentially while both platelets and platelet releasate mediate pro-survival and pro-angiogenic signals in ovarian cancer cells.

Smyth, Paul; O'Toole, Sharon; Spillane, Cathy; Martin, Cara; Gallagher, Michael; Canney, Aoife; Norris, Lucy; Conlon, Niamh; McEvoy, Lynda; Ffrench, Brendan; Stordal, Britta; Keegan, Helen; Finn, Stephen; McEneaney, Victoria; Laios, Alex; Ducree, Jens; Dunne, Eimear; Smith, Leila; Berndt, Michael; Sheils, Orla; Kenny, Dermot; O'Leary, John

2011-01-01

169

Raft localization of Type I Fc? receptor and degranulation of RBL-2H3 cells exposed to decavanadate, a structural model for V2O5.  

PubMed

Vanadium oxides (VOs) have been identified as low molecular weight sensitizing agents associated with occupational asthma and compromised pulmonary immunocompetence. Symptoms of adult onset asthma result, in part, from increased signal transduction by Type I Fc? receptors (Fc?RI) leading to release of vasoactive compounds including histamine from mast cells. Exposure to (VOs) typically occurs in the form of particles which are insoluble. Upon contact with water or biological fluids, (VOs) form a series of soluble oxoanions, one of which is decavanadate, V10O28(6-) abbreviated V10, which is structurally related to a common vanadium oxide, that is vanadium pentoxide, V2O5. Here we investigate whether V10 may be initiating plasma membrane events associated with activation of Fc?RI signal transduction. We show that exposure of RBL-2H3 cells to V10 causes a concentration-dependent increase in degranulation of RBL-2H3 and, in addition, an increase in plasma membrane lipid packing as measured by the fluorescent probe, di-4-ANEPPDHQ. V10 also increases Fc?RI accumulation in low-density membrane fragments, i.e., lipid rafts, which may facilitate Fc?RI signaling. To determine whether V10 effects on plasma membrane lipid packing were similarly observed in Langmuir monolayers formed from dipalmitoylphosphatidylcholine (DPPC), the extent of lipid packing in the presence and absence of V10 and vanadate was compared. V10 increased the surface area of DPPC Langmuir monolayers by 6% and vanadate decreased the surface area by 4%. These results are consistent with V10 interacting with this class of membrane lipids and altering DPPC packing. PMID:23861175

Al-Qatati, Abeer; Fontes, Fabio L; Barisas, B George; Zhang, Dongmei; Roess, Deborah A; Crans, Debbie C

2013-09-01

170

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

PubMed

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 ?-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-?; 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

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

2012-10-01

171

Inhibition of early and late phase allergic reactions by Euphorbia hirta L.  

PubMed

A 95% ethanol extract from whole aerial parts of Euphorbia hirta (EH A001) showed antihistaminic, antiinflammatory and immunosuppressive properties in various animal models. EH A001 inhibited rat peritoneal mast cell degranulation triggered by compound 48/80. It significantly inhibited dextran-induced rat paw edema. EH A001 prevented eosinophil accumulation and eosinophil peroxidase activity and reduced the protein content in bronchoalveolar lavage fluid (BALF) in a 'mild' model of asthma. Moreover, the CD4/CD8 ratio in peripheral blood was suppressed. EH A001 attenuated the release of interleukin-4 (IL-4) and augmented interferon-gamma (IFN-gamma) in ovalbumin-sensitized mouse splenocytes. The results were compared with the effects of known compounds, ketotifen, cetirizine and cyclophosphamide. These findings demonstrated that Euphorbia hirta possessed significant activity to prevent early and late phase allergic reactions. PMID:16557622

Singh, G D; Kaiser, P; Youssouf, M S; Singh, S; Khajuria, A; Koul, A; Bani, S; Kapahi, B K; Satti, N K; Suri, K A; Johri, R K

2006-04-01

172

FcepsilonRI-alpha siRNA inhibits the antigen-induced activation of mast cells.  

PubMed

FcepsilonRI, The high affinity receptor for IgE plays a critical role in triggering the allergic reactions. It is responsible for inducing mast cell degranulation and deliberation of allergy mediators when it is aggregated by allergen and IgE complexes. FcepsilonRI on the mast cells consists of three subunits; alpha chain directly binds IgE, beta chain and dimmer of gamma chains together mediate intracellular signaling. Cross-linking of IgE-bound FcepsilonRI on the surface of mast cells and basophils by the multivalent antigen induces release of chemical mediators. The present in vitro study was designed to investigate the effect of synthetic FcepsilonRI-alpha siRNA on the antigen-induced activation of MC/9 cells. MC/9 cells which are murine mast cells were transfected by FcepsilonRI-alpha siRNA and negative control siRNA. After 6 h, anti-DNP (Dinitrophenyl) IgE was used for the cells sensitization. Then the cells were challenged with Dinitrophenyl-Human Serum Albumin (DNP-HSA) for mast cell degranulation induction before collection of supernatants. The amount of mRNA and protein expression was measured by Real Time PCR and western blot analysis, respectively. Determination of the expression rate of FcepsilonRI-alpha on cell surface was achieved by flow cytometry. ELISA and spectrophotometry methods were used subsequently for measuring the effects of FcepsilonRI-alpha siRNA on antigen-induced histamine and beta-hexosaminidase release. FcepsilonRI-alpha siRNA treated cells showed significant decrease in FcepsilonRI-alpha mRNA and protein expression in comparison to control cells. FcepsilonRI-mediated mast cell release of beta-hexosaminidase and histamine were also inhibited. In this study it was shown that FcepsilonRI-alpha siRNA could suppress FcepsilonRI-alpha expression and inhibited degranulation and histamine release in antigen-stimulated MC/9 cells. In conclusion, knock-down of FcepsilonRI-alpha by siRNA could be a promising method for inhibition of the mast cell-mediated allergic reactions. PMID:20404387

Safaralizadeh, Reza; Soheili, Zahra-Soheila; Deezagi, Abdolkhaleg; Pourpak, Zahra; Samiei, Shahram; Moin, Mostafa

2009-12-01

173

Latent inhibition  

Microsoft Academic Search

Reviews the latent inhibition literature concerning the decremental effects of nonreinforced preexposure to the to-be-conditional stimulus on subsequent learning. Latent inhibition is found to be a broadly based phenomenon appearing across a variety of species (goldfish, goat, sheep, rat, rabbit, dog, human child, and, under special conditions, the human adult) and across a variety of tasks (classical conditioning, avoidance conditioning,

Robert E. Lubow

1973-01-01

174

Corrosion inhibition  

SciTech Connect

A corrosion-inhibiting composition of matter comprising (1) the reaction mass resulting from the reaction of an ..cap alpha..,b-unsaturated hydrocarbyl nitrile and a metal hydrocarbyl sulfonate, (2) an alcohol, (3) a hydrocarbon diluent, and optionally (4) an epoxy resin. The composition is particularly useful in the treatment of downhole metal surfaces in oil and gas wells for inhibiting the corrosion of the metal.

Wu, Y.

1985-12-03

175

Hyaluronic acid inhibits fetal platelet function: implications in scarless healing.  

PubMed

Platelets are important for the initiation of inflammation in adults, but the role of fetal platelets in fetal wound healing is unclear because fetal dermal wounds heal with a minimal inflammatory response and lack of excessive scarring. Because fetal tissue is abundant in glycosaminoglycans (GAGs), predominantly hyaluronic acid (HA), this study was designed to test the hypothesis that HA inhibits the reactivity of platelets and thus contributes to the minimal scarring characteristic of fetal tissue repair. Platelets were isolated from 10 fetal pigs at day 80 of gestation (term, 115 days) and exposed to 0.5 mg/mL of arachidonic acid, an agent shown in prior studies to evoke maximal aggregation and degranulation of fetal platelets. The ability of HA at 0.1 and 0.5 mg/mL to inhibit this response was determined. The presence of HA resulted in a dose-dependent reduction in platelet aggregation at 180 seconds (control, 99.7 +/- 0.3%; HA [0.1 mg/mL] 91.7 +/- 3.8%; and HA [0.5 mg/mL] 48.5 +/- 9.0%; P < .005 v control). The onset of aggregation was also significantly delayed by 0.5 mg/mL of HA (13.5 +/- 2.5 seconds) compared to control (2.9 +/- 0.7 seconds), P < .05. No significant diminution of platelet aggregation could be achieved by the addition of other GAGs at similar concentrations. HA also significantly impaired the release of platelet-derived growth factor (PDGF)-AB from fetal platelets. The authors conclude that HA, the predominant GAG in fetal dermal matrix, inhibits platelet aggregation and cytokine release. This inhibition of platelet aggregation and resultant inflammatory response may explain, in part, the minimal inflammation and scarless healing characteristic of fetal dermal repair. PMID:9247229

Olutoye, O O; Barone, E J; Yager, D R; Uchida, T; Cohen, I K; Diegelmann, R F

1997-07-01

176

Degranulation of polymorphonuclear leukocytes is induced by multivalent cross-linking of wheat germ agglutinin binding site(S) on cell membrane  

Microsoft Academic Search

Polymorphonuclear leukocyte (PMN) surface membrane glycoproteins very likely are involved in the phenomenon of stimulus-response coupling. Previously, we have shown that subagglutinating concentrations of the plant lectin, wheat germ agglutinin (WGA) specifically and irreversibly inhibitedN-formyl-methionyl-leucyl-phenyl-alanine (FMLP)-mediated PMN chemotaxis. WGA did not affect the binding of [3H]FMLP to its receptor on the PMN plasma membrane. We have examined the possibility that

H. Daniel Perez; Richard R. Ong

1984-01-01

177

Sanguinarine suppresses IgE induced inflammatory responses through inhibition of type II PtdIns 4-kinase(s).  

PubMed

The effects of sanguinarine on IgE mediated early signaling mechanisms leading to inflammatory mediators release were investigated. Pretreatment of RBL 2H3 cells with sanguinarine inhibited IgE induced activation of type II PtdIns 4-kinase activity. Concomitant with type II PtdIns 4-kinase inhibition, sanguinarine also inhibited IgE induced degranulation and ? hexosaminidase release in RBL 2H3 cells. In vitro assays showed sanguinarine inhibited type II PtdIns 4-kinase activity in a dose dependent fashion with no effect on PtdIns 3-kinase activity. Fluorescence spectroscopic studies suggested that sanguinarine binds to type II PtdIns 4-kinases ? and ? isoforms with a Kd of 2.4 and 1.8?M, respectively. Kinetic studies showed that sanguinarine competes with PtdIns binding site of type II PtdIns 4-kinase ?. These results suggest that the anti-inflammatory effects of sanguinarine on PtdIns 3-kinase signaling pathway are more likely an indirect effect and emphasize the importance of the cross talk between type II PtdIns 4-kinases and PtdIns 3-kinases. PMID:23899475

Bojjireddy, Naveen; Sinha, Ranjeet Kumar; Panda, Dulal; Subrahmanyam, Gosukonda

2013-07-27

178

5-Lipoxygenase Inhibition of the Fructus of Foeniculum vulgare and Its Constituents.  

PubMed

The fruits of Foeniculum vulgare (Foeniculi Fructus) have been widely used in Chinese medicine as an antiemetic, ameliorating stomach ailments and as an analgesic. In order to establish its potential for antiallergic use, inhibitory actions of the fruiton 5-lipoxgenase (5-LOX) and ?-hexosaminidase release were evaluated. The 70% ethanol extract of this plant material (FR) considerably inhibited 5-LOX-catalyzed leukotriene production from A23187-induced rat basophilic leukemia (RBL)-1 cells. The IC50 was 3.2 ?g/ml. From this extract, 12 major compounds including sabinene, fenchone, ?-terpinene, ?-pinene, limonene, p-anisylacetone, p-anisylaldehyde, estragole (4-allylanisole), trans-anethole, scopoletin, bergapten and umbelliferone were isolated. And it was found that several terpene derivatives including ?-terpinene and fenchone as well as phenylpropanoid, trans-anethole, showed considerable inhibitory action of 5-LOX. In particular, the IC50 of trans-anethole was 51.6 ? M. In contrast, FR and the isolated compounds did not show considerable inhibitory activity on the degranulation reaction of ?-hexosaminidase release from antigen-treated RBL-2H3 cells. Against arachidonic acid-induced ear edema in mice, FR and trans-anethole showed significant inhibition by oral administration at doses of 100-400 mg/kg. In conclusion, FR and several major constituents are 5-LOX inhibitors and they may have potential for treating 5-LOX-related disorders. PMID:24116283

Lee, Je Hyeong; Lee, Dong Ung; Kim, Yeong Shik; Kim, Hyun Pyo

2012-01-01

179

Naturally occurring biflavonoid, ochnaflavone, inhibits cyclooxygenases-2 and 5-lipoxygenase in mouse bone marrow-derived mast cells.  

PubMed

Ochnaflavone is a medicinal herbal product isolated from Lonicera japonica that inhibits cyclooxygenase-2 (COX-2) dependent phases of prostaglandin D2 (PGD2) generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with IC50 values of 0.6 microM. Western blotting probed with specific anti-COX-2 antibodies showed that the decrease in quantity of the PGD2 product was accompanied by a decrease in the COX-2 protein level. In addition, this compound consistently inhibited the production of leukotriene C4 (LTC4) in a dose dependent manner, with an IC50 value of 6.56 microM. These results demonstrate that ochnaflavone has a dual cyclooxygenase-2/5-lipoxygenase inhibitory activity. Furthermore, this compound strongly inhibited degranulation reaction in a dose dependent manner, with an IC50 value of 3.01 microM. Therefore, this compound might provide a basis for novel anti-inflammatory drugs. PMID:16681032

Son, Min Jung; Moon, Tae Chul; Lee, Eun Kyung; Son, Kun Ho; Kim, Hyun Pyo; Kang, Sam Sik; Son, Jong Keun; Lee, Seung Ho; Chang, Hyeun Wook

2006-04-01

180

Inhibition of superoxide anion and elastase release in human neutrophils by 3?-isopropoxychalcone via a cAMP-dependent pathway  

PubMed Central

Chalcone is abundantly present in the plant kingdom and has various biological activities such as anti-inflammatory and antioxidant. In this study, the semisynthetic chalcone derivative, 3?-isopropoxychalcone (H2O7D), was demonstrated to inhibit the generation of superoxide and the release of elastase, as well as to accelerate resequestration of cytosolic calcium in formyl-L-methionyl-L-leucyl-L-phenylalanine-activated human neutrophils. H2O7D displayed no antioxidant or superoxide-scavenging ability, and it failed to alter the subcellular NADPH oxidase activity. H2O7D induced a substantial increase in cAMP but not cGMP levels. The elevation of cAMP formation by H2O7D was inhibited by adenosine deaminase (ADA). Furthermore, The inhibitory effects of H2O7D were reversed by protein kinase (PK)A inhibitors, as well as ADA and a selective A2a-receptor antagonist. H2O7D inhibited phosphodiesterase (PDE) activities, but it did not alter adenylyl cyclase and soluble guanylyl cyclase activities. These results show that the cAMP-elevating effect of H2O7D results from the inhibition of PDE activity and not from the stimulation of cyclase function. Consistent with this, H2O7D potentiated the PGE1-caused inhibitory effects and cAMP formation. In summary, these results indicate that the inhibitory effect of H2O7D is cAMP/PKA dependent, and that it occurs through inhibition of cAMP PDE, which potentiates the autocrine functions of endogenous adenosine. Inhibition of respiratory burst and degranulation in human neutrophils may give this drug the potential to protect against the progression of inflammation.

Hwang, Tsong-Long; Yeh, Shang-Hsin; Leu, Yann-Lii; Chern, Ching-Yuh; Hsu, Hui-Chi

2006-01-01

181

Corrosion inhibiting organic coatings  

SciTech Connect

A corrosion inhibiting coating comprises a mixture of waxes, petroleum jelly, a hardener and a solvent. In particular, a corrosion inhibiting coating comprises candelilla wax, carnauba wax, microcrystalline waxes, white petrolatum, an oleoresin, lanolin and a solvent.

Sasson, E.

1984-10-16

182

Understanding Enzyme Inhibition  

Microsoft Academic Search

While enzyme inhibition is a widely taught subject across chemical and biochemical disciplines, it remains poorly understood. A mental image is presented to facilitate the understanding of inhibition types other than competitive. Subsequently, enzyme inhibition is developed using Vmax\\/Km in place of Km. Interpretation of direct (initial velocity vs substrate concentration) plots makes clear the meanings of competitive, noncompetitive, and

Raymond S. Ochs

2000-01-01

183

Pentoxifylline inhibits Vgamma9/Vdelta2 T lymphocyte activation of patients with active Behçets disease in vitro.  

PubMed

The aim of this study is to evaluate the in vitro effect of pentoxifylline (PTX) on T Vgamma9/Vdelta2 lymphocyte function in Behçets disease (BD). We investigated the effect of PTX on Vgamma9/Vdelta2 T cell expansion and expression of TNFRII receptor and perforin content before and after PTX addition by means of FACS analysis lymphocyte cultures from patients with active and inactive BD and healthy subjects. The addition of PTX at a concentration of 1 mg/ml determined a significant inhibition of cell expansion, a down regulation of TNF receptor expression and inhibited the PMA-induced degranulation of perforin. Taken together these data indicate that PTX is capable of interfering with Vgamma9/Vdelta2 T cell function in BD, and although cell culture models cannot reliably predict all of the potential effects of the drug in vivo, our results encourage the possibility that this drug may find use in a range of immunological disorder characterized by dysregulated cell-mediated immunity. PMID:17880773

Accardo-Palumbo, A; Ferrante, A; Ciccia, F; Cadelo, M; Giardina, A R; Impastato, R; Triolo, G

184

Resuscitation of traumatic hemorrhagic shock patients with hypertonic saline - without dextran - inhibits neutrophil and endothelial cell activation  

PubMed Central

Background Post-traumatic inflammation and excessive neutrophil activation cause multiple organ dysfunction syndrome (MODS), a major cause of death among hemorrhagic shock patients. Traditional resuscitation strategies may exacerbate inflammation and thus novel fluid treatments are needed to reduce these post-traumatic complications. Hypertonic resuscitation fluids inhibit inflammation and reduce MODS in animal models. Here we studied the anti-inflammatory efficacy of hypertonic fluids in a controlled clinical trial. Methods Trauma patients in hypovolemic shock were resuscitated in a pre-hospital setting with 250 ml of either 7.5% hypertonic saline (HS; n=9), 7.5% hypertonic saline + 6% dextran-70 (HSD; n=8), or 0.9% normal saline (NS; n=17). Blood samples were collected on hospital admission and 12 and 24 h post-resuscitation. Multi-color flow cytometry was used to quantify neutrophil expression of cell-surface activation/adhesion (CD11b, CD62L, CD64) and degranulation (CD63, CD66b, CD35) markers as well as oxidative burst activity. Circulating concentrations of soluble intercellular adhesion molecule (sICAM)-1, vascular cell adhesion molecule (sVCAM)-1, P-, E-selectins, myeloperoxidase (MPO), and matrix metallopeptidase (MMP)-9 were assessed with immunoassays. Results MODS, leukocytosis, and mortality were lower in the HS and HSD groups than in the NS group. However, these differences were not statistically significant. HS prevented priming and activation and neutrophil oxidative burst and CD11b and CD66b expression. HS also reduced circulating markers of neutrophil degranulation (MPO and MMP-9) and endothelial cell activation (sICAM-1, cVCAM-1, sE-selectin, and sP-selectin). HSD was less capable than HS of suppressing the upregulation of most of these activation markers. Conclusions This study demonstrates that initial resuscitation with HS but neither NS nor HSD can attenuate post-traumatic neutrophil and endothelial cell activation in hemorrhagic shock patients. These data suggest that hypertonic resuscitation without dextran may inhibit post-traumatic inflammation. However, despite this effect, neither HS nor HSD reduced MODS in trauma patients with hemorrhagic shock.

Junger, Wolfgang G.; Rhind, Shawn G.; Rizoli, Sandro B.; Cuschieri, Joseph; Shiu, Maria Y.; Baker, Andrew J.; Li, Linglin; Shek, Pang N.; Hoyt, David B.; Bulger, Eileen M.

2012-01-01

185

Ginkgetin, a Biflavone from Ginko biloba leaves, inhibits cyclooxygenases-2 and 5-lipoxygenase in mouse bone marrow-derived mast cells.  

PubMed

Ginkgetin, a biflavone from Ginkgo biloba leaves, was previously reported to be a phospholipase A(2) inhibitor and this compound showed the potent antiarthritic activity in rat adjuvant-induced arthritis as well as analgesic activity. This investigation was carried out to find effects on cyclooxygenase-2 (COX-2) in vitro effect. Ginkgetin inhibits COX-2 dependent phases of prostaglandin D(2) (PGD(2)) generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with IC(50) values of 0.75 microM. Western blotting probed with specific anti-COX-2 antibodies showed that the decrease in quantity of the PGD(2) product was accompanied by a decrease in the COX-2 protein level. In addition, this compound consistently inhibited the production of leukotriene C(4) (LTC(4)) in a dose dependent manner, with an IC(50) value of 0.33 microM. These results demonstrate that ginkgetin has a dual cyclooxygenase-2/5-lipoxygenase inhibitory activity. Furthermore, this compound also inhibited degranulation reaction in a dose dependent manner, with an IC(50) value of 6.52 microM. Therefore, this compound might provide a basis for novel anti-inflammatory agents. PMID:16327145

Son, Jong Keun; Son, Min Jung; Lee, Eunkyung; Moon, Tae Chul; Son, Kun Ho; Kim, Cheorl-Ho; Kim, Hyun Pyo; Kang, Sam Sik; Chang, Hyeun Wook

2005-12-01

186

Understanding Enzyme Inhibition  

NASA Astrophysics Data System (ADS)

While enzyme inhibition is a widely taught subject across chemical and biochemical disciplines, it remains poorly understood. A mental image is presented to facilitate the understanding of inhibition types other than competitive. Subsequently, enzyme inhibition is developed using Vmax/Km in place of Km. Interpretation of direct (initial velocity vs substrate concentration) plots makes clear the meanings of competitive, noncompetitive, and mixed inhibition in a manner entirely distinct from current textbook treatments. The effects of inhibitors on enzymes can be seen to be reduced to a simple consideration of actions at zero and infinite substrate concentrations, corresponding to Vmax/Km and Vmax, respectively.

Ochs, Raymond S.

2000-11-01

187

A strain of Lactobacillus casei inhibits the effector phase of immune inflammation.  

PubMed

Some nonpathogenic bacteria were found to have protective effects in mouse models of allergic and autoimmune diseases. These "probiotics" are thought to interact with dendritic cells during Ag presentation, at the initiation of adaptive immune responses. Many other myeloid cells are the effector cells of immune responses. They are responsible for inflammation that accounts for symptoms in allergic and autoimmune diseases. We investigated in this study whether probiotics might affect allergic and autoimmune inflammation by acting at the effector phase of adaptive immune responses. The effects of one strain of Lactobacillus casei were investigated in vivo on IgE-induced passive systemic anaphylaxis and IgG-induced passive arthritis, two murine models of acute allergic and autoimmune inflammation, respectively, which bypass the induction phase of immune responses, in vitro on IgE- and IgG-induced mouse mast cell activation and ex vivo on IgE-dependent human basophil activation. L. casei protected from anaphylaxis and arthritis, and inhibited mouse mast cell and human basophil activation. Inhibition required contact between mast cells and bacteria, was reversible, and selectively affected the Lyn/Syk/linker for activation of T cells pathway induced on engagement of IgE receptors, leading to decreased MAPK activation, Ca(2+) mobilization, degranulation, and cytokine secretion. Also, adoptive anaphylaxis induced on Ag challenge in mice injected with IgE-sensitized mast cells was abrogated in mice injected with IgE-sensitized mast cells exposed to bacteria. These results demonstrate that probiotics can influence the effector phase of adaptive immunity in allergic and autoimmune diseases. They might, therefore, prevent inflammation in patients who have already synthesized specific IgE or autoantibodies. PMID:21810608

Schiffer, Cécile; Lalanne, Ana Inés; Cassard, Lydie; Mancardi, David A; Malbec, Odile; Bruhns, Pierre; Dif, Fariel; Daëron, Marc

2011-08-01

188

Inhibition of neutrophil elastase prevents cathelicidin activation and impairs clearance of bacteria from wounds.  

PubMed

The host defense roles of neutrophil elastase in a porcine skin wound chamber model were explored. Analysis of wound fluid by acid-urea polyacrylamide gel electrophoresis, Western blot, and bacterial overlay confirmed that the neutrophil-derived protegrins constituted the major stable antimicrobial polypeptide in the wound fluid. The application to the wound of 0.10 and 0.25 mM N-methoxysuccinyl-alanine-alanine-proline-valine (AAPV) chloromethyl ketone, a specific neutrophil elastase inhibitor (NEI), blocked the proteolytic activation of protegrins and diminished the associated antimicrobial activity as detected by radial diffusion assay against Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans or by bacterial gel overlay against S epidermidis and E coli. The application of the related cathepsin G inhibitor (CGI), benzyloxycarbonyl-glycine-leucine-phenylalanine (ZGLF) chloromethyl ketone, had no effect. In wound chambers that received 10(6) colony-forming unit (CFU)/mL of S epidermidis, the presence of NEI significantly decreased the 24-hour clearance of bacteria from the wound compared to wounds treated with CGI or solvent only. Neither inhibitor, at 0.10 or 0.25 mM concentration, affected leukocyte accumulation or degranulation in the wound chambers. The in vitro microbicidal decrement due to NEI was restored by an amount of the specific protegrin (PG-1), which was equivalent to the measured difference of protegrin between control and inhibited chambers. Administration of 1 microg/mL exogenous PG-1 4 hours after chamber preparation was sufficient to normalize in vivo antimicrobial activity. Although pharmacologic NEIs are promising candidates as anti-inflammatory drugs, they may impair host defense in part by inhibiting the activation of cathelicidins by neutrophil elastase. PMID:11133774

Cole, A M; Shi, J; Ceccarelli, A; Kim, Y H; Park, A; Ganz, T

2001-01-01

189

Saccadic Inhibition in Reading  

ERIC Educational Resources Information Center

In 5 experiments, participants read text that was briefly replaced by a transient image for 33 ms at random intervals. A decrease in saccadic frequency, referred to as saccadic inhibition, occurred as early as 60-70 ms following the onset of abrupt changes in visual input. It was demonstrated that the saccadic inhibition was influenced by the…

Reingold, Eyal M.; Stampe, Dave M.

2004-01-01

190

Inhibition of selectin binding  

DOEpatents

This invention provides compositions for inhibiting the binding between two cells, one expressing P- or L-selectin on the surface and the other expressing the corresponding ligand. A covalently crosslinked lipid composition is prepared having saccharides and acidic group on separate lipids. The composition is then interposed between the cells so as to inhibit binding. Inhibition can be achieved at an effective oligosaccharide concentration as low as 10.sup.6 fold below that of the free saccharide. Since selectins are involved in recruiting cells to sites of injury, these composition scan be used to palliate certain inflammatory and immunological conditions.

Nagy, Jon O. (Rodeo, CA); Spevak, Wayne R. (Albany, CA); Dasgupta, Falguni (New Delhi, IN); Bertozzi, Caroline (Albany, CA)

2001-10-09

191

Inhibition of selectin binding  

DOEpatents

This invention provides a system for inhibiting the binding between two cells, one expressing P- or L-selectin on the surface and the other expressing the corresponding ligand. A covalently crosslinked lipid composition is prepared having saccharides and acidic group on separate lipids. The composition is then interposed between the cells so as to inhibit binding. Inhibition can be achieved at an effective oligosaccharide concentration as low as 10.sup.6 fold below that of the free saccharide. Since selectins are involved in recruiting cells to sites of injury, this system can be used to palliate certain inflammatory and immunological conditions.

Nagy, Jon O. (Rodeo, CA); Spevak, Wayne R. (Albany, CA); Dasgupta, Falguni (New Delhi, IN); Bertozzi, Carolyn (Albany, CA)

1999-10-05

192

Inhibition of selectin binding  

DOEpatents

This invention provides compositions for inhibiting the binding between two cells, one expressing P- or L-selectin on the surface and the other expressing the corresponding ligand. A covalently crosslinked lipid composition is prepared having saccharides and acidic group on separate lipids. The composition is then interposed between the cells so as to inhibit binding. Inhibition can be achieved at an effective oligosaccharide concentration as low as 10.sup.6 fold below that of the free saccharide. Since selectins are involved in recruiting cells to sites of injury, these composition scan be used to palliate certain inflammatory and immunological conditions.

Nagy, Jon O. (Rodeo, CA); Spevak, Wayne R. (Albany, CA); Dasgupta, Falguni (New Delhi, IN); Bertozzi, Caroline (Albany, CA)

1999-01-01

193

Trazodone and ejaculatory inhibition.  

