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1

Effect of 8-methoxypsoralen plus long-wave ultraviolet (PUVA) radiation on mast cells. II. In vitro PUVA inhibits degranulation of rat peritoneal mast cells induced by compound 48/80  

SciTech Connect

Rat peritoneal mast cells incubated with a histamine liberator, compound 48/80, showed a significantly reduced capacity for releasing histamine following in vitro treatment with 0.1 micrograms/ml of 8-methoxypsoralen (8-MOP) plus 1-5 J/cm2 of long-wave ultraviolet (UVA) irradiation (PUVA). No remarkable inhibition in histamine release was observed in the cells treated with 8-MOP only. Irradiation with 5 J/cm2 of UVA alone exerted an inhibitory effect on histamine release, to a lesser extent than PUVA. PUVA irradiation did not bring any decrease in cell viability or any spontaneous release of histamine from irradiated cells as shown by phase-contrast microscopy and by histamine assay, respectively. These results suggest that PUVA treatment may cause a noncytotoxic disturbance at mast cell membranes or on surface receptors, leading to a decreased capacity for secreting chemical mediators.

Toda, K.; Danno, K.; Tachibana, T.; Horio, T.

1986-07-01

2

Effect of 8-methoxypsoralen 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  

SciTech Connect

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 microliter) and concanavalin A (Con-A) (2.0 mg/ml), or with a mixture of 5-hydroxytryptamine (5-HT) and histamine as vasodilator (1.0 mg/ml and 50 mM, respectively) were examined with time (2 h-14 days). At each time point, an ear swelling response (ESR) was measured with a dial thickness gauge. The rate of mast cell degranulation and mast cell numbers were assessed by light microscopy using toluidine blue-stained semithin (1 micron) sections. ESR induced by compound 48/80 or Con-A was significantly suppressed dose-dependently (greater than 42% inhibition) by PUVA between 2 h-3 days postirradiation as compared with that in nonirradiated control mice, and the value returned to normal levels by 7-14 days. Compound 48/80- or Con-A-induced mast cell degranulation (%) was remarkably decreased between 2 h-3 days (greater than 48% inhibition) in accordance with the suppression in ESR and it was restored to the rates in nonirradiated controls by 7-14 days. Neither ESR nor percent degranulation was affected by UVA radiation only (less than 3.5 J/cm2) or application of 8-MOP only. 5-HT plus histamine-mediated ESR was not altered at all by PUVA throughout the experimental period. Since PUVA radiation itself at given doses did not produce measurable ESR, mast cell degranulation, or a reduction in mast cell numbers, and since PUVA did not affect a normal vascular response to vasodilator, it seemed that decreased skin reactivity to mast cell degranulators by PUVA might be due to a PUVA-induced noncytolytic alteration in mast cell release mechanisms.

Danno, K.; Toda, K.; Horio, T.

1985-08-01

3

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. PMID:23118592

MacIckova, Tatiana; Svitekova, Klara; Nosal, Radomir

2012-01-01

4

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

5

Degranulation of mast cells and inhibition of the response to secretory agents by phototoxic compounds and ultraviolet radiation  

SciTech Connect

The symptoms of cutaneous phototoxicity from coal tar compounds and the nonsteroidal anti-inflammatory drug benoxaprofen are characterized by wheal and flare formation which is mediated by histamine released from dermal mast cells. Rat serosal mast cells were used as an in vitro model system to study the direct effect of phototoxic compounds on mast cell degranulation. The coal tar compounds studied included acridine and pyrene. Combined exposure of cells to acridine and UVA (320 to 400 nm) radiation caused mast cells to degranulate, as assayed by the release of (/sup 3/H)serotonin. Maximum (/sup 3/H)serotonin release (70 to 80%) was obtained with 50 microM acridine and 300 kJ/m2 UVA. Pyrene (25 microM), when photoexcited with UVB (280 to 360 nm) radiation, caused about 80% release of (/sup 3/H)serotonin. No degranulation occurred with 20 microM benoxaprofen and UVB doses up to 7.2 kJ/m2. Trypan blue staining correlated well with degranulation caused by acridine plus UVA; however, with pyrene plus UVB there was greater (/sup 3/H)serotonin release than dye uptake. Excitation of photosensitizers with doses of UV radiation that did not cause trypan blue staining suppressed degranulation of mast cells in response to chemical stimulation. Acridine, pyrene, and benoxaprofen in the presence of UV radiation inhibited the mast cells from responding to compound 48/80 or the calcium ionophore, chlortetracycline. Two other phototoxic compounds, chlorpromazine and deoxytetracycline, also abolished degranulation by compound 48/80. These findings indicate that phototoxic compounds: (1) cause degranulation in the presence of high doses of UV radiation; and (2) suppress degranulation of mast cells in response to secretory stimuli at doses of UV radiation that do not cause release of mediator.

Gendimenico, G.J.; Kochevar, I.E.

1984-11-01

6

Phenolic constituents isolated from Fragaria ananassa Duch. inhibit antigen-stimulated degranulation through direct inhibition of spleen tyrosine kinase activation.  

PubMed

We isolated eight phenolic constituents from Fragaria ananassa Duch. (strawberry) and determined their structures using 1D, 2D-NMR. Among the isolated compounds, linocinnamarin (LN), 1-O-trans-cinnamoyl-beta-d-glucopyranose (CG), and cinnamic acid (CA) exhibited antigen (Ag)-stimulated degranulation in rat basophilic leukemia RBL-2H3 cells. In order to reveal the underlying mechanisms, we examined the effects of LN and CA on cellular responses induced by antigen stimulation. Treatment with both LN and CA markedly inhibited antigen-stimulated elevation of intracellular free Ca(2+) concentration and reactive oxygen species (ROS). Both LN and CA suppressed Ag-stimulated spleen tyrosine kinase (Syk) activation. These results indicate that inhibition of antigen-stimulated degranulation by LN and CA is mainly due to inactivation of Syk/phospholipase Cgamma (PLCgamma) pathways. Our findings suggest that LN and CA isolated from F. ananassa Duch. (strawberry) could be beneficial agents for alleviating symptoms of type I allergy. PMID:20663674

Ninomiya, Masayuki; Itoh, Tomohiro; Ishikawa, Suguru; Saiki, Miho; Narumiya, Kenji; Yasuda, Masaharu; Koshikawa, Kaneyuki; Nozawa, Yoshinori; Koketsu, Mamoru

2010-08-15

7

Suppression of intracellular calcium levels and inhibition of degranulation in RBL-2H3 mast cells by the sesquiterpene lactone parthenolide.  

PubMed

Pretreatment with parthenolide for 60 min inhibited the antigen-induced degranulation of RBL-2H3 mast cells; the IC(50) value being 4.5 ± 0.4 µM. The inhibition was not due to suppression of the phosphatidylinositol 3-kinase pathway because the antigen-induced phosphorylation of Akt was not inhibited by parthenolide. The antigen-induced increase in intracellular calcium levels was prevented by parthenolide, suggesting that parthenolide inhibited the antigen-induced degranulation by suppressing an increase in intracellular calcium levels. In support of this, parthenolide was found to prevent ionomycin-induced degranulation by inhibiting an increase in intracellular calcium levels. Therefore, parthenolide inhibits the degranulation of mast cells by preventing an increase in intracellular calcium levels. PMID:20814853

Hong, Jangja; Aoyama, Suzue; Hirasawa, Noriyasu; Zee, Okpyo; Ishihara, Kenji; Hashida, Chika; Kimura, Michio; Seyama, Toshio; Ohuchi, Kazuo

2011-02-01

8

Primary Human Airway Epithelial Cell-Dependent Inhibition of Human Lung Mast Cell Degranulation  

PubMed Central

Introduction Chronic mast cell activation is a characteristic feature of asthma. BEAS-2B human airway epithelial cells (AEC) profoundly inhibit both constitutive and IgE-dependent human lung mast cell (HLMC) histamine release. The aim of this study was to examine the regulation of HLMC degranulation by primary AEC from healthy and asthmatic subjects, and investigate further the inhibitory mechanism. Methods HLMC were co-cultured with both BEAS-2B and primary AEC grown as monolayers or air-liquid interface (ALI) cultures. Results Both constitutive and IgE-dependent HLMC histamine release were attenuated by BEAS-2B, primary AEC monolayers and ALI cultures. This occurred in the absence of HLMC-AEC contact indicating the presence of a soluble factor. Unlike healthy ALI AEC, asthmatic ALI-AEC did not significantly reduce constitutive histamine release. AEC inhibitory activity was transferable in primary AEC monolayer supernatant, but less active than with Transwell co-culture, suggesting that the inhibitory factor was labile. The AEC inhibitory effects were attenuated by both AEC wounding and pertussis toxin, indicating the involvement of a G0/Gi receptor coupled mechanism. Solid phase extraction of lipids (<10 kDa) removed the AEC inhibitory activity. The lipid derivatives resolvin D1 and D2 and lipoxin A4 attenuated HLMC histamine release in a dose-dependent fashion but were not detectable in co-culture supernatants. Conclusions Primary AEC suppress HLMC constitutive and IgE-dependent histamine secretion through the release of a soluble, labile lipid mediator(s) that signals through the G0/Gi receptor coupled mechanism. Manipulation of this interaction may have a significant therapeutic role in asthma. PMID:22970103

Martin, Neil; Ruddick, Andrew; Arthur, Greer K.; Wan, Heidi; Woodman, Lucy; Brightling, Christopher E.; Jones, Don J. L.; Pavord, Ian D.; Bradding, Peter

2012-01-01

9

Anthocyanins, but not anthocyanidins, from bilberry (Vaccinium myrtillus L.) alleviate pruritus via inhibition of mast cell degranulation.  

PubMed

We have previously reported that bilberry anthocyanins exhibit an anti-pruritic effect in a mouse model of allergic contact dermatitis. It has been reported that anthocyanins are particularly sensitive to thermal treatment and are easily hydrolyzed to anthocyanidins when exposed to high temperatures. The objective of this study was to compare the anti-pruritic effect of anthocyanin-rich quality-controlled bilberry extract and anthocyanidin-rich degraded extract using a mouse model of allergic contact dermatitis. BALB/c mice with allergic contact dermatitis induced by 4 weeks of repeated application of 2,4,6-trinitro-1-chlorobenzene (TNCB) were administered Bilberon-25 orally for 4 weeks after sensitization with TNCB. The effect of Bilberon-25 on pruritus was evaluated by measurement of scratching behavior. RBL-2H3 mast cells were used to investigate the effect of Bilberon-25 on degranulation in 48/80-stimulated mast cells. Compared with nonheated Bilberon-25, the proportion of anthocyanins in heated Bilberon-25 decreased, and the proportion of anthocyanidins was increased in heated-time dependent manner. Treatment with non-heated Bilberon-25 significantly attenuated the TNCB-induced increase in scratching behavior, whereas treatment with 2 h-heated Bilberon-25 did not. Moreover, 300 ?g/mL nonheated Bilberon-25 showed significant inhibition of degranulation in RBL-2H3 mast cells, whereas 2 h-heated Bilberon-25 had no effect at any concentration studied. It is assumed that the inhibitory effect of bilberry anthocyanins on pruritus might be mediated, at least in part, by its inhibitory effect on mast cell degranulation. In conclusion, the anthocyanin-rich but not anthocyanidin-rich bilberry extract may be a useful dietary supplement for skin diseases involving pruritic symptoms, such as chronic allergic contact dermatitis, atopic dermatitis, and rhinitis. PMID:23164040

Yamaura, Katsunori; Ishiwatari, Makiko; Yamamoto, Masao; Shimada, Maki; Bi, Yuanyuan; Ueno, Koichi

2012-12-01

10

Novel anti-ulcer alpha,beta-unsaturated lactones inhibit compound 48/80-induced mast cell degranulation.  

PubMed

The present study was designed to examine the effects of a sesquiterpene lactone isolated from Artemisia douglasiana Besser (dehydroleucodine), a xanthanolide sesquiterpene isolated from Xanthium cavanillesii Schouw (xanthatin) and a semisynthetic butenolide (3-benzyloxymethyl-5H-furan-2-one) on mast cell degranulation induced by compound 48/80. Peritoneal mast cells from male adult Sprague-Dawley rats were purified in Percoll, preincubated in the presence of test lactones (dehydroleucodine, xanthatin or 3-benzyloxymethyl-5H-furan-2-one) and then challenged with the mast cell activator compound 48/80 (10 microg/ml). Concentration-response and kinetic studies of mast cell serotonin release evoked by compound 48/80, evaluation of mast cell viability and morphology by light and electron microscopy, and comparative studies using ketotifen and sodium chromoglycate were carried out. Serotonin release studies, carried out together with morphological studies, showed the effectiveness of the above lactones to stabilize mast cells. The comparative study with ketotifen and sodium chromoglycate, well known mast cell stabilizers, showed the following order of potency dehydroleucodine=xanthatin>3-benzyloxymethyl-5H-furan-2-one> or =ketotifen/sodium chromoglycate to inhibit mast cell serotonin release induced by compound 48/80. The present study provides the first strong evidence in favour of the hypothesis that dehydroleucodine, xanthatin and 3-benzyloxymethyl-5H-furan-2-one inhibit compound 48/80-induced serotonin release from peritoneal mast cells, acting thus as mast cell stabilizers. Our findings may provide an insight into the design of novel pharmacological agents which may be used to regulate the mast cell response. PMID:19344708

Penissi, Alicia B; Vera, Mariano E; Mariani, María L; Rudolph, María I; Ceńal, Juan P; de Rosas, Juan C; Fogal, Teresa H; Tonn, Carlos E; Favier, Laura S; Giordano, Oscar S; Piezzi, Ramón S

2009-06-10

11

Carcinogenic Risk of Bath PUVA in Comparison to Oral PUVA Therapy  

Microsoft Academic Search

The potential carcinogenic risk of bath PUVA therapy was compared to that of systemic (oral) PUVA. An analysis of the epidemiological data on cancer risk following bath PUVA with trimethylpsoralen does not support the conclusion that bath PUVA per se is less carcinogenic than systemic PUVA with 8-methoxypsoralen (8-MOP). Pharmacokinetic studies indicate that both the concentration of 8-MOP in the

S. E. Shephard; R. G. Panizzon

1999-01-01

12

Polyphenols differentially inhibit degranulation of distinct subsets of vesicles in mast cells by specific interaction with granule-type-dependent SNARE complexes.  

PubMed

Anti-allergic effects of dietary polyphenols were extensively studied in numerous allergic disease models, but the molecular mechanisms of anti-allergic effects by polyphenols remain poorly understood. In the present study, we show that the release of granular cargo molecules, contained in distinct subsets of granules of mast cells, is specifically mediated by two sets of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins, and that various polyphenols differentially inhibit the formation of those SNARE complexes. Expression analysis of RBL-2H3 cells for 11 SNARE genes and a lipid mixing assay of 24 possible combinations of reconstituted SNAREs indicated that the only two active SNARE complexes involved in mast cell degranulation are Syn (syntaxin) 4/SNAP (23 kDa synaptosome-associated protein)-23/VAMP (vesicle-associated membrane protein) 2 and Syn4/SNAP-23/VAMP8. Various polyphenols selectively or commonly interfered with ternary complex formation of these two SNARE complexes, thereby stopping membrane fusion between granules and plasma membrane. This led to the differential effect of polyphenols on degranulation of three distinct subsets of granules. These results suggest the possibility that formation of a variety of SNARE complexes in numerous cell types is controlled by polyphenols which, in turn, might regulate corresponding membrane trafficking. PMID:23252429

Yang, Yoosoo; Oh, Jung-Mi; Heo, Paul; Shin, Jae Yoon; Kong, Byoungjae; Shin, Jonghyeok; Lee, Ji-Chun; Oh, Jeong Su; Park, Kye Won; Lee, Choong Hwan; Shin, Yeon-Kyun; Kweon, Dae-Hyuk

2013-03-15

13

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

14

Photochemotherapy (PUVA) in psoriasis and vitiligo.  