PubMed

Sexual adverse effects are common with psychotropics. Rational polypharmacy may confound etiology. This case report describes development of ejaculatory inhibition in a male patient with co-morbid psychiatric diagnoses treated with fluoxetine, divalproex sodium, lamotrigine, trazodone, and clonazepam. Detailed psychotropic history with time-line of adverse effect onset implicated trazodone. Within 48 hours of trazodone discontinuation, ejaculatory inhibition was resolved. Clinicians should be aware that trazodone may cause ejaculatory inhibition, understand that determination of sexual adverse effects necessitates directed and periodic questioning as these symptoms may increase in severity over time, and appreciate that religious patients may find discussing this issue difficult. PMID:17454520

Kaufman, Kenneth R; Marin, Humbarto; Menza, Matthew

194

Biochanin A, a Phytoestrogenic Isoflavone with Selective Inhibition of Phosphodiesterase 4, Suppresses Ovalbumin-Induced Airway Hyperresponsiveness  

PubMed Central

The present study investigated the potential of biochanin A, a phytoestrogenic isoflavone of red clover (Triflolium pratense), for use in treating asthma or chronic obstructive pulmonary disease (COPD). Biochanin A (100??mol/kg, orally (p.o.)) significantly attenuated airway resistance (RL), enhanced pause (Penh), and increased lung dynamic compliance (Cdyn) values induced by methacholine (MCh) in sensitized and challenged mice. It also significantly suppressed an increase in the number of total inflammatory cells, neutrophils, and eosinophils, and levels of cytokines, including interleukin (IL)-2, IL-4, IL-5, and tumor necrosis factor (TNF)-? in bronchoalveolar lavage fluid (BALF) of the mice. However, it did not influence interferon (IFN)-? levels. Biochanin A (100??mol/kg, p.o.) also significantly suppressed the total and ovalbumin (OVA)-specific immunoglobulin E (IgE) levels in the serum and BALF, and enhanced the total IgG2a level in the serum of these mice. The PDE4H/PDE4L value of biochanin A was calculated as >35. Biochanin A did not influence xylazine/ketamine-induced anesthesia. Biochanin A (10~30??M) significantly reduced cumulative OVA (10~100??g/mL)-induced contractions in the isolated guinea pig trachealis, suggesting that it inhibits degranulation of mast cells. In conclusion, red clover containing biochanin A has the potential for treating allergic asthma and COPD.

Ko, Wun-Chang; Lin, Ling-Hung; Shen, Hsin-Yi; Lai, Chi-Yin; Chen, Chien-Ming; Shih, Chung-Hung

2011-01-01

195

Inconsistent locomotion inhibits vection.  

PubMed

We measured the strength of illusory self-motion perception (vection) with and without locomotion on a treadmill. The results revealed that vection was inhibited by inconsistent locomotion, but facilitated by consistent locomotion. PMID:21936303

Seno, Takeharu; Ito, Hiroyuki; Sunaga, Shoji

2011-01-01

196

Inhibition of reservoir scale  

SciTech Connect

This patent describes a treating process for inhibiting scaling by fluid which is produced from a non-carbonate subterranean reservoir via a wellbore. It comprises injecting down the wellbore and into the reservoir a mixture of a phosphonate scale inhibiting compound and a metal chelate where the metal chelate has a lower stability constant (Ke) than the phosphonate inhibitor and where the metal in the metal chelate forms an insoluble salt upon reaction with the phosphonate.

Carlberg, B.L.; Wolfe, N.O.; Pober, K.W.; Nash, W.D.

1989-08-29

197

Method for inhibiting corrosion  

SciTech Connect

A composition comprising the reaction adduct or neutralized product resulting from the reaction of a maleic anhydride and an oil containing a polynuclear aromatic compound is provided which, when applied to a metal surface, forms a corrosion-inhibiting film thereon. The composition is particularly useful in the treatment of down-hole metal surfaces in oil and gas wells to inhibit the corrosion of the metal.

Wu, Y.; Stapp, P. R.

1985-12-03

198

Topical azithromycin and clarithromycin inhibit acute and chronic skin inflammation in sensitized mice, with apparent selectivity for Th2-mediated processes in delayed-type hypersensitivity.  

PubMed

Macrolide antibiotics inhibit the secretion of Th1 cytokines while their effects on the release of Th2 cytokines are variable. We investigated molecular and cellular markers of Th1- and Th2-mediated inflammatory mechanisms and the anti-inflammatory activity of azithromycin and clarithromycin in phorbol 12-myristate 13-acetate (PMA) and oxazolone (OXA)-induced skin inflammation. Dexamethasone (50 ?g/ear), azithromycin, and clarithromycin (500 ?g/ear) reduced TNF-? and interleukin (IL)-1? concentration in ear tissue by inhibiting inflammatory cell accumulation in PMA-induced inflammation. In OXA-induced early delayed-type hypersensitivity (DTH), the macrolides (2 mg/ear) and dexamethasone (25 ?g/ear) reduced ear tissue inflammatory cell infiltration and secretion of IL-4 while clarithromycin also decreased IFN-? concentration. Macrolides showed better activity when administered after the challenge. In OXA-induced chronic DTH, azithromycin (1 mg/ear) reduced the number of ear tissue mast cells and decreased the concentration of IL-4 in ear tissue and of immunoglobulin (Ig)E in serum. Clarithromycin (1 mg/ear) reduced serum IgE concentration, possibly by a mechanism independent of IL-4, while both macrolides attenuated mast cell degranulation. In conclusion, azithromycin and clarithromycin attenuate pro-inflammatory cytokine production and leukocyte infiltration during innate immune reactions, while selectively affecting Th2 rather than Th1 immunity in DTH reactions. PMID:21336676

Iveti? Tkal?evi?, Vanesa; Cuži?, Snježana; Kramari?, Miroslava Dominis; Parnham, Michael J; Erakovi? Haber, Vesna

2012-02-01

199

Lupoid sycosis. Treatment with PUVA and co-trimoxazole.  

PubMed

Lupoid sycosis, a condition refractory to treatment, is probably a chronic scarring form of deep sycosis barbae. Reported here is successful treatment of two longstanding cases of lupoid sycosis using ultraviolet-activated 8-methoxypsoralen in combination with co-trimoxazole. PMID:3500138

Srinivas, C R; Shenoy, K

1987-10-01

200

Method for decreasing radiation load in puva therapy  

SciTech Connect

An improved method is described for treating a psoriatic subject undergoing treatment with a psoralen in conjection with ultraviolet A radiation of from wavelength of 3200 to 4000 angstroms. The improved method comprises prior to initiation of the treatment, pretreating the subject for a period of from 4 to 10 days with an effective amount of an anti-psoriatic polyene compound, and thereafter initiating the treatment with a psoralen in conjunction with ultraviolet A radiation and continuing the treatment concurrently with the administration of the anti-psoriatic polyene compound.

Wolff, K.

1987-02-10

201

Treatment of childhood mycosis fungoides with topical PUVA  

Microsoft Academic Search

Mycosis fungoides is the most common type of cutaneous T-cell lymphoma, which is usually observed in mid to late adulthood. We report 5 cases of mycosis fungoides in children, all presenting as patch- and plaque-stage disease most commonly involving the buttocks. Histologic examination showed in every case the typical features of mycosis fungoides. In 4 of the 5 cases, the

Heike Pabsch; Arno Rütten; Andrea von Stemm; Wilhelm Meigel; Christian A. Sander; Jörg Schaller

2002-01-01

202

Derivative of wheat germ agglutinin specifically inhibits formyl-peptide-induced polymorphonuclear leukocyte chemotaxis by blocking re-expression (or recycling) of receptors  

SciTech Connect

The mechanism of action of a derivative of wheat germ agglutinin (WGA-D) which specifically and irreversibly inhibits N-formyl-methionyl-leucyl-phenylalanine (FMLP)-induced polymorphonuclear leukocyte (PMN) chemotaxis was examined. At a concentration that completely inhibited PMN chemotaxis, WGA-D had no effect on either the uptake or release of (/sup 3/H)-FMLP by PMN. Similarly, WGA-D did not affect either the short-term binding to, or internalization by, PMN of a fluoresceinated FMLP analog. WGA-D did interfere, however, with the re-expression (or recycling) of FMLP receptors by PMN that had been preincubated with 1 ..mu..M FMLP for 10 min at 4/sup 0/C. This effect was specific for WGA-D, because it was not observed when concanavalin A was used. Scatchard plot analysis of FMLP binding to PMN after receptor re-expression demonstrated that WGA-D-treated PMN had a significant diminution in the number of high affinity receptors. WGA-D-mediated inhibition of FMLP receptor re-expression was associated with inhibition of FMLP-induced PMN chemotaxis, but had no effect on either FMLP-induced PMN superoxide anion generation or degranulation. Studies using (/sup 12/%I)-WGA-D demonstrated that PMN did not internalize WGA-D spontaneously. The data indicate that WGA-D perhaps by binding to the FMLP receptor, inhibits FMLP-induced PMN chemotaxis by blocking the re-expression (or recycling) of a population of receptors required for continuous migration.

Perez, H.D.; Elfman, F.; Lobo, E.; Sklar, L.; Chenoweth, D.; Hooper, C.

1986-03-01

203

The Bruton tyrosine kinase inhibitor PCI-32765 ameliorates autoimmune arthritis by inhibition of multiple effector cells  

PubMed Central

Introduction The aim was to determine the effect of the Bruton tyrosine kinase (Btk)-selective inhibitor PCI-32765, currently in Phase I/II studies in lymphoma trials, in arthritis and immune-complex (IC) based animal models and describe the underlying cellular mechanisms. Methods PCI-32765 was administered in a series of murine IC disease models including collagen-induced arthritis (CIA), collagen antibody-induced arthritis (CAIA), reversed passive anaphylactic reaction (RPA), and passive cutaneous anaphylaxis (PCA). Clinical and pathologic features characteristic of each model were examined following treatment. PCI-32765 was then examined in assays using immune cells relevant to the pathogenesis of arthritis, and where Btk is thought to play a functional role. These included proliferation and calcium mobilization in B cells, cytokine and chemokine production in monocytes/macrophages, degranulation of mast cells and its subsequent cytokine/chemokine production. Results PCI-32765 dose-dependently and potently reversed arthritic inflammation in a therapeutic CIA model with an ED50 of 2.6 mg/kg/day. PCI-32765 also prevented clinical arthritis in CAIA models. In both models, infiltration of monocytes and macrophages into the synovium was completely inhibited and importantly, the bone and cartilage integrity of the joints were preserved. PCI-32765 reduced inflammation in the Arthus and PCA assays. In vitro, PCI-32765 inhibited BCR-activated primary B cell proliferation (IC50 = 8 nM). Following Fc?R stimulation, PCI-32765 inhibited TNF?, IL-1? and IL-6 production in primary monocytes (IC50 = 2.6, 0.5, 3.9 nM, respectively). Following Fc?RI stimulation of cultured human mast cells, PCI-32765 inhibited release of histamine, PGD2, TNF-?, IL-8 and MCP-1. Conclusions PCI-32765 is efficacious in CIA, and in IC models that do not depend upon autoantibody production from B cells. Thus PCI-32765 targets not only B lymphocytes but also monocytes, macrophages and mast cells, which are important Btk-expressing effector cells in arthritis.

2011-01-01

204

Inhibition in multiclass classification.  

PubMed

The role of inhibition is investigated in a multiclass support vector machine formalism inspired by the brain structure of insects. The so-called mushroom bodies have a set of output neurons, or classification functions, that compete with each other to encode a particular input. Strongly active output neurons depress or inhibit the remaining outputs without knowing which is correct or incorrect. Accordingly, we propose to use a classification function that embodies unselective inhibition and train it in the large margin classifier framework. Inhibition leads to more robust classifiers in the sense that they perform better on larger areas of appropriate hyperparameters when assessed with leave-one-out strategies. We also show that the classifier with inhibition is a tight bound to probabilistic exponential models and is Bayes consistent for 3-class problems. These properties make this approach useful for data sets with a limited number of labeled examples. For larger data sets, there is no significant comparative advantage to other multiclass SVM approaches. PMID:22594829

Huerta, Ramón; Vembu, Shankar; Amigó, José M; Nowotny, Thomas; Elkan, Charles

2012-05-17

205

Activation of Colonic Mucosal 5-HT4 Receptors Accelerates Propulsive Motility and Inhibits Visceral Hypersensitivity  

PubMed Central

BACKGROUND & AIMS 5-hydroxytryptamine receptor (5-HT4R) agonists promote gastrointestinal motility and attenuate visceral pain, but concerns about adverse reactions have restricted their availability. We tested the hypotheses that 5-HT4 receptors are expressed in the colonic epithelium and that 5-HT4R agonists can act intraluminally to increase motility and reduce visceral hypersensitivity. METHODS Mucosal expression of the 5-HT4R was evaluated by reverse-transcriptase polymerase chain reaction and immunohistochemical analysis of tissues from 5-HT4R(BAC)-enhanced green fluorescent protein mice. Amperometry, histology, and short-circuit current measurements were used to study 5-HT, mucus, and Cl? secretion, respectively. Propulsive motility was measured in guinea pig distal colon, and visceromotor responses were recorded in a rat model of colonic hypersensitivity. 5-HT4R compounds included cisapride, tegaserod, naronapride, SB204070, and GR113808. RESULTS Mucosal 5-HT4 receptors were present in the small and large intestines. In the distal colon, 5-HT4 receptors were expressed by most epithelial cells, including enterochromaffin and goblet cells. Stimulation of 5-HT4Rs evoked mucosal 5-HT release, goblet cell degranulation, and Cl? secretion. Luminal administration of 5-HT4R agonists accelerated propulsive motility; a 5-HT4R antagonist blocked this effect. Bath application of 5-HT4R agonists did not affect motility. Oral or intracolonic administration of 5-HT4R agonists attenuated visceral hypersensitivity. Intracolonic administration was more potent than oral administration, and was inhibited by a 5-HT4R antagonist. CONCLUSIONS Mucosal 5-HT4 receptor activation can mediate the prokinetic and antinociceptive actions of 5-HT4R agonists. Colon-targeted, intraluminal delivery of 5-HT4R agonists might be used to promote motility and alleviate visceral pain, while restricting systemic bioavailability and resulting adverse side effects.

HOFFMAN, JILL M.; TYLER, KARL; MACEACHERN, SARAH J.; BALEMBA, ONESMO B.; JOHNSON, ANTHONY C.; BROOKS, ELICE M.; ZHAO, HONG; SWAIN, GREG M.; MOSES, PETER L.; GALLIGAN, JAMES J.; SHARKEY, KEITH A.; GREENWOOD-VAN MEERVELD, BEVERLEY; MAWE, GARY M.

2012-01-01

206

Compounds that inhibit cholinesterase  

US Patent & Trademark Office Database

Compounds that inhibit cholinesterase activity and, upon hydrolysis release a pharmacologically active agent. The compounds of the invention are employed in methods to treat an individual. The pharmacologically active agent obtained by hydrolysis of the compound can treat, for example, a nervous system condition, a cholinergic deficiency and conditions or diseases associated with a deficiency in a pharmacologically active agent, such as acetylcholine.

Rupniak; Nadia M. J. (Cary, NC); White; James F. (Carlisle, MA); Shiosaki; Kazumi (Wellesley, MA); Leander; J. David (Indianapolis, IN); Du; Shoucheng (Pittsburgh, PA); Coughlin; Daniel J. (Hackettstown, NJ)

2012-01-24

207

Inhibition of avoidance behavior  

Microsoft Academic Search

Conditions for establishing stimuli which inhibit conditioned fear reactions are demonstrated in 3 experiments. Dogs, trained in a shuttle box to avoid shock on a Sidman avoidance schedule, received Pavlovian fear conditioning involving the presentation of tones and shock in various temporal relations. Subsequently, these tones were presented while S performed the avoidance response. Stimuli preceding shock in conditioning increased

Robert A. Rescorla; Vincent M. Lolordo

1965-01-01

208

Arginine Inhibits Serpins  

Microsoft Academic Search

Serine protease inactivators (serpins) are important regulators in biochemistry. Often it is necessary to block the serpin action, that is, to stabilize the sample. The guanidine group of arginine is the ligand for the active center pocket of many serine proteases. Arginine or guanidine inhibits serine proteases, and arginine belongs to the reactive P1-P1' center of many serpins. The plasmatic

Thomas W. Stief

2007-01-01

209

Subsea corrosion inhibition applications  

SciTech Connect

Subsea wells are hard to treat--and mistakes carry high penalties. This article describes some difficulties that beset corrosion inhibition programs and the ways in which computer modeling and laboratory protocols can be used to select optimum products for particular wells and flowlines. In addition, test results are shown for a new inhibitor with dramatic capabilities to control corrosion even in severe slug-flow conditions.

Jovancicevic, V.

2000-04-01

210

Arginine Inhibits Hemostasis Activation  

Microsoft Academic Search

Background: The diagnosis and the therapy of in vivo hemostasis activation is of great clinical importance. Artefactual changes of the hemostasis (i.e., coagulation or fibrinolysis) in vitro have to be prevented. Usual in vitro anticoagulation by sodium citrate does not fully inhibit coagulation—or fibrinolysis—activation. Therefore, there is need for a simple physiologic inhibitor of hemostasis activation both in diagnosis and

Thomas W Stief; Monika Weippert; Volker Kretschmer; Harald Renz

2001-01-01

211

Method of Inhibiting Choroidal Neovascularization.  

National Technical Information Service (NTIS)

The present invention relates to compositions and methods for inhibiting unwanted angiogenesis, particularly those of ocular tissues. The treatment, inhibition, and/or prevention of choroidal neovasculature (CNV) is provided, along with an animal model fo...

R. Wen Z. Luo A. M. Laties

2003-01-01

212

Semantic processing and response inhibition.  

PubMed

The present study examined functional MRI (fMRI) BOLD signal changes in response to object categorization during response selection and inhibition. Young adults (N=16) completed a Go/NoGo task with varying object categorization requirements while fMRI data were recorded. Response inhibition elicited increased signal change in various brain regions, including medial frontal areas, compared with response selection. BOLD signal in an area within the right angular gyrus was increased when higher-order categorization was mandated. In addition, signal change during response inhibition varied with categorization requirements in the left inferior temporal gyrus (lIT). lIT-mediated response inhibition when inhibiting the response only required lower-order categorization, but lIT mediated both response selection and inhibition when selecting and inhibiting the response required higher-order categorization. The findings characterized mechanisms mediating response inhibition associated with semantic object categorization in the 'what' visual object memory system. PMID:24025798

Chiang, Hsueh-Sheng; Motes, Michael A; Mudar, Raksha A; Rao, Neena K; Mansinghani, Sethesh; Brier, Matthew R; Maguire, Mandy J; Kraut, Michael A; Hart, John

2013-11-13

213

Toxic proteins inhibiting protein synthesis  

Microsoft Academic Search

Proteins which destroy various organisms are widely distributed in nature. Some of these proteins exert their toxic effect by inhibiting protein synthesis in a specific manner. Thus, Colicin E 3 kills susceptible bacteria by inhibiting ribosome function. It does this by splitting off a small fragment from the t6S ribosomal RNA thus inactivating the 30S ribosomal subunit. Diphtheria toxin inhibits

Sjur Olsnes; Norsk Hydro

1972-01-01

214

Suppressive effects of Schizandra chinensis Baillon water extract on allergy-related cytokine generation and degranulation in IgE-antigen complex-stimulated RBL-2H3 cells  

PubMed Central

Schizandra chinensis Baillon is a traditional folk medicine plant that is used to treat and prevent several inflammatory diseases and cancer in Korea, but the underlying mechanisms involved in its anti-allergic activity are not fully understood. This study was designed to investigate mechanisms of anti-allergic activity of a Schizandra chinensis Baillon water extract (SCWE) in immunoglobulin E (IgE)-antigen complex-stimulated RBL2H3 cells and to assess whether gastric and intestinal digestion affects the anti-allergic properties of SCWE. Oxidative stress is an important consequence of the allergic inflammatory response. The antioxidant activities of SCWE increased in a concentration-dependent manner. RBL-2H3 cells were sensitized with monoclonal anti-dinitrophenol (DNP) specific IgE, treated with SCWE, and challenged with the antigen DNP-human serum albumin. SCWE inhibited ?-hexosaminidase release and expression of interleukin (IL)-4, IL-13, and tumor necrosis factor-alpha (TNF-?) mRNA and protein in IgE-antigen complex-stimulated RBL2H3 cells. We found that digested SCWE fully maintained its antioxidant activity and anti-allergic activity against the IgE-antigen complex-induced activation of RBL-2H3 cells. SCWE may be useful for preventing allergic diseases, such as asthma. Thus, SCWE could be used as a natural functional ingredient for allergic diseases in the food and/or pharmaceutical industries.

Chung, Mi Ja; Kim, Jeong-Mi; Lee, Sangchul; Kim, Taewoo; Kim, Daejung; Baek, Jongmi; Kim, Taehyuk; Lee, Jaesung; Kim, Kyoungkon; Yoon, Jin A

2012-01-01

215

Suppressive effects of Schizandra chinensis Baillon water extract on allergy-related cytokine generation and degranulation in IgE-antigen complex-stimulated RBL-2H3 cells.  

PubMed

Schizandra chinensis Baillon is a traditional folk medicine plant that is used to treat and prevent several inflammatory diseases and cancer in Korea, but the underlying mechanisms involved in its anti-allergic activity are not fully understood. This study was designed to investigate mechanisms of anti-allergic activity of a Schizandra chinensis Baillon water extract (SCWE) in immunoglobulin E (IgE)-antigen complex-stimulated RBL2H3 cells and to assess whether gastric and intestinal digestion affects the anti-allergic properties of SCWE. Oxidative stress is an important consequence of the allergic inflammatory response. The antioxidant activities of SCWE increased in a concentration-dependent manner. RBL-2H3 cells were sensitized with monoclonal anti-dinitrophenol (DNP) specific IgE, treated with SCWE, and challenged with the antigen DNP-human serum albumin. SCWE inhibited ?-hexosaminidase release and expression of interleukin (IL)-4, IL-13, and tumor necrosis factor-alpha (TNF-?) mRNA and protein in IgE-antigen complex-stimulated RBL2H3 cells. We found that digested SCWE fully maintained its antioxidant activity and anti-allergic activity against the IgE-antigen complex-induced activation of RBL-2H3 cells. SCWE may be useful for preventing allergic diseases, such as asthma. Thus, SCWE could be used as a natural functional ingredient for allergic diseases in the food and/or pharmaceutical industries. PMID:22586497

Chung, Mi Ja; Kim, Jeong-Mi; Lee, Sangchul; Kim, Taewoo; Kim, Daejung; Baek, Jongmi; Kim, Taehyuk; Lee, Jaesung; Kim, Kyoungkon; Yoon, Jin A; Choe, Myeon

2012-04-30

216

Attentional load inhibits vection.  

PubMed

In this study, we examined the effects of cognitive task performance on the induction of vection. We hypothesized that, if vection requires attentional resources, performing cognitive tasks requiring attention should inhibit or weaken it. Experiment 1 tested the effects on vection of simultaneously performing a rapid serial visual presentation (RSVP) task. The results revealed that the RSVP task affected the subjective strength of vection. Experiment 2 tested the effects of a multiple-object-tracking (MOT) task on vection. Simultaneous performance of the MOT task decreased the duration and subjective strength of vection. Taken together, these findings suggest that vection induction requires attentional resources. PMID:21491162

Seno, Takeharu; Ito, Hiroyuki; Sunaga, Shoji

2011-07-01

217

Fc receptor-? subunits with both polar or non-polar amino acids at position of T22 are capable of restoring surface expression of the high-affinity IgE receptor and degranulation in ? subunit-deficient rat basophilic leukemia cells.  

PubMed

The high-affinity IgE receptor (Fc?RI) is formed by the IgE-binding ? subunit, ? subunit and ? subunits homodimer. All three subunits are required for proper expression of the receptor on the plasma membrane of mast cells and basophils. However, the exact molecular mechanism of inter-subunit interactions required for correct expression and function of the Fc?RI complex remains to be identified. A recent study suggested that polar aspartate at position 194 within the transmembrane domain of the ? subunit could interact by hydrogen bonding with polar threonine at position 22 in the transmembrane domains of the ? subunits. To verify this, we used previously isolated rat basophilic leukemia (RBL)-2H3 variant cells deficient in the expression of the Fc?RI-? subunit (FcR-?), and transfected them with DNA vectors coding for FcR-? of the wild-type or mutants in which T22 was substituted for nonpolar alanine (T22A mutant) or polar serine (T22S mutant). Analysis of the transfectants showed that both T22A and T22S mutants were capable to restore surface expression of the Fc?RI similar to wild-type FcR-?. Furthermore, cells transfected with wild-type, T22A or T22S FcR-? showed comparably enhanced Fc?RI-mediated degranulation. Our data indicate that substitution of FcR-? T22 with non-polar amino acid does not interfere with surface expression of the Fc?RI and its signaling capacity. PMID:22964482

Rashid, Amir; Housden, Jonathan E M; Helm, Birgit A; Draber, Petr

2012-09-08

218

Oxazolidinones Inhibit Cellular Proliferation via Inhibition of Mitochondrial Protein Synthesis  

Microsoft Academic Search

bacterial protein synthesis. The oxazolidinones inhibit mitochondrial protein synthesis, as shown by (35S)me- thionine incorporation into intact rat heart mitochondria. Treatment of K562 human erythroleukemia cells with the oxazolidinone eperezolid resulted in a time- and concentration-dependent inhibition of cell prolifer- ation. The cells remained viable, but an increase in doubling time was observed with eperezolid treatment. Inhibition was reversible, since

Eva E. Nagiec; Luping Wu; Steve M. Swaney; John G. Chosay; Daniel E. Ross; Joan K. Brieland; Karen L. Leach

2005-01-01

219

TLR7 inhibition  

PubMed Central

Pancreatic ductal adenocarcinoma is associated with a poor prognosis: For local disease, the 5-y survival rate is approximately 20% and median survival in locally advanced disease is only about 10 mo. Carcinogenesis is associated with chronic inflammation showing that innate immunity can be a double-edged sword. Here, we discuss recent findings of Ochi et al. in The Journal of Clinical Investigation who described a novel role for TLR7 in the development and progression of pancreatic cancer through interference with cell cycle regulation and by activation of multiple cell signaling pathways. Of note, inhibition of TLR7 signaling in a mouse p48Cre;KrasG12D pancreatic cancer model protected against tumor progression thus paving the road for TLR-blocking strategies to combat tumors.

Eigenbrod, Tatjana; Dalpke, Alexander H.

2013-01-01

220

Firefly luciferase inhibition.  

PubMed

Firefly luciferase (Luc) is the most studied of the luciferase enzymes and the mechanism and kinetics of the reactions catalyzed by this enzyme have been relatively well characterized. Luc catalyzes the bioluminescent reaction involving firefly luciferin (D-LH(2)), adenosine triphosphate (ATP), magnesium ion and molecular oxygen with the formation of an electronically excited species (oxyluciferin), inorganic pyrophosphate (PPi), carbon dioxide and adenosine monophosphate (AMP). Luc also catalyzes other non-luminescent reactions, which can interfere with the light production mechanism. Following electronic relaxation, the excited oxyluciferin emits radiation in the visible region of the electromagnetic spectrum (550-570 nm). Among the various possible compounds, several classes of inhibitory substances interfere with the activity of this enzyme: here, we consider substrate-related compounds, intermediates or products of the Luc catalyzed reactions, in addition to anesthetics and, fatty acids. This review summarizes the main inhibitors of Luc and the corresponding inhibition kinetic parameters. PMID:20655239

Leitão, João M M; Esteves da Silva, Joaquim C G

2010-07-03

221

How Inhibition Shapes Cortical Activity  

PubMed Central

Summary Cortical processing reflects the interplay of synaptic excitation and synaptic inhibition. Rapidly accumulating evidence is highlighting the crucial role of inhibition in shaping spontaneous and sensory-evoked cortical activity and thus underscores how a better knowledge of inhibitory circuits is necessary for our understanding of cortical function. We discuss current views of how inhibition regulates the function of cortical neurons and point to a number of important open questions.

Isaacson, Jeffery S.; Scanziani, Massimo

2011-01-01

222

SPIRULINA PLATENSIS INHIBITS ANAPHYLACTIC REACTION  

Microsoft Academic Search

We investigated the effects of the powders of Spirulina platensis (SPP) on anaphylactic reactions. SPP inhibited compound 4880-induced anaphylactic shock 100% with doses of 0.5, and 1.0 mg\\/g body weight (BW). SPP significantly inhibited serum histamine levels induced by compound 4880 in rats. SPP (0.5 mg\\/g BW) inhibited to 68.7% passive cutaneous anaphylaxis activated by antidinitrophenyl (DNP) IgE. SPP dose-dependently

Huh-Nam Yang; Eun-Hee Lee; Hyung-Min Kim

1997-01-01

223

Inhibition of Glioma Cell Lysosome Exocytosis Inhibits Glioma Invasion  

PubMed Central

Cancer cells invade by secreting enzymes that degrade the extracellular matrix and these are sequestered in lysosomal vesicles. In this study, the effects of the selective lysosome lysing drug GPN and the lysosome exocytosis inhibitor vacuolin-1 on lysosome exocytosis were studied to determine their effect on glioma cell migration and invasion. Both GPN and vacuolin-1 evidently inhibited migration and invasion in transwell experiments and scratch experiments. There are more lysosomes located on the cell membrane of glioma cells than of astrocytes. GPN decreased the lysosome number on the cell membrane. We found that rab27A was expressed in glioma cells, and colocalized with cathepsin D in lysosome. RNAi-Rab27A inhibited lysosome cathepsin D exocytosis and glioma cell invasion in an in vitro assay. Inhibition of cathepsin D inhibited glioma cell migration. The data suggest that the inhibition of lysosome exocytosis from glioma cells plays an important modulatory role in their migration and invasion.

Zhu, Keqing

2012-01-01

224

Inhibition of glioma cell lysosome exocytosis inhibits glioma invasion.  

PubMed

Cancer cells invade by secreting enzymes that degrade the extracellular matrix and these are sequestered in lysosomal vesicles. In this study, the effects of the selective lysosome lysing drug GPN and the lysosome exocytosis inhibitor vacuolin-1 on lysosome exocytosis were studied to determine their effect on glioma cell migration and invasion. Both GPN and vacuolin-1 evidently inhibited migration and invasion in transwell experiments and scratch experiments. There are more lysosomes located on the cell membrane of glioma cells than of astrocytes. GPN decreased the lysosome number on the cell membrane. We found that rab27A was expressed in glioma cells, and colocalized with cathepsin D in lysosome. RNAi-Rab27A inhibited lysosome cathepsin D exocytosis and glioma cell invasion in an in vitro assay. Inhibition of cathepsin D inhibited glioma cell migration. The data suggest that the inhibition of lysosome exocytosis from glioma cells plays an important modulatory role in their migration and invasion. PMID:23029308

Liu, Yu; Zhou, Yijiang; Zhu, Keqing

2012-09-28

225

Infant predictors of behavioural inhibition  

Microsoft Academic Search

Behavioural inhibition in the second year of life is a hypothesized predictor for shyness, social anxiety and depression in later childhood, adolescence and even adulthood. To search for the earliest indicators of this fundamental temperamental trait, this study examined whether behavioural characteristics in early infancy can predict behavioural inhibition, as previously postulated. The results show that infant crying to unfamiliar

Eva Moehler; Jerome Kagan; Rieke Oelkers-Ax; Romuald Brunner; Luise Poustka; Johann Haffner; Franz Resch

2008-01-01

226

Behavioral Inhibition in Young Children.  

ERIC Educational Resources Information Center

Study of children aged 21 to 31 months tentatively concludes: (1)behavioral tendency to be inhibited or uninhibited with unfamiliar people or during unfamiliar events is moderately stable across time and context; and (2)moderately negative relationship exists between behavioral inhibition and heart rate variability, and positive relationship…

Garcia Coll, Cynthia; And Others

1984-01-01

227

Stimulation with inhibited acidizing fluids  

Microsoft Academic Search

Production and injection wells are stimulated with an inhibited acidizing microemulsion containing hydrocarbon (external phase), surfactant, and acid. The acid is inhibited from reacting with the reservoir rock until it has penetrated the rock face. About 5 to 500 gal of the microemulsion per vertical foot of formation are useful to stimulate the wells. Carbonate reservoirs are particulary suited for

C. T. Presley; R. E. Smith

1974-01-01

228

Therapeutic alliance and behavior inhibition  

Microsoft Academic Search

The study examined whether the quality of the therapeutic alliance is associated with a tendency toward behavior inhibition. Inhibition was measured by the frequency with which the clients used the word “not” and by their verbal productivity. In treatment sessions with low-quality therapeutic alliance, clients tended to use the word “not” more often and speak fewer words. Results suggest that

Johannes Michalak; Melanie Wiethoff; Dietmar Schulte

2005-01-01

229

Inhibition of cellulases by phenols  

Microsoft Academic Search

Enzyme hydrolysis of pretreated cellulosic materials slows as the concentration of solid biomass material increases, even though the ratio of enzyme to cellulose is kept constant. This form of inhibition is distinct from substrate and product inhibition, and has been noted for lignocellulosic materials including wood, corn stover, switch grass, and corn wet cake at solids concentrations greater than 10g\\/L.

Eduardo Ximenes; Youngmi Kim; Nathan Mosier; Bruce Dien; Michael Ladisch

2010-01-01

230

Inhibition of Pyk2 blocks lung inflammation and injury in a mouse model of acute lung injury  

PubMed Central

Background Proline-rich tyrosine kinase 2 (Pyk2) is essential in neutrophil degranulation and chemotaxis in vitro. However, its effect on the process of lung inflammation and edema formation during LPS induced acute lung injury (ALI) remains unknown. The goal of the present study was to determine the effect of inhibiting Pyk2 on LPS-induced acute lung inflammation and injury in vivo. Methods C57BL6 mice were given either 10 mg/kg LPS or saline intratracheally. Inhibition of Pyk2 was effected by intraperitoneal administration TAT-Pyk2-CT 1 h before challenge. Bronchoalveolar lavage analysis of cell counts, lung histology and protein concentration in BAL were analyzed at 18 h after LPS treatment. KC and MIP-2 concentrations in BAL were measured by a mouse cytokine multiplex kit. The static lung compliance was determined by pressure-volume curve using a computer-controlled small animal ventilator. The extravasated Evans blue concentration in lung homogenate was determined spectrophotometrically. Results Intratracheal instillation of LPS induced significant neutrophil infiltration into the lung interstitium and alveolar space, which was attenuated by pre-treatment with TAT-Pyk2-CT. TAT-Pyk2-CT pretreatment also attenuated 1) myeloperoxidase content in lung tissues, 2) vascular leakage as measured by Evans blue dye extravasation in the lungs and the increase in protein concentration in bronchoalveolar lavage, and 3) the decrease in lung compliance. In each paradigm, treatment with control protein TAT-GFP had no blocking effect. By contrast, production of neutrophil chemokines MIP-2 and keratinocyte-derived chemokine in the bronchoalveolar lavage was not reduced by TAT-Pyk2-CT. Western blot analysis confirmed that tyrosine phosphorylation of Pyk2 in LPS-challenged lungs was reduced to control levels by TAT-Pyk2-CT pretreatment. Conclusions These results suggest that Pyk2 plays an important role in the development of acute lung injury in mice and that pharmacological inhibition of Pyk2 might provide a potential therapeutic strategy in the pretreatment for patients at imminent risk of developing acute lung injury.

2012-01-01

231

Catalase is inhibited by flavonoids.  

PubMed

Catalases, heme enzymes, which catalyze decomposition of hydrogen peroxide to water and molecular oxygen, belong to the antioxidant defense system of the cell. In this work we have shown that catalase from bovine liver is inhibited by flavonoids. The inhibition is, at least partially, due to the formation of hydrogen bonds between catalase and flavonoids. In the presence of some flavonoids the formation of unreactive catalase compound II has been detected. The most potent catalase inhibitors among the tested flavonoids have appeared myricetin, epicatechin gallate and epigallocatechin gallate. The relationship between the degree of enzyme inhibition and molecular structure of flavonoids has been analyzed. PMID:23567286

Krych, Justyna; Gebicka, Lidia

2013-04-06

232

Aluminum inhibits erythropoiesis in vitro.  

PubMed Central

Anemia has been associated with aluminum intoxication in patients on chronic dialysis and in animals. In studies presented here, in vitro human erythroid culture was used to delineate the effects of aluminum on normal hematopoiesis. Aluminum by itself in routine culture, even at very high levels (1,035 ng/ml), did not significantly affect erythroid colony growth. The addition of human transferrin to the culture, however, resulted in a marked dose-dependent inhibition of erythroid, but not myeloid colony growth. At all doses, CFU-E progenitors showed greater inhibition than burst-forming units (BFU-E). Aluminum inhibition was not overcome by increasing the dose of erythropoietin or adding additional burst-promoting activity to the culture. Inhibition by aluminum was directly related to the number of binding sites on transferrin in the culture, and was not observed in the presence of fully iron-saturated transferrin. Images

Mladenovic, J

1988-01-01

233

Phosphanilic Acid Inhibits Dihydropteroate Synthase.  

National Technical Information Service (NTIS)

Intact cells of Pseudomonas aeruginosa were more susceptible to phosphanilic acid (PA) than cells of Escherichia coli. In cell extract, the dihydropteroate synthases of P. aeruginosa and E. coli were about equally susceptible to inhibition by PA. These re...

R. G. Eagon A. T. McManus

1989-01-01

234

Direct renin inhibition: clinical pharmacology  

Microsoft Academic Search

Initial attempts to inhibit renin in humans have faced numerous difficulties. Molecular modeling and X-ray crystallography\\u000a of the active site of renin have led to the development of new orally active renin inhibitors such as aliskiren. Aliskiren\\u000a has a low bioavailality (2.6% to 5%) compensated by its high potency to inhibit renin and a long plasma half-life (24 to 40 h),

Michel Azizi

2008-01-01

235

Interleukin8 and Markers of Neutrophil Degranulation in Pleural Effusions  

Microsoft Academic Search

In order to know the degree of interleukin-8 (IL-8) production in the pleural space and its relation- ship to neutrophil activation, IL-8, neutrophil elastase (NE), and myeloperoxidase (MPO) were as- sessed in blood and pleural fluid (PF) of 219 patients with pleural effusions. Correlations between blood and PF IL-8, NE, and MPO were either absent or weak, except for IL-8

ROSA M. SEGURA; JOSÉ ALEGRE; ENCARNA VARELA; RAMON MARTI; JOSEP M. SURIÑACH; JORDI JUFRESA; LLUIS ARMADANS; CARLES PASCUAL

1998-01-01

236

Pyrazine-based Syk kinase inhibitors.  

PubMed

A series of aminopyrazines as inhibitors of Syk kinase activity and showing inhibition of LAD2 cells degranulation is described. Optimization of the carboxamide motif with aminomethylpiperidines provided high potency inhibiting Syk but low cellular activity. Amides of cis and trans adamantanol showed good inhibitory activity against Syk as well as remarkable activity in LAD2 cells degranulation assay. PMID:22425453

Forns, Pilar; Esteve, Cristina; Taboada, Lorena; Alonso, Juan Antonio; Orellana, Adelina; Maldonado, Mónica; Carreño, Cristina; Ramis, Isabel; López, Manel; Miralpeix, Montserrat; Vidal, Bernat

2012-03-02

237

Inhibition of Hageman factor activation.  

PubMed

A method for studying inhibitors of the contact stages of blood coagulation is described. A number of positively charged substances were shown to inhibit the contact stages. The inhibitory substances include spermine, cytochrome c, ribonuclease, and lysozyme. The inhibitory effect of these substances was neutralized by the addition of an activated plasma thromboplastin antecedent, factor XI, (PTA) fraction. Other positively charged substances including protamine, hexadimethrine, polylysine, polyornithine, methylene blue, and ortho-toluidine blue also inhibited the contact stages of coagulation, but the inhibitory effect on coagulation was not neutralized by the activated PTA fraction. Negatively charged substances such as heparin and insulin did not inhibit the contact stages of coagulation. Cytochrome c inhibited Celite adsorption of a partially purified Hageman factor fraction, and cytochrome, ribonuclease, spermine, and lysozome inhibited the adsorption of Hageman factor from PTA-deficient plasma. Very much smaller quantities of Celite completely adsorbed Hageman factor from the fraction rather than from whole plasma, which suggested the possibility that plasma contains an inhibitor or inhibitors of Hageman factor adsorption. Furthermore cytochrome c, spermine, ribonuclease, and lysozyme inhibited the coagulant activity of the following activators of the Hageman and PTA factors: Celite, kaolin, sodium stearate, ellagic acid, and skin. It is suggested that negatively charged sites on these activators are critical for adsorption and activation and that inhibition results from neutralization of the negatively charged sites by the adsorbed inhibtor. Tests with polylysine polymers indicate that inhibitory activity is directly related to molecular size over the molecular weight range of 4000 to 100,000. PMID:5645860

Nossel, H L; Rubin, H; Drillings, M; Hsieh, R

1968-05-01

238

Inhibition of carcinogenesis by retinoids.  

PubMed Central

Experimental investigations of the antineoplastic effects of retinoids are reviewed in this paper. In vitro studies have shown that the hyperplastic and metaplastic response to chemical carcinogens of mouse prostate cultures is suppressed by the addition of retinoids to the culture medium, that retinoids can partially inhibit the morphologic transformation of 10T 1/2 cells by physical or chemical carcinogens, and that the growth of some non-neoplastic and some neoplastic cell lines can be inhibited by retinoids. In vivo studies have shown that retinoids can suppress papilloma and carcinoma development (the promotion phase) in the two-stage skin carcinogenesis assay, inhibit mammary and bladder carcinogenesis in mice and rats, and inhibit the growth of some transplantabletumor lines. So far it has not been possible to inhibit predictably tumour formation in the intestinal tract or the respiratory tract of rodents. Almost all the synthetic retinoids have a higher therapeutic index than the natural retinoids in the prevention or treatment of cancer.

Nettesheim, P.

1980-01-01

239

Presynaptic inhibition of elicited neurotransmitter release  

Microsoft Academic Search

Activation of presynaptic receptors for a variety of neurotransmitters and neuromodulators inhibits transmitter release at many synapses. Such presynaptic inhibition might serve as a means of adjusting synaptic strength or preventing excessive transmitter release, or both. Previous evidence showed that presynaptic modulators inhibit Ca2+ channels and activate K+ channels at neuronal somata. These modulators also inhibit spontaneous transmitter release by

Ling-Gang Wu; Peter Saggau

1997-01-01

240

Inhibition of seed germination by quinolizidine alkaloids  

Microsoft Academic Search

Germination of Lactuca sativa L. was inhibited by mixtures of quinolizidine alkaloids. The alkaloid esters resulted in the strongest inhibition: 6 mM 13-tigloyloxylupanine inhibited germination by 100%, whereas the other lupin alkaloids, such as lupanine and sparteine, gave a 45 and 20% inhibition, respectively. Seedlings of Lupinus albus L., which are not affected by quinolizidine alkaloids, excrete lupanine and 13-tigloyloxylupanine

Michael Wink

1983-01-01

241

Post-Stop-Signal Adjustments: Inhibition Improves Subsequent Inhibition  

ERIC Educational Resources Information Center

Performance in the stop-signal paradigm involves a balance between going and stopping, and one way that this balance is struck is through shifting priority away from the go task, slowing responses after a stop signal, and improving the probability of inhibition. In 6 experiments, the authors tested whether there is a corresponding shift in…

Bissett, Patrick G.; Logan, Gordon D.

2012-01-01

242

Homo economicus belief inhibits trust.  

PubMed

As a foundational concept in economics, the homo economicus assumption regards humans as rational and self-interested actors. In contrast, trust requires individuals to believe partners' benevolence and unselfishness. Thus, the homo economicus belief may inhibit trust. The present three experiments demonstrated that the direct exposure to homo economicus belief can weaken trust. And economic situations like profit calculation can also activate individuals' homo economicus belief and inhibit their trust. It seems that people's increasing homo economicus belief may serve as one cause of the worldwide decline of trust. PMID:24146907

Xin, Ziqiang; Liu, Guofang

2013-10-16

243

Homo Economicus Belief Inhibits Trust  

PubMed Central

As a foundational concept in economics, the homo economicus assumption regards humans as rational and self-interested actors. In contrast, trust requires individuals to believe partners’ benevolence and unselfishness. Thus, the homo economicus belief may inhibit trust. The present three experiments demonstrated that the direct exposure to homo economicus belief can weaken trust. And economic situations like profit calculation can also activate individuals’ homo economicus belief and inhibit their trust. It seems that people’s increasing homo economicus belief may serve as one cause of the worldwide decline of trust.

Xin, Ziqiang; Liu, Guofang

2013-01-01

244

Glucotoxicity inhibits late steps of insulin exocytosis.  

PubMed

Prolonged exposure of beta-cells to high glucose (glucotoxicity) diminishes insulin secretion in response to glucose and has been linked to altered generation of metabolism-secretion coupling factors. We have investigated whether glucotoxicity may also alter calcium handling and late steps in secretion such as exocytosis. Clonal INS-1E beta-cells cultured at high glucose (20 or 30 mM vs. 5.5 mM) for 72 h exhibited elevated basal intracellular calcium ([Ca2+]i), which was KATP-channel dependent and due to long-term activation of protein kinase A. An increased amplitude and shortened duration of depolarization-evoked rises in [Ca2+]i were apparent. These changes were probably linked to the observed increased filling of intracellular stores and to short-term activation of protein kinase A. Insulin secretion was reduced not only by acute stimulation with either glucose or KCl but more importantly by direct calcium stimulation of permeabilized cells. These findings indicate a defect in the final steps of exocytosis. To confirm this, we measured expression levels of some 30 proteins implicated in trafficking/exocytosis of post-Golgi vesicles. Several proteins required for calcium-induced exocytosis of secretory granules were down-regulated, such as the soluble N-ethylmaleimide-sensitive factor-sensitive factor attachment receptor (SNARE) proteins VAMP-2 [vesicle (v)-SNARE, vesicle-associated membrane protein 2] and syntaxin 1 as well as complexin. VAMP-2 was also reduced in human islets. In contrast, cell immunostaining and expression levels of several fluorescent proteins suggested that other post-trans-Golgi trafficking steps and compartments are preserved and that cells were not degranulated. Thus, these studies indicate that, in addition to known metabolic changes, glucotoxicity impedes generation of signals for secretion and diminishes the efficiency of late steps in exocytosis. PMID:17204559

Dubois, Mathilde; Vacher, Pierre; Roger, Benoît; Huyghe, Deborah; Vandewalle, Brigitte; Kerr-Conte, Julie; Pattou, François; Moustaïd-Moussa, Naima; Lang, Jochen

2007-01-04

245

Inhibition of adherent scale accumulations  

Microsoft Academic Search

A method is described for inhibiting the deposition of scale in or on equipment used in the production of fluids and also in the pores and passageways of the formation in the immediate vicinity of the well bore. The method consists of emplacing a composition comprising an organophosphorus compound, for sequestering ions which impart hardeners to water, and an adsorption

T. J. Nolan; C. F. Smith

1969-01-01

246

Islam Does Not Inhibit Science.  

ERIC Educational Resources Information Center

|Compares the science/religion relationship in both Christian and Islamic countries. Presents Muslim scholars' ideas about the presence of humans on earth. Presents ideas on active nature, Noah's curse, and the age of the universe. Refutes the notion that Islam inhibited science and advocates the belief that Islam promoted science. (YDS)|

Shanavas, T. O.

1999-01-01

247

Inhibition of return in microsaccades  

Microsoft Academic Search

Inhibition of return (IOR) is the term used to describe the phenomenon whereby stimuli appearing at recently attended locations are reacted to less efficiently than stimuli appearing at locations that have not yet been attended. In the present study, we employed a typical IOR paradigm with peripheral uninformative cues while participants maintained their eyes at fixation. Eye position was monitored

Giovanni Galfano; Elena Betta; Massimo Turatto

2004-01-01

248

Corrosion inhibition by quaternary amines  

Microsoft Academic Search

Quaternary ammonium compounds are excellent inhibitors of acid corroison, and seem to influence the anodic partial reaction more than the cathodic. This behavior is not readily interpreted in terms of physical vs. chemical adsorption, since these compounds do not possess bonding for chemisorption. Increasing the hydrogen bulk in the inhibitor molecule markedly increases the inhibition efficiency, which is to be

R. M. Hurd; H. Raiszadeh

1970-01-01

249

Inhibited N2O4.  

National Technical Information Service (NTIS)

This program is concerned with evaluating a new storable liquid oxidizer INTO, which is nitrogen tetroxide (NTO) inhibited with a fluorine oxidizer. The best fluorine oxidizer has been found to be FNO2. Storability tests of INTO in stainless-steel, alumin...

A. D. Lev E. J. Junkins H. E. Dubb H. H. Rogers J. Gerhauser

1967-01-01

250

Inhibition among olfactory receptor neurons  

PubMed Central

Often assumed to be epiphenomena of a cell’s activity, extracellular currents and resulting potential changes are increasingly recognized to influence the function of other cells in the vicinity. Experimental evidence shows that even small electric fields can modulate spike timing in neurons. Moreover, when neurons are brought close together experimentally or in pathological conditions, activity in one neuron can excite its neighbors. Inhibitory ephaptic mechanisms, however, may depend on more specialized coupling among cells. Recent studies in the Drosophila olfactory system have shown that excitation of a sensory neuron can inhibit its neighbor, and it was speculated that this interaction was ephaptic. Here we give an overview of ephaptic interactions that effect changes in spike timing, excitation or inhibition in diverse systems with potential relevance to human neuroscience. We examine the mechanism of the inhibitory interaction in the Drosophila system and that of the well-studied ephaptic inhibition of the Mauthner cell in more detail. We note that both current towards and current away from the local extracellular environment of a neuron can inhibit it, but the mechanism depends on the specific architecture of each system.

Van der Goes van Naters, Wynand

2013-01-01

251

Post-stop-signal adjustments: inhibition improves subsequent inhibition.  

PubMed

Performance in the stop-signal paradigm involves a balance between going and stopping, and one way that this balance is struck is through shifting priority away from the go task, slowing responses after a stop signal, and improving the probability of inhibition. In 6 experiments, the authors tested whether there is a corresponding shift in priority toward the stop task, speeding reaction time to the stop signal. Consistent with this hypothesis, stop-signal reaction time (SSRT) decreased on the trial immediately following a stop signal in each experiment. Experiments 2-4 used 2 very different stop signals within a modality, and stopping improved when the stop stimulus repeated and alternated. Experiments 5 and 6 presented stop signals in different modalities and showed that SSRT improved only when the stop stimulus repeated within a modality. These results demonstrate within-modality post-stop-signal speeding of response inhibition. PMID:22268912

Bissett, Patrick G; Logan, Gordon D

2012-01-23

252

Dimethylphosphoryl-inhibited human cholinesterases: inhibition, reactivation, and aging kinetics  

Microsoft Academic Search

Human poisoning by organophosphates bearing two methoxy groups, e.g. by malathion, paraoxon-methyl, dimethoate and oxydemeton-methyl,\\u000a is generally considered to be rather resistant to oxime therapy. Since the oxime effectiveness is influenced not only by its\\u000a reactivating potential but also by inhibition, aging and spontaneous reactivation kinetics, experiments were performed with\\u000a human acetyl- (AChE) and butyrylcholinesterase (BChE) to determine the respective

F. Worek; C. Diepold; P. Eyer

1999-01-01

253

Osteogenic Inhibition in Multiple Myeloma  

PubMed Central

Objective: Multiple myeloma (MM) is a plasma cell malignancy where plasma cells are increased in the bone marrow (BM) and usually do not enter peripheral blood, but produce harmful factors creating problems in these patients (e.g. malignant plasma cells over activate osteoclasts and inhibit osteoblasts with factors like RANKL and DKK). These factors are a main cause of bone lesion in MM patients. Recently SOST gene which responsible to encodes the sclerostin protein was identify. This protein specifically inhibits Wnt signaling in osteoblasts (inhibition of osteoblast differentiation and proliferation) and decrease bone formation and can also cause bone lesion in MM patients. Materials and Methods: In this experimental study, human myeloma cell lines (U266 b1) were purchased from Pasteur Institute of Iran. Samples consisted of BM aspirates from the iliac crest of MM patients. BM with more than 70% plasma cell were selected for our study (6 patients) and one healthy donor. RNA extraction was done with Qiagen kit. was undertaken on mRNA of samples and cell lines. Also we purchased unrestricted somatic stem cells from Bonyakhte Company to evaluate the effect of soluble factors from myeloma cell lines on osteogenic differentiation medium. Results: Our results showed that SOST is expressed significantly in primary myeloma cells derived from MM patients and myeloma cell lines. In other words, patients with more bone problems, express SOST in their plasma cells at a higher level. In addition, myeloma cells inhibit osteoblast differentiation in progenitor cells from umbilical cord blood stem cell (UCSC) in osteogenic inducing medium. Conclusion: There are many osteoblast maturation inhibitory factors such as DKK, Sfrp and Sclerostin that inhibit maturation of osteoblast in bone. Among osteoblast inhibitory agents (DKK, Sfrp, Sclerostin) sclerostin has the highest specificity and therefore will have less side effect versus non-specific inhibitory agents. Our results also show that based on SOST expression in MM, there is a potential to inhibit sclerostin with antibody or alternative methods and prevent bone lesion in MM patients with the least side effect.

Habibi, Hussain; Abroun, Saeid; Hajifathali, Abbas; Soleimani, Masoud; Kaviani, Saeid; Kalantari, Nasim; Eslahchi, Susan

2013-01-01

254

Tunneling inhibition for subwavelength light.  

PubMed

We show that light tunneling inhibition may take place in suitable dynamically modulated waveguide arrays for light spots whose features are remarkably smaller than the wavelength of light. We found that tunneling between neighboring waveguides can be suppressed for specific frequencies of the out-of-phase refractive index modulation, affording undistorted propagation of the input subwavelength light spots over hundreds of Rayleigh lengths. Tunneling inhibition turns out to be effective only when the waveguide separation in the array is above a critical threshold. Inclusion of a weak focusing nonlinearity is shown to improve localization. We analyze the phenomenon in purely dielectric structures and also in arrays containing periodically spaced metallic layers. PMID:23903159

Huang, Changming; Shi, Xianling; Ye, Fangwei; Kartashov, Yaroslav V; Chen, Xianfeng; Torner, Lluis

2013-08-01

255

Inhibition of lymphoproliferation by dipyridamole.  

PubMed

Dipyridamole (DP, Persantin) was examined for its effects on the proliferation of mitogen-stimulated murine splenocytes and L1210 leukemia cells. In keeping with its reported activity as an inhibitor of nucleoside transport, DP inhibited incorporation by lymphoid cells of labeled thymidine and uridine ino macromolecules. That this inhibition resulted from activities in addition to suppression of nucleoside transport was verified by measured decreases of cellular DNA and viable cell numbers. In addition, protein synthesis was also decreased as indicated by labeled valine incorporation and total protein content of the cells. The rapid accumulation of cAMP in phytohemagglutinin-stimulated splenocytes in the presence of DP may provide an explanation for the anti-proliferative effect of DP on lymphoid cells. PMID:7092928

Farmer, J L; Prager, M D

1982-04-01

256

Threat interferes with response inhibition.  

PubMed

A potential threat, such as a spider, captures attention and engages executive functions to adjust ongoing behavior and avoid danger. We and many others have reported slowed responses to neutral targets in the context of emotional distractors. This behavioral slowing has been explained in the framework of attentional competition for limited resources with emotional stimuli prioritized. Alternatively, slowed performance could reflect the activation of avoidance/freezing-type motor behaviors associated with threat. Although the interaction of attention and emotion has been widely studied, little is known on the interaction between emotion and executive functions. We studied how threat-related stimuli (spiders) interact with executive performance and whether the interaction profile fits with a resource competition model or avoidance/freezing-type motor behaviors. Twenty-one young healthy individuals performed a Go-NoGo visual discrimination reaction time (RT) task engaging several executive functions with threat-related and emotionally neutral distractors. The threat-related distractors had no effect on the RT or the error rate in the Go trials. The NoGo error rate, reflecting failure in response inhibition, increased significantly because of threat-related distractors in contrast to neutral distractors, P less than 0.05. Thus, threat-related distractors temporarily impaired response inhibition. Threat-related distractors associated with increased commission errors and no effect on RT does not suggest engagement of avoidance/freezing-type motor behaviors. The results fit in the framework of the resource competition model. A potential threat calls for evaluation of affective significance as well as inhibition of undue emotional reactivity. We suggest that these functions tax executive resources and may render other executive functions, such as response inhibition, temporarily compromised when the demands for resources exceed availability. PMID:22494999

Hartikainen, Kaisa M; Siiskonen, Anna R; Ogawa, Keith H

2012-05-01

257

Presynaptic irregularity and pacemaker inhibition  

Microsoft Academic Search

It is known (e.g., Perkel et al., 1964) that when a pacemaker neuron elicits IPSP's in another, there are domains called “paradoxical segments” where in the steady-state i) faster inhibitory discharges determine faster inhibited ones, and ii) pre- and postsynaptic spikes are “locked” in an invariant forward-and-backward positioning in time, spikes alternating in the ratios 1:1 (1 pere for 1

A. F. Kohn; A. Freitas da Rocha; J. P. Segundo

1981-01-01

258

Orlistat Inhibits Dietary Cholesterol Absorption  

Microsoft Academic Search

Objective: Orlistat decreases the absorption of dietary triglycerides by inhibiting intestinal lipases. Orlistat therapy is associated with a greater decline in plasma low-density lipoprotein-cholesterol concentrations than that expected from weight loss alone. Therefore, we evaluated the effect of orlistat treatment on dietary cholesterol absorption as a possible mechanism for the independent effect of orlistat on plasma cholesterol concentration.Research Methods and

Bettina Mittendorfer; Richard E. Ostlund; Bruce W. Patterson; Samuel Klein

2001-01-01

259

The inhibition of acquired fear  

Microsoft Academic Search

A conditioned stimulus (CS) associated with a fearsome unconditioned stimulus (US) generates learned fear. Acquired fear is\\u000a at the root of a variety of disorders, among which are phobias, generalized anxiety, and the posttraumatic stress disorder\\u000a (PTSD). The simplest way to inhibit learned fear is to extinguish it, which is usually done by repeatedly presenting the CS\\u000a alone, so that

Iván Izquierdo; Martín Cammarota; Mónica R. M. Vianna; Lía R. M. Bevilaqua

2004-01-01

260

Cancer inhibition by green tea  

Microsoft Academic Search

Green tea is now an acknowledged cancer preventive in Japan. This paper discusses several important features of (?)-epigallocatechin gallate (EGCG), the main constituent of green tea and tea polyphenols. EGCG and other tea polyphenols inhibited growth of human lung cancer cell line, PC-9 cells with G2\\/M arrest. 3H-EGCG administered by p.o. intubation into mouse stomach revealed that small amounts of

Hirota Fujiki; Masami Suganuma; Sachiko Okabe; Naoko Sueoka; Atsumasa Komori; Eisaburo Sueoka; Tomoko Kozu; Yukiko Tada; Kenji Suga; Kazue Imai; Kei Nakachi

1998-01-01

261

Method for inhibiting activation of macrophages, inhibiting formation of osteoclasts, inhibiting function of osteoclasts, and/or activating osteoblasts  

US Patent & Trademark Office Database

A method for inhibiting the activation of macrophages, inhibiting the formation of osteoclasts, inhibiting the function of osteoclasts, and/or activating osteoblasts in a mammal is provided. The method comprises the administration of an effective amount of kinsenoside of formula (I) or a pharmaceutically acceptable salt or ester thereof to the mammal: ##STR00001##

2011-12-27

262

Inhibition of Malarial DNA Polymerase Alpha.  

National Technical Information Service (NTIS)

Plant extracts have been surveyed in an effort to locate natural principles capable of mediating potent, specific inhibition of malaria DNA polymerase alpha. Several extracts containing putative polymerase inhibitors have been shown to inhibit cultured Pl...

S. M. Hecht

1992-01-01

263

Retroactive Inhibition, Hypnosis, and Hypnotic Amnesia.  