PubMed

Phototherapy with photochemotherapy (PUVA) is a well-known and well-studied modality for the treatment of psoriasis, which involves systemic or topical administration of chemicals known as psoralens and administration of ultraviolet light in increasing dosages after requisite time gap. PUVA is also used in the treatment of widespread vitiligo with moderately good results, though it is being surpassed by ultraviolet B (UVB), which is equally or slightly more efficacious with fewer side effects. PUVA induces repigmentation by varying mechanisms such as stimulation of melanogenesis, immunomodulation and activation of growth factors, though the exact mechanism is still speculative. There are various studies evaluating the efficacy of PUVA in psoriasis as well as in vitiligo, either alone or in combination with other immunosuppressants like azathioprine and calcipotriene. PMID:25382505

Shenoi, Shrutakirthi D; Prabhu, Smitha

2014-01-01

15

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  

SciTech Connect

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/sup +/ channels. Here the authors show that mast cell degranulating (MCD) peptide from bee venom inhibits the binding of /sup 125/I-labeled ..beta..-Butx to chick and rat brain membranes with apparent K/sub i/ values of 180 nM and 1100 nM, respectively. The mechanisms of inhibition of MCD peptide is noncompetitive, as is inhibition of /sup 125/I-..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 Ca/sup 2 +/ by ethylene glycol bis(..beta..-aminoethyl ether)-N,N,N',N'-tetraacetic acid inhibits the binding of /sup 125/I-..beta..-Butx by lowering its affinity to brain membranes.

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

1988-02-09

16

Neutrophil degranulation inhibits potential hydroxyl-radical formation. Relative impact of myeloperoxidase and lactoferrin release on hydroxyl-radical production by iron-supplemented neutrophils assessed by spin-trapping techniques.  

PubMed Central

Hydroxyl radical (.OH) formation by neutrophils in vitro requires exogenous iron. Two recent studies [Britigan, Rosen, Thompson, Chai & Cohen (1986) J. Biol. Chem. 261, 17026-17032; Winterbourn (1987) J. Clin. Invest. 78, 545-550] both reported that neutrophil degranulation could potentially inhibit the formation of .OH, but differed in their conclusions as to the responsible factor, myeloperoxidase (MPO) or lactoferrin (LF). By using a previously developed spin-trapping system which allows specific on-line detection of superoxide anion (O2-) and .OH production, the impact of MPO and LF release on neutrophil .OH production was compared. When iron-diethylenetriaminepenta-acetic acid-supplemented neutrophils were stimulated with phorbol myristate acetate or opsonized zymosan, .OH formation occurred, but terminated prematurely in spite of continued O2- generation. Inhibition of MPO by azide increased the magnitude, but not the duration, of .OH formation. No azide effect was noted when MPO-deficient neutrophils were used. Anti-LF antibody increased both the magnitude and duration of .OH generation. Pretreatment of neutrophils with cytochalasin B to prevent phagosome formation did not alter the relative impact of azide or anti-LF on neutrophil .OH production. An effect of azide or anti-LF on spin-trapped-adduct stability was eliminated as a confounding factor. These data indicate that neutrophils possess two mechanisms for limiting .OH production. Implications for neutrophil-derived oxidant damage are discussed. PMID:2557840

Britigan, B E; Hassett, D J; Rosen, G M; Hamill, D R; Cohen, M S

1989-01-01

17

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

18

The role of activated adenosine receptors in degranulation of human LAD2 mast cells.  

PubMed

Mast cell degranulation triggers hypersensitivity reactions at the body-environment interface. Adenosine modulates degranulation, but enhancement and inhibition have both been reported. Which of four adenosine receptors (ARs) mediate modulation, and how, remains uncertain. Also uncertain is whether adenosine reaches mast cell ARs by autocrine ATP release and ecto-enzymatic conversion. Uncertainties partly reflect species and cell heterogeneity, circumvented here by focusing on homogeneous human LAD2 cells. Quantitative PCR detected expression of A2A, A2B, and A3, but not A1, ARs. Nonselective activation of ARs with increasing NECA monotonically enhanced immunologically or C3a-stimulated degranulation. NECA alone stimulated degranulation slightly. Selective AR antagonists did not affect C3a-stimulated degranulation. NECA's enhancement of C3a-triggered degranulation was partially inhibited by separate application of each selective antagonist, and abolished by simultaneous addition of antagonists to the three ARs. Only the A2A antagonist separately inhibited NECA's enhancement of immunologically stimulated degranulation, which was abolished by simultaneous addition of the three selective antagonists. Immunological or C3a activation did not stimulate ATP release. NECA also enhanced immunologically triggered degranulation of mouse bone marrow derived mast cells (BMMCs), which was partially reduced only by simultaneous addition of the three antagonists or by the nonselective antagonist CGS15943. BMMCs also expressed A2A, A2B, and A3 ARs. but not A1AR detectably. We conclude that (a) A1AR is unnecessary for LAD2 degranulation or AR enhancement; (b) A2A, A2B, and A3 ARs all contribute to pharmacologic AR enhancement of LAD2 and BMMC degranulation; and (c) LAD2 cells depend on microenvironmental adenosine to trigger AR modulation. PMID:24595664

Leung, Chi Ting; Li, Ang; Banerjee, Juni; Gao, Zhan-Guo; Kambayashi, Taku; Jacobson, Kenneth A; Civan, Mortimer M

2014-09-01

19

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. PMID:24086543

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

2013-01-01

20

Human-IgE-induced degranulation of mouse mast cells.  

PubMed

The relations between human IgE and mouse peritoneal mast cells were studied in vitro. Non-heated human IgE sensitizes the mouse mast cells for degranulation on challenge with anti-human IgE. This capacity is lost after heating of human IgE at 56 degrees C. The degranulation only occurs in determined quantitative IgE-anti-IgE relationships, an excess of one or the other reagent inhibiting the reaction. Sensitization is practically instanteneous, and the degranulation is independent on the order of addition of the human IgE and anti-IgE. The human IgE can be removed from mouse peritoneal mast cells by a single washing. The results show that human IgE is unable to bind firmly to mouse peritoneal mast cells in vitro. It seems to induce the formation of biologically active human IgE-anti-human IgE complexes, which act on mouse mast cells and induce their degranulation. PMID:1244207

Wyczolkowska, J; Prouvost-Danon, A

1976-01-01

21

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

22

Mathematical model of laser PUVA psoriasis treatment  

NASA Astrophysics Data System (ADS)

In order to optimize laser PUVA psoriasis treatment we develop the mathematical model of the dynamics of cell processes within epidermis. We consider epidermis as a structure consisting of N cell monolayers. There are four kinds of cells that correspond to four epidermal strata. The different kinds of cells can exist within a given monolayer. We assume that the following cell processes take place: division, death and transition from one stratum to the following. Discrete transition of cells from stratum j to j + 1 approximates to real differentiation.

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

1991-05-01

23

A role for calcineurin in degranulation of murine cytotoxic T lymphocytes.  

PubMed

The immunosuppressive drugs cyclosporin A (CsA) and FK506 bind to distinct families of intracellular proteins, cyclophilins, and FK506 binding proteins (FKBP) respectively, termed immunophilins. Immuno-suppressant-immunophilin complexes bind to and inhibit the activity of calcineurin, a calcium-dependent serine/threonine phosphatase. CsA is known to inhibit degranulation in CTL as assessed by N benzyloxylcarbonyl-L-lysine thiobenzyl ester-esterase release assays. We have investigated whether calcineurin phosphatase activity is involved in this degranulation. Both CsA and FK506 are shown to inhibit N benzyloxylcarbonyl-L-lysine thiobenzyl esteresterase release in murine CTL clones induced either by cognate target or by PMA and the calcium ionophore A23187. Inhibition is concentration dependent and is observed at drug concentrations that specifically inhibit cellular calcineurin. The FK506-binding immunophilin FKBP12, as well as calcineurin, are shown to be present in these cells by immunoblotting analysis. Rapamycin, a macrolide antibiotic thought to compete with FK506 for binding to common FKBP receptor sites, antagonizes the effects of FK506 on both degranulation and calcineurin activity. Neither the degranulation nor the effect of the immunosuppressants is affected by the protein synthesis inhibitor cycloheximide. These observations suggest a role for calcineurin in CTL degranulation. Thus, in addition to its previously described role in lymphokine gene activation, calcineurin also appears to be involved in T cell activation processes which do not require protein synthesis. PMID:7681074

Dutz, J P; Fruman, D A; Burakoff, S J; Bierer, B E

1993-04-01

24

Influence of PUVA and UVB radiation on delayed hypersensitivity in the guinea pig  

SciTech Connect

Exposure of guinea pigs to UVA (320--400 nm) radiation following administration of 8-methoxypsoralen by gavage (referred to by the acronym, PUVA) or exposure to UVB (290--320 nm) radiation, produced suppression of the cutaneous delayed hypersensitivity reaction at the site of exposure to radiation and at distant nonexposed sites. In these experiments, the animals were immunized by injection of dinitrophenyl-bovine gamma-globulin (DNP-BGG) in complete Freund's adjuvant and delayed hypersensitivity responses were provoked by intradermal injections of DNP-BGG, DNP and BGG on the flanks. Exposure to erythemogenic doses of either PUVA or UVB radiation for 7 days prior to immunization and for the 7 days between immunization and challenge (total period of radiation: 14 days) produced inhibiton of responses to each of the test substances. In addition, treatment with erythemogenic doses of PUVA either for 7 days prior to immunization or during the interval between immunization and challenge with DNP-BGG, inhibited the delayed hypersensitivity responses at the site of irradiation and at a nonexposed site. These findings suggest that in vivo exposure to nonionizing radiation leads to both local and systemic alteration of certain immune responses.

Morison, W.L.; Parrish, J.A.; Woehler, M.E.; Krugler, J.I.; Bloch, K.J.

1981-06-01

25

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

26

Induction of E-selectin-dependent leukocyte recruitment by mast cell degranulation in human skin grafts transplanted on SCID mice.  

PubMed Central

Previous in vitro data indicate that degranulation of human mast cells triggers the induction of endothelial molecules important in leukocyte adhesion. In vivo experimental systems have not previously existed, however, to determine whether human mast cell degranulation is sufficient stimulus for leukocyte recruitment. To study this question, neonatal foreskins were transplanted onto immunodeficient mice. The grafts contained physiological numbers of human dermal mast cells that could be degranulated by a number of secretagogues that activate mast cells by different mechanisms. Degranulation was associated with an inflammatory response characterized by edema, up-regulation primarily of microvessel E-selectin, and influx of neutrophils. Leukocyte emigration associated with mast cell degranulation was inhibited by a monoclonal antibody against human E-selectin. These data indicate that degranulation of human mast cells in the human/SCID mouse model provokes cellular inflammation in skin. The ability to significantly inhibit early leukocyte infiltration with an antibody against E-selectin in this model supports the hypothesis that this molecule plays an important role in mast-cell-induced inflammation. Images Figure 1 Figure 2 Figure 4 Figure 6 PMID:8546205

Christofidou-Solomidou, M.; Murphy, G. F.; Albelda, S. M.

1996-01-01

27

Effect of methylmercury on the rat mast cell degranulation  

NASA Astrophysics Data System (ADS)

Methylmercury is the well-known neurotoxicant as weil as a modulator of the immune system. We investigated the effects of MeHg on the rat mast cell degranulation induced by nonimmunological stimuli (the selective liberator of histamine, compound 48/80, and calcium ionophore A23187) both in vivo and in vitro. In 8, 12 and 15 days afterthe final administration of MeHg we observed the suppression of calcium ionophore A23187-and 48/80-induced histamine release, which enhanced with time. In experiments in vitro incubation of peritoneal mast cells with MeHg alone in the dose range 10^{-8} to 10^{-6} did not induce mast cell degranulation, however modified the activation of mast cells by compound 48/80, and calcium ionophore A23187. We observed activation of stimulated secretion by preliminary incubation with low dose of MeHg 10^{-8} M and inhibition by dose of MeHg 10^{-6} M. These results show that MeHg treatment can modify mast cell function in vivo and in vitro and provide insight into the understanding what role this cell has in the pathogenesis of Minamata disease-comlected disorders.

Graevskaya, E. E.; Yasutake, A.; Aramai, R.; Rubin, A. B.

2003-05-01

28

Mathematical modeling for laser PUVA treatment of psoriasis  

NASA Astrophysics Data System (ADS)

The justifaction of method of the laser PUVA (LPUVA) therapy, the description of an UVA therapeutic system, the preliminary results of using the nitrogen gas laser as an UVA source for LPUVA chamber and in some other fields of application in dermatology are given.

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

1991-06-01

29

Effect of Pakistani medicinal plants on IgE/antigen- and ionophore-induced mucosal mast cells degranulation.  

PubMed

Cumulative evidence has now demonstrated the stimulation of mucosal mast cells by both allergic and non-allergic triggers and their inhibition as a potential therapeutic target in many diseases like food allergy and ulcerative colitis. Hence, we screened medicinal plants from Pakistan against antigen- and ionophore-induced degranulation of mucosal mast cells. Aqueous ethanol extracts were screened. IgE/antigen- and A23187-induced degranulation of mucosal-type murine bone marrow derived mast cells (mBMMCs) were screening assays and ?-hexosaminidase released from degranulated mBMMCs was measured. Real time-polymerase chain reaction was employed to examine the expression of TNF-? and IL-4 mRNA. Acetoxychavicol acetate, was examined by degranulation assays and real time-PCR. Among the ten plants screened against IgE/antigen stimulated degranulation, five plants; Alpinia galangal, Mentha arvensis, Myrtus communis, Polygonum bistorta and Syzygium aromaticum demonstrated significant (p<0.01) suppression of the degranulation at 100 ?g/ml. Of them, Alpinia galangal showed significant (p<0.01) inhibition at 32 mg/ml. In A23187-induced degranulation, all plants showed significant (p<0.01) inhibition at 100 ?g/ml except Tamarix dioica. Again Alpinia galangal exhibited significant (p<0.01) suppression at 32 ?g/ml. In a concentration dependent assay, Alpinia galangal revealed significant suppression at 10 ?g/ml against A23187-stimulated degranulation. Acetoxychavicol acetate demonstrated significant (p<0.01) inhibition at 3.2 ?M in IgE/antigen-treated cells and at 10 ?M in A23187-treated cells. Furthermore, both Alpinia galangal and acetoxychavicol acetate suppressed the IgE/antigen- and A23187-enhanced mRNA expression of inflammatory cytokines, TNF-a and IL-4, in mBMMCs. Our findings revealed the suppressive effect of Alpinia galangal and acetoxychavicol acetate on degranulation of mBMMCs by allergic and non-allergic stimuli, which can be utilized for future drug development against food allergy or ulcerative colitis. PMID:25016264

Zaidi, Syed Faisal; Kim, Ji-Hyun; Tomoe, Yashiro; Usmanghani, Khan; Kadowaki, Makoto

2014-07-01

30

Detection of Human Papillomavirus DNA in PUVA-Associated Non-Melanoma Skin Cancers  

Microsoft Academic Search

Psoralen and UVA (PUVA) photochemotherapy is associated with a dose-dependent increased risk of nonmelanoma skin cancer in patients treated for psoriasis. Like ultraviolet B radiation, PUVA is both mutagenic and immunosuppressive and may thus act as a complete carcinogen; however, the reversed squamous to basal cell carcinoma ratio (SCC:BCC) in PUVA-treated patients, also seen in immunosuppressed renal transplant recipients, suggests

Catherine A Harwood; Patricia J Spink; T Surentheran; Irene M Leigh; John L M Hawke; Charlotte M Proby; Judith Breuer; Jane M McGregor

1998-01-01

31

Treatment of psoriasis by oral PUVA therapy combined with aromatic retinoid (Ro 10-9359; Tigason).  