National Technical Information Service (NTIS)

An experiment was performed to investigate the relationship of hypnosis and posthypnotic amnesia to retroactive inhibition. Four groups of 10 Ss each learned lists of adjectives in a retroactive inhibition paradigm. Two of the groups learned the interveni...

K. R. Graham A. Patton

1967-01-01

264

Inhibition of adenovirus multiplication by metabolic inhibitors  

Microsoft Academic Search

Summary Under conditions of one-step growth the multiplication of adenovirus 19 in HeLa cells was inhibited by 7 inhibitors of DNA synthesis (see Table 1), by cycloheximide, streptovitacin A, actinomycin D and mitomycin D. The inhibition involved the formation of infectious virus and of capsid proteins. The viral CPE was not inhibited by inhibitors of DNA synthesis; cycloheximide, streptovitacin and

R. Wigand; Josepha Schmieder

1973-01-01

265

Inhibited reflection in uniaxial crystals.  

PubMed

When an ordinary or extraordinary ray that propagates through a birefringent crystal is reflected it gives rise to two reflected rays whose directions may be calculated with formulas similar to Snell's law for refraction. When the reflection angle is greater than the incidence angle there is a critical angle for which the reflected ray is grazing, and for values of the incidence angle greater than this critical value the reflected ray no longer exists. We call this phenomenon inhibited reflection. We show how the critical angles may be calculated, and an experiment that visualizes the phenomenon shows good agreement with theory. PMID:19749887

Simon, M C; Echarri, R M

1989-03-01

266

Huntingtin inhibits caspase-3 activation  

PubMed Central

Huntington's disease results from a mutation in the HD gene encoding for the protein huntingtin. The function of huntingtin, although beginning to be elucidated, remains largely unclear. To probe the prosurvival function of huntingtin, we modulate levels of wild-type huntingtin in a number of cellular and in vivo models. Huntingtin depletion resulted in caspase-3 activation, and overexpression of huntingtin resulted in caspase-3 inhibition. Additionally, we demonstrate that huntingtin physically interacts with active caspase-3. Interestingly, mutant huntingtin binds active caspase-3 with a lower affinity and lower inhibitory effect on active caspase-3 than does wild-type huntingtin. Although reduction of huntingtin levels resulted in caspase-3 activation in all conditions examined, the cellular response was cell-type specific. Depletion of huntingtin resulted in either overt cell death, or in increased vulnerability to cell death. These data demonstrate that huntingtin inhibits caspase-3 activity, suggesting a mechanism whereby caspase-mediated huntingtin depletion results in a detrimental amplification cascade leading to further caspase-3 activation, resulting in cell dysfunction and cell death.

Zhang, Yu; Leavitt, Blair R; van Raamsdonk, Jeremy M; Dragatsis, Ioannis; Goldowitz, Dan; MacDonald, Marcy E; Hayden, Michael R; Friedlander, Robert M

2006-01-01

267

Graphene: corrosion-inhibiting coating.  

PubMed

We report the use of atomically thin layers of graphene as a protective coating that inhibits corrosion of underlying metals. Here, we employ electrochemical methods to study the corrosion inhibition of copper and nickel by either growing graphene on these metals, or by mechanically transferring multilayer graphene onto them. Cyclic voltammetry measurements reveal that the graphene coating effectively suppresses metal oxidation and oxygen reduction. Electrochemical impedance spectroscopy measurements suggest that while graphene itself is not damaged, the metal under it is corroded at cracks in the graphene film. Finally, we use Tafel analysis to quantify the corrosion rates of samples with and without graphene coatings. These results indicate that copper films coated with graphene grown via chemical vapor deposition are corroded 7 times slower in an aerated Na(2)SO(4) solution as compared to the corrosion rate of bare copper. Tafel analysis reveals that nickel with a multilayer graphene film grown on it corrodes 20 times slower while nickel surfaces coated with four layers of mechanically transferred graphene corrode 4 times slower than bare nickel. These findings establish graphene as the thinnest known corrosion-protecting coating. PMID:22299572

Prasai, Dhiraj; Tuberquia, Juan Carlos; Harl, Robert R; Jennings, G Kane; Rogers, Bridget R; Bolotin, Kirill I

2012-02-10

268

Pharmacological inhibition of poly(ADP-ribose) polymerase inhibits angiogenesis  

SciTech Connect

Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme which plays an important role in regulating cell death and cellular responses to DNA repair. Pharmacological inhibitors of PARP are being considered as treatment for cancer both in monotherapy as well as in combination with chemotherapeutic agents and radiation, and were also reported to be protective against untoward effects exerted by certain anticancer drugs. Here we show that pharmacological inhibition of PARP with 3-aminobenzamide or PJ-34 dose-dependently reduces VEGF-induced proliferation, migration, and tube formation of human umbilical vein endothelial cells in vitro. These results suggest that treatment with PARP inhibitors may exert additional benefits in various cancers and retinopathies by decreasing angiogenesis.

Rajesh, Mohanraj [Section On Oxidative Stress Tissue Injury, Laboratory of Physiological Studies, NIAAA, National Institutes of Health, 5625 Fishers Lane, MSC-9413, Bethesda, MD 20892-9413 (United States); Mukhopadhyay, Partha [Section On Oxidative Stress Tissue Injury, Laboratory of Physiological Studies, NIAAA, National Institutes of Health, 5625 Fishers Lane, MSC-9413, Bethesda, MD 20892-9413 (United States); Batkai, Sandor [Section On Oxidative Stress Tissue Injury, Laboratory of Physiological Studies, NIAAA, National Institutes of Health, 5625 Fishers Lane, MSC-9413, Bethesda, MD 20892-9413 (United States); Godlewski, Grzegorz [Section On Oxidative Stress Tissue Injury, Laboratory of Physiological Studies, NIAAA, National Institutes of Health, 5625 Fishers Lane, MSC-9413, Bethesda, MD 20892-9413 (United States); Hasko, Gyoergy [Department of Surgery, UMDNJ-New Jersey Medical School, Newark, NJ 07103 (United States); Liaudet, Lucas [Department of Intensive Care Medicine, University Hospital, 1011 Lausanne (Switzerland); Pacher, Pal [Section On Oxidative Stress Tissue Injury, Laboratory of Physiological Studies, NIAAA, National Institutes of Health, 5625 Fishers Lane, MSC-9413, Bethesda, MD 20892-9413 (United States)]. E-mail: pacher@mail.nih.gov

2006-11-17

269

Amiodarone Inhibits Apamin-Sensitive Potassium Currents  

PubMed Central

Background Apamin sensitive potassium current (IKAS), carried by the type 2 small conductance Ca2+-activated potassium (SK2) channels, plays an important role in post-shock action potential duration (APD) shortening and recurrent spontaneous ventricular fibrillation (VF) in failing ventricles. Objective To test the hypothesis that amiodarone inhibits IKAS in human embryonic kidney 293 (HEK-293) cells. Methods We used the patch-clamp technique to study IKAS in HEK-293 cells transiently expressing human SK2 before and after amiodarone administration. Results Amiodarone inhibited IKAS in a dose-dependent manner (IC50, 2.67±0.25 µM with 1 µM intrapipette Ca2+). Maximal inhibition was observed with 50 µM amiodarone which inhibited 85.6±3.1% of IKAS induced with 1 µM intrapipette Ca2+ (n?=?3). IKAS inhibition by amiodarone was not voltage-dependent, but was Ca2+-dependent: 30 µM amiodarone inhibited 81.5±1.9% of IKAS induced with 1 µM Ca2+ (n?=?4), and 16.4±4.9% with 250 nM Ca2+ (n?=?5). Desethylamiodarone, a major metabolite of amiodarone, also exerts voltage-independent but Ca2+ dependent inhibition of IKAS. Conclusion Both amiodarone and desethylamiodarone inhibit IKAS at therapeutic concentrations. The inhibition is independent of time and voltage, but is dependent on the intracellular Ca2+ concentration. SK2 current inhibition may in part underlie amiodarone's effects in preventing electrical storm in failing ventricles.

Turker, Isik; Yu, Chih-Chieh; Chang, Po-Cheng; Chen, Zhenhui; Sohma, Yoshiro; Lin, Shien-Fong; Chen, Peng-Sheng; Ai, Tomohiko

2013-01-01

270

Inhibition of vection by red.  

PubMed

We investigated the effects of colors on vection induction. Expanding optical flows during one's forward self-motion were simulated by moving dots. The dots and the background were painted in equiluminant red and green. Experiments 1 and 2 showed that vection was weaker when the background was red than when the background was green. In addition, Experiment 3 showed that vection was weaker when the moving dots were red than when the dots were green. Experiment 4 demonstrated that red dots on a red background induced very weak vection, as compared with green dots on a green background. In Experiments 5 and 6, we showed that the present results could not be explained by a luminance artifact. Furthermore, Experiment 7 showed that a moving red grating induced weaker vection than did a green one. We concluded that a red visual stimulus inhibits vection. PMID:20675807

Seno, Takeharu; Sunaga, Shoji; Ito, Hiroyuki

2010-08-01

271

Corrosion inhibition using mercury intensifiers  

SciTech Connect

This patent describes an intensified corrosion inhibitor composition for inhibiting the corrosion of steel in the presence of an acidic medium. It comprises: an effective amount of an acid soluble mercury metal intensifier; and a corrosion inhibitor. This patent also describes a method of treating a subterranean well for enhancement of production within the well, comprising the steps of introducing and positioning within the well a high alloy stec surface exposable to a treatment fluid therewith; introducing into the well and contacting the surface with a treatment fluid comprising an acidic injection medium, an acid corrosion inhibitor, and an intensifier for deposition on or effective treatment contact with the surface, the intensifier comprising an acid soluble mercury metal site circulating the fluid into the well for contact with at least one production zone within the well.

Cizek, A.

1990-03-05

272

Genistein treatment of cells inhibits arenavirus infection.  

PubMed

Arenaviridae is a family of enveloped viruses some of which are capable of causing hemorrhagic fever syndromes in humans. In this report, we demonstrate that treatment of host cells with the tyrosine kinase inhibitor genistein inhibits infection of cells with the New World arenavirus Pichindé (PICV). The greatest degree of inhibition was observed in pre-treated target cells, but modest inhibition of infection was also seen when drug was added to cultures up to 48h after infection. We show that PICV-induced phosphorylation of the activating transcription factor-2 protein (ATF-2) and cyclic adenosine monophosphate response element binding protein (CREB) is inhibited following genistein treatment. Lastly, genistein treatment also inhibited transduction of cells with pseudotyped retrovirus particles expressing envelope proteins of the Old World arenavirus Lassa virus. These results demonstrate that kinase activity is required for arenavirus infection and that therapeutics designed to inhibit kinase activity should be explored. PMID:17961732

Vela, Eric M; Bowick, Gavin C; Herzog, Norbert K; Aronson, Judith F

2007-10-08

273

Silver-Palladium Surfaces Inhibit Biofilm Formation  

Microsoft Academic Search

Undesired biofilm formation is a major concern in many areas. In the present study, we investigated biofilm-inhibiting properties of a silver-palladium surface that kills bacteria by generating microelectric fields and electrochemical redox processes. For evaluation of the biofilm inhibition efficacy and study of the biofilm inhibition mechanism, the silver-sensitive Escherichia coli J53 and the silver-resistant E. coli J53(pMG101) strains were

Wen-Chi Chiang; Casper Schroll; Lisbeth Rischel Hilbert; P. Moller; Tim Tolker-Nielsen

2009-01-01

274

Creatinine Inhibits D-Amino Acid Oxidase  

Microsoft Academic Search

Inhibition of D-amino acid oxidase (DAO) activity by various uremic retention products and guanidino compounds was investigated. Creatinine (CTN) was found to inhibit DAO at a similar concentration in the sera of uremic patients. The inhibition was competitive and the Ki value was 2.7 mM. Moreover, CTN was shown to interact with flavin adenine dinucleotide (FAD), a coenzyme of DAO.

Y. Nohara; J. Suzuki; T. Kinoshita; M. Watanabe

2002-01-01

275

Direct inhibition of methanogenesis by ferric iron  

Microsoft Academic Search

Observed inhibition of methanogenesis under Fe(III)-reducing conditions is usually explained by competition of methanogens and Fe(III)-reducing bacteria for the common substrates acetate and hydrogen. However, substrate competition alone cannot explain the strong inhibition of methanogenesis during Fe(III)-reduction. We demonstrate direct inhibition of methanogenesis by amorphous Fe(OH)3 at concentrations between 0 and 10 mM in experiments with pure cultures of methanogens.

Peter M. van Bodegom; Johannes C. M. Scholten; Alfons J. M. Stams

2004-01-01

276

Mast cell stabilization, lipoxygenase inhibition, hyaluronidase inhibition, antihistaminic and antispasmodic activities of Aller-7, a novel botanical formulation for allergic rhinitis.  

PubMed

Allergic rhinitis, also known as hay fever, rose fever or summer catarrh, is a major challenge to health professionals. A large number of the world's population, including approximately 40 million Americans, suffers from allergic rhinitis. A novel, botanical formulation (Aller-7) has been developed for the treatment of allergic rhinitis using a combination of extracts from seven medicinal plants, including Phyllanthus emblica, Terminalia chebula, T. bellerica, Albizia lebbeck, Piper nigrum, Zingiber officinale and P. longum, which have a proven history of efficacy and health benefits. The clinical manifestations of allergy are due to a number of mediators that are released from mast cells. The effect of Aller-7 on rat mesenteric mast cell degranulation was studied by incubating different concentrations of Aller-7 and challenging them with a degranulating agent, compound 48/80. The inhibitory activity of Aller-7 was determined against lipoxygenase and hyaluronidase, the key enzymes involved in the initiation and maintenance of inflammatory responses. Furthermore, most of these manifestations are due to histamine, which causes vasodilatation, increasing capillary permeability and leading to bronchoconstriction. Hence, the antihistaminic activity of Aller-7 was determined is isolated guinea pig ileum substrate using cetirizine as a positive control. The antispasmodic effect of Aller-7 on contractions of guinea pig tracheal chain was determined using papaverine and cetirizine as controls. Aller-7 exhibited potent activity in all these in vitro models tested, thus demonstrating the novel anti-allergic potential of Aller-7. PMID:14708456

Amit, A; Saxena, V S; Pratibha, N; D'Souza, P; Bagchi, M; Bagchi, D; Stohs, S J

2003-01-01

277

Sphingosine inhibits angiotensin-stimulated aldosterone synthesis.  

PubMed

Sphingosine and other protein kinase C inhibitors were tested for their ability to inhibit aldosterone synthesis by bovine adrenal glomerulosa cells. Sphingosine inhibited angiotensin (AII)-stimulated aldosterone synthesis (IC50 of 5 microM). At doses that totally blocked steroidogenesis, sphingosine did not affect protein synthesis or [125I]AII binding to cells. Sphingosine also inhibited dibutyryl cyclic AMP (dbcAMP)-stimulated aldosterone synthesis. Sphingosine inhibited pregnenolone synthesis from cholesterol, but not the conversion of progesterone or 20 alpha-hydroxycholesterol to aldosterone. These results suggest that sphingosine inhibits steroidogenesis at a locus close to that where stimulation occurs by AII and dbcAMP. Other protein kinase C inhibitors were tested. Retinal, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), and staurosporine inhibited aldosterone synthesis stimulated by AII and dbcAMP. Retinal and H-7 also inhibited progesterone conversion to aldosterone, and retinal blocked [125I]AII binding. Staurosporine was more specific, inhibiting AII-stimulated aldosteronogenesis at concentrations which had little effect on conversion of progesterone to aldosterone. Because they inhibited dbcAMP stimulation, none of the inhibitors was sufficiently specific to use as a probe of the role of protein kinase C. The IC50 of sphingosine suggests that this or related products of lipid hydrolysis could act as endogenous regulators of adrenal cell function. PMID:1851631

Elliott, M E; Jones, H M; Tomasko, S; Goodfriend, T L

1991-04-01

278

Analgesia by inhibiting tetrahydobiopterin synthesis  

PubMed Central

Physiological control of the co-factor tetrahydrobiopterin (BH4) is tight in normal circumstances but levels increase pathologically in the injured somatosensory system. BH4 is an essential co-factor in the production of serotonin, dopamine, epinephrine, norepinephrine and nitric oxide. Excess BH4 levels cause pain, likely through excess production of one or more of these neurotransmitters or signaling molecules. The rate limiting step for BH4 production is GTP Cyclohydrolase 1 (GCH1). A human GCH1 gene haplotype exists that leads to less GCH1 transcription, translation, and therefore enzyme activity, following cellular stress. Carriers of this haplotype produce less BH4 and therefore feel less pain, especially following nerve injury where BH4 production is pathologically augmented. Sulfasalazine (SSZ) an FDA approved anti-inflammatory agent of unknown mechanism of action, has recently been shown to be a sepiapterin reductase (SPR) inhibitor. SPR is part of the BH4 synthesis cascade and is also upregulated by nerve injury. Inhibiting SPR will reduce BH4 levels and therefore should act as an analgesic. We propose SSZ as a novel anti-neuropathic pain medicine.

Costigan, Michael; Latremoliere, Alban; Woolf, Clifford J.

2012-01-01

279

Plant phenolics inhibit neutrophil elastase.  

PubMed

Human neutrophil elastase (HNE) is a serine protease, which is present in its active form in inflamed tissue as well as in psoriatic lesions. In extension of our research on natural compounds as inhibitors of HNE or of its release, several phenolics of different size were tested. The ellagitannins agrimoniin and pedunculagin were the most potent direct HNE inhibitors (IC (50) = 0.9 and 2.8 microM, respectively). Ligand docking calculations provided evidence that inhibition may occur in an unspecific manner. Agrimoniin also showed anti-proliferative effects in the ATP assay (IC (50) = 3.2 microM), suggesting that this type of tannin could have beneficial effects in the treatment of diseases such as psoriasis. Tests with other phenolics combined with ligand docking experiments revealed that, besides the presence of ORTHO-dihydroxy groups, a specific lipophilic shape is necessary for an inhibitory activity. The phenolic genistein deserves special interest as an inhibitor of elastase release because its effect was remarkably potent (IC (50) = 0.6 microM). PMID:17024589

Hrenn, Andrea; Steinbrecher, Thomas; Labahn, Andreas; Schwager, Joseph; Schempp, Christoph M; Merfort, Irmgard

2006-10-01

280

Glutamatergic inhibition in sensory neocortex.  

PubMed

In the mammalian brain, glutamate and gamma-aminobutyric acid are considered major excitatory and inhibitory neurotransmitters, respectively. However, we have found evidence that glutamate can also act as a postsynaptic inhibitory neurotransmitter in layer 4 of the neocortex. Using whole-cell recordings from layer 4 neurons in slice preparations from the mouse visual, auditory, and somatosensory cortices, we found that metabotropic glutamate receptor (mGluR) agonists (ACPD, APDC, and DCG IV) elicit a robust, long-lasting hyperpolarization that is abolished by the group II mGluR antagonist, MCCG. This response largely involves a K(+) conductance mediated by G-protein activity and GIRK channels. Furthermore, electrical and photostimulation of the intracortical inputs to layer 4 elicits a similar hyperpolarization that is blocked by group II mGluR antagonists. This novel inhibition mediated by group II mGluRs may be an unappreciated mechanism for refining cortical receptive fields in layer 4 and may enable synaptic gain control during periods of high activity. PMID:19176638

Lee, Charles C; Sherman, S Murray

2009-01-28

281

Inhibition in Autism: Children with Autism Have Difficulty Inhibiting Irrelevant Distractors but Not Prepotent Responses  

ERIC Educational Resources Information Center

|Resistance to distractor inhibition tasks have previously revealed impairments in children with autism. However, on the classic Stroop task and other prepotent response tasks, children with autism show intact inhibition. These data may reflect a distinction between prepotent response and resistance to distractor inhibition. The current study…

Adams, Nena C.; Jarrold, Christopher

2012-01-01

282

Inhibition and Facilitation of Nucleic Acid Amplification  

Microsoft Academic Search

Factors that inhibit the amplification of nucleic acids by PCR are present with target DNAs from many sources. The inhib- itors generally act at one or more of three essential points in the reaction in the following ways: they interfere with the cell lysis necessary for extraction of DNA, they interfere by nucleic acid degradation or capture, and they inhibit

IAN G. WILSON

1997-01-01

283

Hydrogen production from inhibited anaerobic composters  

Microsoft Academic Search

This paper investigated hydrogen production from a model lignocellulosic waste in inhibited solid substrate anaerobic digesters. Acetylene at 1% vv in the headspace was as effective as bromoethanesulfonate in inhibiting methanogenic activity in batch anaerobic composters containing 25% (wv) total organic solids inoculated with an undefined cellulotytic consortium derived from anaerobic digesters. Acetylene also had no effect on the rate

R. Sparling; D. Risbey; H. M. Poggi-Varaldo

1997-01-01

284

Mechanisms of Rotenone-induced Proteasome Inhibition  

PubMed Central

The etiology of Parkinson’s disease is unclear but appears to involve mitochondrial dysfunction, proteasome inhibition, and environmental toxins. It has been shown that pesticides, including the complex I inhibitor rotenone, cause proteasome inhibition but the mechanism of rotenone-induced proteasome dysfunction remains largely unknown. In this study, we examined the role of mitochondrial inhibition, oxidative stress, and microtubule dysfunction as potential mediators of rotenone-induced proteasome inhibition. Proteasome activity (26S) was measured in HEK and SK-N-MC cells expressing an EGFP-U degron fusion protein that is selectively degraded by the proteasome. We found that complex I and III inhibition led to the production of peroxides and decreased proteasome activity. We also found that rotenone increased nitric oxide production and nitric oxide and peroxynitrites led to proteasome inhibition. The effects of rotenone were attenuated by anti-oxidants and nitric oxide synthase inhibition. Since rotenone can also inhibit microtubule assembly, we tested a specific MT inhibitor and found it led to proteasome dysfunction. Rotenone also led to a decrease in 20S proteasome activity and 20S proteasome subunit immunoreactivity without a change in subunit mRNA. Together, these data suggest that rotenone-induced decreases in proteasome activity are due to increased degradation of proteasome components secondary to oxidative damage and possibly microtubule dysfunction.

Chou, Arthur P.; Li, Sharon; Fitzmaurice, Arthur G.; Bronstein, Jeff M.

2010-01-01

285

Pyruvate inhibition of pyruvate dehydrogenase kinase  

Microsoft Academic Search

Both prolonged starvation and hyperthyroidism evoke stable increases in cardiac pyruvate dehydrogenase kinase (PDHK) activity. Pyruvate inhibits PDHK in rat heart mitochondria with activation of PDHC. The sensitivity of PDHK to inhibition by pyruvate declines after prolonged starvation. In the present study, pyruvate concentrations giving 50% active complex (PDHa) in mitochondria from fed, control and fed, hyperthyroid rats were 0.3

David A. Priestman; Karen A. Orfali; Mary C. Sugden

1996-01-01

286

Factors Impacting the Child with Behavioral Inhibition  

ERIC Educational Resources Information Center

Various factors influence the developmental course of the behaviorally inhibited child. These factors include reciprocating, contextual factors, such as the child's own traits, the environment, the maternal characteristics, and the environment. Behaviorally inhibited children show physiological and behavioral signs of fear and anxiety when…

Hornbuckle, Suzanne R.

2010-01-01

287

Optimal Decision Making in Neural Inhibition Models  

ERIC Educational Resources Information Center

|In their influential "Psychological Review" article, Bogacz, Brown, Moehlis, Holmes, and Cohen (2006) discussed optimal decision making as accomplished by the drift diffusion model (DDM). The authors showed that neural inhibition models, such as the leaky competing accumulator model (LCA) and the feedforward inhibition model (FFI), can mimic the…

van Ravenzwaaij, Don; van der Maas, Han L. J.; Wagenmakers, Eric-Jan

2012-01-01

288

Inhibition of cyclic photophosphorylation by peroxyacetyl nitrate  

Microsoft Academic Search

The present paper describes the inhibitory effect of PAN on cyclic photophosphorylation by chloroplasts isolated from Black Valentine bean leaves. If the photophosphorylation reaction mixture is gassed with PAN during the assay, inhibition of photophosphorylation results. Moreover, inhibition of photophosphorylation is also observed if the complete reaction mixture containing the chloroplasts is gassed in complete darkness with PAN immediately before

J. Koukol; W. M. Jr. Dugger; N. O. Belser

1963-01-01

289

Substrate inhibition kinetics of phenol biodegradation  

SciTech Connect

Phenol biodegradation was studied in batch experiments using an acclimated inoculum and initial phenol concentrations ranging from 0.1 to 1.3 g/L. Phenol depletion an associated microbial growth were monitored over time to provide information that was used to estimate the kinetics of phenol biodegradation. Phenol inhibited biodegradation at high concentrations, and a generalized substrate inhibition model based on statistical thermodynamics was used to describe the dynamics of microbial growth in phenol. For experimental data obtained in this study, the generalized substrate inhibition model reduced to a form that is analogous to the Andrews equation, and the biokinetic parameters {micro}{sub max}, maximum specific growth; K{sub s}, saturation constant; and K{sub i}, inhibition constant were estimated as 0.251 h{sup {minus}1}, 0.011 g/L, and 0.348 g/L, respectively, using a nonlinear least squares technique. Given the wide variability in substrate inhibition models used to describe phenol biodegradation, an attempt was made to justify selection of particular model based on theoretical considerations. Phenol biodegradation data from nine previously published studies were used in the generalized substrate inhibition model to determine the appropriate form of the substrate inhibition model. In all nine cases, the generalized substrate inhibition model reduced to a form analogous to the Andrews equation suggesting the suitability of the Andrews equation to describe phenol biodegradation data.

Goudar, C.T.; Ganji, S.H.; Pujar, B.G.; Strevett, K.A.

2000-02-01

290

Optimal Decision Making in Neural Inhibition Models  

ERIC Educational Resources Information Center

In their influential "Psychological Review" article, Bogacz, Brown, Moehlis, Holmes, and Cohen (2006) discussed optimal decision making as accomplished by the drift diffusion model (DDM). The authors showed that neural inhibition models, such as the leaky competing accumulator model (LCA) and the feedforward inhibition model (FFI), can mimic the…

van Ravenzwaaij, Don; van der Maas, Han L. J.; Wagenmakers, Eric-Jan

2012-01-01

291

INHIBITION OF AFLATOXIN BIOSYNTHESIS BY TANNIC ACID  

Technology Transfer Automated Retrieval System (TEKTRAN)

Tree nut research has demonstrated that aflatoxin (AF) biosynthesis appears to be inhibited by gallic acid (GA). It is hypothesized that the release of GA from hyrolyzable tannins present in the plant seed coat or hull tissue by fungal tannase enzyme is responsible for the observed inhibition of AF...

292

Enzyme Inhibition Based Biosensors: A Review  

Microsoft Academic Search

This article reviewed the recent advances in the development of biosensors based on enzyme inhibition. They are an important alternative as compared to conventional analytical techniques due to their high selectivity and sensitivity. Since the most potent inhibitors of enzymes are heavy metals and pesticides, these enzyme inhibition based biosensors have a wide application in the field of environmental safety,

Lata Sheo Bachan Upadhyay; Nishant Verma

2012-01-01

293

Amine inhibiting; how good is it  

Microsoft Academic Search

The Amine Guard ST corrosion inhibition system eliminates corrosion as a design and operating constraint, saving capital and operating costs and increasing acid gas removal capacity. The system involves two corrosion inhibitors that are initially added to the ciculating solution on parts per million to passivate the unit. Once inhibited, unit amine concentration can be increased to 30wt% MEA or

1985-01-01

294

Inhibition of aluminum corrosion using Opuntia extract  

Microsoft Academic Search

The inhibitive action of the mucilage extracted from the modified stems of prickly pears, toward acid corrosion of aluminum, is tested using weight loss, thermometry, hydrogen evolution and polarization techniques. It was found that the extract acts as a good corrosion inhibitor for aluminum corrosion in 2.0 M HCl solution. The inhibition action of the extract was discussed in view

A. Y. El-Etre

2003-01-01

295

Invertebrate presynaptic inhibition and motor control  

Microsoft Academic Search

Presynaptic inhibition is a widespread mechanism among invertebrates and its study has developed quite independently from that which has occurred in vertebrates. However, it is striking that recent studies on presynaptic inhibition in sensory afferents of Arthropod have shown great similarities with presynaptic control exerted in the mammalian spinal cord primary afferents (Gossard et al. 1989; Rudomin et al. 1991):

F. Clarac; D. Cattaert

1996-01-01

296

Corrosion inhibiting lubricants for separable connectors  

Microsoft Academic Search

Microcrystalline wax by itself or in combination with polyphenyl ether inhibits corrosion, increases contact wear life, and lasts for reasonable times at higher operational temperatures. All other lubricant combinations evaluated either did not inhibit corrosion and improve wear performance or have sufficient longevity for practical contact applications. In addition to evaporative loss, lubricant mobility and absorption into the substrate cause

DON W. RICE; KARIN BREDFELDT; JOE KRAL

1985-01-01

297

A Qualitative Approach to Enzyme Inhibition  

ERIC Educational Resources Information Center

|Most general biochemistry textbooks present enzyme inhibition by showing how the basic Michaelis-Menten parameters K[subscript m] and V[subscript max] are affected mathematically by a particular type of inhibitor. This approach, while mathematically rigorous, does not lend itself to understanding how inhibition patterns are used to determine the…

Waldrop, Grover L.

2009-01-01

298

Optimal Decision Making in Neural Inhibition Models  

Microsoft Academic Search

In their influential Psychological Review article, Bogacz, Brown, Moehlis, Holmes, and Cohen (2006) discussed optimal decision making as accomplished by the drift diffusion model (DDM). The authors showed that neural inhibition models, such as the leaky competing accumulator model (LCA) and the feedforward inhibition model (FFI), can mimic the DDM and accomplish optimal decision making. Here we show that these

Don van Ravenzwaaij; Eric-Jan Wagenmakers

2012-01-01

299

Inhibition of Ethylene Biosynthesis by Salicylic Acid  

PubMed Central

Salicylic acid inhibited ethylene formation from ACC in self-buffered (pH 3.8) pear (Pyrus communis) cell suspension cultures with a K1app of about 10 micromolar after 1 to 3 hours incubation. Inhibition appeared noncompetitive. Among 22 related phenolic compounds tested, only acetylsalicylic acid showed similar levels of inhibition. Inhibition by salicylic acid was inversely dependent on the pH of the culture medium and did not require a continuous external supply of salicylate. When compared to known inhibitors of the ethylene forming enzyme, cobalt, n-propyl gallate, and dinitrophenol, inhibition by salicylic acid most closely resembled that by dinitrophenol but salicylic acid did not produce the same degree of respiratory stimulation. Results are discussed in terms of other known effects of salicylic acid on plants, pH-dependency, and the possible influence of salicylic acid on electron transport.

Leslie, Charles A.; Romani, Roger J.

1988-01-01

300

Inhibition of ethylene production by rhizobitoxine.  

PubMed

Rhizobitoxine, an inhibitor of methionine biosynthesis in Salmonella typhimurium, inhibited ethylene production about 75% in light-grown sorghum seedlings and in senescent apple tissue. Ethylene production stimulated by indoleacetic acid and kinetin in sorghum was similarly inhibited. With both apple and sorghum, the inhibition could only be partially relieved by additions of methionine. A methionine analogue, alpha-keto-gamma-methylthiobutyric acid, which has been suggested as an intermediate between methionine and ethylene, had no effect on the inhibition.Incorporation of (14)C from added methionine-(14)C into ethylene was curtailed by rhizobitoxine to about the same extent as was ethylene production. These results suggest that rhizobitoxine interferes with ethylene biosynthesis by blocking the conversion of methionine to ethylene and not indirectly by inhibiting the biosynthesis of methionine. Ethylene production by Penicillium digitatum, a fungus which produces ethylene via pathways not utilizing methionine as a precursor, was not affected by rhizobitoxine. PMID:16657720

Owens, L D; Lieberman, M; Kunishi, A

1971-07-01

301

Inhibition of Experimental Dental Caries by Antibiotics  

PubMed Central

A variety of antibiotic and chemotherapeutic agents were tested for their ability to inhibit the development of dental caries in Sprague-Dawley rats receiving the drugs in a coarse-particle sucrose-containing diet. Drugs which inhibit gram-positive microorganisms were effective inhibitors of caries, whereas agents which are active solely against gram-negative bacteria did not inhibit caries development. In vivo efficacy of the agents tested generally, but not invariably, paralleled in vitro inhibition of the growth of Streptococcus mutans strain FA-1, an organism which was isolated from carious Sprague-Dawley rats and which is known to induce caries in gnotobiotic Sprague-Dawley rats. Caries was significantly inhibited when 1-ephenamine penicillin (20 units/mg) was administered intermittently in the diet, 1 day per week or 1 week of every 4 weeks, but protection against caries was greatest when the same amount of the drug was fed continuously.

Fitzgerald, Robert J.

1972-01-01

302

Ulcerated Necrobiosis Lipoidica: A Combined Treatment Approach with Dermatosurgery and PUVA  

Microsoft Academic Search

Ulcerated necrobiosis lipoidica is one of the differential diagnoses in leg ulcers. The diagnosis is confirmed by histopathology. The authors report on a 68-year-old female patient with a history of chronic venous insufficiency who developed a chronic leg ulcer that did not respond to good ulcer care and compression bandaging. Skin biopsies revealed necrobiosis lipoidica. The patient was recently discovered

Erich Köstler; Uwe Wollina

2003-01-01

303

Refractory livedoid vasculitis responding to PUVA: a report of four cases.  

PubMed

Livedoid vasculitis is a chronic disease characterized by recurrent painful irregularly shaped ulcers, which heal with scars, most commonly located on feet or lower extremities. This condition is often resistant to the therapy. We report four cases with refractory livedoid vasculitis that responded to systemic psoralens and ultraviolet A radiation therapy. PMID:15888134

Tuchinda, C; Leenutaphong, V; Sudtim, S; Lim, H W

2005-06-01

304

Photochemotherapy of intimal hyperplasia using Psoralen activated by uv light in porcine model  

Microsoft Academic Search

Psoralen activated by UVA light (PUVA) was investigated as a means of inhibiting smooth muscle cell proliferation resulting from balloon injury. Twenty kilogram domestic swine were anesthetized and underwent balloon angioplasty to create a 133% overstretch injury. Assignments of treatment and control were randomized between the left anterior descending (LAD) and circumflex (LCX) coronaries arteries. The animals were given with

Lisa A. Buckley; Kenton W. Gregory; Deborah T. Bahlman; Hanqun Shangguan; Henner Fahrenbach; Eli Rosenthal; Peter C. Block

1996-01-01

305

Regulation of spatial selectivity by crossover inhibition.  

PubMed

Signals throughout the nervous system diverge into parallel excitatory and inhibitory pathways that later converge on downstream neurons to control their spike output. Converging excitatory and inhibitory synaptic inputs can exhibit a variety of temporal relationships. A common motif is feedforward inhibition, in which an increase (decrease) in excitatory input precedes a corresponding increase (decrease) in inhibitory input. The delay of inhibitory input relative to excitatory input originates from an extra synapse in the circuit shaping inhibitory input. Another common motif is push-pull or "crossover" inhibition, in which increases (decreases) in excitatory input occur together with decreases (increases) in inhibitory input. Primate On midget ganglion cells receive primarily feedforward inhibition and On parasol cells receive primarily crossover inhibition; this difference provides an opportunity to study how each motif shapes the light responses of cell types that play a key role in visual perception. For full-field stimuli, feedforward inhibition abbreviated and attenuated responses of On midget cells, while crossover inhibition, though plentiful, had surprisingly little impact on the responses of On parasol cells. Spatially structured stimuli, however, could cause excitatory and inhibitory inputs to On parasol cells to increase together, adopting a temporal relation very much like that for feedforward inhibition. In this case, inhibitory inputs substantially abbreviated a cell's spike output. Thus inhibitory input shapes the temporal stimulus selectivity of both midget and parasol ganglion cells, but its impact on responses of parasol cells depends strongly on the spatial structure of the light inputs. PMID:23575830

Cafaro, Jon; Rieke, Fred

2013-04-10

306

Regulation of Spatial Selectivity by Crossover Inhibition  

PubMed Central

Signals throughout the nervous system diverge into parallel excitatory and inhibitory pathways that later converge on downstream neurons to control their spike output. Converging excitatory and inhibitory synaptic inputs can exhibit a variety of temporal relationships. A common motif is feedforward inhibition, in which an increase (decrease) in excitatory input precedes a corresponding increase (decrease) in inhibitory input. The delay of inhibitory input relative to excitatory input originates from an extra synapse in the circuit shaping inhibitory input. Another common motif is push-pull or “crossover” inhibition, in which increases (decreases) in excitatory input occur together with decreases (increases) in inhibitory input. Primate On midget ganglion cells receive primarily feedforward inhibition and On parasol cells receive primarily crossover inhibition; this difference provides an opportunity to study how each motif shapes the light responses of cell types that play a key role in visual perception. For full-field stimuli, feedforward inhibition abbreviated and attenuated responses of On midget cells, while crossover inhibition, though plentiful, had surprisingly little impact on the responses of On parasol cells. Spatially structured stimuli, however, could cause excitatory and inhibitory inputs to On parasol cells to increase together, adopting a temporal relation very much like that for feedforward inhibition. In this case, inhibitory inputs substantially abbreviated a cell’s spike output. Thus inhibitory input shapes the temporal stimulus selectivity of both midget and parasol ganglion cells, but its impact on responses of parasol cells depends strongly on the spatial structure of the light inputs.

Cafaro, Jon; Rieke, Fred

2013-01-01

307

Mechanisms of cholinesterase inhibition by inorganic mercury.  

PubMed

The poorly known mechanism of inhibition of cholinesterases by inorganic mercury (HgCl2) has been studied with a view to using these enzymes as biomarkers or as biological components of biosensors to survey polluted areas. The inhibition of a variety of cholinesterases by HgCl2 was investigated by kinetic studies, X-ray crystallography, and dynamic light scattering. Our results show that when a free sensitive sulfhydryl group is present in the enzyme, as in Torpedo californica acetylcholinesterase, inhibition is irreversible and follows pseudo-first-order kinetics that are completed within 1 h in the micromolar range. When the free sulfhydryl group is not sensitive to mercury (Drosophila melanogaster acetylcholinesterase and human butyrylcholinesterase) or is otherwise absent (Electrophorus electricus acetylcholinesterase), then inhibition occurs in the millimolar range. Inhibition follows a slow binding model, with successive binding of two mercury ions to the enzyme surface. Binding of mercury ions has several consequences: reversible inhibition, enzyme denaturation, and protein aggregation, protecting the enzyme from denaturation. Mercury-induced inactivation of cholinesterases is thus a rather complex process. Our results indicate that among the various cholinesterases that we have studied, only Torpedo californica acetylcholinesterase is suitable for mercury detection using biosensors, and that a careful study of cholinesterase inhibition in a species is a prerequisite before using it as a biomarker to survey mercury in the environment. PMID:17355286

Frasco, Manuela F; Colletier, Jacques-Philippe; Weik, Martin; Carvalho, Félix; Guilhermino, Lúcia; Stojan, Jure; Fournier, Didier

2007-03-12

308

Inhibition of enzymatic cellulolysis by phenolic compounds.  

PubMed

Phenolics derived from lignin and other plant components can pose significant inhibition on enzymatic conversion of cellulosic biomass materials to useful chemicals. Understanding the mechanism of such inhibition is of importance for the development of viable biomass conversion technologies. In native plant cell wall, most of the phenolics and derivatives are found in polymeric lignin. When biomass feedstocks are pretreated (prior to enzymatic hydrolysis), simple or oligomeric phenolics and derivatives are often generated from lignin modification/degradation, which can inhibit biomass-converting enzymes. To further understand how such phenolic substances may affect cellulase reaction, we carried out a comparative study on a series of simple and oligomeric phenolics representing or mimicking the composition of lignin or its degradation products. Consistent to previous studies, we observed that oligomeric phenolics could exert more inhibition on enzymatic cellulolysis than simple phenolics. Oligomeric phenolics could inactivate cellulases by reversibly complexing them. Simple and oligomeric phenolics could also inhibit enzymatic cellulolysis by adsorbing onto cellulose. Individual cellulases showed different susceptibility toward these inhibitions. Polyethylene glycol and tannase could respectively bind and degrade the studied oligomeric phenolics, and by doing so mitigate the oligomeric phenolic's inhibition on cellulolysis. PMID:22112906

Tejirian, Ani; Xu, Feng

2010-11-18

309

Inhibition of muscle force by vanadate.  

PubMed Central

Vanadate (Vi), an analogue of inorganic phosphate (Pi), is known to bind tightly with a long half life to the myosin MgATPase site, producing a complex which inhibits force. Both of these ligands bind to an actin.myosin.ADP state that follows the release of Pi in the enzymatic cycle, and their effects on muscle fibers and proteins in solution provide information on the properties of this state. The inhibition of active force generation began to occur at a [Vi] of 5 microM and was 90% complete at a [Vi] of 1 mM. Hill plots of the inhibition of force by Vi approximated that expected for a simple binding isotherm. Similar plots were obtained at both 25 degrees C and 5 degrees C. A simple binding isotherm is not expected to occur in a muscle fiber where steric constraints imposed by the intact filaments should introduce more complexity into the energetics of ligand binding. The inhibition of MgATPase activity for acto-subfragment-1 to 50% of controls occurred at a [Vi] which was only 20-fold higher than that required to inhibit force generation in fibers to the same level. Some models of actomyosin interactions would predict that the range of [Vi] required for complete force inhibition in fibers and the difference in the [Vi] required for inhibition in fibers and of myosin in solution would both be much larger.

Wilson, G J; Shull, S E; Cooke, R

1995-01-01

310

Homeostatic Competition between Phasic and Tonic Inhibition.  

PubMed

The GABAA receptors are the major inhibitory receptors in the brain and are localized at both synaptic and extrasynaptic membranes. Synaptic GABAA receptors mediate phasic inhibition, whereas extrasynaptic GABAA receptors mediate tonic inhibition. Both phasic and tonic inhibitions regulate neuronal activity, but whether they regulate each other is not very clear. Here, we investigated the functional interaction between synaptic and extrasynaptic GABAA receptors through various molecular manipulations. Overexpression of extrasynaptic ?6?3?-GABAA receptors in mouse hippocampal pyramidal neurons significantly increased tonic currents. Surprisingly, the increase of tonic inhibition was accompanied by a dramatic reduction of the phasic inhibition, suggesting a possible homeostatic regulation of the total inhibition. Overexpressing the ?6 subunit alone induced an up-regulation of ? subunit expression and suppressed phasic inhibition similar to overexpressing the ?6?3? subunits. Interestingly, blocking all GABAA receptors after overexpressing ?6?3? receptors could not restore the synaptic GABAergic transmission, suggesting that receptor activation is not required for the homeostatic interplay. Furthermore, insertion of a gephyrin-binding-site (GBS) into the ?6 and ? subunits recruited ?6GBS?3?GBS receptors to postsynaptic sites but failed to rescue synaptic GABAergic transmission. Thus, it is not the positional effect of extrasynaptic ?6?3? receptors that causes the down-regulation of phasic inhibition. Overexpressing ?5?3?2 subunits similarly reduced synaptic GABAergic transmission. We propose a working model that both synaptic and extrasynaptic GABAA receptors may compete for limited receptor slots on the plasma membrane to maintain a homeostatic range of the total inhibition. PMID:23839941

Wu, Xia; Huang, Lanting; Wu, Zheng; Zhang, Ce; Jiang, Dongyun; Bai, Yuting; Wang, Yun; Chen, Gong

2013-07-09

311

Inhibition of Myosin ATPase by Vanadate Ion  

Microsoft Academic Search

Inhibition of the myosin ATPase by vanadate ion (Vi) has been studied in 90 mM NaCl\\/5 mM MgCl2\\/20 mM Tris\\\\cdot HCl, pH 8.5, at 25 degrees C. Although the onset of inhibition during the assay is slow and dependent upon Vi concentration (kapp≈ 0.3 M-1 s-1), the final level of inhibition approaches 100%, provided the Vi concentration is in slight

Charles C. Goodno

1979-01-01

312

Connexin-43 hemichannels opened by metabolic inhibition.  

PubMed

The cause of altered ionic homeostasis leading to cell death during ischemia and metabolic inhibition is unclear. Hemichannels, which are precursors to gap junctions, are nonselective ion channels that are permeable to molecules of less than Mr 1000. We show that hemichannels open upon exposure to calcium-free solutions when they are either heterologously overexpressed in HEK293 cells or endogenously expressed in cardiac ventricular myocytes. In the presence of normal extracellular calcium, hemichannels open during metabolic inhibition. During ischemia and other forms of metabolic inhibition, activation of relatively few hemichannels will seriously compromise the cell's ability to maintain ionic homeostasis, which is an essential step promoting cell death. PMID:9867835

John, S A; Kondo, R; Wang, S Y; Goldhaber, J I; Weiss, J N

1999-01-01

313

Inhibition of Threonine Dehydratase Is Herbicidal.  

PubMed Central

Threonine dehydratase, the first enzyme in isoleucine biosynthesis, catalyzes deamination and dehydration of threonine to produce 2-ketobutyrate and ammonia. An antimetabolite, 2-(1-cyclohexen-3(R)-yl)-S-glycine (CHG), inhibits the plant enzyme. CHG inhibits the growth of Black Mexican Sweet corn (Zea mays) cells and of Arabidopsis thaliana plants. The herbicidal effects of CHG can be reversed by 2-ketobutyrate, other intermediates of isoleucine biosynthesis, and by isoleucine itself. These results suggest that the herbicidal effects observed with CHG are a consequence of inhibition of threonine dehydratase. The enzyme could be a potential target site for an herbicide screening program.

Szamosi, I. T.; Shaner, D. L.; Singh, B. K.

1994-01-01

314

Voluntary Inhibition of Galvanic Skin Response.  

National Technical Information Service (NTIS)

An experiment was designed to assess the effectiveness of instructional set in voluntary inhibition of Galvanic Skin Response (GSR). Male subjects were assigned three treatment groups, each of which treated the problem under different instructions. Analys...

W. H. Ton J. R. Boulger

1971-01-01

315

The Mechanism of Corrosion Inhibition by Dinonylnaphthalenesulfonates.  

National Technical Information Service (NTIS)

Operability of combat and support equipment can be seriously compromised by rusting of power train components. As a preventative measure, most lubricants in the Army Supply System are rust inhibited. Sulfonates, such as the petroleum sulfonates and salts ...

P. J. Kennedy

1978-01-01

316

Wolbachia and arbovirus inhibition in mosquitoes.  

PubMed

Wolbachia is a maternally inherited intracellular bacteria that can manipulate the reproduction of their insect hosts, and cytoplasmic incompatibility allows them to spread through mosquito populations. When particular strains of Wolbachia are transferred into certain Aedes mosquito species, the transmission capacity of important arthropod-borne viruses can be suppressed or abolished in laboratory challenges. Viral inhibition is associated with higher densities of transinfecting Wolbachia compared with wild-type strains of the bacterium. The upregulation of innate immune effectors can contribute to virus inhibition in Aedes aegypti, but does not seem to be required. Modulation of autophagy and lipid metabolism, and intracellular competition between viruses and bacteria for lipids, provide promising hypotheses for the mechanism of inhibition. Transinfecting virus-inhibiting strains can produce higher fitness costs than wild-type mosquito Wolbachia; however, this is not always the case, and the wMel strain has already been introduced to high frequency in wild Ae. aegypti populations. PMID:24059916

Sinkins, Steven P

2013-10-01

317

Inhibition of human intestinal ?-glucosidases by calystegines.  

PubMed

Calystegines are polyhydroxylated nortropane alkaloids found in Convolvulaceae, Solanaceae, and other plant families. These plants produce common fruits and vegetables. The calystegine structures resemble sugars and suggest interaction with enzymes of carbohydrate metabolism. Maltase and sucrase are ?-glucosidases contributing to human carbohydrate degradation in the small intestine. Inhibition of these enzymes by orally administered drugs is one option for treatment of diabetes mellitus type 2. In this study, inhibition of maltase and sucrase by calystegines A3 and B2 purified from potatoes was investigated. In silico docking studies confirmed binding of both calystegines to the active sites of the enzymes. Calystegine A3 showed low in vitro enzyme inhibition; calystegine B2 inhibited mainly sucrose activity. Both compounds were not transported by Caco-2 cells indicating low systemic availability. Vegetables rich in calystegine B2 should be further investigated as possible components of a diet preventing a steep increase in blood glucose after a carbohydrate-rich meal. PMID:23697377

Jockovi?, Nebojša; Fischer, Wiebke; Brandsch, Matthias; Brandt, Wolfgang; Dräger, Birgit

2013-06-03

318

EEG Correlates of Reinforced Behavioral Inhibition.  

National Technical Information Service (NTIS)

Three cats, bearing chronically implanted cortical electrodes, were trained in an instrumental vigilance situation to inhibit licking a foodcup for 15 - 25 sec prior to the onset of a stimulus signalling availability of a milk reward. Electrocortical acti...

N. Weinberger L. Yeudall D. B. Lindsley

1968-01-01

319

Specific inhibition of phototropism in corn seedlings.  

PubMed

Geotropism was used as a control for the specificity of potential inhibitors of phototropism by the coleoptiles of corn (Zea mays) seedlings. The compounds tested fall into three categories showing: (a) no inhibition of either phototropism or geotropism (KCl); (b) nonspecific inhibition of both phototropism and geotropism (KCN); and (c) specific inhibition of phototropism (KI, NaN(3), and phenylacetic acid). Simultaneous irradiation of coleoptiles with phototropically inert light in addition to the phototropically active blue light also results in an inhibition of phototropism. Since azide, iodide, and phenylacetic acid are known to interact with flavins while a simultaneous irradiation with a phototropically inert light may depopulate the first triplet state of flavins, these data support the hypothesis that the photoreceptor pigment for phototropism in corn is a flavin. PMID:16660174

Schmidt, W; Hart, J; Filner, P; Poff, K L

1977-11-01

320

Methods for Inhibiting Cutaneous Inflammation and Hyperpigmentation.  

National Technical Information Service (NTIS)

This invention provides a method of preventing or treating in a subject contact dermatitis which comprises administering to the subject an amount of a compound capable of inhibiting the stem cell factor signaling pathway effective to prevent or treat cont...

B. J. Longley

2005-01-01

321

Methods for Inhibition of NKT Cells.  

National Technical Information Service (NTIS)

Molecules that interact with the NKT cell antigen receptor and its counterpart antigen presenting molecule, but which inhibit the NKT cell immune function, are administered to a patient. Conditions of particular interest include the treatment of systemic ...

D. T. Umetsu E. H. Meyer S. Strober

2005-01-01

322

Prepulse-elicited startle in prepulse inhibition  

Microsoft Academic Search

BackgroundPrepulse inhibition (PPI) has become a major experimental paradigm in the study of psychiatric disorders. In this study, a potential confound in measurement and interpretation of PPI, namely startle reactions to so-called “nonstartling” prepulses, was examined.

Johannes C Dahmen; Philip J Corr

2004-01-01

323

Corrosion Inhibition in High Temperature Environment.  

National Technical Information Service (NTIS)

This invention pertains to the use of tin oxide as a corrosion resistant material for preventing or inhibiting high temperature corrosion by molten sulfate-vanadate deposits and gaseous sulfur trioxide formed in engines or other high temperature apparatus...

R. E. Jones

1993-01-01

324

BROMODICHLOROMETHANE INHIBITS HUMAN PLACENTAL TROPHOBLAST DIFFERENTIATION  

EPA Science Inventory

BROMODICHLOROMETHANE INHIBITS HUMAN PLACENTAL TROPHOBLAST DIFFERENTIATION Jiangang Chen, Twanda L. Thirkill, Peter N. Lohstroh, Susan R. Bielmeier, Michael G. Narotsky, Deborah S. Best, Randy A. Harrison, Kala Natarajan, Rex A. Pegram, Bill L. Lasley, and Gordon C. Do...

325

Naloxone Inhibits Superoxide Release from Human Neutrophils.  

National Technical Information Service (NTIS)

Using the superoxide dismutase inhibitable reduction of cytochrome c assay, we studied, the effect of (-) naloxone on N-formyl-methionyl-leucyl-phenylalanine (FMLP) stimulated superoxide (O2-) release from human neutrophils. Neutrophils were pre-incubated...

C. O. Simpkins N. Ives E. Tate M. Johnson

1985-01-01

326

Surround inhibition in the motor system  

Microsoft Academic Search

Surround inhibition is a physiological mechanism to focus neuronal activity in the central nervous system. This so-called\\u000a center-surround organization is well known in sensory systems, where central signals are facilitated and eccentric signals\\u000a are inhibited in order to sharpen the contrast between them. There is evidence that this mechanism is relevant to skilled\\u000a motor behavior, and it is deficient, for

Sandra Beck; Mark Hallett

2011-01-01

327

Corrosion inhibition of steel by bacteria  

SciTech Connect

Mild steel was exposed to Pseudomonas sp. S9 or Serratia marcescens in synthetic seawater. An increase in corrosion resistance over that i natural seawater was monitored by electrochemical techniques. Biological analyses were performed to characterize the system. The inhibition effect also was observed when mild steel was coated with bacteria and then immersed in synthetic seawater. When specimens coated with bacteria were transferred to a natural seawater flow system, the inhibition effect disappeared during the first 2 weeks.

Hernandez, G.; Kucera, V.; Thierry, D.; Pedersen, A. (Swedish Corrosion Inst., Stockholm (Sweden)); Hermansson, M. (Univ. of Gothenburg (Sweden). Dept. of General and Marine Microbiology)

1994-08-01

328

Emotion and Inhibition: Pride Versus Happiness  

Microsoft Academic Search

The central question of my thesis is how different positive emotions affect inhibition. Katzir, Eyal, Meiran, and Kessler (2010) addressed this question using an antisaccade task and found that happiness decreased inhibition compared to pride, which they attribute to the links between pride and long-term goals and happiness and short-term goals. I attempted to generalize their results to a color-naming

Emery K. Hilles

2012-01-01

329

Matrix metalloproteinase inhibition by green tea catechins  

Microsoft Academic Search

We have investigated the effects of different biologically active components from natural products, including green tea polyphenols (GTP), resveratrol, genistein and organosulfur compounds from garlic, on matrix metalloproteinase (MMP)-2, MMP-9 and MMP-12 activities. GTP caused the strongest inhibition of the three enzymes, as measured by fluorescence assays using gelatin or elastin as substrates. The inhibition of MMP-2 and MMP-9 caused

Michel Demeule; Mathieu Brossard; Martine Pagé; Denis Gingras; Richard Béliveau

2000-01-01

330

Seed extracts inhibiting protein synthesis in vitro.  

PubMed Central

Of 33 seed extracts examined, 12 inhibited protein synthesis in a rabbit reticulocyte lysate. This activity seems to be due to a protein, since (i) it was recovered with the (NH4)2SO4 precipitate, (ii) it was retained by dialysis membranes, and (iii) in all cases but one was destroyed by boiling. Only the extracts from the seeds of Adenia digitata and, to a lower extent, of Euonymus europaeus inhibited protein synthesis in intact cells.

Gasperi-Campani, A; Barbieri, L; Morelli, P; Stirpe, F

1980-01-01

331

Tryptophan Inhibits Biofilm Formation by Pseudomonas aeruginosa  

PubMed Central

Biofilm formation by Pseudomonas aeruginosa has been implicated in the pathology of chronic wounds. Both the d and l isoforms of tryptophan inhibited P. aeruginosa biofilm formation on tissue culture plates, with an equimolar ratio of d and l isoforms producing the greatest inhibitory effect. Addition of d-/l-tryptophan to existing biofilms inhibited further biofilm growth and caused partial biofilm disassembly. Tryptophan significantly increased swimming motility, which may be responsible in part for diminished biofilm formation by P. aeruginosa.

Brandenburg, Kenneth S.; Rodriguez, Karien J.; McAnulty, Jonathan F.; Murphy, Christopher J.; Abbott, Nicholas L.; Schurr, Michael J.

2013-01-01

332

Atmospheric Photochemical Reactions Inhibited by Iodine.  

PubMed

The inhibition by iodine of the atmosphere photochemical reaction of olefin with nitrogen dioxide has been confirmed. The presence of iodine in concentrations comparable to those of the reactants retards the formation of aldehyde, peroxyacetyl nitrate, and aerosol as well as the disappearance of olefin. The reaction of iodine with atomic oxygen may account for this inhibition. A number of other potential inhibitors were found to be ineffective. PMID:17821006

Stephens, E R; Linnell, R H; Reckner, L

1962-11-16

333

Inhibition of heme peroxidases by melamine.  

PubMed

In 2008 melamine-contaminated infant formula and dairy products in China led to over 50,000 hospitalizations of children due to renal injuries. In North America during 2007 and in Asia during 2004, melamine-contaminated pet food products resulted in numerous pet deaths due to renal failure. Animal studies have confirmed the potent renal toxicity of melamine combined with cyanuric acid. We showed previously that the solubility of melamine cyanurate is low at physiologic pH and ionic strength, provoking us to speculate how toxic levels of these compounds could be transported through the circulation without crystallizing until passing into the renal filtrate. We hypothesized that melamine might be sequestered by heme proteins, which could interfere with heme enzyme activity. Four heme peroxidase enzymes were selected for study: horseradish peroxidase (HRP), lactoperoxidase (LPO), and cyclooxygenase-1 and -2 (COX-1 and -2). Melamine exhibited noncompetitive inhibition of HRP (K(i)??9.5 ± 0.7?mM), and LPO showed a mixed model of inhibition (K(i)??14.5 ± 4.7?mM). The inhibition of HRP and LPO was confirmed using a chemiluminescent peroxidase assay. Melamine also exhibited COX-1 inhibition, but inhibition of COX-2 was not detected. Thus, our results demonstrate that melamine inhibits the activity of three heme peroxidases. PMID:22852071

Vanachayangkul, Pattaraporn; Tolleson, William H

2012-07-18

334

Inhibition of Heme Peroxidases by Melamine  

PubMed Central

In 2008 melamine-contaminated infant formula and dairy products in China led to over 50,000 hospitalizations of children due to renal injuries. In North America during 2007 and in Asia during 2004, melamine-contaminated pet food products resulted in numerous pet deaths due to renal failure. Animal studies have confirmed the potent renal toxicity of melamine combined with cyanuric acid. We showed previously that the solubility of melamine cyanurate is low at physiologic pH and ionic strength, provoking us to speculate how toxic levels of these compounds could be transported through the circulation without crystallizing until passing into the renal filtrate. We hypothesized that melamine might be sequestered by heme proteins, which could interfere with heme enzyme activity. Four heme peroxidase enzymes were selected for study: horseradish peroxidase (HRP), lactoperoxidase (LPO), and cyclooxygenase-1 and -2 (COX-1 and -2). Melamine exhibited noncompetitive inhibition of HRP (Ki??9.5 ± 0.7?mM), and LPO showed a mixed model of inhibition (Ki??14.5 ± 4.7?mM). The inhibition of HRP and LPO was confirmed using a chemiluminescent peroxidase assay. Melamine also exhibited COX-1 inhibition, but inhibition of COX-2 was not detected. Thus, our results demonstrate that melamine inhibits the activity of three heme peroxidases.