PubMed

The authors discuss results observed in 126 patients affected with severe psoriasis covering more than 40% of the whole body area, some of them representing failures of oral photochemotherapy (PUVA). They were treated according to 5 different schedules, 3 of them combining aromatic retinoid Ro 10-9359 (AR) with PUVA therapy. The most effective results were obtained with a schedule entailing initial treatment for a 2-week period with AR only, followed on the 15th day by the adjunction of classic PUVA therapy with progressive daily decrease of AR dosage (schedule C). It was possible to reduce the frequency and duration of PUVA treatments and the amount of energy used although to a lesser degree than described by other authors. Even more important, far longer remissions were obtained than with PUVA therapy alone, even where the ratio of clearing was identical. This combination therapy made it possible to recover over 70% of the complete or relative failures of PUVA monotherapy. Thus the combination of AR + PUVA therapy (RE-PUVA) as in this schedule appears to be the most important improvement ot PUVA since its introduction as a therapy for psoriasis. PMID:7250475

Grupper, C; Berretti, B

1981-01-01

32

Dual regulation of mast cell degranulation through IgE receptor-mediated modulation of M2-type pyruvate kinase.  

PubMed

It was reported that mast cell degranulation is inversely related to the enzymatic activity of M2-type pyruvate kinase (M2PK). This study shows that activation of high-affinity IgE receptor (Fc?RI) evokes a sequential dual regulation of M2PK, i.e., an immediate decrement followed by slow phase increment of enzymatic activities. Changes in the activities of M2PK and mast cell degranulation showed similar time course after antigenic stimulation of Fc?RI. The immediate inhibition of M2PK involved tyrosine phosphorylation, and subsequently led to a cellular accumulation of glycolytic intermediates, including fructose 1,6-biphosphate (FBP), a feedforward activator of M2PK. As the cellular levels of FBP were increased, both the enzymatic acitivity of M2PK and mast cell degranulation slowly returned to near basal levels. A-Raf, when exogenously introduced into RBL-2H3 cells, phosphorylated M2PK on the serine residues, elevated enzyme activities of M2PK, and resulted in the inhibition of degranulation. These results suggest that dual regulation of M2PK which involves the phosphorylation of M2PK and accumulation of a feedforward activator of M2PK plays important roles in the control of mast cell degranulation. PMID:24497038

Zheng, Mei; Cho, Dong-Im; Le, Hang Thi; Cheon, Seung Hoon; Kim, Kyeong-Man

2014-09-01

33

Modulation of basophils' degranulation and allergy-related enzymes by monomeric and dimeric naphthoquinones.  

PubMed

Allergic disorders are characterized by an abnormal immune response towards non-infectious substances, being associated with life quality reduction and potential life-threatening reactions. The increasing prevalence of allergic disorders demands for new and effective anti-allergic treatments. Here we test the anti-allergic potential of monomeric (juglone, menadione, naphthazarin, plumbagin) and dimeric (diospyrin and diosquinone) naphthoquinones. Inhibition of RBL-2H3 rat basophils' degranulation by naphthoquinones was assessed using two complementary stimuli: IgE/antigen and calcium ionophore A23187. Additionally, we tested for the inhibition of leukotrienes production in IgE/antigen-stimulated cells, and studied hyaluronidase and lipoxidase inhibition by naphthoquinones in cell-free assays. Naphthazarin (0.1 µM) decreased degranulation induced by IgE/antigen but not A23187, suggesting a mechanism upstream of the calcium increase, unlike diospyrin (10 µM) that reduced degranulation in A23187-stimulated cells. Naphthoquinones were weak hyaluronidase inhibitors, but all inhibited soybean lipoxidase with the most lipophilic diospyrin, diosquinone and menadione being the most potent, thus suggesting a mechanism of competition with natural lipophilic substrates. Menadione was the only naphthoquinone reducing leukotriene C4 production, with a maximal effect at 5 µM. This work expands the current knowledge on the biological properties of naphthoquinones, highlighting naphthazarin, diospyrin and menadione as potential lead compounds for structural modification in the process of improving and developing novel anti-allergic drugs. PMID:24587235

Pinho, Brígida R; Sousa, Carla; Valentăo, Patrícia; Oliveira, Jorge M A; Andrade, Paula B

2014-01-01

34

Modulation of Basophils' Degranulation and Allergy-Related Enzymes by Monomeric and Dimeric Naphthoquinones  

PubMed Central

Allergic disorders are characterized by an abnormal immune response towards non-infectious substances, being associated with life quality reduction and potential life-threatening reactions. The increasing prevalence of allergic disorders demands for new and effective anti-allergic treatments. Here we test the anti-allergic potential of monomeric (juglone, menadione, naphthazarin, plumbagin) and dimeric (diospyrin and diosquinone) naphthoquinones. Inhibition of RBL-2H3 rat basophils' degranulation by naphthoquinones was assessed using two complementary stimuli: IgE/antigen and calcium ionophore A23187. Additionally, we tested for the inhibition of leukotrienes production in IgE/antigen-stimulated cells, and studied hyaluronidase and lipoxidase inhibition by naphthoquinones in cell-free assays. Naphthazarin (0.1 µM) decreased degranulation induced by IgE/antigen but not A23187, suggesting a mechanism upstream of the calcium increase, unlike diospyrin (10 µM) that reduced degranulation in A23187-stimulated cells. Naphthoquinones were weak hyaluronidase inhibitors, but all inhibited soybean lipoxidase with the most lipophilic diospyrin, diosquinone and menadione being the most potent, thus suggesting a mechanism of competition with natural lipophilic substrates. Menadione was the only naphthoquinone reducing leukotriene C4 production, with a maximal effect at 5 µM. This work expands the current knowledge on the biological properties of naphthoquinones, highlighting naphthazarin, diospyrin and menadione as potential lead compounds for structural modification in the process of improving and developing novel anti-allergic drugs. PMID:24587235

Pinho, Brigida R.; Sousa, Carla; Valentao, Patricia; Oliveira, Jorge M. A.; Andrade, Paula B.

2014-01-01

35

Negative Regulation of Fc?RI-mediated Degranulation by CD81  

PubMed Central

Signaling through the high affinity receptor for immunoglobulin E (Fc?RI) results in the coordinate activation of tyrosine kinases before calcium mobilization. Receptors capable of interfering with the signaling of antigen receptors, such as Fc?RI, recruit tyrosine and inositol phosphatases that results in diminished calcium mobilization. Here, we show that antibodies recognizing CD81 inhibit Fc?RI-mediated mast cell degranulation but, surprisingly, without affecting aggregation-dependent tyrosine phosphorylation, calcium mobilization, or leukotriene synthesis. Furthermore, CD81 antibodies also inhibit mast cell degranulation in vivo as measured by reduced passive cutaneous anaphylaxis responses. These results reveal an unsuspected calcium-independent pathway of antigen receptor regulation, which is accessible to engagement by membrane proteins and on which novel therapeutic approaches to allergic diseases could be based. PMID:9334370

Fleming, Tony J.; Donnadieu, Emmanuel; Song, Chang Ho; Laethem, Francois Van; Galli, Stephen J.; Kinet, Jean-Pierre

1997-01-01

36

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

37

Granulocytes without Degranulation: Neutrophil Function in Granule-Depleted Cytoplasts  

Microsoft Academic Search

Neutrophils respond to a variety of stimuli by generating superoxide anion, degranulating, and aggregating. Because it has been suggested that fusion of granules with the plasmalemma (degranulation) is necessary for aggregation and superoxide anion generation, we have tested whether these responses can be demonstrated in ``neutrophilic cytoplasts'' (granule-free vesicles of cytoplasm enclosed by plasmalemma). When examined by electron microscopy, cytoplasts

H. M. Korchak; D. Roos; K. N. Giedd; E. M. Wynkoop; K. Vienne; L. E. Rutherford; J. P. Buyon; A. M. Rich; G. Weissmann

1983-01-01

38

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. PMID:22343473

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

2012-01-01

39

Anti-degranulating activity in rat basophil leukemia RBL-2H3 cells of flavanone glycosides and their aglycones in citrus fruits.  

PubMed

The anti-degranulating activity of flavonoids present in Citrus fruits was comprehensively evaluated. Among these, hesperetin and naringenin, respectively aglycones of hesperidin and narirutin, showed significant activity. The targets of hesperetin and naringenin were found: hesperetin inhibited phosphorylation of Syk and Akt, while naringenin suppressed the expression of Lyn and inhibited the phosphorylation of Akt. These results suggest that hesperetin and naringenin inhibit degranulation by suppression of pathway signals and reduce the symptoms of allergy by inhibiting phosphorylation of Akt, which leads to the suppression of cytokines. In addition, hesperetin showed inhibitory activity against the degranulation induced by calcium ionophores, indicating that hesperetin exerts its inhibitory activity by stabilizing the membrane structure. PMID:22903244

Murata, Kazuya; Takano, Seiya; Masuda, Megumi; Iinuma, Munekazu; Matsuda, Hideaki

2013-07-01

40

hsa-miR-4516 mediated downregulation of STAT3/CDK6/UBE2N plays a role in PUVA induced apoptosis in keratinocytes.  

PubMed

Psoriasis is a chronic inflammatory skin disorder mediated by cross-talk occurring between epidermal keratinocytes, dermal vascular cells and immunocytes. Literature reveals that Signal transducer and activator of transcription 3 (STAT3), a protein involved in transmitting extracellular signals to the nucleus, is a possible important link between keratinocytes and immunocytes and is crucial to the development of psoriasis. Although photochemotherapy using UV in combination with 8 methoxypsoralen is one of the most effective therapy for moderate to severe plaque psoriasis, its mechanism of action is largely unknown. Herein, we studied the change in miRNA profiles of cultured human keratinocytes (HaCaT cells) before and after in vitro PUVA treatment by 8 methoxypsoralen and found significant up regulation of hsa-miR-4516. We for the first time demonstrate that ectopic expression of hsa-miR-4516 directly targets STAT3 protein by binding to its 3'UTR in HaCaT cells as confirmed by Luciferase reporter assays and Western blot analysis. We further show that overexpression of hsa-miR-4516 downregulates STAT3, p-STAT3, CDK6, and UBE2N proteins that are consistently upregulated in psoriasis and induces apoptosis in HaCaT cells. We also observed that anti-miR-4516 treatment was able to partially inhibit PUVA-induced apoptosis, suggesting that miR-4516 is involved in PUVA-induced apoptosis. Taken together, these results not only indicate the mechanistic involvement of hsa-miR-4516 in PUVA mediated effects by down-regulating STAT3 in HaCaT keratinocytes, but also highlight the potential of hsa-miR-4516 in development of novel therapeutic strategies. J. Cell. Physiol. 229: 1630-1638, 2014. © 2014 Wiley Periodicals, Inc. PMID:24610393

Chowdhari, Shruti; Saini, Neeru

2014-11-01

41

Induction of an auto-anti-IgE response in rats. IV. Effects on mast cell degranulation.  

PubMed Central

Induction of an auto-anti-IgE (auto-aIgE) response in the rat inhibits both total and specific IgE production and alters the distribution of mast cell (MC) subpopulations identified by differential Alcian blue/safranin staining. We have extended these observations by characterizing the auto-aIgE antibodies and determining their effects on MC degranulation in vitro and in vivo. An auto-aIgE response was induced in bacillus Calmette-Guérin (BCG)-primed rats by injecting a conjugate of highly purified rat IgE myeloma (IR2) coupled to tuberculin-derived purified protein derivative (PPD). Anti-IgE autoantibodies were almost exclusively IgG2a. The intradermal injection of auto-aIgE into untreated rats induced local MC degranulation as shown by a strong immediate skin response. Histologically there was evidence of significant degranulation of safranin staining connective tissue MC (SMC) in the skin but not of the Alcian blue staining MC (ABMC) in the sub-epidermal region. The induced degranulation was epsilon-chain specific; immunopurified anti-idiotypic antibodies raised to the IgE IR2 myeloma had no MC degranulating activity. When administered locally, auto-aIgE inhibited a subsequent passive cutaneous anaphylaxis (PCA) response elicited by anti-ovalbumin IgE. In addition, the PCA response was significantly decreased in animals with an ongoing auto-aIgE response. Immunopurified auto-aIgE also induced histamine release in vitro from rat peritoneal MC. These results are discussed in the context of naturally occurring autoantibodies to IgE present in patients with allergic disease. Images Figure 3 PMID:7684359

Jaffery, G; Bell, E B; Coleman, J W

1993-01-01

42

Induction of an auto-anti-IgE response in rats. IV. Effects on mast cell degranulation.  

PubMed

Induction of an auto-anti-IgE (auto-aIgE) response in the rat inhibits both total and specific IgE production and alters the distribution of mast cell (MC) subpopulations identified by differential Alcian blue/safranin staining. We have extended these observations by characterizing the auto-aIgE antibodies and determining their effects on MC degranulation in vitro and in vivo. An auto-aIgE response was induced in bacillus Calmette-Guérin (BCG)-primed rats by injecting a conjugate of highly purified rat IgE myeloma (IR2) coupled to tuberculin-derived purified protein derivative (PPD). Anti-IgE autoantibodies were almost exclusively IgG2a. The intradermal injection of auto-aIgE into untreated rats induced local MC degranulation as shown by a strong immediate skin response. Histologically there was evidence of significant degranulation of safranin staining connective tissue MC (SMC) in the skin but not of the Alcian blue staining MC (ABMC) in the sub-epidermal region. The induced degranulation was epsilon-chain specific; immunopurified anti-idiotypic antibodies raised to the IgE IR2 myeloma had no MC degranulating activity. When administered locally, auto-aIgE inhibited a subsequent passive cutaneous anaphylaxis (PCA) response elicited by anti-ovalbumin IgE. In addition, the PCA response was significantly decreased in animals with an ongoing auto-aIgE response. Immunopurified auto-aIgE also induced histamine release in vitro from rat peritoneal MC. These results are discussed in the context of naturally occurring autoantibodies to IgE present in patients with allergic disease. PMID:7684359

Jaffery, G; Bell, E B; Coleman, J W

1993-04-01

43

Fyn kinase controls Fc{epsilon}RI receptor-operated calcium entry necessary for full degranulation in mast cells  

SciTech Connect

IgE-antigen-dependent crosslinking of the high affinity IgE receptor (Fc{epsilon}RI) on mast cells leads to degranulation, leukotriene synthesis and cytokine production. Calcium (Ca{sup 2+}) mobilization is a sine qua non requisite for degranulation, allowing the rapid secretion of stored pro-inflammatory mediators responsible for allergy symptoms. Fyn is a Src-family kinase that positively controls Fc{epsilon}RI-induced mast cell degranulation. However, our understanding of the mechanism connecting Fyn activation to secretion of pre-synthesized mediators is very limited. We analyzed Fc{epsilon}RI-dependent Ca{sup 2+} mobilization in bone marrow-derived mast cells (BMMCs) differentiated from WT and Fyn -/- knock out mice. Fyn -/- BMMCs showed a marked defect in extracellular Ca{sup 2+} influx after Fc{epsilon}RI crosslinking but not after thapsigargin addition. High concentrations of Gadolinium (Gd{sup 3+}) partially blocked Fc{epsilon}RI-induced Ca{sup 2+} influx in WT cells but, in contrast, completely inhibited Ca{sup 2+} mobilization in Fyn -/- cells. Low concentrations of an inhibitor of the canonical transient receptor potential (TRPC) Ca{sup 2+} channels (2-aminoethoxyphenyl-borane, 2-APB) blocked Fc{epsilon}RI-induced maximal Ca{sup 2+} rise in WT but not in Fyn -/- cells. Ca{sup 2+} entry through Fyn-controlled, 2-APB sensitive channels was found to be important for full degranulation and IL-2 mRNA accumulation in WT cells. Immunoprecipitation assays showed that Fyn kinase interacts with TRPC 3/6/7 channels after IgE-antigen stimulation, but its association is not related to protein tyrosine phosphorylation. Results indicate Fyn kinase mediates the receptor-dependent activation of TRPC channels that contribute to degranulation in Fc{epsilon}RI-stimulated mast cells.