Vanachayangkul, Pattaraporn; Tolleson, William H.

2012-01-01

335

Grape Seed Extracts Inhibit Platelet Aggregation by Inhibiting Protein Tyrosine Phosphatase.  

PubMed

Platelets play an important role in various thrombotic diseases, including myocardial infarction. Because red wine consumption is inversely associated with death due to ischemic heart diseases, the effects of grape components on platelet function have been extensively investigated. Grape seed extracts (GSEs) reportedly inhibit platelet aggregation; however, the underlying mechanism has not been elucidated. We discovered that GSEs inhibit platelet aggregation induced by collagen and thrombin-receptor agonist peptide and increase basal levels of tyrosine phosphorylation, which was also observed in the presence of a protein tyrosine phosphatase (PTP) inhibitor. An in vitro phosphatase assay indicated that GSE dose dependently inhibited PTP-1B and Src homology 2 domain-containing phosphatase-1 activity, which positively regulates platelet aggregation. We propose that GSEs inhibit platelet aggregation by inhibiting tyrosine phosphatase activity. Moreover, we showed that GSE ingestion inhibited platelet aggregation in mice without enhancing tail bleeding, implying that GSE supplementation might be beneficial to prevention of thrombotic diseases. PMID:23478570

Jin, Joseph Wuxun; Inoue, Osamu; Suzuki-Inoue, Katsue; Nishikawa, Go; Kawakami, Yoshinori; Hisamoto, Masashi; Okuda, Tohru; Ozaki, Yukio

2013-03-10

336

Inhibition in autism: children with autism have difficulty inhibiting irrelevant distractors but not prepotent responses.  

PubMed

Resistance to distractor inhibition tasks have previously revealed impairments in children with autism. However, on the classic Stroop task and other prepotent response tasks, children with autism show intact inhibition. These data may reflect a distinction between prepotent response and resistance to distractor inhibition. The current study investigated this possibility using tasks that systematically manipulated inhibitory load. Findings showed that children with autism performed comparably to typically developing and learning disabled controls on a prepotent response inhibition stop-signal task but showed significant inhibitory impairment on a modified flanker resistence to distractor inhibition task. Although the results are clearly consistent with the suggestion that autism is associated with a specific deficit in resistance to distractor inhibition, they may in fact be related to an increased perceptual capacity in autism. PMID:21830170

Adams, Nena C; Jarrold, Christopher

2012-06-01

337

Phosphatidic acid inhibits blue light-induced stomatal opening via inhibition of protein phosphatase 1 [corrected].  

PubMed

Stomata open in response to blue light under a background of red light. The plant hormone abscisic acid (ABA) inhibits blue light-dependent stomatal opening, an effect essential for promoting stomatal closure in the daytime to prevent water loss. However, the mechanisms and molecular targets of this inhibition in the blue light signaling pathway remain unknown. Here, we report that phosphatidic acid (PA), a phospholipid second messenger produced by ABA in guard cells, inhibits protein phosphatase 1 (PP1), a positive regulator of blue light signaling, and PA plays a role in stimulating stomatal closure in Vicia faba. Biochemical analysis revealed that PA directly inhibited the phosphatase activity of the catalytic subunit of V. faba PP1 (PP1c) in vitro. PA inhibited blue light-dependent stomatal opening but did not affect red light- or fusicoccin-induced stomatal opening. PA also inhibited blue light-dependent H(+) pumping and phosphorylation of the plasma membrane H(+)-ATPase. However, PA did not inhibit the autophosphorylation of phototropins, blue light receptors for stomatal opening. Furthermore, 1-butanol, a selective inhibitor of phospholipase D, which produces PA via hydrolysis of phospholipids, diminished the ABA-induced inhibition of blue light-dependent stomatal opening and H(+) pumping. We also show that hydrogen peroxide and nitric oxide, which are intermediates in ABA signaling, inhibited the blue light responses of stomata and that 1-butanol diminished these inhibitions. From these results, we conclude that PA inhibits blue light signaling in guard cells by PP1c inhibition, accelerating stomatal closure, and that PP1 is a cross talk point between blue light and ABA signaling pathways in guard cells. PMID:20498335

Takemiya, Atsushi; Shimazaki, Ken-ichiro

2010-05-24

338

Phosphatidic Acid Inhibits Blue Light-Induced Stomatal Opening via Inhibition of Protein Phosphatase 11[OA  

PubMed Central

Stomata open in response to blue light under a background of red light. The plant hormone abscisic acid (ABA) inhibits blue light-dependent stomatal opening, an effect essential for promoting stomatal closure in the daytime to prevent water loss. However, the mechanisms and molecular targets of this inhibition in the blue light signaling pathway remain unknown. Here, we report that phosphatidic acid (PA), a phospholipid second messenger produced by ABA in guard cells, inhibits protein phosphatase 1 (PP1), a positive regulator of blue light signaling, and PA plays a role in stimulating stomatal closure in Vicia faba. Biochemical analysis revealed that PA directly inhibited the phosphatase activity of the catalytic subunit of V. faba PP1 (PP1c) in vitro. PA inhibited blue light-dependent stomatal opening but did not affect red light- or fusicoccin-induced stomatal opening. PA also inhibited blue light-dependent H+ pumping and phosphorylation of the plasma membrane H+-ATPase. However, PA did not inhibit the autophosphorylation of phototropins, blue light receptors for stomatal opening. Furthermore, 1-butanol, a selective inhibitor of phospholipase D, which produces PA via hydrolysis of phospholipids, diminished the ABA-induced inhibition of blue light-dependent stomatal opening and H+ pumping. We also show that hydrogen peroxide and nitric oxide, which are intermediates in ABA signaling, inhibited the blue light responses of stomata and that 1-butanol diminished these inhibitions. From these results, we conclude that PA inhibits blue light signaling in guard cells by PP1c inhibition, accelerating stomatal closure, and that PP1 is a cross talk point between blue light and ABA signaling pathways in guard cells.

Takemiya, Atsushi; Shimazaki, Ken-ichiro

2010-01-01

339

Inhibition in Autism: Children with Autism have Difficulty Inhibiting Irrelevant Distractors but not Prepotent Responses  

Microsoft Academic Search

Resistance to distractor inhibition tasks have previously revealed impairments in children with autism. However, on the classic\\u000a Stroop task and other prepotent response tasks, children with autism show intact inhibition. These data may reflect a distinction\\u000a between prepotent response and resistance to distractor inhibition. The current study investigated this possibility using\\u000a tasks that systematically manipulated inhibitory load. Findings showed that

Nena C. Adams; Christopher Jarrold

340

Impaired interhemispheric inhibition in writer's cramp  

PubMed Central

Objectives: Reduced cortical inhibition is a feature of focal hand dystonia and this likely contributes to excessive muscle contractions. Inhibition from the opposite hemisphere, known as interhemispheric inhibition (IHI), was studied bidirectionally in 7 right-handed patients with writer's cramp (WC) and age-matched healthy controls in a cross-sectional physiologic study. Methods: IHI was measured with paired transcranial magnetic stimulation with the conditioning stimulus applied to the motor cortex and the test stimulus applied to the contralateral motor cortex. Surface EMG was measured in right and left first dorsal interosseous muscles during rest, and while holding a pen between the thumb and index finger at 20% maximum voluntary contraction with the right dystonia-affected hand. The time course and magnitude of IHI was studied at interstimulus intervals of 6, 8, 10, 12, 30, 40, and 50 msec between the conditioning stimulus and test stimulus. Results: In WC at rest, IHI was significantly reduced in the dystonia-affected right hand (IHI from right to left motor cortex) at both short (SIHI, 10–12 msec) and long (LIHI, 30–40 msec) intervals compared to the unaffected hand. Compared to controls, SIHI and LIHI were reduced in the dystonia-affected hand only. There was no difference in IHI between controls and WC during the task of holding a pen. Conclusions: In WC, both SIHI and LIHI are reduced in the dystonia-affected hand compared to the unaffected hand and to healthy controls. Impaired IHI may contribute to excessive muscle contraction in WC. GLOSSARY ANOVA = analysis of variance; CS = conditioning stimulus; FDI = first dorsal interosseous; FHD = focal hand dystonia; GABA = gamma-aminobutyric acid; IHI = interhemispheric inhibition; ISI = interstimulus interval; LIHI = long interhemispheric inhibition; MEP = motor evoked potential; MVC = maximum voluntary contraction; SICI = short-interval intracortical inhibition; SIHI = short interhemispheric inhibition; TMS = transcranial magnetic stimulation; TS = test stimulus; WC = writer's cramp.

Nelson, A.J.; Hoque, T.; Gunraj, C.; Ni, Z.; Chen, R.

2010-01-01

341

Continuous injection of corrosion-inhibiting liquids  

SciTech Connect

A portable system is described for the continuous injection of corrosion-inhibiting chemical into a production well, comprising: a portable skid; a corrosion-inhibiting chemical tank, and a water tank, mounted on the skid; pump means for pumping an desired amounts and proportions of chemical and water from the tanks for injection into a production well. The pump means is mounted on the skid. A conduit means operatively interconnects is the pumps and tanks for delivery of corrosion-inhibiting chemical to a production well, the conduit means including an end conduit for operative interconnection to a production well. A control means is mounted on the skid for controlling the operation of the pump means to provide desired amounts and proportions of a mix of corrosion-inhibiting chemical and water to the end conduit. A method is described for delivering a mix of corrosion-inhibiting chemical and water to a production well utilizing a portable skid having a chemical tank and water tank mounted thereon, comprising: transporting the skid to a single production well site; operatively interconnecting the chemical and water tanks to an injection tube string, or an annulus associated with a side mandrel, of the production well; and controlling delivery of a mix of corrosion-inhibiting chemical and water from the tanks to the production well so that any desired amounts and proportions of a mix of chemical and water are continuously injected into the well to provide corrosion-inhibiting of a production tube string of the well without interruption of production through the production tube string.

Spivey, M.F.

1987-01-13

342

CMP substitutions preferentially inhibit polysialic acid synthesis  

PubMed Central

It is widely reported that derivatives of sugar moieties can be used to metabolically label cell surface carbohydrates or inhibit a particular glycosylation. However, few studies address the effect of substitution of the cytidylmonophosphate (CMP) portion on sialyltransferase activities. Here we first synthesized 2?-O-methyl CMP and 5-methyl CMP and then asked if these CMP derivatives are recognized by ?2,3-sialyltransferases (ST3Gal-III and ST3Gal-IV), ?2,6-sialyltransferase (ST6Gal-I), and ?2,8-sialyltransferase (ST8Sia-II, ST8Sia-III, and ST8Sia-IV). We found that ST3Gal-III and ST3Gal-IV but not ST6Gal-I was inhibited by 2?-O-methyl CMP as potently as by CMP, while ST3Gal-III, ST3Gal-IV, and ST6Gal-I were moderately inhibited by 5-methyl CMP. Previously, it was reported that polysialyltransferase ST8Sia-II but not ST8Sia-IV was inhibited by CMP N-butylneuraminic acid. We found that ST8Sia-IV as well as ST8Sia-II and ST8Sia-III are inhibited by 2?-O-methyl CMP as robustly as by CMP and moderately by 5-methyl CMP. Moreover, the addition of CMP, 2?-O-methyl CMP, and 5-methyl CMP to the culture medium resulted in the decrease of polysialic acid expression on the cell surface and NCAM of Chinese hamster ovary cells. These results suggest that 2?-O-methyl CMP and 5-methyl CMP can be used to preferentially inhibit sialyltransferases, in particular, polysialyltransferases in vitro and in vivo. Such inhibition may be useful to determine the function of a carbohydrate synthesized by a specific sialyltransferase such as polysialyltransferase.

Miyazaki, Tatsuo; Angata, Kiyohiko; Seeberger, Peter H.; Hindsgaul, Ole; Fukuda, Minoru

2009-01-01

343

IGF-1 receptor antagonism inhibits autophagy.  

PubMed

Inhibition of the insulin/insulin-like growth factor signalling pathway increases lifespan and protects against neurodegeneration in model organisms, and has been considered as a potential therapeutic target. This pathway is upstream of mTORC1, a negative regulator of autophagy. Thus, we expected autophagy to be activated by insulin-like growth factor-1 (IGF-1) inhibition, which could account for many of its beneficial effects. Paradoxically, we found that IGF-1 inhibition attenuates autophagosome formation. The reduced amount of autophagosomes present in IGF-1R depleted cells can be, at least in part, explained by a reduced formation of autophagosomal precursors at the plasma membrane. In particular, IGF-1R depletion inhibits mTORC2, which, in turn, reduces the activity of protein kinase C (PKC?/?). This perturbs the actin cytoskeleton dynamics and decreases the rate of clathrin-dependent endocytosis, which impacts autophagosome precursor formation. Finally, with important implications for human diseases, we demonstrate that pharmacological inhibition of the IGF-1R signalling cascade reduces autophagy also in zebrafish and mice models. The novel link we describe here has important consequences for the interpretation of genetic experiments in mammalian systems and for evaluating the potential of targeting the IGF-1R receptor or modulating its signalling through the downstream pathway for therapeutic purposes under clinically relevant conditions, such as neurodegenerative diseases, where autophagy stimulation is considered beneficial. PMID:23804751

Renna, Maurizio; Bento, Carla F; Fleming, Angeleen; Menzies, Fiona M; Siddiqi, Farah H; Ravikumar, Brinda; Puri, Claudia; Garcia-Arencibia, Moises; Sadiq, Oana; Corrochano, Silvia; Carter, Sarah; Brown, Steve D M; Acevedo-Arozena, Abraham; Rubinsztein, David C

2013-06-25

344

Matrix metalloproteinase inhibition in atherosclerosis and stroke.  

PubMed

Matrix metalloproteinases (MMPs) are a family of tightly regulated, zinc-dependent proteases that degrade extracellular matrix (ECM), cell surface, and intracellular proteins. Vascular remodeling, whether as a function of normal physiology or as a consequence of a myriad of pathological processes, requires degradation of the ECM. Thus, the expression and activity of many MMPs are up-regulated in numerous conditions affecting the vasculature and often exacerbate vascular dysfunction. A growing body of evidence supports the rationale of using MMP inhibitors for the treatment of cardiovascular diseases, stroke, and chronic vascular dementia. This manuscript will examine promising targets for MMP inhibition in atherosclerosis and stroke, reviewing findings in preclinical animal models and human patient studies. Strategies for MMP inhibition have progressed beyond chelating the catalytic zinc to functional blocking antibodies and peptides that target either the active site or exosites of the enzyme. While the inhibition of MMP activity presents a rational therapeutic avenue, the multiplicity of roles for MMPs and the non-selective nature of MMP inhibitors that cause unintended side-effects hinder full realization of MMP inhibition as therapy for vascular disease. For optimal therapeutic effects to be realized, specific targets for MMP inhibition in these pathologies must first be identified and then attacked by potent and selective agents during the most appropriate timepoint. PMID:23865428

Roycik, M D; Myers, J S; Newcomer, R G; Sang, Q-X A

2013-09-01

345

Speech-induced modulation of interhemispheric inhibition.  

PubMed

This study aimed to determine the effects of speech and mastication on interhemispheric inhibition between the right and left primary motor areas (M1s) by using transcranial magnetic stimulation (TMS). Motor-evoked potentials (MEPs) were recorded from the first dorsal interossei (FDIs) of each hand of 10 healthy right-handed subjects under 3 conditions: at rest (control), during mastication (non-verbal oral movement), and during speech (reading aloud). Test TMS was delivered following conditioning TMS of the contralateral M1 at various interstimulus intervals. Under all conditions, the MEPs in the left FDIs were significantly inhibited after conditioning of the left M1 (i.e. inhibition of the right M1 by TMS of the left hemisphere). In contrast, the left M1 was significantly inhibited by the right hemisphere only during the control and mastication tasks, but not speech task. These results suggest that speech may facilitate the activity of the dominant M1 via functional connectivity between the speech area and the left M1, or may modify the balance of interhemispheric interactions, by suppressing inhibition of the dominant hemisphere by the non-dominant hemisphere. Our findings show a novel aspect of interhemispheric dominance and may improve therapeutic strategies for recovery from stroke. PMID:23123786

Kano, Tadashige; Kobayashi, Masahito; Ohira, Takayuki; Yoshida, Kazunari

2012-11-02

346

Inhibition of bacterial luminescence by cerulenin  

SciTech Connect

Bacterial luminescence is very sensitive to cerulenin, a fungal inhibitor of fatty acid (FA) synthesis. Cerulenin does not inhibit luciferase itself, but rather the synthesis of its aldehyde substrate by FA reductase. The acyl-CoA reductase (58 kDa) component of the Photobacterium phosphoreum FA reductase complex was inhibited by cerulenin in vitro. Similarly, acylation of the corresponding Vibrio harveyi 57 kDa protein with (/sup 3/H)myristic acid was preferentially decreased, while cerulenin had no effect on the activities of luciferase or the acyltransferase (32 kDa) responsible for FA supply to luminescence. Light emission of wild type V. harveyi was less sensitive to cerulenin at 10 ..mu..g/ml (5-fold decrease at 1h) than that of the FA-stimulatable dark mutant M17 (100-fold inhibition), which lacks the 32 kDa acyltransferase. The V. harveyi reductase subunit was also labeled by (/sup 3/H)tetrahydrocerulenin in vivo in M17 but not wild type cells; this labeling could be prevented by preincubating M17 cells with cerulenin or FA. These results suggest that (a) cerulenin specifically and covalently inhibits the reductase component of aldehyde synthesis, and (b) this enzyme is partially protected from inhibition in vivo in the wild type cell.

Byers, D.M.; Wall, L.A.; Meighen, E.A.

1986-05-01

347

Hypothalamic glucagon signaling inhibits hepatic glucose production.  

PubMed

Glucagon activates hepatic protein kinase A (PKA) to increase glucose production, but the gluco-stimulatory effect is transient even in the presence of continuous intravenous glucagon infusion. Continuous intravenous infusion of insulin, however, inhibits glucose production through its sustained actions in both the liver and the mediobasal hypothalamus (MBH). In a pancreatic clamp setting, MBH infusion with glucagon activated MBH PKA and inhibited hepatic glucose production (HGP) in rats, as did central glucagon infusion in mice. Inhibition of glucagon receptor-PKA signaling in the MBH and hepatic vagotomy each negated the effect of MBH glucagon in rats, whereas the central effect of glucagon was diminished in glucagon receptor knockout mice. A sustained rise in plasma glucagon concentrations transiently increased HGP, and this transiency was abolished in rats with negated MBH glucagon action. In a nonclamp setting, MBH glucagon infusion improved glucose tolerance, and inhibition of glucagon receptor-PKA signaling in the MBH enhanced the ability of intravenous glucagon injection to increase plasma glucose concentrations. We also detected a similar enhancement of glucose concentrations that was associated with a disruption in MBH glucagon signaling in rats fed a high-fat diet. We show that hypothalamic glucagon signaling inhibits HGP and suggest that hypothalamic glucagon resistance contributes to hyperglycemia in diabetes and obesity. PMID:23685839

Mighiu, Patricia I; Yue, Jessica T Y; Filippi, Beatrice M; Abraham, Mona A; Chari, Madhu; Lam, Carol K L; Yang, Clair S; Christian, Nikita R; Charron, Maureen J; Lam, Tony K T

2013-05-19

348

Evidence that dimethyl sulfoxide inhibits defects of copper deficiency by inhibition of glycation  

Microsoft Academic Search

Prior studies have indicated that dimethyl sulfoxide (DMSO), when fed to rats, can inhibit the cardiac enlargement and anemia of a concurrent dietary copper (Cu) deficiency. Because DMSO is capable of chemically destroying the hydroxyl radical, its inhibition of defects of Cu deficiency was taken as evidence that those defects resulted from oxidative stress. To examine this conclusion further, rats

Jack T. Saari

1996-01-01

349

Mapuche Herbal Medicine Inhibits Blood Platelet Aggregation  

PubMed Central

12 plant species traditionally used by the Mapuche people in Chile to treat wounds and inflammations have been evaluated for their direct blood platelet inhibition. Seven of the 12 tested plant species showed platelet inhibitory effect in sheep blood, and four of these were also able to inhibit the ADP- (5.0??M) and collagen- (2.0??g/mL) induced aggregations in human blood. These four species in respective extracts (in brackets) were Blechnum chilense (MeOH), Luma apiculata (H2O), Amomyrtus luma (DCM?:?MeOH 1?:?1) and Cestrum parqui (DCM?:?MeOH 1?:?1). The platelet aggregating inhibitory effects of A. luma (DCM?:?MeOH 1?:?1), and L. apiculata (H2O) were substantial and confirmed by inhibition of platelet surface activation markers.

Falkenberg, Susan Skanderup; Tarnow, Inge; Guzman, Alfonso; M?lgaard, Per; Simonsen, Henrik Toft

2012-01-01

350

Mapuche herbal medicine inhibits blood platelet aggregation.  

PubMed

12 plant species traditionally used by the Mapuche people in Chile to treat wounds and inflammations have been evaluated for their direct blood platelet inhibition. Seven of the 12 tested plant species showed platelet inhibitory effect in sheep blood, and four of these were also able to inhibit the ADP- (5.0??M) and collagen- (2.0??g/mL) induced aggregations in human blood. These four species in respective extracts (in brackets) were Blechnum chilense (MeOH), Luma apiculata (H(2)O), Amomyrtus luma (DCM?:?MeOH 1?:?1) and Cestrum parqui (DCM?:?MeOH 1?:?1). The platelet aggregating inhibitory effects of A. luma (DCM?:?MeOH 1?:?1), and L. apiculata (H(2)O) were substantial and confirmed by inhibition of platelet surface activation markers. PMID:22028732

Falkenberg, Susan Skanderup; Tarnow, Inge; Guzman, Alfonso; Mølgaard, Per; Simonsen, Henrik Toft

2011-10-20

351

Inhibition of steel corrosion by thiourea derivatives  

SciTech Connect

The thiourea group of sulfur compounds has important theoretical and practical applications. Thioureas have been studied extensively, but their inhibition mechanism is not fully understood. The effect of thiourea; allylthiourea; N,N[prime]-diethylthiourea; N,N[prime]-di-isopropylthiourea; phenylthiourea; thiocarbanilide; and symdiotolylthiourea on the corrosion reaction and on the amount of H[sub 2] absorbed by cold-rolled mild steel in 1 N H[sub 2]SO[sub 4] at 40 C was studied. Inhibitor efficiency increased with increases in molecular weight and inhibitor concentration. Higher inhibitor concentrations decreased H[sub 2] pickup. Thiourea accelerated corrosion reactions and H[sub 2] pickup at higher concentrations. Potential studies showed cathodic reactions were inhibited at lower concentrations and anodic reactions were inhibited at higher concentrations. Results were based on the adsorption theory, and all inhibitors studied followed the Langmuir isotherm.

Singh, I. (National Metallurgical Lab., Jamshedpur (India))

1993-06-01

352

Black Tea Polyphenols Inhibit Tumor Proteasome Activity  

PubMed Central

Tea is a widely consumed beverage and its constituent polyphenols have been associated with potential health benefits. Although black tea polyphenols have been reported to possess potent anticancer activities, the effect of its polyphenols, theaflavins on the tumor’s cellular proteasome function, an important biological target in cancer prevention, has not been carefully studied. Here black tea extract (T5550) enriched in theaflavins inhibited the chymotrypsin-like (CT) activity of the proteasome and proliferation of human multiple myeloma cells in a dose-dependent manner. Also an isolated theaflavin (TF-1) can bind to, and inhibit the purified 20S proteasome, accompanied by suppression of tumor cell proliferation, suggesting that the tumor proteasome is an important target whose inhibition is at least partially responsible for the anti-cancer effects of black tea.

MUJTABA, TASKEEN; DOU, Q. PING

2012-01-01

353

Inhibition of transcription by platinum antitumor compounds  

PubMed Central

Cisplatin, carboplatin, and oxaliplatin are three FDA-approved members of the platinum anticancer drug family. These compounds induce apoptosis in tumor cells by binding to nuclear DNA, forming a variety of structural adducts and triggering cellular responses, one of which is the inhibition of transcription. In this report we present (i) a detailed review of the structural investigations of various Pt-DNA adducts and the effects of these lesions on global DNA geometry; (ii) research detailing inhibition of cellular transcription by Pt-DNA adducts; and (iii) a mechanistic analysis of how DNA structural distortions induced by platinum damage may inhibit RNA synthesis in vivo. A thorough understanding of the molecular mechanism of action of platinum antitumor agents will aid in the development of new compounds in the family.

Todd, Ryan C.; Lippard, Stephen J.

2009-01-01

354

Inhibition of return to successively cued spatial locations  

Microsoft Academic Search

Inhibition of return refers to a bias against returning attention to a location that has been recently attended. Experiments are reported that examined inhibition of return to multiple exogenously cued spatial locations. When 2 peripheral locations were cued in succession, inhibition was found for only the 1 most recently cued location. In addition, more inhibition occurred at the location of

Jay Pratt; Richard A. Abrams

1995-01-01

355

Characteristics of rabbit muscle adenylate kinase inhibition by ascorbate.  

PubMed

Earlier studies [1-3] showed that of the glycolytic enzymes, the muscle isozymes PFK-1, LDH, and AK were inhibited by ascorbic acid. These studies on the characteristics of the inhibition of RMAK by ascorbate are part of a hypothesis [3] that ascorbate facilitates the storage of skeletal muscle glycogen by inhibiting glycolysis when the muscle is at rest. These studies examine conditions for RMAK inhibition, prevention of inhibition, and reversal of ascorbate inhibition. We found that the concentration of RMAK was an important condition for inhibition. Above 200 nM RMAK, inhibition by ascorbate could not be demonstrated and below that concentration RMAK became increasingly sensitive to ascorbate inhibition. Associated with increased sensitivity to inhibition by ascorbate is a deviation from a linear to a concave relationship between low RMAK concentrations and enzyme activity. At low RMAK concentrations, the concave relationship becomes convex in the presence of muscle aldolase. In addition, aldolase reverses inhibitions by ascorbate. A comparison of inhibition of RMAK byascorbate and inhibition of LDH-m4 [3] is discussed. Other proteins prevent RMAK inhibition but do not reverse inhibition by ascorbate. The role of RMAK as a factor in the control of the rate of glycolysis is presented as is the role of compartmentalization with respect to the proposed role for ascorbate inhibition. PMID:16570507

Russell, Percy J; Williams, Anita; Abbott, Ami; DeRosales, Bibiane; Vargas, Reynaldo

2006-02-01

356

Product inhibition of five Hypocrea jecorina cellulases.  

PubMed

Product inhibition of cellulolytic enzymes has been deemed a critical factor in the industrial saccharification of cellulosic biomass. Several investigations have addressed this problem using crude enzyme preparations or commercial (mixed) cellulase products, but quantitative information on individual cellulases hydrolyzing insoluble cellulose remains insufficient. Such knowledge is necessary to pinpoint and quantify inhibitory weak-links in cellulose hydrolysis, but has proven challenging to come by. Here we show that product inhibition of mono-component cellulases hydrolyzing unmodified cellulose may be monitored by calorimetry. The key advantage of this approach is that it directly measures the rate of hydrolysis while being essentially blind to the background of added product. We investigated the five major cellulases from Hypocrea jecorina (anamorph: Tricoderma reesei), Cel7A (formerly CBH1), Cel6A (CBH2), Cel7B (EG1), Cel5A (EG2) and Cel12A (EG3), for their sensitivity to the products glucose and cellobiose. The strongest inhibition was found for Cel7A, which showed a 50% activity-loss in 19 mM cellobiose (IC(50)=19 mM). The other exoglucanase, Cel6A, was much less inhibited by cellobiose, but showed the highest sensitivity to glucose among all investigated enzymes. The endoglucanases Cel12A and Cel7B were moderately inhibited by cellobiose (IC(50)=60-80 mM), and weakly inhibited by glucose (IC(50)=350-380 mM). The highest resistance to both products was found for Cel5A, which retained about 75% of its activity at the highest investigated concentrations (respectively 65 mM cellobiose and 1000 mM glucose). PMID:23410927

Murphy, Leigh; Bohlin, Christina; Baumann, Martin J; Olsen, Søren N; Sørensen, Trine H; Anderson, Lars; Borch, Kim; Westh, Peter

2013-01-14

357

Targeting Methanopterin Biosynthesis To Inhibit Methanogenesis  

PubMed Central

This paper describes the design, synthesis, and successful employment of inhibitors of 4-(?-d-ribofuranosyl)aminobenzene-5?-phosphate (RFA-P) synthase, which catalyzes the first committed step in the biosynthesis of methanopterin, to specifically halt the growth of methane-producing microbes. RFA-P synthase catalyzes the first step in the synthesis of tetrahydromethanopterin, a key cofactor required for methane formation and for one-carbon transformations in methanogens. A number of inhibitors, which are N-substituted derivatives of p-aminobenzoic acid (pABA), have been synthesized and their inhibition constants with RFA-P synthase have been determined. Based on comparisons of the inhibition constants among various inhibitors, we propose that the pABA binding site in RFA-P synthase has a relatively large hydrophobic pocket near the amino group. These enzyme-targeted inhibitors arrest the methanogenesis and growth of pure cultures of methanogens. Supplying pABA to the culture relieves the inhibition, indicating a competitive interaction between pABA and the inhibitor at the cellular target, which is most likely RFAP synthase. The inhibitors do not adversely affect the growth of pure cultures of the bacteria (acetogens) that play a beneficial role in the rumen. Inhibitors added to dense ruminal fluid cultures (artificial rumena) halt methanogenesis; however, they do not inhibit volatile fatty acid (VFA) production and, in some cases, VFA levels are slightly elevated in the methanogenesis-inhibited cultures. We suggest that inhibiting methanopterin biosynthesis could be considered in strategies to decrease anthropogenic methane emissions, which could have an environmental benefit since methane is a potent greenhouse gas.