Sanchez-Miranda, Elizabeth; Ibarra-Sanchez, Alfredo [Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados (Cinvestav), Sede Sur, Calzada de los Tenorios 235, Col. Granjas Coapa, CP 14330 Mexico City (Mexico)] [Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados (Cinvestav), Sede Sur, Calzada de los Tenorios 235, Col. Granjas Coapa, CP 14330 Mexico City (Mexico); Gonzalez-Espinosa, Claudia, E-mail: cgonzal@cinvestav.mx [Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados (Cinvestav), Sede Sur, Calzada de los Tenorios 235, Col. Granjas Coapa, CP 14330 Mexico City (Mexico)] [Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados (Cinvestav), Sede Sur, Calzada de los Tenorios 235, Col. Granjas Coapa, CP 14330 Mexico City (Mexico)

2010-01-22

44

The influence of the sesquiterpene lactones from Geigeria on mast cell degranulation.  

PubMed

The sesquiterpene lactones isolated from Geigeria were found to be incapable of inducing rat peritoneal mast cell degranulation at levels of 0.3-1.6 mM. The sulphydryl reagent, N-ethylmaleimide, too was unable to trigger mast cell secretion. Instead, it was observed that these compounds inhibited the release of histamine induced by Compound 48/80. Pretreatment of the lactones and N-ethylmaleimide with the amino acid, L-cysteine, reduced their inhibition ability of histamine release to a considerable extent, but not completely. Geigerin(V), which lacks an alpha-methylene group and the chemically prepared cysteine-adduct of dihydrogriesenin(I), were also capable of inhibiting mast cell secretion by Compound 48/80, but to a lesser extent. PMID:2440443

Gaspar, A R; Verschoor, J A; Neitz, A W; Vermeulen, N M

1987-08-01

45

Inhibitory effects of thunberginols A, B, and F on degranulations and releases of TNF-alpha and IL-4 in RBL-2H3 cells.  

PubMed

Thunberginols A, B, and F from the processed leaves of Hydrangea macrophylla var. thunbergii (Hydrangeae Dulcis Folium) substantially inhibited the degranulations by antigen and calcium ionophore A23187, and the releases of TNF-alpha and IL-4 by antigen in RBL-2H3 cells. Phyllodulcin and hydrangenol also showed significant inhibition for the antigen-induced degranulations, but their effects were weaker than those of thunberginols A, B, and F. Among them, thunberginol B showed the most potent activity. With regard to structural requirements of thunberginols for the activity, the 3,4-double bond was essential for the strong activity and the 6-hydroxyl group and lactone ring enhanced the activity. Thunberginols A, B, and F inhibited increase in intracellular free Ca2+ levels, which is an essential process for the degranulation and production of cytokines, in RBL-2H3 cells induced by antigen, but not by calcium ionophore A23187. These results suggested that these active compounds inhibited the degranulation processes both before and after increase in intracellular free Ca2+ levels. PMID:17268088

Wang, Qilong; Matsuda, Hisashi; Matsuhira, Koudai; Nakamura, Seikou; Yuan, Dan; Yoshikawa, Masayuki

2007-02-01

46

Galectin-9 Enhances Cytokine Secretion, but Suppresses Survival and Degranulation, in Human Mast Cell Line  

PubMed Central

Galectin-9 (Gal-9), a lectin having a ?-galactoside-binding domain, can induce apoptosis of Th1 cells by binding to TIM-3. In addition, Gal-9 inhibits IgE/Ag-mediated degranulation of mast cell/basophilic cell lines by binding to IgE, thus blocking IgE/Ag complex formation. However, the role of Gal-9 in mast cell function in the absence of IgE is not fully understood. Here, we found that recombinant Gal-9 directly induced phosphorylation of Erk1/2 but not p38 MAPK in a human mast cell line, HMC-1, which does not express Fc?RI. Gal-9 induced apoptosis and inhibited PMA/ionomycin-mediated degranulation of HMC-1 cells. On the other hand, Gal-9 induced cytokine and/or chemokine production by HMC-1 cells, dependent on activation of ERK1/2 but not p38 MAPK. In addition, the lectin activity of Gal-9 was required for Gal-9-mediated cytokine secretion by HMC-1 cells. These observations suggest that Gal-9 has dual properties as both a regulator and an activator of mast cells. PMID:24465902

Iikura, Motoyasu; Niki, Toshiro; Hirashima, Mitsuomi; Iwaya, Keichi; Tsuda, Hitoshi; Nonoyama, Shigeaki; Matsuda, Akio; Saito, Hirohisa; Matsumoto, Kenji; Nakae, Susumu

2014-01-01

47

Moxibustion activates mast cell degranulation at the ST25 in rats with colitis  

PubMed Central

AIM: To investigate the effects of moxibustion on the morphology and function of mast cells (MC) at Tianshu (ST25) in rats with trinitro-benzene-sulfonic acid (TNBS)-induced colitis. METHODS: A total of 53 male Sprague-Dawley rats were randomly divided into a normal group and experimental group. In the experimental group, a rat model of TNBS-induced colitis was established, and the rats were then randomly divided into a model group, moxibustion group, moxibustion plus disodium cromoglycate (M + DC) group and moxibustion plus normal saline (M + NS) group. Rats in the moxibustion group received suspended moxibustion at bilateral ST25 for 10 min, once a day for 7 d. Rats in the M + DC and M + NS groups were pretreated with disodium cromoglycate and normal saline at bilateral ST25, respectively, and were then concurrently subjected to the same treatment as rats in the moxibustion group. The hematoxylin-eosin staining method was used to observe histology of the colon and the toluidine blue-improved method was used to observe mast cells at ST25 acupoint areas. RESULTS: An improvement in colonic injury in the moxibustion group was observed and the degranulation ratio of MC at ST25 acupoint was markedly higher in the moxibustion group than in the model group (45.91 ± 11.41 vs 32.58 ± 8.28, P < 0.05). After inhibition of degranulation of MC at ST25 by disodium cromoglycate, no improvement in colon tissue injury was observed. CONCLUSION: Moxibustion exerted its effect on healing impaired colonic mucosa in rats with TNBS-induced colitis by increasing the degranulation ratio of local MC, but had little effect on the morphology of MC at ST25 acupoint. PMID:21990955

Shi, Yin; Qi, Li; Wang, Jing; Xu, Ming-Shu; Zhang, Dan; Wu, Lu-Yi; Wu, Huan-Gan

2011-01-01

48

6Thioguanine Resistant Peripheral Blood Lymphocytes in Humans Following Psoralen, Long-Wave Ultraviolet Light (PUVA) Therapy  

Microsoft Academic Search

A recently described method that enumerates variant 6-thioguanine resistant peripheral blood lymphocytes present in vivo in man as a potential marker of somatic cell mutations occurring in vivo was used to study 18 psoriatic patients receiving PUVA therapy, 10 conventinally treated psoriatic patients, 10 vitiligo patients receiving PUVA therapy and 7 untreated individuals with vitiligo. Variant lymphocyte frequencies determined for

Gary H. Strauss; Richard J. Albertini; Paul A. Krusinski; Richard D. Baughman

1979-01-01

49

Effect of a single UVB or PUVA exposure on immediate and delayed skin hypersensitivity reactions in humans  

Microsoft Academic Search

A single UVB or PUVA exposure given 4 days prior to skin testing affected skin responses both to contact allergens and to histamine and the histamine liberator, compound 48\\/80. The delayed contact hypersensitivity reactions were attenuated by UVB in 75% and by PUVA in 79% of the tests. The immediate skin reactions to histamine and compound 48\\/80 were diminished by

K. Kalimo; L. Koulu; C. T. Jansén

1983-01-01

50

Changes in neutrophil surface-receptor expression after stimulation with FMLP, endotoxin, interleukin-8 and activated complement compared to degranulation.  

PubMed

Neutrophil activation induces changes in the expression of surface receptors and may lead to degranulation. Surface expression of beta2-integrins, l-selectin, complement receptor 1 (CR-1), decay-accelerating factor (DAF), C5a receptor, intercellular adhesion molecule-1 (ICAM-1) and ICAM-3 was compared by flow cytometry on isolated neutrophils stimulated with phorbol 12-myristate 13-acetate (PMA), N-formyl-methionyl-leucyl-phenylalanine (FMLP), endotoxin or interleukin-8 and on neutrophils in whole blood anti-coagulated with the thrombin inhibitor lepirudin and stimulated with cobra venom factor to induce complement activation. Myeloperoxidase and lactoferrin in the supernatants were quantified in enzyme immunoassays. With high enough doses, all stimulants induced significant upregulation of beta2-integrins, CR-1 and DAF and downregulation of l-selectin. ICAM-3 was either unchanged or somewhat downregulated. Only FMLP and PMA induced significant upregulation of ICAM-1. Combined measurement of beta2-integrins and l-selectin permitted graded evaluation of early neutrophil activation. Measurement of degranulation showed no differences compared to unstimulated controls due to substantial spontaneous degranulation of isolated neutrophils by rewarming from 4 degrees C and incubation at 37 degrees C. Spontaneous activation was less in ethylenediaminetetraacetic acid-anti-coagulated blood, but calcium chelation may also inhibit the stimulated responses. There was large activation of unstimulated neutrophils in lepirudin-anti-coagulated blood at 37 degrees C, obscuring changes induced by stimulation, which may render this anti-coagulant unsuitable for studies of neutrophils. PMID:14723618

Videm, V; Strand, E

2004-01-01

51

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

52

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

53

Oral Psoralen and Ultraviolet-A Light (PUVA) Treatment of Psoriasis and Persistent Risk of Nonmelanoma Skin Cancer  

Microsoft Academic Search

Background\\/Methods: The treatment of psoriasis with high- dose exposure to oral psoralen and ultraviolet-A light (i.e., PUVA) substantially increases the risk of cutaneous squa- mous cell cancer, but not of basal cell cancer, within a decade of beginning treatment. To assess the persistence of cancer risk among individuals treated with PUVA, including those who discontinued therapy long ago and those

Robert S. Stern; Elissa J. Liebman

54

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

55

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

56

Influence of PUVA and UVB Radiation on Delayed Hypersensitivity in the Guinea Pig  

Microsoft Academic Search

Exposure of guinea pigs to UVA (320–400 nm) radiation following administration of 8-methoxypsoralen by gavage (referred to by the acronym, PUVA) or exposure to UVB (290–320 nm) radiation, produced suppression of the cutaneous delayed hypersensitivity reaction at the site of exposure to radiation and at distant nonexposed sites. In these experiments, the animals were immunized by injection of dinitrophenyl-bovine gamma-globulin

Warwick L. Morison; John A. Parrish; Michael E. Woehler; Joel I. Krugler; Kurt J. Bloch

1981-01-01

57

Psoralen plus ultraviolet A (PUVA) soaks and UVB TL01 treatment for chronic hand dermatoses  

PubMed Central

Chronic eczematous hand dermatoses with and without contact allergies are complex diseases, which makes it a challenge to select the best treatment and obtain an optimal patient experience and a satisfactory treatment result. The aim of this study was to evaluate retrospectively the clinical effect and patient experience of local treatment with psoralen plus ultraviolet A (PUVA) soaks and TL01 phototherapy for severe chronic hand dermatoses, and also to evaluate the quality of life for the subgroup of patients with allergic contact dermatitis including Compositae allergy. A retrospective evaluation of results for 94 consecutive patients having received a total of 121 treatment courses with local PUVA soaks or TL01 phototherapy for one of the following diagnoses (n=number of treatment courses): psoriasis (n=19), hyperk-eratotic hand eczema (n=27), Pustulosis Palmoplantaris (PPP) (n=22), vesicular eczema (n=16), Compositae dermatitis (n=24), and allergic contact dermatitis (n=13). Moreover, semi-structured interviews with 6 selected patients having multiple contact allergies including Compositae allergy were used to evaluate quality of life. As a result, we found that PUVA soaks has good effect in patients with psoriasis and hyperkeratotic hand eczema and local phototherapy for chronic hand dermatoses is a useful treatment option in selected cases. PMID:25386313

Jensen, Lisbeth; Stensgaard, Anette; Andersen, Klaus Ejner

2012-01-01

58

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

59

Impact of Actin Rearrangement and Degranulation on the Membrane Structure of Primary Mast Cells: A Combined Atomic Force and Laser  

E-print Network

Impact of Actin Rearrangement and Degranulation on the Membrane Structure of Primary Mast Cells Research, Santa Barbara, California ABSTRACT Degranulation of bone marrow-derived mast cells (BMMCs). In the case of mast cells, degranulation is also implicated in membrane morphological changes (10

Liu, Gang-yu

60

Increased Degranulation of Natural Killer Cells during Acute HCV Correlates with the Magnitude of Virus-specific T cell Responses  

PubMed Central

Background/Aims Natural killer (NK) cells provide early defense against viral infections by killing infected cells and producing cytokines that inhibit viral replication. NK cells also interact with dendritic cells (DCs) and this reciprocal interaction regulates both innate and adaptive immunity. Genetic studies have suggested that NK cell activity is a determinant of HCV infectious outcome but a functional correlation was not established. We hypothesized that increased NK cell activity during acute HCV infection will correlate with spontaneous viral clearance. Methods We used multiparametric flow cytometry to monitor longitudinally the phenotype and activity of NK cells in a cohort of intravenous drug users following HCV exposure. Three groups were studied: acute HCV with chronic evolution (n=13); acute resolving HCV (n=11); and exposed un-infected individuals (n=10). We examined the expression of several NK cell activating and inhibitory receptors, IFN-? production and CD107a degranulation upon stimulation and the kinetics of NK cell responses relative to T cell responses. Results We observed decreased expression of the inhibitory NKG2A receptor on NK cells following spontaneous HCV clearance. In addition, we’ve observed increased NK cell degranulation during acute HCV irrespective of infectious outcome. NK cells peak responses preceded or coincided with peak T cell responses. Furthermore, NK cell degranulation correlated with the magnitude of HCV-specific T cells. Conclusions Our results demonstrate that NK cells are activated during acute HCV regardless of infection outcome and may play an indirect role through induction and priming of T cell responses. PMID:20688412

Pelletier, Sandy; Drouin, Christian; Bedard, Nathalie; Khakoo, Salim I.; Bruneau, Julie; Shoukry, Naglaa H.

2014-01-01

61

Emodin attenuates A23187-induced mast cell degranulation and tumor necrosis factor-? secretion through protein kinase C and I?B kinase 2 signaling.  

PubMed

Mast cells are known to play a pivotal role in allergic diseases. Cross-linking of the high-affinity IgE receptor (Fc?RI) is known to be one of the major causes that lead to degranulation and allergic inflammation. An increase in intracellular calcium (Ca(2+)) concentration also triggers degranulation, bypassing receptor activation. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is known to exhibit a variety of pharmacological activities including anti-allergic effects. However, the detailed molecular mechanisms involved in exhibiting anti-allergic effects by emodin were remained to be clarified. In the present investigation we report the regulatory function of emodin on the allergic signal mediators through Ca(2+) ionophore activation in mast cells. Emodin significantly inhibited A23187-induced tumor necrosis factor-? production and degranulation through the attenuation of protein kinase C, I?B kinase 2, and soluble N-ethylmaleimide-sensitive fusion factor attachment protein receptor complex formation, bypassing Fc?RI activation. Data from our study indicated that emodin acts by regulating multiple signaling pathways in inhibiting the allergic reactions in mast cells. PMID:24239713

Kim, Dong-Young; Kang, Tae-Bong; Shim, Do-Wan; Sun, Xiao; Han, Ji-Won; Ji, Young-Eun; Kim, Tack-Joong; Koppula, Sushruta; Lee, Kwang-Ho

2014-01-15

62

IgE-induced degranulation of mucosal mast cells is negatively regulated via nicotinic acetylcholine receptors.  

PubMed

The autonomic nervous system is known to mediate mast cell activation. We investigated expression of nicotinic acetylcholine receptors (nAChRs) in mucosal-type mast cells and their contribution to the regulation of mast cell activation. Expression of mRNA of nAChR alpha4, alpha7, and beta2 subunits were detected in specially differentiated mucosal-type murine bone marrow-derived mast cells (mBMMCs). Pretreatment with non-specific nAChRs agonists, acetylcholine, nicotine and epibatidine and a specific alpha7 subunit agonist GTS-21 significantly inhibited antigen-induced degranulation of mBMMCs in a dose-dependent manner and GTS-21-induced inhibition was significantly blocked by alpha7 subunit antagonist, alpha-bungarotoxin. Furthermore, confocal microscopy also demonstrated surface binding of alpha-bungarotoxin on mBMMCs. Our findings indicate that mucosal mast cell activation may be negatively regulated mainly through nAChR alpha7 subunit, suggesting that nAChRs are involved in neuronal-mucosal mast cell interactions. PMID:18848921

Kageyama-Yahara, Natsuko; Suehiro, Yoko; Yamamoto, Takeshi; Kadowaki, Makoto

2008-12-01

63

Mast cell degranulation prior to ischemia decreases ischemia-reperfusion injury in the canine small intestine  

Microsoft Academic Search

Objective: To determine the impact of previous mast cell degranulation on intestinal ischemia-reperfusion-induced mucosal damaged.¶Materials: The hemodynamic and morphological consequences of complete arterial occlusion were evaluated in anesthetized dogs. The mast cell degranulator Cremophor-El (n=5) and Compound 48\\/80 (n=5) were used to investigate the involvement of gastrointestinal mast cells in ischemia-reperfusion-induced tissue reactions. Seven dogs subjected to complete segmental arterial

M. Boros; J. Kaszaki; B. ÖrdÖgh; S. Nagy

1999-01-01

64

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

65

Studies on the Specific Degranulation of Mast Cell Sensitized by Several Allergens in Vitro  

PubMed Central

Food allergy is a major health issue worldwide. Mast cells play a very important role in the immediate hypersensitivity for which mast cell degranulation needs to be studied extensively. In this study, an approach was taken to study the characteristics of sensitized mast cell degranulation in vitro, which associated with the study of mast cells and animal models. BALB/c mice were immunized respectively by several food allergens, then blood and peritoneal mast cells were collected at different time points. A dynamic determination was carried out between mast cells and serumal IgE. Comparative analysis on sequential time points showed that there was a close coincidence between mast cell degranulation and IgE antibody titers in sensitized BALB/c mice. Furthermore, it is interesting that sensitized mast cells could implement specific degranulation against the challenges in vitro, but the closely tropomyosins induced mast cell degranulation displayed cross reactions. This is very similar to IgE resisting the allergens in vivo. The study disclosed some characteristics on mast cells, coming from sensitized BALB/c mice, degranulation in vitro. PMID:19403066

Guo, Yongchao; Li, Zhenxing; Lin, Hong; Samee, Haider; Khalid, Jamil

2009-01-01

66

Differential analysis of experimental hypermelanosis induced by UVB, PUVA, and allergic contact dermatitis using a brownish guinea pig model  

Microsoft Academic Search

In moderately colored guinea-pig skin, UVB, PUVA, and allergic contact dermatitis were shown to induce hyperpigmentation that resembled the pigmentary changes observed in mongoloid human skin. Using this model, we examined the effects of chemical agents, including tyrosinase inhibitors and sunscreen agents, on the color changes induced by UV irradiation. The daily exposure of brownish guinea-pig skin to UVB irradiation

G. Imokawa; M. Kawai; Y. Mishima; I. Motegi

1986-01-01

67

Suppressive effects of carotenoids on the antigen-induced degranulation in RBL-2H3 rat basophilic leukemia cells.  

PubMed

In this study, the anti-degranulation effects of fifteen carotenoids were evaluated using RBL-2H3 rat basophilic leukemia cell line as a mast cell model. Nine carotenoids, fucoxanthin, zeaxanthin, ?-carotene, astaxanthin, 3-hydroxyechinenone, fucoxanthinol, lycopene, ?-cryptoxanthin, and siphonaxanthin significantly suppressed antigen-induced mast cell degranulation. Under the same conditions, the cellular carotenoid contents were quantified using high performance liquid chromatography-photodiode array (HPLC-PDA). There was no correlation between the cellular carotenoid contents and their anti-degranulation activities. These results indicate that the differences in the anti-degranulation activities of carotenoids were not related to their uptake by the cells. PMID:24492380

Manabe, Yuki; Hirata, Takashi; Sugawara, Tatsuya

2014-01-01

68

Flow microfluorometric analysis of phagocyte degranulation in bacteria-infected whole human blood cell cultures  

NASA Astrophysics Data System (ADS)

A quantitative flow microfluorometric method was used to study the intensity of human blood phagocyte degranulation in response to viable staphylococcus aureus or Yersinia pestis cells. Microorganisms were added directly to defibrinated whole blood. Uninfected and infected blood samples were incubated at 37 degrees C to 8 h. The results were recorded in dynamics after the staining of whole blood with acridine orange solution. Lymphocytes with a low azurophilic granule per cell content were discriminated from phagocytes by the measurement of single cell red cytoplasmic granule fluorescence. 30,000 cells in each sample were examined. S. aureus cells caused a dose-dependent decrease in the number of phagocytes having a high red cytoplasmic fluorescence intensity and a corresponding increase in the weakly fluorescence cell population. In the presence of an initial S. aureus-to-phagocyte ratio more than 1:1, degranulation was measured after 3 h of incubation and to 8 h the percentage of degranulated phagocytes was at least 100 percent Y. pestis cells grown for 48 h at 28 degrees C caused at same condition as the degranulation only about 50 percent of cells. Y.pestis EV cells preincubated in broth for 12 h at 37 degrees C did no stimulate the phahocyte degranulation. The results of these studies suggest that analysis of cell populations via flow microfluorimeter technology may be a powerful tool in analysis bacterial infection.

Kravtsov, Alexander L.; Bobyleva, Elena V.; Grebenyukova, Tatyana P.; Kuznetsov, Oleg S.; Kulyash, Youri V.

2002-07-01

69

Induction of Paneth cell degranulation by orally administered Toll-like receptor ligands.  

PubMed

The secretory activity of Paneth cells is related to the bacterial milieu in the small intestine; however, the molecules involved in inducing Paneth cell secretion of enzymes and antimicrobial peptides are not well-defined. Mice treated orally with CpG-oligodeoxynucleotide (ODN), an agonist of Toll-like receptor (TLR) 9, showed rapid and massive Paneth cell degranulation. CpG-ODN-induced degranulation was not observed in TLR9(-/-) mice or in chimeric TLR9(-/-) mice reconstituted with wild-type (WT) bone marrow, but was observed in WT mice reconstituted with TLR9(-/-) bone marrow, indicating a role for TLR9-expressing gastrointestinal cells in CpG recognition. The TLR3 agonist polyinosinic-polycytidylic acid also induced rapid degranulation, whereas the TLR4 and TLR5 agonists LPS and flagellin, respectively, induced late degranulation mediated by TNF-?. Our evidence that TLR9 and TLR3 agonists induce Paneth cell degranulation points to the need for further studies of the mechanisms underlying Paneth cell function as an avenue toward preventing infection and treating inflammatory bowel diseases. PMID:21567398

Rumio, Cristiano; Sommariva, Michele; Sfondrini, Lucia; Palazzo, Marco; Morelli, Daniele; Viganň, Laura; De Cecco, Loris; Tagliabue, Elda; Balsari, Andrea

2012-03-01

70

Hypohalous acid-modified human serum albumin induces neutrophil NADPH oxidase activation, degranulation, and shape change.  

PubMed

Halogenated lipids, proteins, and lipoproteins formed in reactions with myeloperoxidase (MPO)-derived hypochlorous acid (HOCl) and hypobromous acid (HOBr) can contribute to the regulation of functional activity of cells and serve as mediators of inflammation. Human serum albumin (HSA) is the major plasma protein target of hypohalous acids. This study was performed to assess the potency of HSA modified by HOCl (HSA-Cl) and HOBr (HSA-Br) to elicit selected neutrophil responses. HSA-Cl/Br were found to induce neutrophil degranulation, generation of reactive oxygen intermediates, shape change, and actin cytoskeleton reorganization. Thus HSA-Cl/Br can initially act as a switch and then as a feeder of the "inflammatory loop" under oxidative stress. In HSA-Cl/Br-treated neutrophils, monoclonal antibodies against CD18, the ? subunit of ?2 integrins, reduced the production of superoxide anion radicals and hydrogen peroxide as well as MPO exocytosis, suggesting that CD18 contributed to neutrophil activation. HSA-Cl/Br-induced neutrophil responses were also inhibited by genistein, a broad-specificity tyrosine kinase inhibitor, and wortmannin, a phosphoinositide 3-kinase (PI3K) inhibitor, supporting the notion that activation of both tyrosine kinase and PI3K may play a role in neutrophil activation by HSA modified in MPO-dependent reactions. These results confirm the hypothesis that halogenated molecules formed in vivo via MPO-dependent reactions can be considered as a new class of biologically active substances potentially able to contribute to activation of myeloid cells in sites of inflammation and serve as inflammatory response modulators. PMID:24384524

Gorudko, Irina V; Grigorieva, Daria V; Shamova, Ekaterina V; Kostevich, Valeria A; Sokolov, Alexey V; Mikhalchik, Elena V; Cherenkevich, Sergey N; Arnhold, Jürgen; Panasenko, Oleg M

2014-03-01

71

Technical report: effects of PUVA treatment on the optical properties of blood/tissue storage bags during extracorporeal photochemotherapy.  

PubMed

Extracorporeal photochemotherapy (photopheresis, ECP) is a novel therapeutic method for patients who do not respond to immunosuppressive medications, and gaining interest in the treatment of Graft-vs-Host Disease. This paper is focused on the optical transmission properties of plastic bags which can be used in an independent (off-line) method of ECP, and reports the results of spectral measurements on various bags of different chemical compositions, with and without PUVA treatment. Regarding their higher and more uniform UVA transmission values, FEP based bags perform superior to the others. Considering its UVB absorption and UVA transmission properties, the EVA bag is a good choice, while Polyimide Kapton-FEP plastic film should not be considered for use in ECP. PUVA treatment of blood bags may affect their optical behaviour, and causes reduction of transmission of the material in UV range of the spectrum. PMID:17962078

Keskin, Ali Umit

2007-10-01

72

Ultrastructural Modification of the Plasma Membrane in HUT 102 Lymphoblasts by Long-Wave Ultraviolet Light, Psoralen, and PUVA  

Microsoft Academic Search

Ultrastructural alterations of the plasma membrane in HUT 102 lymphoblasts were assessed after a 2-h interaction with a suprapharmacologic (15 ?\\/m1) concentration of 8-MOP, 2-h irradiation with UVA (2.1 mW\\/cm2), and the exposure of the HUT 102 cells to PUVA under the same conditions.The dark reaction of HUT cells with 8-MOP resulted in the disappearance of microvilli, the emergence of

George I. Malinin; Hilda K. Lo; Francis J. Hornicek; Theodore I. Malinin

1990-01-01

73

Phosphorylation of SNAP-23 by I?B Kinase 2 Regulates Mast Cell Degranulation  

PubMed Central

SUMMARY Mast cells are known to play a pivotal role in allergic diseases. Cross-linking of the high-affinity receptor for IgE (Fc?RI) leads to degranulation and allergic inflammation; however, the regulatory mechanisms of IgE-dependent exocytosis remain unknown. We show here that I?B kinase (IKK) 2 in mast cells plays critical roles in IgE-mediated anaphylaxis in vivo, and IgE-mediated degranulation in vitro, in an NF-kB-independent manner. Upon Fc?RI stimulation, IKK2 phosphorylates SNAP-23, the target membrane soluble N-ethylmaleimide-sensitive fusion factor attachment protein receptor (SNARE), and ectopic expression of a phosphomimetic mutant of SNAP-23 partially rescued the impaired IgE-mediated degranulation in IKK2-deficient mast cells. These results suggest that IKK2 phosphorylation of SNAP-23 leads to degranulation and anaphylactic reactions. While this reaction is NF-kB-independent, we additionally show that IKK2 also regulates late-phase allergic reactions promoted by the release of proinflammatory cytokines in an NF-kB-dependent manner. The findings suggest that IKK2 is a central player in allergic reactions. PMID:18692471

Suzuki, Kotaro; Verma, Inder M.

2008-01-01

74

The role of SHIP in mast cell degranulation and IgE-induced mast cell survival  

Microsoft Academic Search

Atopic disorders are on the increase in the Western world and are due, at least in part, to an overactive mast cell response. A better understanding of the intracellular signalling pathways that regulate both mast cell degranulation and the secretion of arachidonic acid metabolites and inflammatory cytokines could help in the treatment of these disorders. The src homology 2-containing inositol-polyphosphate

Michael Huber; Janet Kalesnikoff; Michael Reth; Gerald Krystal

2002-01-01

75

Administration of 8-methoxypsoralen and ultraviolet A irradiation (PUVA) induces turnover of mast cells in the skin of C57BL/6 mice.  

PubMed

Administration of 8-methoxypsoralen followed by ultraviolet A irradiation (PUVA treatment) has been used as a therapy for urticaria pigmentosa. The effect of PUVA treatment on cutaneous mast cells in mice was investigated by using giant granules of mast cells from C57BL/6-bgJ/bgJ (Chediak-Higashi syndrome) mice as a marker. C57BL/6-(+)/+ mice were lethally irradiated and rescued by bone marrow transplantation from C57BL/6-bgJ/bgJ mice. In the radiation chimeras, mast cells in the skin were of +/+ type and mast-cell precursors migrating in the bloodstream were bgJ/bgJ. When PUVA treatment was applied to the skin of the radiation chimeras, the total number of mast cells continued to decrease until the third week after the treatment and then recovered to pre-treatment levels. The initial reduction was attributed to the decrease of +/(+)-type mast cells, and the subsequent recovery to be as a result of the increase of bgJ/bgJ-type mast cells. This observation may explain the fact that the therapeutic effect of PUVA treatment is transient. Symptoms of urticaria pigmentosa become manifest after the cessation of PUVA treatment probably because new mast cells differentiate from bone marrow-derived precursors. PMID:2384693

Toyota, N; Kitamura, Y; Ogawa, K

1990-09-01

76

Norepinephrine-induced cardiac hypertrophy and fibrosis are not due to mast cell degranulation.  