Dumitru, Razvan; Palencia, Hector; Schroeder, Scott D.; DeMontigny, Bree A.; Takacs, James M.; Rasche, Madeline E.; Miner, Jess L.; Ragsdale, Stephen W.

2003-01-01

358

Surface modification for aluminium pigment inhibition.  

PubMed

This review concerns surface treatment of aluminium pigments for use in water borne coatings. Aluminium pigments are commonly used in coatings to give a silvery and shiny lustre to the substrate. Such paints and inks have traditionally been solvent borne, since aluminium pigment particles react with water. For environmental and health reasons solvent borne coatings are being replaced by water borne and the aluminium pigments then need to be surface modified in order to stand exposure to water. This process is called inhibition and both organic and inorganic substances are used as inhibiting agents. The organic inhibiting agents range from low molecular weight substances, such as phenols and aromatic acids, via surfactants, in particular alkyl phosphates and other anionic amphiphiles, to high molecular weight compounds, such as polyelectrolytes. A common denominator for them all is that they contain a functional group that interacts specifically with aluminium at the surface. A particularly strong interaction is obtained if the inhibiting agent contains functional groups that form chelating complex with surface Al(III). Encapsulation of the pigment can be made by in situ polymerization at the surface of the pigment and a recent approach is to have the polymerization occur within a double layer of adsorbed surfactant. The inorganic route is dominated by coating with silica, and recent progress has been made using an alkoxide, such as tetraethoxysilane as silica precursor. Such silica coated aluminium pigments are comparable in performance to chromate inhibited pigments and thus offer a possible heavy metal-free alternative. There are obvious connections between surface modifications made to prevent the pigment to react with water and inhibition of corrosion of macroscopic aluminium surfaces. PMID:17239333

Karlsson, Philip; Palmqvist, Anders E C; Holmberg, Krister

2007-01-18

359

Human SRY inhibits ?-catenin-mediated transcription  

PubMed Central

In most mammals, sex is determined by the presence or absence of the SRY gene. SRY encodes a DNA binding HMG-box transcription factor which, during embryogenesis, is the initial trigger of testis differentiation from the bipotential gonad, yet its precise mode of function remains unclear. In ovarian development, R-spondin1 and Wnt4 act through the Wnt/?-catenin signaling pathway to regulate TCF-dependent expression of unknown target genes and repress testis development. Conversely, SRY may be necessary to prevent the development of ovaries by inhibiting the action of ovarian-determining genes. We hypothesize that SRY prevents Wnt/?-catenin signaling, thereby inhibiting ovarian development. In HEK293T cells, SRY repressed ?-catenin-mediated TCF-dependent gene activation in the presence of a specific GSK3? inhibitor or an activated ?-catenin mutant, suggesting that SRY inhibits Wnt signaling at the level of ?-catenin. Three SRY mutant proteins with nuclear localization defects, encoded by XY male-to-female patients, failed to inhibit ?-catenin; surprisingly four SRY sex reversed mutants with defective DNA binding activity showed near wild-type SRY inhibitory activity. Moreover the potent transactivator SRY-VP16 fusion protein also showed wild-type SRY inhibitory activity. Thus SRY inhibition of ?-catenin involves neither DNA binding nor transactivation functions of SRY. ?-catenin and SRY interact in-vitro and SRY expression triggered ?-catenin localization into specific nuclear bodies in NT2/D1 and Hela cells. We conclude that SRY inhibits ?-catenin-mediated Wnt signaling by a novel nuclear function of SRY that could be important in sex determination.

Bernard, Pascal; Sim, Helena; Knower, Kevin; Vilain, Eric; Harley, Vincent

2008-01-01

360

Saposin C Protects Glucocerebrosidase against ?-Synuclein Inhibition.  

PubMed

Mutations in GBA1, the gene for glucocerebrosidase (GCase), are genetic risk factors for Parkinson disease (PD). ?-Synuclein (?-Syn), a protein implicated in PD, interacts with GCase and efficiently inhibits enzyme activity. GCase deficiency causes the lysosomal storage disorder Gaucher disease (GD). We show that saposin C (Sap C), a protein vital for GCase activity in vivo, protects GCase against ?-syn inhibition. Using nuclear magnetic resonance spectroscopy, site-specific fluorescence, and Förster energy transfer probes, Sap C was observed to displace ?-syn from GCase in solution and on lipid vesicles. Our results suggest that Sap C might play a crucial role in GD-related PD. PMID:24070323

Yap, Thai Leong; Gruschus, James M; Velayati, Arash; Sidransky, Ellen; Lee, Jennifer C

2013-10-01

361

Cadmium inhibits plasma membrane calcium transport  

Microsoft Academic Search

Summary The interaction of Cd2+ with the plasma membrane Ca2+-transporting ATPase of fish gills was studied. ATP-driven Ca2+-transport in basolateral membrane (BLM) vesicles was inhibited by Cd2+ with anI50 value of 3.0nm at 0.25 µm free Ca2+ using EGTA, HEEDTA and NTA to buffer Ca2+ and Cd2+ concentrations. The inhibition was competitive in nature since theK0.5 value for Ca2+ increased

P. M. Verbost; G. Flik; R. A. C. Lock; S. E. Wendelaar Bonga

1988-01-01

362

Inhibition of intracellular replication by pyridinylimidazoles  

US Patent & Trademark Office Database

Substituted pyridinylimidazoles SB203580 and SB202190 strongly inhibit replication and cause stage conversion from active tachyzoites to relatively dormant bradyzoites of the medically important, obligate intracellular parasite Toxoplasma gondii. The pyridinylimidazoles probably mediate these effects by acting on a presently unidentified homologue(s) of human p38-mitogen activated protein kinase present in the tachyzoites. SB203580 also significantly enhanced in vitro inhibition of T. gondii replication by the approved anti-Toxoplasma drug pyrimethamine. The pyridinylimidazoles and related compounds disclosed herein could thus be significant adjuncts to currently available therapies.

2003-11-18

363

Inhibition of the acetylcholine receptor by histrionicotoxin.  

PubMed

1 The action of C5-decahydrohistrionicotoxin (C5-HTX) has been investigated on the extrajunctional acetylcholine (ACh) receptors of denervated rat muscle. 2 C5-HTX causes both a rapid and slow reduction in amplitude of iontophoretic ACh potentials evoked at all frequencies from the extrajunctional receptors. 3 C5-HTX also causes a time-dependent inhibition of the iontophoretic potentials evoked at frequencies greater than 0.02 Hz. This inhibition was observed either alone or superimposed upon desensitization, and may be caused by a similar mechanism to desensitization. PMID:7378635

Anwyl, R; Narahashi, T

1980-04-01

364

Inhibition of the acetylcholine receptor by histrionicotoxin.  

PubMed Central

1 The action of C5-decahydrohistrionicotoxin (C5-HTX) has been investigated on the extrajunctional acetylcholine (ACh) receptors of denervated rat muscle. 2 C5-HTX causes both a rapid and slow reduction in amplitude of iontophoretic ACh potentials evoked at all frequencies from the extrajunctional receptors. 3 C5-HTX also causes a time-dependent inhibition of the iontophoretic potentials evoked at frequencies greater than 0.02 Hz. This inhibition was observed either alone or superimposed upon desensitization, and may be caused by a similar mechanism to desensitization.

Anwyl, R.; Narahashi, T.

1980-01-01

365

Inhibition of Ent -kaurene oxidation by cytokinins  

Microsoft Academic Search

Cytokinins, which have some structural similarities to ancymidol, a plant growth retardant, were tested for their effects\\u000a on the cell-free oxidation ofent-kaurene. Results indicate that several cytokinins inhibit this reaction in microsomal extracts of liquid endosperm from immature\\u000a wild cucumber seeds. N6-cyclohexanemethyladenine was the most active (inhibiting 50% of the controlent-kaurene oxidation at 2×10?6 M). N6-isoamyladenine, N6-benzyladenine, N6-(?2-isopentenyl)adenine and dihydrozeatin

Ronald C. Coolbaugh

1984-01-01

366

Selective Inhibition of Initiating Ribosomes by Spectinomycin  

PubMed Central

Spectinomycin at low concentrations inhibits initiating ribosomes but not ribosomes already engaged in chain elongation. The initiating ribosomes are blocked in some step after formation of the initiation complex, probably the first translocation. Cells inhibited by spectinomycin accumulate polysomes, and these have proved to be unstable polyinitiation complexes: they can be pulse-labeled with methionine but not with valine, and they disappear after addition of rifampicin. Hence, the blocked ribosomes evidently are released and then reinitiate. In heterozygotes this cyclic reinitiation by the sensitive ribosomes, each blocking an initiation site for an average of 10-15 min, can explain (just as with streptomycin) the dominance of sensitivity over resistance.

Wallace, Brian J.; Tai, Phang-Cheng; Davis, Bernard D.

1974-01-01

367

Behavioral Inhibition in Children with Learning Disabilities  

ERIC Educational Resources Information Center

|Children with reading disabilities (RD, n = 17), mathematical disabilities (MD, n = 22), combined reading and mathematical disabilities (RD + MD, n = 28) and control peers (n = 45) were tested on behavioral inhibition with a Go/no-go task in a picture, letter and digit-modality. In contrast to children without RD, children with RD made…

De Weerdt, Frauke; Desoete, Annemie; Roeyers, Herbert

2013-01-01

368

Optical Interference Coatings for Inhibiting of Counterfeiting  

Microsoft Academic Search

Counterfeiting of valuable papers and identification documents made of paper or plastics, such as banknotes, credit cards, passports, etc., is presently inhibited through the use of inks of many colours, intricate engraved designs on special papers which sometimes contain watermarks or embedded coloured paper platelets or metal threads. These methods have not always offered adequate protection. It is proposed to

J. A. Dobrowolski; K. M. Baird; P. D. Carman; A. Waldorf

1973-01-01

369

Response inhibition and attentional control in anxiety  

Microsoft Academic Search

Traditionally, anxiety has been associated with a selective attentional bias for threat and a decreased capacity in attentional control. In two different experiments, we investigated whether individuals with different levels of self-reported state anxiety (Experiment 1) and induced anxiety (Experiment 2) had impaired response inhibition processes (attentional control deficit) as characterized by a different response style in the presence of

Antonia Pilar Pacheco-Unguetti; Alberto Acosta; Juan Lupiáñez; Naiker Román; Nazanin Derakshan

2012-01-01

370

Subcortical contributions to multitasking and response inhibition  

Microsoft Academic Search

The involvement of the prefrontal cortex in executive control has been well established. It is, however, as yet unclear whether the basal ganglia and the cerebellum as components of frontostriatal\\/frontocerebellar networks also contribute to the executive domains multitasking and response inhibition. To investigate this issue, groups of patients with selective vascular lesions of the basal ganglia (n=13) or the cerebellum

Patrizia Thoma; Benno Koch; Katrin Heyder; Michael Schwarz; Irene Daum

2008-01-01

371

Subcortical contributions to multitasking and response inhibition.  

PubMed

The involvement of the prefrontal cortex in executive control has been well established. It is, however, as yet unclear whether the basal ganglia and the cerebellum as components of frontostriatal/frontocerebellar networks also contribute to the executive domains multitasking and response inhibition. To investigate this issue, groups of patients with selective vascular lesions of the basal ganglia (n=13) or the cerebellum (n=14) were compared with matched healthy control groups. Several paradigms assessing the ability to process concurrent visual and auditory input and to simultaneously perform verbal and manual responses as well as the inhibition of habitual or newly acquired response tendencies were administered. Basal ganglia patients showed marked response slowing during coordination of sensory input from different modalities and high error rates during the inhibition of overlearned responses. There was no clear evidence of a cerebellar involvement in multitasking or response suppression. Taken together, the findings provided evidence for a striatal involvement in both multitasking and response inhibition, emphasizing the functional implication of subcortical components in frontostriatal circuits. PMID:18692526

Thoma, Patrizia; Koch, Benno; Heyder, Katrin; Schwarz, Michael; Daum, Irene

2008-07-22

372

Structural basis of aquaporin inhibition by mercury  

PubMed Central

The aquaporin family of channels was defined based on the inhibition of water transport by mercurial compounds. Despite the important role of mercurials, little is known about the structural changes involved upon mercury binding leading to channel inhibition. To elucidate the mechanism we designed a mutant, T183C, of aquaporin Z (AqpZ) patterned after the known mercury-sensitive site of aquaporin 1 (AQP1) and determined the x-ray crystal structures of the unbound and mercury blocked states. Superposition of the two structures shows no conformational rearrangement upon mercury binding. In the blocked structure, there are two mercury sites – one bound to Cys183 and occluding the pore, and a second, also bound to the same cysteine but found buried in an interstitial cavity. To test the mechanism of blockade we designed a different mutant, L170C, to produce a more effective mercury block at the pore site. In a dose-response inhibition study, this mutant was 20 times more sensitive to mercury than wild-type AqpZ and 4 times more sensitive than T183C. The x-ray structure of L170C shows four mercury atoms at, or near, the pore site defined in the T183C structure and no structural change upon mercury binding. Thus, we elucidate a steric inhibition mechanism for this important class of channels by mercury.

Savage, David F.; Stroud, Robert M.

2012-01-01

373

Search Asymmetry, Sustained Attention, and Response Inhibition  

ERIC Educational Resources Information Center

|In the present experiment, we used search asymmetry to test whether the sustained attention to response task is a better measure of response inhibition or sustained attention. Participants performed feature present and feature absent target detection tasks using either a sustained attention to response task (SART; high Go low No-Go) or a…

Stevenson, Hugh; Russell, Paul N.; Helton, William S.

2011-01-01

374

Inhibition of Amyloid-? Aggregation in Alzheimer Disease.  

PubMed

The assembly of naturally occurring amyloid peptides into cytotoxic oligomeric and fibrillar aggregates is believed to be a major pathologic event in over 25 human diseases. Blocking of or interfering with the aggregation of amyloid peptides such as amyloid-? (A?) using small organic molecules, peptides and peptidomimetics, and nanoparticles that selectively bind or inhibit A? aggregates is a promising strategy for the development of novel pharmaceutical approaches and agents to treat Alzheimer disease (AD). In a broad sense, considering many common features in structure, kinetics, and biological activity of amyloid peptides, potent inhibitors and associated inhibition strategies that are developed for targeting A? aggregation could also be generally applied to other amyloid-forming peptides in "protein-aggregation diseases". Due to the complex nature of A? self-assembly process, increasing knowledge in high-resolution structures of A? oligomers, atomic-level A?-inhibitor binding information, and cost-effective high-throughput screening method will improve our fundamental understanding of amyloid formation and inhibition mechanisms, as well as practical design of pharmaceutical strategies and drugs to treat AD. This review summarizes major findings, recent advances, and future challenges for the development of new A?-aggregation inhibitors, mainly focusing on three major classes of A? inhibitors with associated inhibition mechanisms and practical examples. PMID:23713775

Wang, Qiuming; Yu, Xiang; Li, Lingyan; Zheng, Jie

2013-05-22

375

Psychiatric drugs and inhibited female orgasm  

Microsoft Academic Search

The available evidence concerning sexual side effects of psychiatric drugs suggests that inhibited female orgasm may be associated with the use of heterocyclic antidepressants, monoamine oxidase inhibitors, benzodiazepines, and neuroleptics. Possible mechanisms of action including anticholinergic, alpha adrenergic blockade, and serotonergic effects are discussed.

R. T. Segraves

1988-01-01

376

Emotional inhibition: A discourse analysis of disclosure  

Microsoft Academic Search

Evidence generated within the emotional disclosure paradigm (EDP) suggests that talking or writing about emotional experiences produces health benefits, but recent meta-analyses have questioned its efficacy. Studies within the EDP typically rely upon a unidimensional and relatively unsophisticated notion of emotional inhibition, and tend to use quantitative forms of content analysis to identify associations between percentages of word types and

Darren Ellis; John Cromby

2011-01-01

377

Emotional inhibition: A discourse analysis of disclosure  

Microsoft Academic Search

Evidence generated within the emotional disclosure paradigm (EDP) suggests that talking or writing about emotional experiences produces health benefits, but recent meta-analyses have questioned its efficacy. Studies within the EDP typically rely upon a unidimensional and relatively unsophisticated notion of emotional inhibition, and tend to use quantitative forms of content analysis to identify associations between percentages of word types and

Darren Ellis; John Cromby

2012-01-01

378

Antibacterial Agents That Inhibit Lipid a Biosynthesis  

Microsoft Academic Search

Lipid A constitutes the outer monolayer of the outer membrane of Gram-negative bacteria and is essential for bacterial growth. Synthetic antibacterials were identified that inhibit the second enzyme (a unique deacetylase) of lipid A biosynthesis. The inhibitors are chiral hydroxamic acids bearing certain hydrophobic aromatic moieties. They may bind to a metal in the active site of the deacetylase. The

H. Russell Onishi; Barbara A. Pelak; Lynn S. Gerckens; Lynn L. Silver; Frederick M. Kahan; Meng-Hsin Chen; Arthur A. Patchett; Susan M. Galloway; Sheryl A. Hyland; Matt S. Anderson; Christian R. H. Raetz

1996-01-01

379

INHIBITION OF AFLATOXIN BIOSYNTHESIS BY GALLIC ACID  

Technology Transfer Automated Retrieval System (TEKTRAN)

Aflatoxin (AF) biosynthesis is inhibited by gallic acid present in tree nuts. During invasion by Aspergillus flavus, fungal tannase releases gallic acid (GA) from the hydolyzable tannins present in the pellicle of walnut and the hull of pistachio. Previous studies have shown that GA content of the...

380

INHIBITION OF TOMATO RIPENING BY 1-METHYLCYCLOPROPENE  

Technology Transfer Automated Retrieval System (TEKTRAN)

The capacity for 1-methylcyclopropene (MCP) to inhibit color change and firmness loss for tomato fruit was evaluated as a function of MCP concentration, multiple and continuous applications, and stage of ripeness. In addition, the relationship between external fruit color and itnernal color, aroma,...

381

Inhibition of methanogenesis by human bile.  

PubMed Central

The factors that regulate methanogenesis in humans have not been established. The presence of bile acid, which is lost into the colon from the small intestine, may be an important regulatory factor of methanogenesis. To examine this possibility, the effect of human bile on methane production by faecal cultures, and the in vivo effect of biliary diversion on breath methane excretion in a methanogenic choledochostomy patient, were investigated. Faecal suspensions (0.1%) from five methanogenic humans were incubated anaerobically with bile (0.3-30%) from three choledochostomy patients, and headspace methane measured by gas chromatography. All biles inhibited headspace methane. Inhibition of methanogenesis was dose dependent, plateaued at 10-30% bile concentration, and was abolished by 0.6% cholestyramine. The maximum inhibition by bile, median (range), was 38 (0.9-56)% of control methane values. Reversal of the bile fistula in the fourth choledochostomy patient converted that subject from methanogenic to 'non-methanogenic' status, It is concluded that inhibition of methanogens in the caecum by bile acid could significantly reduce the number of methanogens in the colon. This and the effect of transit time could explain much of the known epidemiology of 'non-methanogenesis', which has been related to obesity, (comparatively) fast colonic transit in healthy persons, and to small intestinal Crohn's disease.

Florin, T H; Woods, H J

1995-01-01

382

Angiotensin inhibition and malignancies: a review  

Microsoft Academic Search

After an early report that patients treated with angiotensin-converting enzyme (ACE) inhibitors had a lower than expected incidence of cancers, there was a large number of publications investigating the possible pathophysiological mechanism mediating this effect, as well as population studies comparing the incidence of cancers in patients treated with agents inhibiting the renin–angiotensin system with their incidence in the general

T Rosenthal; I Gavras

2009-01-01

383

Tetracyclines inhibit activated B cell function  

Microsoft Academic Search

Tetracyclines have recently been shown to exert a number of pleiotropic anti-inflammatory and immunomodulatory activities, independent of their antibiotic properties. These include the ability to inhibit metalloproteinases (MP), a class of enzymes involved in crucial cellular functions such as the shedding of soluble mediators and their receptors from the cell surface, as well as interaction with, and remodeling of, the

Igor I. Kuzin; Jennifer E. Snyder; Gregory D. Ugine; Dongming Wu; Sang Lee; Timothy Bushnell; Richard A. Insel; Faith M. Young; Andrea Bottaro

2001-01-01

384

Intrarenal dopamine inhibits progression of diabetic nephropathy.  

PubMed

The kidney has a local intrarenal dopaminergic system, and in the kidney, dopamine modulates renal hemodynamics, inhibits salt and fluid reabsorption, antagonizes the renin-angiotensin system, and inhibits oxidative stress. The current study examined the effects of alterations in the intrarenal dopaminergic system on kidney structure and function in models of type 1 diabetes. We studied catechol-O-methyl-transferase (COMT)(-/-) mice, which have increased renal dopamine production due to decreased dopamine metabolism, and renal transplantation was used to determine whether the effects seen with COMT deficiency were kidney-specific. To determine the effects of selective inhibition of intrarenal dopamine production, we used mice with proximal tubule deletion of aromatic amino acid decarboxylase (ptAADC(-/-)). Compared with wild-type diabetic mice, COMT(-/-) mice had decreased hyperfiltration, decreased macula densa cyclooxygenase-2 expression, decreased albuminuria, decreased glomerulopathy, and inhibition of expression of markers of inflammation, oxidative stress, and fibrosis. These differences were also seen in diabetic mice with a transplanted kidney from COMT(-/-) mice. In contrast, diabetic ptAADC(-/-) mice had increased nephropathy. Our study demonstrates an important role of the intrarenal dopaminergic system to modulate the development and progression of diabetic kidney injury and indicate that the decreased renal dopamine production may have important consequences in the underlying pathogenesis of diabetic nephropathy. PMID:22688335

Zhang, Ming-Zhi; Yao, Bing; Yang, Shilin; Yang, Haichun; Wang, Suwan; Fan, Xiaofeng; Yin, Huiyong; Fogo, Agnes B; Moeckel, Gilbert W; Harris, Raymond C

2012-06-11

385

Reduced response readiness delays stop signal inhibition  

Microsoft Academic Search

Examined the effect of response readiness on the stopping of motor responses. 13 subjects (Ss; undergraduates) performed a primary task requiring a speeded choice reaction on go trials and response inhibition on no go trials. An occasional cue informed Ss that a no-go trial was imminent but left them uncertain about the number of go trials separating the cue and

G. D. Logan; Molen van der M. W; Wildenberg van den W. P. M

2002-01-01

386

Motor cortex inhibition induced by acoustic stimulation  

Microsoft Academic Search

The influence of the brainstem motor system on cerebral motor areas may play an important role in motor control in health and disease. A new approach to investigate this interaction in man is combining acoustic stimulation activating the startle system with transcranial magnetic stimulation (TMS) over the motor cortex. However, it is unclear whether the inhibition of TMS responses following

Andrea A. Kühn; Andrew Sharott; Thomas Trottenberg; Andreas Kupsch; Peter Brown

2004-01-01

387

Oral bacteria inhibit Helicobacter pylori growth  

Microsoft Academic Search

Various oral bacterial species were found to inhibit the growth of Helicobacter pylori strains. The growth inhibitory activities of most of these oral bacteria were adversely affected by heating at 80°C for 60 min or by protease treatment, indicating that these bacteria produce bacteriocin-like inhibitory proteins against H. pylori strains. The antagonistic effects of oral bacteria against H. pylori may

Kazuyuki Ishihara; Tadashi Miura; Ryuta Kimizuka; Yoko Ebihara; Yoshio Mizuno; Katsuji Okuda

1997-01-01

388

Illustrating Enzyme Inhibition Using Gibbs Energy Profiles  

ERIC Educational Resources Information Center

Gibbs energy profiles have great utility as teaching and learning tools because they present students with a visual representation of the energy changes that occur during enzyme catalysis. Unfortunately, most textbooks divorce discussions of traditional kinetic topics, such as enzyme inhibition, from discussions of these same topics in terms of…

Bearne, Stephen L.

2012-01-01

389

Motivational Influences on Response Inhibition Measures  

ERIC Educational Resources Information Center

Psychological research has placed great emphasis on inhibitory control due to its integral role in normal cognition and clinical disorders. The stop-signal task and associated measure--stop-signal reaction time (SSRT)--provides a well-established paradigm for measuring response inhibition. However, motivational influences on stop-signal…

Leotti, Lauren A.; Wager, Tor D.

2010-01-01

390

Nitrite inhibition of denitrification by Pseudomonas fluorescens  

SciTech Connect

Using a pure culture of Pseudomonas fluorescens as a model system nitrite inhibition of denitrification was studied. A mineral media with acetate and nitrate as sole electron donor and acceptor, respectively, was used. Results obtained in continuous stirred-tank reactors (CSTR) operated at pH values between 6.6 and 7.8 showed that growth inhibition depended only on the nitrite undissociated fraction concentration (nitrous acid). A mathematical model to describe this dependence is put forward. The maximum nitrous acid concentration compatible with cell growth and denitrification activity was found to be 66 {mu}g N/L. Denitrification activity was partially associated with growth, as described by the Luedeking-Piret equation. However, when the freshly inoculated reactor was operated discontinuously, nitrite accumulation caused growth uncoupling from denitrification activity. The authors suggest that these results can be interpreted considering that (a) nitrous acid acts as a proton uncoupler; and (b) cultures continuously exposed to nitrous acid prevent the uncoupling effect but not the growth inhibition. Examination of the growth dependence on nitrite concentration at pH 7.0 showed that adapted cultures (growth on CSTR) are less sensitive to nitrous acid inhibition than the ones cultivated in batch.

Almeida, J.S.; Julio, S.M.; Reis, M.A.M. [FCT/UNL, Monte da Caparica (Portugal); Carrondo, M.J.T. [FCT/UNL, Monte da Caparica (Portugal)]|[Inst. de Biologia Experimental e Tecnologica, Oeiras (Portugal)

1995-05-05

391

Role of RANKL inhibition in osteoporosis  

Microsoft Academic Search

When the rate of bone resorption exceeds that of bone formation, destruction of bone tissue occurs, resulting in a fragile skeleton. The clinical consequences, namely osteoporosis and fragility fractures, are common and costly problems. Treatments that normalize the balance of bone turnover by inhibiting bone resorption preserve bone mass and reduce fracture risk. The discovery of receptor activator of nuclear

Michael McClung

2007-01-01

392

Inhibition of deterioration of rubbers by hydroaromatics  

SciTech Connect

Based on the results obtained from previous works, which concluded that hydrogen donating hydroaromatics can be available as radical scavengers in inhibiting the deterioration of hydrocarbon products at lower oxygen partial pressure, a hydroaromatic type inhibitor which contains various hydroaromatics as its main components produced from coal tar fraction was examined by adding it to natural rubber (NR) and styrene-butadiene rubber (SBR). It was found that the inhibitor was as effective as the conventional amine-type inhibitor. From practical viewpoint, heavy hydroaromatics from petroleum (HHAP) was produced by the hydrogenation of the highly aromatic oil from the heavy fraction of petroleum to improve the physical properties of the previous inhibitor from coal tar fraction. From the deterioration tests for NR, SBR, and chloroprene (CR), the following results could be obtained: (1) HHAP showed excellent inhibiting abilities toward NR and CR, exceeding the conventional inhibitor; (2) inhibiting effect toward SBR could be recognized, viscosity and flex cracking were improved by the addition of HHAP. From these results, the hydrogen donation from hydroaromatic is considered to be effective in inhibiting the deterioration of rubbers.

Kubo, Junichi (Nippon Oil Co., Naka-ku (Japan))

1993-03-01

393

Inhibition of Return in Children and Adolescents.  

ERIC Educational Resources Information Center

Compared the timecourse of inhibition of return (IOR) of young children to that of older children and adolescents in single and double cue procedures. Found no IOR in the young children unless a double cue was used, but for older groups, found IOR at all intervals with a double cue and the typical crossover pattern, with early facilitation…

MacPherson, Amy C.; Klein, Raymond M.; Moore, Chris

2003-01-01

394

Inhibition of denitrification by ultraviolet radiation  

NASA Astrophysics Data System (ADS)

It has been shown that UV-A (? = 320- 400 nm) and UV-B (? = 280 - 320 nm) inhibit photosynthesis, nitrogen fixation and nitrification. The purpose of this study was to determine the effects, if any, on denitrification in a microbial community inhabiting the intertidal. The community studied is the microbial mat consisting primarily of Lyngbya that inhabits the Pacific marine intertidal, Baja California, Mexico. Rates of denitrification were determined using the acetylene blockage technique. Pseudomonas fluorescens (ATCC # 17400) was used as a control organism, and treated similarly to the mat samples. Samples were incubated either beneath a PAR transparent, UV opaque screen (OP3), or a mylar screen to block UV-B, or a UV transparent screen (UVT) for 2 to 3 hours. Sets of samples were also treated with nitrapyrin to inhibit nitrification, or DCMU to inhibit photosynthesis and treated similarly. Denitrification rates were greater in the UV protected samples than in the UV exposed samples the mat samples as well as for the Ps. fluorescens cultures. Killed controls exhibited no activity. In the DCMU and nitrapyrin treated samples denitrification rates were the same as in the untreated samples. These data indicate that denitrification is directly inhibited by UV radiation.

Mancinelli, R. L.; White, M. R.

395

Mechanisms of gas hydrate formation and inhibition  

Microsoft Academic Search

The formation of gas hydrates in gas and oil subsea pipelines often results in blockage and shutdown of these pipelines. Modern control methods depend on understanding the mechanisms through which gas hydrates form. This paper reviews our recent studies of clathrate hydrate formation and inhibition mechanisms using neutron diffraction, differential scanning calorimetry (DSC) and a multiple cell photo-sensing instrument. The

C. A. Koh; R. E. Westacott; W. Zhang; K. Hirachand; J. L. Creek; A. K. Soper

2002-01-01

396

Tuning ionic liquids for hydrate inhibition.  