PubMed

The norepinephrine (NE)-induced hypertrophy of the left ventricle (LV) in the rat is preceded by increased interleukin (IL)-6 expression and associated with LV fibrosis. We have examined whether the elevated level of IL-6 may be due to mast cell degranulation. Therefore we tested the effect of cromoglycate sodium salt (cromolyn), an inhibitor of mast cell degranulation with anti-inflammatory and membrane-stabilizing activity, on the increased expression of IL-6 mRNA and of mRNAs of proteins involved in the remodelling of the extracellular matrix (ECM) which is induced by NE (0.1 mg/kg x h). After 4 h, the NE-induced increase in IL-6 mRNA expression was not influenced by cromolyn (20 mg/kg x h). Cromolyn-infusion for 3 days did not affect the extent of LV hypertrophy induced by NE, as measured by the LV weight/body weight (LVW/BW) ratio and by atrial natriuretic peptide (ANP) expression. Cromolyn induced a slight depression of the NE-induced elevation of the matrix metalloproteinase (MMP)-2. However, it did not affect the NE-induced elevated levels of mRNAs of collagen I and III and the tissue inhibitor of matrix metalloproteinase (TIMP)-2. Since cromolyn did not reduce the NE-effects in rat hearts in vivo we conclude that mast cell degranulation seems not to be involved in them. PMID:14577597

Briest, Wilfried; Rassler, Beate; Deten, Alexander; Zimmer, Heinz-Gerd

2003-10-01

77

Central role of mitochondria and p53 in PUVA-induced apoptosis in human keratinocytes cell line NCTC-2544  

SciTech Connect

Despite strong evidence concerning the high efficiency of PUVA therapy (psoralen plus UVA light), its mechanism of action has not yet been fully elucidated. In this study, we have evaluated in a cell line of human keratinocytes (NCTC-2544) the effects of two linear psoralen derivatives, 8-methoxypsoralen (8-MOP) and 5-methoxypsoralen (5-MOP), that are widely used in PUVA therapy and two angular derivatives, Angelicin (ANG) and 4,6,4'-trymetyl angelicin (TMA). All derivatives photoinduce cellular death, TMA being the most active compound. The cell cycle analysis showed that the four derivatives induce, 24 h after irradiation, a cell cycle arrest in G1 phase later followed by massive apoptosis. The G1 arrest is correlated to an increase in the expression of p21{sup Waf1/Cip1}, a protein associated with the cell cycle block and apoptosis. Furthermore, treatment of NCTC-2544 resulted in p53 activation by 5-MOP, 8-MOP, and ANG but not TMA and its phosphorylation at serine-15. The levels of p21{sup Waf1/Cip1} paralleled p53 protein staining pattern suggesting that p53 activation correlated with p21{sup Waf1/Cip1} induction. Simultaneous to p53 activation, psoralens induced mitochondrial depolarization, cytochrome c release, mitochondrial production of reactive oxygen species, as well as caspase-3 and -9 activation. Thus these results strongly indicate the necessity of p53 activation and the induction of the apoptotic machinery downstream of mitochondria.

Viola, Giampietro [Department of Pharmaceutical Sciences, University of Padova, Via Marzolo 5, 35131 Padova (Italy)], E-mail: giampietro.viola.1@unipd.it; Fortunato, Elena; Cecconet, Laura; Del Giudice, Laura [Department of Pediatrics, University of Padova, via Giustiniani 3, Padova (Italy); Dall'Acqua, Francesco [Department of Pharmaceutical Sciences, University of Padova, Via Marzolo 5, 35131 Padova (Italy); Basso, Giuseppe [Department of Pediatrics, University of Padova, via Giustiniani 3, Padova (Italy)

2008-02-15

78

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. PMID:15380024

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

2004-01-01

79

Inhibitory effects of flavonoids isolated from Fragaria ananassa Duch on IgE-mediated degranulation in rat basophilic leukemia RBL-2H3  

Microsoft Academic Search

We isolated the 4 kinds of flavonoids from strawberry ‘Nohime’ and examined the effect of these flavonoids on the degranulation in RBL-2H3 cells. The flavonoids were found to suppress the degranulation from Ag-stimulated RBL-2H3 cells to different extents. To disclose the inhibitory mechanism of degranulation by flavonoids, we examined their effects on the intracellular free Ca2+ concentration ([Ca2+]i) and the

Tomohiro Itoh; Masayuki Ninomiya; Masaharu Yasuda; Kaneyuki Koshikawa; Yoshihiro Deyashiki; Yoshinori Nozawa; Yukihiro Akao; Mamoru Koketsu

2009-01-01

80

Evaluation of PUVA-Induced Skin Side Effects in Patients Referred to the Imam Reza Hospital of Mashhad in 2005-2007  

PubMed Central

Background: Systemic oral psoralens plus UVA therapy (PUVA) is a therapeutic method used with considerable success in many different skin disorders. PUVA therapy causes some cutaneous and noncutaneous side effects and in the present research we deal with cutaneous side effects. Aims: Evaluation of patients to know the different skin side effects of PUVA and their importance. Materials and Methods: All patients referred to the phototherapy unit of Imam Reza Hospital of Mashhad entered the research and skin examination was taken place initially and every 3 months thereafter. Whenever any side effect appeared, it was recorded in the information sheet. Results: One hundred and twenty-eight patients were included in the research, 61 were male between 15 and 75 years and 67 were female between 10 and 61 years of age. Age of female patients at the time of cutaneous side effect appearance was less than male patients. The most common early side effect was pruritus (34.3%) and the rarest was telangiectasia (0.7%). One case of late side effect in the form of squamous cell carcinoma was observed in a patient who had received other carcinogenic drugs as well. Complications such as skin dryness, pruritus, erythema and burning sensation occurred at low doses of UVA, while dermatitis, severe limb pain and acne at moderate doses and PUVA lentigines, hypertrichosis and lichenoid lesions appeared at high doses of UVA. Conclusion: Considering the significant therapeutic effects and few serious side effects, PUVA therapy is a suitable and safe method for treatment of certain skin diseases. PMID:24700955

Maleki, Masoud; Yazdanpanah, Mohammad Javad; Hamidi, Hamid; Jokar, Leila

2014-01-01

81

Inhibitory effects of water-soluble low-molecular-weight ?-(1,3-1,6) D-glucan isolated from Aureobasidium pullulans 1A1 strain black yeast on mast cell degranulation and passive cutaneous anaphylaxis.  

PubMed

We investigated the effects of water-soluble low-molecular-weight ?-(1,3-1,6) D-glucan isolated from Aureobasidium pullulans 1A1 strain black yeast (LMW-?-glucan) on mast cell-mediated anaphylactic reactions. Although it is known that LMW-?-glucan has anti-tumor, anti-metastatic and anti-stress effects, the roles of LMW-?-glucan in immediate-type allergic reactions have not been fully investigated. We examined whether LMW-?-glucan could inhibit mast cell degranulation and passive cutaneous anaphylaxis (PCA). LMW-?-glucan dose-dependently inhibited the degranulation of both rat basophilic leukemia (RBL-2H3) and cultured mast cells (CMCs) activated by calcium ionophore A23187 or IgE. However, LMW-?-glucan had no cytotoxicity towards RBL-2H3 cells and CMCs. Furthermore, orally administered LMW-?-glucan inhibited the IgE-induced PCA reaction in mice. These results show LMW-?-glucan to be a possible compound for the effective therapeutic treatment of allergic diseases. PMID:22232243

Sato, Harumi; Kobayashi, Yuko; Hattori, Atsushi; Suzuki, Toshio; Shigekawa, Munekazu; Jippo, Tomoko

2012-01-01

82

Study of cell degranulation with simultaneous microscope imaging and capillary electrophoresis  

SciTech Connect

The physical release of single granules from individual rat peritoneal mast cells (RPMCs) was monitored by video recording of the degranulating cells by a high-resolution charge-coupled device (CCD) microscope system. The bright granular core disappears from the image as the vesicular content is dissolved on contact with the extra-cellular fluid. After a fixed time delay, the exocytotic product, serotonin, was detected by capillary electrophoresis coupled with laser-induced native fluorescence (LINF-CE). The timing of the two events is mostly correlated, which supports a fast release mechanism of the granular products. {copyright} {ital 1999} {ital Society for Applied Spectroscopy}

Su, H.; Yeung, E.S. [Ames Laboratory-USDOE and Department of Chemistry, Iowa State University, Ames, Iowa 50011 (United States)] [Ames Laboratory-USDOE and Department of Chemistry, Iowa State University, Ames, Iowa 50011 (United States)

1999-07-01

83

The circulating proteinase inhibitor ?-1 antitrypsin regulates neutrophil degranulation and autoimmunity.  

PubMed

Pathological inflammation and autoimmune disease frequently involve elevated neutrophil activity in the absence of infectious agents. Tumor necrosis factor-? (TNF-?) contributes to many of the problems associated with autoimmune diseases. We investigated the ability of serum ?-1 antitrypsin (AAT) to control TNF-? biosynthesis and signaling in neutrophils and assessed whether AAT deficiency (AATD) is a TNF-?-related disease. In vitro studies demonstrate that serum AAT coordinates TNF-? intracellular signaling and neutrophil degranulation of tertiary and secondary granules via modulation of ligand-receptor interactions. AATD patients homozygous for the Z allele were characterized by increased activation of the TNF-? system, as demonstrated by increased membrane TNF-? levels and increased plasma concentrations of TNF receptor 1 and neutrophil-released secondary and tertiary granule proteins. The incidence of autoantibodies directed against degranulated lactoferrin and surface protein accessible to these antibodies was increased in ZZ-AATD, leading to an enhanced rate of neutrophil reactive oxygen species production. Treatment of ZZ-AATD individuals with AAT augmentation therapy resulted in decreased membrane TNF-? expression and plasma levels of granule antigenic proteins and immunoglobulin G class autoantibodies. These results provide a mechanism by which AAT augmentation therapy affects TNF-? signaling in the circulating neutrophil, indicating promising potential of this therapy for other TNF-?-related diseases. PMID:24382893

Bergin, David A; Reeves, Emer P; Hurley, Killian; Wolfe, Rebecca; Jameel, Ramia; Fitzgerald, Sean; McElvaney, Noel G

2014-01-01

84

The use of fractal dimension and lacunarity in the characterization of mast cell degranulation in rainbow trout (Onchorhynchus mykiss).  

PubMed

Fractal analysis is a reliable method for describing, summarizing object complexity and heterogeneity and has been widely used in biology and medicine to deal with scale, size and shape management problems. The aim of present survey was to use fractal analysis as a complexity measure to characterize mast cells (MCs) degranulation in a rainbow trout ex vivo model (isolated organ bath). Compound 48/80, a condensation product of N-methyl-p-methoxyphenethylamine with formaldehyde, was adopted as MCs degranulation agent in trout intestinal strips. Fractal dimension (D), as a measure of complexity, 'roughness' and lacunarity (?), as a measure of rotational and translational invariance, heterogeneity, in other words, of the texture, were compared in MCs images taken from intestinal strips before and after compound 48/80 addition to evaluate if and how they were affected by degranulation. Such measures were also adopted to evaluate their discrimination efficacy between compound 48/80 degranulated group and not degranulated group and the results were compared with previously reported data obtained with conventional texture analysis (image histogram, run-length matrix, co-occurrence matrix, autoregressive model, wavelet transform) on the same experimental material. Outlines, skeletons and original greyscale images were fractal analysed to evaluate possible significant differences in the measures values according to the analysed feature. In particular, and considering outline and skeleton as analysed features, fractal dimensions from compound 48/80 treated intestinal strips were significantly higher than the corresponding untreated ones (paired t and Wilcoxon test, p < 0.05), whereas corresponding lacunarity values were significantly lower (paired Wilcoxon test, p < 0.05) but only for outline as analysed feature. Outlines roughness increase is consistent with an increased granular mediators interface, favourable for their biological action; while lacunarity (image heterogeneity) reduction is consistent with the biological informative content decrease, due to granule content depletion. In spite of the significant differences in fractal dimension and lacunarity values registered according to the analysed feature (greyscale obtained values were, on average, lower than those obtained from outlines and skeletons; General Linear Model, p < 0.01), the discrimination power between not degranulated and degranulated MCs was, on average, the same and fully comparable with previously performed texture analysis on the same experimental material (outline and skeleton misclassification error, 20% [two false negative cases]; greyscale misclassification error, 30% [two false negative cases and one false positive case]). Fractal analysis proved to be a reliable and objective method for the characterization of MCs degranulation. PMID:25087582

Manera, M; Dezfuli, B S; Borreca, C; Giari, L

2014-11-01

85

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

86

Defective chemiluminescence response in differentiated HL60 cells due to impaired degranulation.  

PubMed

In the presence of dimethyl sulfoxide, the promyelocytic leukemic cell line, HL60, differentiates into apparently mature polymorphonuclear leukocytes. When correlating the superoxide production from HL60 cells with the number of phagocytozing and NBT-positive cells, no difference was observed in comparison with normal peripheral blood leukocytes. In contrast, the luminol-dependent chemiluminescence was greatly impaired in the differentiated HL60 cells. Analysis of degranulation, i.e., release of myeloperoxidase and N-acetyl-beta-glucosaminidase- and myeloperoxidase-mediated iodination by HL60 cells, suggested that the defective chemiluminescence response observed in HL60 cells may be due to impaired release of myeloperoxidase from azurophilic granulae. This may lead to impaired microbicidal activity in these cells. PMID:3008851

Stendahl, O; Andersson, T; Dahlgren, C; Magnusson, K E

1986-05-01

87

Isoallergen variations contribute to the overall complexity of effector cell degranulation: effect mediated through differentiated IgE affinity.  

PubMed

Most allergens exist in several variants (isoallergens), each of which may be recognized differently by patient IgE. We have previously shown that several properties of the IgE repertoire, including IgE affinity and IgE clonality, are important factors determining degranulation responses of effector cells involved in type I allergic reactions. However, less is known about how the repertoire of naturally occurring isoallergens may affect this response. Thus, in this study, we investigated how individual rIgE Ab clones derived from a human subject are able to distinguish among variants of Der p 2 isoallergens and assessed the impact on basophil degranulation. Biacore analyses showed that individual rIgE clones cloned from an individual allergic to house dust mites recognized Der p 2 with binding affinities varying up to 100-fold between different Der p 2 isoforms. In a well-defined biological system consisting of human basophils sensitized with low rIgE clonality, degranulation responses were directly related to rIgE affinity toward particular rDer p 2 isoallergens. However, basophils sensitized with polyclonal patients' sera showed no differences in degranulation responses toward the different rDer p 2 isoallergens. In conclusion, our study shows that individual IgE Abs are able to bind single allergens with a broad range of affinities due to natural isoallergen variations, contributing further to the overall complexity of IgE-allergen interactions at the effector cell surface, which is, however, blurred by the polyclonal nature of patients' IgE repertoires. PMID:20348423

Christensen, Lars H; Riise, Erik; Bang, Laerke; Zhang, Chunqing; Lund, Kaare

2010-05-01

88

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. PMID:20571036

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

2010-01-01

89

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

PubMed Central

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.

2011-01-01

90

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

2011-08-01

91

A neutrophil intrinsic impairment affecting Rab27a and degranulation in cystic fibrosis is corrected by CFTR potentiator therapy.  