PubMed

Pyrrolidinium cation-based ionic liquids were synthesized, and their inhibition effects on methane hydrate formation were investigated. It was found that the ionic liquids shifted the hydrate equilibrium line to a lower temperature at a specific pressure, while simultaneously delaying gas hydrate formation. PMID:21547283

Kim, Ki-Sub; Kang, Jeong Won; Kang, Seong-Pil

2011-05-06

397

Erotic stimuli and aggression: Facilitation or inhibition  

Microsoft Academic Search

Attempted to reconcile previous results on the relationship of erotic stimuli and aggression. 81 male undergraduates were either insulted or not insulted prior or subsequent to observing erotic stimuli of varying levels of arousal inducements. It was found, in support of prior research, that mildly erotic stimuli had an inhibiting effect on aggression when viewed subsequent to anger arousal, whereas

Edward Donnerstein; Marcia Donnerstein; Ronald Evans

1975-01-01

398

Trimethyltin Reduces Recurrent Inhibition in Rats.  

National Technical Information Service (NTIS)

Rats with electrodes chronically implanted in the perforant path for electrical stimulation, and dentate gyrus for recording were treated with a single oral administration of either saline, 5 mg/kg trimethyltin (TMT) or 6 mg/kg TMT. Recurrent inhibition w...

R. S. Dyer W. K. Boyes

1984-01-01

399

Inhibited Solid Propellant Composition Containing Beryllium Hydride.  

National Technical Information Service (NTIS)

An object of this invention is to provide a composition of beryllium hydride and carboxy-terminated polybutadiene which is stable. Another object of this invention is to provide a method for inhibiting the reactivity of beryllium hydride toward carboxy-te...

W. W. Thompson

1978-01-01

400

Corrosion Inhibiting Engine Oils. Part 2.  

National Technical Information Service (NTIS)

In anticipation of corrosion problems during long term storage of F-107 gas turbine engines in air-launched cruise missiles, a program was undertaken to develop a corrosion inhibiting engine oil with performance characteristics at least equal to those spe...

G. C. Brown P. A. Warner R. J. Meehan W. J. Purvis

1982-01-01

401

Corrosion inhibition in high temperature environment  

SciTech Connect

This invention pertains to the use of tin oxide as a corrosion resistant material for preventing or inhibiting high temperature corrosion by molten sulfate-vanadate deposits and gaseous sulfur trioxide formed in engines or other high temperature apparatus which burn materials containing sodium, sulfur, and vanadium.

Jones, R.E.

1993-06-28

402

Molybdate in corrosion inhibition - A review  

Microsoft Academic Search

It has been nearly 50 y since molybdate compounds were first identified and put to practical use as corrosion inhibitors. Molybdates are now among the most broadly applied inhibitors, chiefly because of their efficacy toward both ferrous and nonferrous metals and their very low order of toxicity. This review summarizes fundamental and applied studies dealing with molybdates in corrosion inhibition

M. S. Vukasovich; J. P. G. Farr

1986-01-01

403

Target Predictability, Sustained Attention, and Response Inhibition  

ERIC Educational Resources Information Center

|We examined whether the sustained attention to response task is a better measure of response inhibition or sustained attention. Participants performed a number detection task for 37.3 min using either a Sustained Attention to Response Task (SART; high Go low No-Go) or a more traditionally formatted vigilance task (TFT; high No-Go low Go) response…

Carter, Leonie; Russell, Paul N.; Helton, William S.

2013-01-01

404

Diacetylene Derivatives: Corrosivity and Inhibitive Effect  

Microsoft Academic Search

Steels were tested for corrosion resistance in simulated media and in a pilot plant for the synthesis of 3(5)-methylpyrazole, butoxybut-1-en-3-yne, and 3(5)-methyl-1-vinylpyrazole. 3(5)-Methylpyrazole was found to effectively inhibit the corrosion of carbon steel in solutions of sulfuric acid, methanol, and fertilizers containing carbamide and ammonium nitrate.

B. A. Gru

2004-01-01

405

Illustrating Enzyme Inhibition Using Gibbs Energy Profiles  

ERIC Educational Resources Information Center

|Gibbs energy profiles have great utility as teaching and learning tools because they present students with a visual representation of the energy changes that occur during enzyme catalysis. Unfortunately, most textbooks divorce discussions of traditional kinetic topics, such as enzyme inhibition, from discussions of these same topics in terms of…

Bearne, Stephen L.

2012-01-01

406

Cumulative Intertrial Inhibition in Repeated Visual Search  

ERIC Educational Resources Information Center

|In the present study the author examined visual search when the items remain visible across trials but the location of the target varies. Reaction times for inefficient search cumulatively increased with increasing numbers of repeated search trials, suggesting that inhibition for distractors carried over successive trials. This intertrial…

Takeda, Yuji

2007-01-01

407

Kasugamycin inhibition of bacterial sporulation. Final report  

SciTech Connect

Kasugamycin has been observed to specifically inhibit the sporulation process in Bacillus subtilis at a level below that showing any effect on vegetative growth. A new locus, Ksg-D, has been identified as a locus responsible of Ksg resistant sporulation. Ksg-D may affect the cellular permeability barrier to the drug. (ACR)

Bott, K.F.

1980-01-01

408

Aromatase Inhibition in a Transcriptional Network Context  

EPA Science Inventory

A variety of chemicals in the environment have the potential to inhibit aromatase, an enzyme critical to estrogen synthesis. We examined the responses of female fathead minnow ovaries (FHM, Pimephales promelas) to a model aromatase inhibitor, fadrozole, using a transcriptional ne...

409

Voriconazole Inhibits Melanization in Cryptococcus neoformans  

Microsoft Academic Search

Voriconazole is a triazole antifungal drug that inhibits ergosterol synthesis and has broad activity against yeast and molds. While studying the interaction of voriconazole and Cryptococcus neoformans, we noted that cells grown in the presence of subinhibitory concentrations of voriconazole reduced melanin pigmentation. We investigated this effect systematically by assessing melanin production in the presence of voriconazole, am- photericin B,

Luis R. Martinez; Patricia Ntiamoah; Attila Gacser; Arturo Casadevall; Joshua D. Nosanchuk

2007-01-01

410

Triptolide inhibits amyloid-? production and protects neural cells by inhibiting CXCR2 activity.  

PubMed

Triptolide, a biologically active natural product from Tripterygium wilfordii, protects neurons from inflammation-mediated damage. Our results showed for the first time that triptolide inhibited the expression of CXCR2 and presenilin in a neuroblastoma cell line SHSY5Ysw. Moreover, triptolide potently inhibited amyloid-?1-42 production with IC50 value of 30 pM in HEK293sw cells or 2 nM in SHSY5Ysw cells, respectively. We also demonstrated that triptolide prevented primary cortical neurons from chemokine CXCL1-induced cytotoxicity. Therefore, our study indicates that the neural protective effect of triptolide is largely mediated by inhibiting CXCR2 activity. PMID:22986777

Wang, Ju; Shi, Zi-Qi; Xu, Xiaojun; Xin, Gui-Zhong; Chen, Jun; Qi, Lian-Wen; Li, Ping

2013-01-01

411

WEE1 inhibition sensitizes osteosarcoma to radiotherapy  

PubMed Central

Background The use of radiotherapy in osteosarcoma (OS) is controversial due to its radioresistance. OS patients currently treated with radiotherapy generally are inoperable, have painful skeletal metastases, refuse surgery or have undergone an intralesional resection of the primary tumor. After irradiation-induced DNA damage, OS cells sustain a prolonged G2 cell cycle checkpoint arrest allowing DNA repair and evasion of cell death. Inhibition of WEE1 kinase leads to abrogation of the G2 arrest and could sensitize OS cells to irradiation induced cell death. Methods WEE1 expression in OS was investigated by gene-expression data analysis and immunohistochemistry of tumor samples. WEE1 expression in OS cell lines and human osteoblasts was investigated by Western blot. The effect of WEE1 inhibition on the radiosensitivity of OS cells was assessed by cell viability and caspase activation analyses after combination treatment. The presence of DNA damage was visualized using immunofluorescence microscopy. Cell cycle effects were investigated by flow cytometry and WEE1 kinase regulation was analyzed by Western blot. Results WEE1 expression is found in the majority of tested OS tissue samples. Small molecule drug PD0166285 inhibits WEE1 kinase activity. In the presence of WEE1-inhibitor, irradiated cells fail to repair their damaged DNA, and show higher levels of caspase activation. The inhibition of WEE1 effectively abrogates the irradiation-induced G2 arrest in OS cells, forcing the cells into premature, catastrophic mitosis, thus enhancing cell death after irradiation treatment. Conclusion We show that PD0166285, a small molecule WEE1 kinase inhibitor, can abrogate the G2 checkpoint in OS cells, pushing them into mitotic catastrophe and thus sensitizing OS cells to irradiation-induced cell death. This suggests that WEE1 inhibition may be a promising strategy to enhance the radiotherapy effect in patients with OS.

2011-01-01

412

Neural Synchrony during Response Production and Inhibition  

PubMed Central

Inhibition of irrelevant information (conflict monitoring) and/or of prepotent actions is an essential component of adaptive self-organized behavior. Neural dynamics underlying these functions has been studied in humans using event-related brain potentials (ERPs) elicited in Go/NoGo tasks that require a speeded motor response to the Go stimuli and withholding a prepotent response when a NoGo stimulus is presented. However, averaged ERP waveforms provide only limited information about the neuronal mechanisms underlying stimulus processing, motor preparation, and response production or inhibition. In this study, we examine the cortical representation of conflict monitoring and response inhibition using time-frequency analysis of electroencephalographic (EEG) recordings during continuous performance Go/NoGo task in 50 young adult females. We hypothesized that response inhibition would be associated with a transient boost in both temporal and spatial synchronization of prefrontal cortical activity, consistent with the role of the anterior cingulate and lateral prefrontal cortices in cognitive control. Overall, phase synchronization across trials measured by Phase Locking Index and phase synchronization between electrode sites measured by Phase Coherence were the highest in the Go and NoGo conditions, intermediate in the Warning condition, and the lowest under Neutral condition. The NoGo condition was characterized by significantly higher fronto-central synchronization in the 300–600 ms window, whereas in the Go condition, delta- and theta-band synchronization was higher in centro-parietal regions in the first 300 ms after the stimulus onset. The present findings suggest that response production and inhibition is supported by dynamic functional networks characterized by distinct patterns of temporal and spatial synchronization of brain oscillations.

Muller, Viktor; Anokhin, Andrey P.

2012-01-01

413

VISUALIZATION-BASED ANALYSIS FOR A MIXED-INHIBITION BINARY PBPK MODEL: DETERMINATION OF INHIBITION MECHANISM  

EPA Science Inventory

A physiologically-based pharmacokinetic (PBPK) model incorporating mixed enzyme inhibition was used to determine the mechanism of metabolic interactions occurring during simultaneous exposures to the organic solvents chloroform and trichloroethylene (TCE). Visualization-based se...

414

Reciprocal inhibition of inhibition: a circuit motif for flexible categorization in stimulus selection.  

PubMed

As a precursor to the selection of a stimulus for gaze and attention, a midbrain network categorizes stimuli into "strongest" and "others." The categorization tracks flexibly, in real time, the absolute strength of the strongest stimulus. In this study, we take a first-principles approach to computations that are essential for such categorization. We demonstrate that classical feedforward lateral inhibition cannot produce flexible categorization. However, circuits in which the strength of lateral inhibition varies with the relative strength of competing stimuli categorize successfully. One particular implementation--reciprocal inhibition of feedforward lateral inhibition--is structurally the simplest, and it outperforms others in flexibly categorizing rapidly and reliably. Strong predictions of this anatomically supported circuit model are validated by neural responses measured in the owl midbrain. The results demonstrate the extraordinary power of a remarkably simple, neurally grounded circuit motif in producing flexible categorization, a computation fundamental to attention, perception, and decision making. PMID:22243757

Mysore, Shreesh P; Knudsen, Eric I

2012-01-12

415

Acquired resistance to BRAF inhibition can confer cross-resistance to combined BRAF/MEK inhibition.  

PubMed

Aberrant activation of the BRAF kinase occurs in ?60% of melanomas, and although BRAF inhibitors have shown significant early clinical success, acquired resistance occurs in most patients. Resistance to chronic BRAF inhibition often involves reactivation of mitogen-activated protein kinase (MAPK) signaling, and the combined targeting of BRAF and its downstream target MAPK/ERK kinase (MEK) may delay or overcome resistance. To investigate the efficacy of combination BRAF and MEK inhibition, we generated melanoma cell clones resistant to the BRAF inhibitor GSK2118436. These BRAF inhibitor-resistant sublines acquired resistance through several distinct mechanisms, including the acquisition of activating N-RAS mutations and increased accumulation of COT1. These alterations uniformly promoted MAPK reactivation and most conferred resistance to MEK inhibition and to the concurrent inhibition of BRAF and MEK. These data indicate that melanoma tumors are likely to develop heterogeneous mechanisms of resistance, many of which will confer resistance to multiple MAPK inhibitory therapies. PMID:22437314

Gowrishankar, Kavitha; Snoyman, Stephanie; Pupo, Gulietta M; Becker, Therese M; Kefford, Richard F; Rizos, Helen

2012-03-22

416

The Inhibition of the Thermal Discolouration of Polyacrylonitrile, Part 2 Investigation into the Inhibition Mechanism.  

National Technical Information Service (NTIS)

The inhibition of anaerobic thermal discoloration of polyacrylonitrile by maleimide was demonstrated by IR-spectroscopy. Investigations of the solubility of polyacrylonitrile samples heated in the presence of maleimide support previous concepts on the mec...

J. Runge

1972-01-01

417

Reaction time inhibition from subliminal cues: Is it related to inhibition of return?  

Microsoft Academic Search

Task-irrelevant visual cues with near zero visibility proved apt to retard reaction time for the detection of supraliminal visual targets presented at the cued location. The time course of the effect was similar to that of the so-called inhibition-of return (IOR), which is assumed to be due to the withdrawal of attention from the inhibited location. However the present subliminal

Sonia Mele; Silvia Savazzi; Carlo A. Marzi; Giovanni Berlucchi

2008-01-01

418

Inhibiting platelet-stimulated blood coagulation by inhibition of mitochondrial respiration.  

PubMed

Platelets are important mediators of blood coagulation that lack nuclei, but contain mitochondria. Although the presence of mitochondria in platelets has long been recognized, platelet mitochondrial function remains largely unaddressed. On the basis of a small amount of literature that suggests platelet mitochondria are functional, we hypothesized that the inhibition of platelet mitochondria disrupts platelet function and platelet-activated blood coagulation. To test this hypothesis, members of the tetrazole, thiazole, and 1,2,3-triazole families of small molecule heterocycles were screened for the ability to inhibit isolated mitochondrial respiration and coagulation of whole blood. The families of heterocycles screened were chosen on the basis of the ability of the heterocycle family to inhibit a biomimetic model of cytochrome c oxidase (CcO). The strength of mitochondrial inhibition correlates with each compound's ability to deter platelet stimulation and platelet-activated blood clotting. These results suggest that for this class of molecules, inhibition of blood coagulation may be occurring through a mechanism involving mitochondrial inhibition. PMID:22308457

Barile, Christopher J; Herrmann, Paul C; Tyvoll, David A; Collman, James P; Decreau, Richard A; Bull, Brian S

2012-01-30

419

Disinhibition is easier learned than inhibition. The effects of (dis)inhibition training on food intake.  

PubMed

Impulsivity seems to be a strong candidate when it comes to psychological factors leading to overeating and eventually to obesity (Guerrieri, Nederkoorn, & Jansen, 2008). The question is whether reversing the logic and strengthening an individual's inhibitory skills will be equally potent against overeating. In the current study the stop signal task was adjusted so that one group of female students (n=21) gradually got more trials in which they could practise inhibition (inhibition), whereas another group (n=20) gradually got more trials in which they had to react quickly, without having time to think or inhibit (impulsivity). A third group (n=20) did a neutral reading task (control). The participants in the impulsivity group had a significantly higher caloric intake during a subsequent taste test, whereas the inhibition group did not differ from the control group. Hence, the data support that impulsivity is a direct cause of overeating. However, the concept of inhibition training needs to be investigated further. Issues like the specificity of inhibition training (general vs. food specific) need to be addressed and used to optimise the training so that its effectiveness can be tested within clinical settings. PMID:22521403

Guerrieri, Ramona; Nederkoorn, Chantal; Jansen, Anita

2012-04-17

420

Mullerian inhibiting substance inhibits ovarian cell growth through an Rb-independent mechanism.  

PubMed

Müllerian inhibiting substance (MIS), a transforming growth factor-beta family member, causes regression of the Müllerian duct in male embryos. MIS overexpression in transgenic mice ablates the ovary, and MIS inhibits the growth of ovarian cancer cell lines in vitro, suggesting a key role for this hormone in postnatal development of the ovary. This report describes a mechanism for MIS-mediated growth inhibition in both a human epithelial ovarian cancer cell line and a cell line derived from normal ovarian surface epithelium, which is the origin of human epithelial ovarian cancers. MIS-treated cells accumulated in the G(1) phase of the cell cycle and subsequently underwent apoptosis. MIS up-regulated the cyclin-dependent kinase inhibitor p16 through an MIS type II receptor-mediated mechanism and inhibited growth in the absence of detectable or inactive Rb protein. Prolonged treatment with MIS down-regulated the Rb-related protein p130 and increased the Rb family-regulated transcription factor E2F1, overexpression of which inhibited growth. These findings demonstrate that p16 is required for MIS-mediated growth inhibition in ovarian epithelial cells and tumor cells and suggest that up-regulation of E2F1 also plays a role in this process. PMID:10958795

Ha, T U; Segev, D L; Barbie, D; Masiakos, P T; Tran, T T; Dombkowski, D; Glander, M; Clarke, T R; Lorenzo, H K; Donahoe, P K; Maheswaran, S

2000-11-24

421

Studies of reversible inhibition, irreversible inhibition, and activation of alkaline phosphatase by capillary electrophoresis.  

PubMed

Reversible inhibition, irreversible inhibition, and activation of calf intestinal alkaline phosphatase (EC 3.1.3.1) have been studied by capillary electrophoresis. The capillary electrophoretic enzyme-inhibitor assays were based on electrophoretic mixing of inhibitor and enzyme zones in a substrate-filled capillary. Enzyme inhibition was indicated by a decrease in product formation detected in the capillary by laser-induced fluorescence. Reversible enzyme inhibitors could be quantified by Michaelis-Menten treatment of the electrophoretic data. Reversible, competitive inhibition of alkaline phosphatase by sodium vanadate and sodium arsenate has been examined, and reversible, noncompetitive inhibition by theophylline has been studied. The K(i) values determined for these reversible inhibitors using capillary electrophoresis are within the range of values reported in the literature for the same enzyme-inhibitor combinations. Irreversible inhibition of alkaline phosphatase by EDTA at concentrations of 1.0mM and above has been observed. Activation of alkaline phosphatase has also been observed for EDTA at concentrations from 20 to 400 microM. PMID:12202238

Whisnant, Angela R; Gilman, S Douglass

2002-08-15

422

Adenovirus-induced inhibition of cellular DNase.  

PubMed Central

During the productive infection of KB cells by adenovirus type 5 (Ad5), there is a progressive decrease in the level of cellular DNase activity towards single-stranded DNA, in contrast to DNA polymerase which remains relatively constant throughout the infection. This decrease is prevented by the inhibition of protein synthesis by cycloheximide. The inhibition of DNase activity does not occur after infection by Ad5 ts125, a DNA-negative mutant which fails to induce the adenovirus-specific DNA binding protein. In contrast, infection by Ad5 ts36, a DNA-negative mutant which complements ts125, does result in decreased levels of DNase. A mechanism is discussed in which the DNA binding protein protects viral replicative intermediates from degradation by cellular DNase.

Nass, K; Frenkel, G D

1978-01-01

423

Carrageenans inhibit growth-factor binding.  

PubMed Central

Carrageenans, a family of polysulphated carbohydrates, inhibited binding of basic fibroblast growth factor (bFGF), transforming growth factor beta 1 (TGF beta 1) and platelet-derived growth factor (PDGF). iota-Carrageenan was the most potent bFGF antagonist (IC50 = 0.4 +/- 0.1 microgram/ml), kappa-carrageenan was the most potent PDGF antagonist (IC50 = 1.7 +/- 1.3 micrograms/ml) and lambda-carrageenan was the most potent TGF beta 1 antagonist (IC50 = 19 +/- 2 micrograms/ml). None of the carrageenans, at concentrations up to 200 micrograms/ml, inhibited binding of insulin-like growth factor 1 or transforming growth factor alpha. Carrageenans are selective growth-factor antagonists and have potential for the treatment of disorders associated with the over-production of certain growth factors.

Hoffman, R

1993-01-01

424

Inhibition of tumor angiogenesis mediated by cartilage  

PubMed Central

Capillary proliferation induced by tumor is shown to be inhibited by neonatal scapular cartilage. Using the rabbit cornea as an assay, the cartilage implant decreased the rate of capillary growth, induced by tumor, by an average of 75%. Vascularization was prevented completely in 28% of tumors. The inhibitory effect of small cartilage implants operates over distances of up to 2.0 mm and displays a gradient from the cartilage source. The experiments suggest that the cartilage inhibitor does not antagonize tumor angiogenesis factor, but appears to inhibit capillary proliferation directly. The inhibitory material does not elicit an inflammatory response in either the rabbit cornea or in the chick chorioallantoic membrane. Thus with further purification, it may prove useful as a means of maintining tumor dormancy by "antiangiogenesis."

1975-01-01

425

Inhibition of Escherichia coli B by Homoarginine  

PubMed Central

Homoarginine inhibits the growth of Escherichia coli B, but not of E. coli K-12. These two strains also differ in regard to repressibility of the arginine-forming enzymes. In K-12, arginine acts as a repressor whereas in B it does not. The latter difference is determined by different alleles of a regulator gene, arg R. In K-12 × B crosses, it was shown that the genetic determinant for homoarginine sensitivity is closely linked to or identical with arg R. Homoarginine-resistant mutants of B were isolated. The biochemical mechanism of homoarginine inhibition is not known. However, whether or not a strain is sensitive to homoarginine seems to depend on the intracellular level of arginine. In B this level is relatively low and inflexible as a result of the action of a repressor whose formation is determined by the B-specific allele of arg R.

Peyru, Graciela M.; Maas, Werner K.

1967-01-01

426

AMPK inhibition in health and disease  

PubMed Central

All living organisms depend on dynamic mechanisms that repeatedly reassess the status of amassed energy, in order to adapt energy supply to demand. The AMP-activated protein kinase (AMPK) ??? heterotrimer has emerged as an important integrator of signals managing energy balance. Control of AMPK activity involves allosteric AMP and ATP regulation, auto-inhibitory features and phosphorylation of its catalytic (?) and regulatory (? and ?) subunits. AMPK has a prominent role not only as a peripheral sensor but also in the central nervous system as a multifunctional metabolic regulator. AMPK represents an ideal second messenger for reporting cellular energy state. For this reason, activated AMPK acts as a protective response to energy stress in numerous systems. However, AMPK inhibition also actively participates in the control of whole body energy homeostasis. In this review, we discuss recent findings that support the role and function of AMPK inhibition under physiological and pathological states.

Viollet, Benoit; Horman, Sandrine; Leclerc, Jocelyne; Lantier, Louise; Foretz, Marc; Billaud, Marc; Giri, Shailendra; Andreelli, Fabrizio

2010-01-01

427

Emotional inhibition: a discourse analysis of disclosure.  

PubMed

Evidence generated within the emotional disclosure paradigm (EDP) suggests that talking or writing about emotional experiences produces health benefits, but recent meta-analyses have questioned its efficacy. Studies within the EDP typically rely upon a unidimensional and relatively unsophisticated notion of emotional inhibition, and tend to use quantitative forms of content analysis to identify associations between percentages of word types and positive or negative health outcomes. In this article, we use a case study to show how a qualitative discourse analysis has the potential to identify more of the complexity linking the disclosure practices and styles that may be associated with emotional inhibition. This may illuminate the apparent lack of evidence for efficacy of the EDP by enabling more comprehensive theorisations of the variations within it. PMID:21678182

Ellis, Darren; Cromby, John

2011-07-07

428

Compartmentalization of GABAergic inhibition by dendritic spines.  

PubMed

?-aminobutyric acid-mediated (GABAergic) inhibition plays a critical role in shaping neuronal activity in the neocortex. Numerous experimental investigations have examined perisomatic inhibitory synapses, which control action potential output from pyramidal neurons. However, most inhibitory synapses in the neocortex are formed onto pyramidal cell dendrites, where theoretical studies suggest they may focally regulate cellular activity. The precision of GABAergic control over dendritic electrical and biochemical signaling is unknown. By using cell type-specific optical stimulation in combination with two-photon calcium (Ca(2+)) imaging, we show that somatostatin-expressing interneurons exert compartmentalized control over postsynaptic Ca(2+) signals within individual dendritic spines. This highly focal inhibitory action is mediated by a subset of GABAergic synapses that directly target spine heads. GABAergic inhibition thus participates in localized control of dendritic electrical and biochemical signaling. PMID:23661763

Chiu, Chiayu Q; Lur, Gyorgy; Morse, Thomas M; Carnevale, Nicholas T; Ellis-Davies, Graham C R; Higley, Michael J

2013-05-10

429

Modified atmosphere packaging inhibits browning in fennel  

Microsoft Academic Search

The effects of modified atmosphere packaging (MAP) to inhibit browning of the butt end cut zone of fennel bulbs stored during 14 days at 0°C followed by complementary air storage during 3 days at 15°C were studied. Selected bulbs were placed in 35?m oriented polypropylene bags or in plastic baskets heat-sealed with nonperforated or perforated (control) polypropylene film. Changes in

V. H Escalona; E Aguayo; P Gómez; F Artés

2004-01-01

430

Inhibition of MXR transport by acridine derivatives  

US Patent & Trademark Office Database

This invention provides methods that are useful for inhibiting a MXR transporter in a cell overexpressing a MXR gene but not overexpressing a Pgp gene by contacting the cell with an acridine derivative. The invention also provides for a method of treating a mammal suffering from a cancer, which overexpressing a MXR gene but not overexpress a Pgp gene, by the co-administration of a chemotherapeutic and an acridine derivative.

2003-02-18

431

Inhibition of lipid oxidation by carnosine  

Microsoft Academic Search

The antioxidant activity of carnosine, a ?-alanine-histidine dipeptide found in skeletal muscle, was investigated. Carnosine\\u000a (25 mM) inhibited the catalysis of lipid oxidation by iron, hemoglobin, lipoxidase and singlet oxygen from 35–96% suggesting\\u000a that the antioxidant mechanism of carnosine is not solely due to metal chelation. Heating the carnosine at 100°C for 15 min\\u000a had no effect on its ability

Eric A. Decker; Habibollah Faraji

1990-01-01

432

Doxycycline-mediated Inhibition of Choroidal Neovascularization  

PubMed Central

Purpose Doxycycline, a broad spectrum antibiotic, has certain anti-angiogenic properties and can inhibit matrix metalloproteinases (MMPs/gelatinases). We investigated the effects of doxycycline on choroidal neovascularization (CNV), and regulation of MMP-2/-9 and pigment epithelium-derived factor (PEDF). Methods Doxycycline was orally administered to rats at 500, 50, 5, and 0.5 mg/kg/day, using non-treated animals as controls. Experimental CNV was induced with laser 7 days after doxycycline treatment started. At seven days post-induction, animals were euthanized, and eyes collected. RPE/choroid flat-mounts were labeled with isolectin IB4 to determine CNV lesion volumes using confocal microscopy and Volocity® software. MMP-2, MMP-9 and PEDF protein levels were determined by ELISA. MMP catalytic activity was determined in solution using fluorogenic gelatin and peptide substrates, by gelatin zymography in SDS-PAGE and by in situ DQ-gelatin zymography in RPE/choroid sections. Results CNV complex lesion volumes decreased with doxycycline in a dose-response relationship. A dosage of 500 mg/kg/day caused a 70% inhibition of CNV complex volume compared to control animals. Doxycycline elevated PEDF levels in plasma, and did not affect the plasma pro- and active MMP-2 and MMP-9 levels. However, the in vitro enzymatic activities of purified MMP-2 and MMP-9 declined significantly with doxycycline. MMP-2, MMP-9 and gelatinolytic activities in situ increased early in CNV lesion development. Doxycycline treatments and exogenous additions inhibited gelatinolytic activities in CNV lesions. Conclusions Doxycycline effectively hampered the progression of experimental CNV. The results suggest that orally administrated doxycycline can reach the choroid to attenuate proteolytic enzymes that remodel Bruch's membrane and promote the anti-angiogenic PEDF to inhibit neovascularization.

Samtani, S.; Amaral, J.; Campos, M.; Fariss, R. N.; Becerra, S. P.

2010-01-01

433

Conformational inhibition of the HCV IRES RNA  

PubMed Central

The internal ribosome entry site (IRES), a highly conserved structured element of the hepatitis C virus genomic RNA, is an attractive target for antiviral drugs. Here we show that benzimidazole inhibitors of the HCV replicon act by conformational induction of a widened interhelical angle in the IRES subdomain IIa which facilitates the undocking of subdomain IIb from the ribosome and ultimately leads to inhibition of IRES-driven translation in HCV-infected cells.

Parsons, Jerod; Castaldi, M. Paola; Dutta, Sanjay; Dibrov, Sergey M.; Wyles, David L.; Hermann, Thomas

2009-01-01