PubMed

Studies have endeavored to reconcile whether dysfunction of neutrophils in people with cystic fibrosis (CF) is a result of the genetic defect or is secondary due to infection and inflammation. In this study, we illustrate that disrupted function of the CF transmembrane conductance regulator (CFTR), such as that which occurs in patients with ?F508 and/or G551D mutations, correlates with impaired degranulation of antimicrobial proteins. We demonstrate that CF blood neutrophils release less secondary and tertiary granule components compared with control cells and that activation of the low-molecular-mass GTP-binding protein Rab27a, involved in the regulation of granule trafficking, is defective. The mechanism leading to impaired degranulation involves altered ion homeostasis caused by defective CFTR function with increased cytosolic levels of chloride and sodium, yet decreased magnesium measured in CF neutrophils. Decreased magnesium concentration in vivo and in vitro resulted in significantly decreased levels of GTP-bound Rab27a. Treatment of G551D patients with the ion channel potentiator ivacaftor resulted in normalized neutrophil cytosolic ion levels and activation of Rab27a, thereby leading to increased degranulation and bacterial killing. Our results confirm that intrinsic alterations of circulating neutrophils from patients with CF are corrected by ivacaftor, thus illustrating additional clinical benefits for CFTR modulator therapy. PMID:24934256

Pohl, Kerstin; Hayes, Elaine; Keenan, Joanne; Henry, Michael; Meleady, Paula; Molloy, Kevin; Jundi, Bakr; Bergin, David A; McCarthy, Cormac; McElvaney, Oliver J; White, Michelle M; Clynes, Martin; Reeves, Emer P; McElvaney, Noel G

2014-08-14

92

A neutrophil intrinsic impairment affecting Rab27a and degranulation in cystic fibrosis is corrected by CFTR potentiator therapy  

PubMed Central

Studies have endeavored to reconcile whether dysfunction of neutrophils in people with cystic fibrosis (CF) is a result of the genetic defect or is secondary due to infection and inflammation. In this study, we illustrate that disrupted function of the CF transmembrane conductance regulator (CFTR), such as that which occurs in patients with ?F508 and/or G551D mutations, correlates with impaired degranulation of antimicrobial proteins. We demonstrate that CF blood neutrophils release less secondary and tertiary granule components compared with control cells and that activation of the low-molecular-mass GTP-binding protein Rab27a, involved in the regulation of granule trafficking, is defective. The mechanism leading to impaired degranulation involves altered ion homeostasis caused by defective CFTR function with increased cytosolic levels of chloride and sodium, yet decreased magnesium measured in CF neutrophils. Decreased magnesium concentration in vivo and in vitro resulted in significantly decreased levels of GTP-bound Rab27a. Treatment of G551D patients with the ion channel potentiator ivacaftor resulted in normalized neutrophil cytosolic ion levels and activation of Rab27a, thereby leading to increased degranulation and bacterial killing. Our results confirm that intrinsic alterations of circulating neutrophils from patients with CF are corrected by ivacaftor, thus illustrating additional clinical benefits for CFTR modulator therapy. PMID:24934256

Pohl, Kerstin; Hayes, Elaine; Keenan, Joanne; Henry, Michael; Meleady, Paula; Molloy, Kevin; Jundi, Bakr; Bergin, David A.; McCarthy, Cormac; McElvaney, Oliver J.; White, Michelle M.; Clynes, Martin; McElvaney, Noel G.

2014-01-01

93

Two modes of lytic granule fusion during degranulation by natural killer cells  

PubMed Central

Lytic granules in cytotoxic lymphocytes, which include T cells and natural killer (NK) cells, are secretory lysosomes that release their content upon fusion with the plasma membrane (PM), a process known as degranulation. Although vesicle exocytosis has been extensively studied in endocrine and neuronal cells, much less is known about the fusion of lytic granules in cytotoxic lymphocytes. Here, we used total internal reflection fluorescence microscopy to examine lytic granules labeled with fluorescently tagged Fas ligand (FasL) in the NK cell line NKL stimulated with phorbol ester and ionomycin and in primary NK cells activated by physiological receptor–ligand interactions. Two fusion modes were observed: complete fusion, characterized by loss of granule content and rapid diffusion of FasL at the PM; and incomplete fusion, characterized by transient fusion pore opening and retention of FasL at the fusion site. The pH-sensitive green fluorescence protein (pHluorin) fused to the lumenal domain of FasL was used to visualize fusion pore opening with a time resolution of 30?ms. Upon incomplete fusion, pHluorin emission lasted several seconds in the absence of noticeable diffusion. Thus, we conclude that lytic granules in NK cells undergo both complete and incomplete fusion with the PM, and propose that incomplete fusion may promote efficient recycling of lytic granule membrane after the release of cytotoxic effector molecules. PMID:21483445

Liu, Dongfang; Martina, Jose A; Wu, Xufeng S; Hammer III, John A; Long, Eric O

2011-01-01

94

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

PubMed

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. PMID:24689187

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

2013-06-01

95

DOCK5 functions as a key signaling adaptor that links Fc?RI signals to microtubule dynamics during mast cell degranulation.  

PubMed

Mast cells play a key role in the induction of anaphylaxis, a life-threatening IgE-dependent allergic reaction, by secreting chemical mediators that are stored in secretory granules. Degranulation of mast cells is triggered by aggregation of the high-affinity IgE receptor, Fc?RI, and involves dynamic rearrangement of microtubules. Although much is known about proximal signals downstream of Fc?RI, the distal signaling events controlling microtubule dynamics remain elusive. Here we report that DOCK5, an atypical guanine nucleotide exchange factor (GEF) for Rac, is essential for mast cell degranulation. As such, we found that DOCK5-deficient mice exhibit resistance to systemic and cutaneous anaphylaxis. The Rac GEF activity of DOCK5 is surprisingly not required for mast cell degranulation. Instead, DOCK5 associated with Nck2 and Akt to regulate microtubule dynamics through phosphorylation and inactivation of GSK3?. When DOCK5-Nck2-Akt interactions were disrupted, microtubule formation and degranulation response were severely impaired. Our results thus identify DOCK5 as a key signaling adaptor that orchestrates remodeling of the microtubule network essential for mast cell degranulation. PMID:24913231

Ogawa, Kana; Tanaka, Yoshihiko; Uruno, Takehito; Duan, Xuefeng; Harada, Yosuke; Sanematsu, Fumiyuki; Yamamura, Kazuhiko; Terasawa, Masao; Nishikimi, Akihiko; Côté, Jean-François; Fukui, Yoshinori

2014-06-30

96

Synthesis of 3-substituted isocoumarins and their inhibitory effects on degranulation of RBL-2H3 cells induced by antigen.  

PubMed

Eleven 3-substituted isocoumarins and a benzylidenephthalide were synthesized through thermal cyclization reaction of delta- and gamma-ketoamides, respectively. Subsequent deprotection of the hydroxyl groups of the resulting isocoumarin and benzylidenephthalide compounds afforded thunberginols A, B, and F, respectively, which originated from the processed leaves of Hydrangea macrophylla SERINGE var. thunbergii MAKINO. The synthesized isocoumarins and thunberginols were evaluated for their anti-allergic activity, in which thunberginol B exhibited the highest inhibitory potency on the degranulation of RBL-2H3 cells induced by antigen. Structure-activity relationship studies were carried out to determine the necessary substituents on the 3-phenylisocoumarin skeleton for inhibitory activity. PMID:18758098

Kurume, Ai; Kamata, Yasuhiro; Yamashita, Masayuki; Wang, Qilong; Matsuda, Hisashi; Yoshikawa, Masayuki; Kawasaki, Ikuo; Ohta, Shunsaku

2008-09-01

97

The effects of endothelin-1 on degranulation, cytokine, and growth factor production by skin-derived mast cells.  

PubMed

Endothelin-1 (ET-1), originally described as a vasoconstrictor, is now known to be involved in pathogenesis of various disorders including vascular, inflammatory, and fibrotic diseases. Recent studies suggest that mast cells are also involved in the same pathological conditions. In this study, we tested a hypothesis that ET-1 would affect mast cell functions and contribute to such disease conditions, using fetal skin-derived cultured mast cells (FSMC) and bone marrow-derived cultured mast cells (BMMC). FSMC expressed ET receptors (ET(A) and ET(B)) at mRNA and protein levels, whereas BMMC expressed lower levels of ET(A), and little, if any, ET(B). ET-1 induced degranulation by FSMC, but not by BMMC through ET(A)-mediated pathways. ET-1 at different concentrations exerted the reciprocal effects on degranulation by IgE-bound FSMC. Furthermore, ET-1 induced TNF-alpha and IL-6 production by FSMC, but not by BMMC, and significantly enhanced VEGF production and TGF-beta1 mRNA expression by FSMC. Finally, ET-1 was produced by FSMC, but not by BMMC in response to Toll-like receptor ligands. These results indicate contrasting impacts of ET-1 on distinct mast cell populations. We propose that ET-1 may participate in pathological conditions of various disorders via its multi-functional effects on mast cells under certain conditions. PMID:15214039

Matsushima, Hironori; Yamada, Nobuo; Matsue, Hiroyuki; Shimada, Shinji

2004-07-01

98

Inhibitory effects of flavonoids isolated from Fragaria ananassa Duch on IgE-mediated degranulation in rat basophilic leukemia RBL-2H3.  

PubMed

We isolated the 4 kinds of flavonoids from strawberry 'Nohime' and examined the effect of these flavonoids on the degranulation in RBL-2H3 cells. The flavonoids were found to suppress the degranulation from Ag-stimulated RBL-2H3 cells to different extents. To disclose the inhibitory mechanism of degranulation by flavonoids, we examined their effects on the intracellular free Ca(2+) concentration ([Ca(2+)]i) and the intracellular signaling pathway such as Lyn, Syk, and PLCgammas. The intracellular free Ca(2+) concentration ([Ca(2+)]i) was elevated by Fc epsilonRI activation, but these flavonoid treatments reduced the elevation of [Ca(2+)]i by suppressing Ca(2+) influx. Kaempferol strongly suppressed the activation of Syk and PLCgammas. It was thus suggested that suppression of Ag-stimulated degranulation by the flavonoids is mainly due to suppression of [Ca(2+)]i elevation and Syk activation. These results suggested that strawberry would be of some ameliorative benefit for the allergic symptoms. PMID:19596200

Itoh, Tomohiro; Ninomiya, Masayuki; Yasuda, Masaharu; Koshikawa, Kaneyuki; Deyashiki, Yoshihiro; Nozawa, Yoshinori; Akao, Yukihiro; Koketsu, Mamoru

2009-08-01

99

Polydatin (PD) inhibits IgE-mediated passive cutaneous anaphylaxis in mice by stabilizing mast cells through modulating Ca{sup 2+} mobilization  

SciTech Connect

Mast cells play a key role in the pathogenesis of asthma and are a promising target for therapeutic intervention in asthma. This study investigated the effects of polydatin (PD), a resveratrol glucoside, on mast cell degranulation upon cross-linking of the high-affinity IgE receptors (Fc?RI), as well as the anti-allergic activity of PD in vivo. Herein, we demonstrated that PD treatment for 30 min suppressed Fc?RI-mediated mast cell degranulation in a dose-dependent manner. Concomitantly, PD significantly decreased Fc?RI-mediated Ca{sup 2+} increase in mast cells. The suppressive effects of PD on Fc?RI-mediated Ca{sup 2+} increase were largely inhibited by using LaCl{sub 3} to block the Ca{sup 2+} release-activated Ca{sup 2+} channels (CRACs). Furthermore, PD significantly inhibited Ca{sup 2+} entry through CRACs evoked by thapsigargin (TG). Knocking down protein expression of Orai1, the pore-forming subunit of CRACs, significantly decreased PD suppression of Fc?RI-induced intracellular Ca{sup 2+} influx and mast cell degranulation. In a mouse model of mast cell-dependent passive cutaneous anaphylaxis (PCA), in vivo PD administration suppressed mast cell degranulation and inhibited anaphylaxis. Taken together, our data indicate that PD stabilizes mast cells by suppressing Fc?RI-induced Ca{sup 2+} mobilization mainly through inhibiting Ca{sup 2+} entry via CRACs, thus exerting a protective effect against PCA. -- Highlights: ? Polydatin can prevent the pathogenesis of passive cutaneous anaphylaxis in mice. ? Polydatin stabilizes mast cells by decreasing Fc?RI-mediated degranulation. ? Polydatin suppresses Ca{sup 2+} entry through CRAC channels in mast cells.

Yuan, Meichun [Department of Pathophysiology, School of Medicine, Shenzhen University, Shenzhen 518060 (China) [Department of Pathophysiology, School of Medicine, Shenzhen University, Shenzhen 518060 (China); Department of Physiology, Hubei University of Medicine, Shiyan (China); Li, Jianjie [State Key Laboratory of Respiratory Disease for Allergy at Shengzhen University, Shenzhen 518060 (China)] [State Key Laboratory of Respiratory Disease for Allergy at Shengzhen University, Shenzhen 518060 (China); Lv, Jingzhang [Shenzhen Entry-Exit Inspection and Quarantine Bureau, Shenzhen 518045 (China)] [Shenzhen Entry-Exit Inspection and Quarantine Bureau, Shenzhen 518045 (China); Mo, Xucheng; Yang, Chengbin [State Key Laboratory of Respiratory Disease for Allergy at Shengzhen University, Shenzhen 518060 (China)] [State Key Laboratory of Respiratory Disease for Allergy at Shengzhen University, Shenzhen 518060 (China); Chen, Xiangdong [Department of Pathophysiology, School of Medicine, Shenzhen University, Shenzhen 518060 (China)] [Department of Pathophysiology, School of Medicine, Shenzhen University, Shenzhen 518060 (China); Liu, Zhigang [State Key Laboratory of Respiratory Disease for Allergy at Shengzhen University, Shenzhen 518060 (China)] [State Key Laboratory of Respiratory Disease for Allergy at Shengzhen University, Shenzhen 518060 (China); Liu, Jie, E-mail: ljljz@yahoo.com [Department of Pathophysiology, School of Medicine, Shenzhen University, Shenzhen 518060 (China)] [Department of Pathophysiology, School of Medicine, Shenzhen University, Shenzhen 518060 (China)

2012-11-01

100

Involvement of Class II Phosphoinositide 3-Kinase ?-Isoform in Antigen-Induced Degranulation in RBL-2H3 Cells  

PubMed Central

In this study, we present findings that suggest that PI3K-C2?, a member of the class II phosphoinositide 3-kinase (PI3K) subfamily, regulates the process of Fc?RI-triggered degranulation. RBL-2H3 cells were transfected with shRNA targeting PI3K-C2?. The knockdown impaired the Fc?RI-induced release of a lysosome enzyme, ?-hexosaminidase, without affecting the intracellular Ca2+ mobilization. The release of mRFP-tagged neuropeptide-Y, a reporter for the regulated exocytosis, was also decreased in the PI3K-C2?-deficient cells. The release was increased significantly by the expression of the siRNA-resistant version of PI3K-C2?. In wild-type cells, Fc?RI stimulation induced the formation of large vesicles, which were associated with CD63, a marker protein of secretory granules. On the vesicles, the existence of PI3K-C2? and PtdIns(3,4)P2 was observed. These results indicated that PI3K-C2? and its product PtdIns(3,4)P2 may play roles in the secretory process. PMID:25357130

Nigorikawa, Kiyomi; Hazeki, Kaoru; Guo, Ying; Hazeki, Osamu

2014-01-01

101

Platelet degranulation and glycoprotein IIbIIIa opening are not related to bleeding phenotype in severe haemophilia A patients.  

PubMed

Recently we reported data suggesting that platelets could compensate for the bleeding phenotype in severe haemophilia A (HA). The aim of this study was to confirm these results in a larger population with a detailed characterisation of clinical phenotype. Patients with diagnostic severe HA (FVIII:C <1%) were scored for clinical phenotype by integrating data on age at first joint bleed, joint damage, bleeding frequency and FVIII consumption. Phenotype was defined as onset of joint bleeding-score + arthropathy-score + joint bleeding-score + (2* treatment intensity-score). After a washout period of three days, blood was collected for measurement of basal level of platelet activation, platelet reactivity, endothelial cell activation and presence of procoagulant phospholipids in plasma. Thirty-three patients with severe HA were included, 13 patients with a mild, 12 patients with an average and eight patients with a severe clinical phenotype. No relevant differences in basal level of platelet activation, platelet reactivity, endothelial cell activation and procoagulant phospholipids between all three groups were observed. The mean annual FVIII consumption per kg did not correlate with the platelet P-selectin expression and glycoprotein (GP)IIbIIIa activation on platelets. In conclusion, variability in clinical phenotype in patients with diagnostic severe HA is not related to platelet activation or reactivity, measured as platelet degranulation and platelet GPIIbIIIa opening. PMID:24477967

van Bladel, Esther R; Schutgens, Roger E G; Fischer, Kathelijn; de Groot, Philip G; Roest, Mark

2014-06-01

102

Accumulation of Major Histocompatibility Complex Class II Molecules in Mast Cell Secretory Granules and Their Release upon Degranulation  

PubMed Central

To investigate the relationship between major histocompatibility complex (MHC) class II compartments, secretory granules, and secretory lysosomes, we analyzed the localization and fate of MHC class II molecules in mast cells. In bone marrow-derived mast cells, the bulk of MHC class II molecules is contained in two distinct compartments, with features of both lysosomal compartments and secretory granules defined by their protein content and their accessibility to endocytic tracers. Type I granules display internal membrane vesicles and are accessed by exogenous molecules after a time lag of 20 min; type II granules are reached by the endocytic tracer later and possess a serotonin-rich electron-dense core surrounded by a multivesicular domain. In these type I and type II granules, MHC class II molecules, mannose-6-phosphate receptors and lysosomal membrane proteins (lamp1 and lamp2) localize to small intralumenal vesicles. These 60–80-nm vesicles are released along with inflammatory mediators during mast cell degranulation triggered by IgE-antigen complexes. These observations emphasize the intimate connection between the endocytic and secretory pathways in cells of the hematopoietic lineage which allows regulated secretion of the contents of secretory lysosomes, including membrane proteins associated with small vesicles. PMID:9398681

Raposo, Graca; Tenza, Danielle; Mecheri, Salahedine; Peronet, Roger; Bonnerot, Christian; Desaymard, Catherine

1997-01-01

103

Involvement of Pacific oyster CgPGRP-S1S in bacterial recognition, agglutination and granulocyte degranulation.  

PubMed

Peptidoglycan recognition protein (PGRP) recognizes invading bacteria through their peptidoglycans (PGN), a component of the bacterial cell wall. Insect PGRPs contribute to effective immune systems as inducers of other host defense responses, while this function has not been reported from PGRP of bivalves. In this study, recombinant CgPGRP-S1S (rCgPGRP-S1S), produced in the mantle and the gill, was synthesized and used to elucidate the immunological function of CgPGRP-S1S. rCgPGRP-S1S bound specifically to DAP-type PGN and to Escherichia coli cells, but not to other DAP-type PGN-containing bacterial species, Vibrio anguillarum, or Bacillus subtilis. Antibacterial activity was not detected, but E. coli cells were agglutinated. Moreover, in addition to these direct interactions with bacterial cells, rCgPGRP-S1S induced secretion of granular contents by hemocyte degranulation. Taken together, these results suggest for the first time that a PGRP of bivalves is, just as in insects, involved in host defense, not only by direct interaction with bacteria, but also by triggering other defense pathways. PMID:24201133

Iizuka, Masao; Nagasaki, Toshihiro; Takahashi, Keisuke G; Osada, Makoto; Itoh, Naoki

2014-03-01

104

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. PMID:21214543

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

2011-01-01

105

Immune Response to Snake Envenoming and Treatment with Antivenom; Complement Activation, Cytokine Production and Mast Cell Degranulation  

PubMed Central

Background Snake bite is one of the most neglected public health issues in poor rural communities worldwide. In addition to the clinical effects of envenoming, treatment with antivenom frequently causes serious adverse reactions, including hypersensitivity reactions (including anaphylaxis) and pyrogenic reactions. We aimed to investigate the immune responses to Sri Lankan snake envenoming (predominantly by Russell's viper) and antivenom treatment. Methodology/Principal Findings Plasma concentrations of Interleukin (IL)-6, IL-10, tumor necrosis factor ? (TNF?), soluble TNF receptor I (sTNFRI), anaphylatoxins (C3a, C4a, C5a; markers of complement activation), mast cell tryptase (MCT), and histamine were measured in 120 Sri Lankan snakebite victims, both before and after treatment with antivenom. Immune mediator concentrations were correlated with envenoming features and the severity of antivenom-induced reactions including anaphylaxis. Envenoming was associated with complement activation and increased cytokine concentrations prior to antivenom administration, which correlated with non-specific systemic symptoms of envenoming but not with coagulopathy or neurotoxicity. Typical hypersensitivity reactions to antivenom occurred in 77/120 patients (64%), satisfying criteria for a diagnosis of anaphylaxis in 57/120 (48%). Pyrogenic reactions were observed in 32/120 patients (27%). All patients had further elevations in cytokine concentrations, but not complement activation, after the administration of antivenom, whether a reaction was noted to occur or not. Patients with anaphylaxis had significantly elevated concentrations of MCT and histamine. Conclusions/Significance We have demonstrated that Sri Lankan snake envenoming is characterized by significant complement activation and release of inflammatory mediators. Antivenom treatment further enhances the release of inflammatory mediators in all patients, with anaphylactic reactions characterised by high levels of mast cell degranulation but not further complement activation. Anaphylaxis is probably triggered by non allergen-specific activation of mast cells and may be related to the quality of available antivenom preparations, as well as a priming effect from the immune response to the venom itself. PMID:23936562

Stone, Shelley F.; Isbister, Geoffrey K.; Shahmy, Seyed; Mohamed, Fahim; Abeysinghe, Chandana; Karunathilake, Harendra; Ariaratnam, Ariaranee; Jacoby-Alner, Tamara E.; Cotterell, Claire L.; Brown, Simon G. A.

2013-01-01

106

The Subunit of the Type I Fc Receptor Is a Target for Peptides Inhibiting IgE-Mediated Secretory Response of Mast Cells1  

Microsoft Academic Search

Peptides originally derived from complement component C3a were earlier shown to inhibit the type I FcR (FcRI)-mediated degranulation of mucosal type mast cells. In the present study, we show that C3a7, a peptide with a natural sequence, and its modified derivative, C3a9, are powerful inhibitors of the above response of both serosal and mucosal type mastocytes. We demonstrate that these

Marton Andrasfalvy; Hajna Peterfy; Janos Matko ´; Jakub Abramson; Krisztina Kerekes; Gyorgy Vamosi; Israel Pecht; Anna Erdei

107

Antiallergic and antiasthmatic effects of a novel enhydrazinone ester (CEE-1): inhibition of activation of both mast cells and eosinophils.  

PubMed

Activation of mast cells and eosinophils is a fundamental process in the pathophysiology of allergic diseases. We have previously reported that the novel enhydrazinone ester CEE-1 (ethyl 4-phenylhydrazinocyclohex-3-en-2-oxo-6-phenyl-1-oate) possesses potent anti-inflammatory activity. We have now tested whether the compound also possesses antiallergic and antiasthmatic effects in vitro and in vivo. The compound significantly inhibited degranulation and leukotriene C4 (LTC4) release from activated human eosinophils, as well as IgE-dependent degranulation and LTC4 release from passively sensitized rat basophilic leukemia cells and bone marrow-derived mouse mast cells. In human eosinophils, the drug was more potent in inhibiting degranulation than LTC4 release {IC50 = 0.4 ?M [confidence interval (CI): 0.1-0.9] versus 3.8 ?M (CI: 0.9-8.3)}, whereas in mast cells the reverse was essentially the case. The drug did not affect stimulus-induced calcium transients in eosinophils but significantly inhibited early phosphorylation of extracellular signal-regulated kinases 1/2 and p38-mitogen-activated protein kinases (MAPK). In vivo, topical application of 4.5-15 mg/kg of the compound significantly inhibited allergen-induced passive cutaneous anaphylaxis in mice. Similarly, in the mouse asthma model, the intranasal administration of 6.5-12.5 mg/kg of the compound significantly inhibited bronchial inflammation and eosinophil accumulation in bronchial lavage fluid, as well as abolishing airway hyper-responsiveness to methacholine. These results show that CEE-1 inhibits the activation of both mast cells and eosinophils in vitro, probably by blocking MAPK-activation pathways, and that these effects are translated into antiallergic and antiasthmatic effects in vivo. The compound, therefore, has potential application in the treatment of asthma and other allergic diseases. PMID:24917545

Ezeamuzie, Charles I; El-Hashim, Ahmed Z; Renno, Waleed M; Edafiogho, Ivan O

2014-08-01

108

A peptide against the N-terminus of myristoylated alanine-rich C kinase substrate inhibits degranulation of human leukocytes in vitro.  

PubMed

Leukocytes synthesize a variety of inflammatory mediators that are packaged and stored in the cytoplasm within membrane-bound granules. Upon stimulation, the cells secrete the granule contents via an exocytotic process whereby the granules translocate to the cell periphery, the granule membranes fuse with the plasma membrane, and the granule contents are released extracellularly. We have reported previously that another exocytotic process, release of mucin by secretory cells of the airway epithelium, is regulated by the myristoylated alanine-rich C kinase substrate (MARCKS) (Li Y, Martin LD, Spizz G, Adler KB. MARCKS protein is a key molecule regulating mucin secretion by human airway epithelial cells in vitro. J Biol Chem 2001;276:40982-40990; Singer M, Martin LD, Vargaftig BB, Park J, Gruber AD, Li Y, Adler KB. A MARCKS-related peptide blocks mucus hypersecretion in a mouse model of asthma. Nat Med 2004;10:193-196). In those studies, mucin secretion in vitro and in vivo was attenuated by a synthetic peptide identical to the N-terminus of MARCKS, named the MANS peptide (Li and colleagues, 2001). In this study, we used the MANS peptide to investigate possible involvement of MARCKS in secretion of leukocyte granule proteins. In neutrophils isolated from human blood, phorbol 12-myristate 13-acetate-induced myeloperoxidase release was attenuated in a concentration-dependent manner by MANS but not by equal concentrations of a missense control peptide. In additional studies using human leukocyte cell lines, secretion of eosinophil peroxidase from the eosinophil-like cell line HL-60 clone 15, lysozyme from the monocytic leukemia cell line U937, and granzyme from the lymphocyte natural killer cell line NK-92 were attenuated by preincubation of the cells with MANS but not with the missense control peptide. The results indicate that MARCKS protein may play an important role in the secretion of membrane-bound granules from different leukocytes. MARCKS may be an important component of secretory pathways associated with release of granules by different cell types. PMID:16543603

Takashi, Shuji; Park, Joungjoa; Fang, Shijing; Koyama, Sekiya; Parikh, Indu; Adler, Kenneth B

2006-06-01

109

A Sensitive High Throughput ELISA for Human Eosinophil Peroxidase: A Specific Assay to Quantify Eosinophil Degranulation from Patient-derived Sources  

PubMed Central

Quantitative high throughput assays of eosinophil-mediated activities in fluid samples from patients in a clinical setting have been limited to ELISA assessments for the presence of the prominent granule ribonucleases, ECP and EDN. However, the demonstration that these ribonucleases are expressed by leukocytes other than eosinophils, as well as cells of non-hematopoietic origin, limits the usefulness of these assays. Two novel monoclonal antibodies recognizing eosinophil peroxidase (EPX) were used to develop an eosinophil-specific and sensitive sandwich ELISA. The sensitivity of this EPX-based ELISA was shown to be similar to that of the commercially available ELISA kits for ECP and EDN. More importantly, evidence is also presented confirming that among these granule protein detection options, EPX-based ELISA is the only eosinophil-specific assay. The utility of this high throughput assay to detect released EPX was shown in ex vivo degranulation studies with isolated human eosinophils. In addition, EPX-based ELISA was used to detect and quantify eosinophil degranulation in several in vivo patient settings, including bronchoalveolar lavage fluid obtained following segmental allergen challenge of subjects with allergic asthma, induced sputum derived from respiratory subjects following hypotonic saline inhalation, and nasal lavage of chronic rhinosinusitis patients. This unique EPX-based ELISA thus provides an eosinophil-specific assay that is sensitive, reproducible, and quantitative. In addition, this assay is adaptable to high throughput formats (e.g., automated assays utilizing microtiter plates) using the diverse patient fluid samples typically available in research and clinical settings. PMID:22750539

Ochkur, Sergei I.; Kim, John Dongil; Protheroe, Cheryl A.; Colbert, Dana; Condjella, Rachel M.; Bersoux, Sophie; Helmers, Richard A.; Moqbel, Redwan; Lacy, Paige; Kelly, Elizabeth A.; Jarjour, Nizar N.; Kern, Robert; Peters, Anju; Schleimer, Robert P.; Furuta, Glenn T.; Nair, Parameswaran; Lee, James J.; Lee, Nancy A.

2012-01-01

110

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

111

Effects of Tumour Necrosis Factor Alpha and Interleukin1 Alpha and Beta on Human Neutrophil Migration, Respiratory Burst and Degranulation  

Microsoft Academic Search

Recombinant human tumour necrosis factor alpha (rHuTNF?) was shown to inhibit human neutrophil migration in the presence or absence of a chemotactic gradient generated with the tripeptide, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), at doses of 20–100 U\\/106 cells. In contrast, neither recombinant human interleukin-1 alpha (rHuIL-1?), rHuIL-1?, human leucocyte-derived IL-l? (lHuIL-l?) nor lHuIL-1? contained neutrophil migration inhibition properties. However, both the interleukins (lHuIL-1?,

Antonio Ferrante; Madhuri Nandoskar; Alfred Walz; David H. B. Goh; Ingeborg C. Kowanko

1988-01-01

112

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. PMID:19480699

Fung, Peter Chin Wan

2009-01-01

113

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. PMID:22706316

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

2012-01-01

114

Inhibition of calcium-independent phospholipase A2 prevents inflammatory mediator production in pulmonary microvascular endothelium.  

PubMed

Inhalation of allergens can result in mast cell degranulation and release of granule contents, including tryptase, in the lung. Injury to human pulmonary microvascular endothelial cells (HMVEC-L) can also result in activation of the coagulation cascade and thrombin generation. We hypothesize that these proteases activate calcium-independent phospholipase A2 (iPLA2), in HMVEC-L, leading to the production of membrane phospholipids-derived inflammatory mediators. Both thrombin and tryptase stimulation of HMVEC-L increased iPLA2 activity that was inhibited by pretreatment with the iPLA2 selective inhibitor bromoenol lactone (BEL). Arachidonic acid and prostaglandin I2 (PGI2) release were also increased in tryptase and thrombin stimulated cells and inhibited by BEL pretreatment. Pretreating the endothelial cells with AACOCF3 a cytosolic PLA2 inhibitor did not inhibit tryptase or thrombin induced arachidonic acid and PGI2 release. In addition thrombin and tryptase also increased HMVEC-L platelet activating factor (PAF) production that significantly contributes to the recruitment and initial adherence of polymorphonuclear neutrophils (PMN) to the endothelium. Tryptase or thrombin stimulated increase in PMN adherence to the endothelium was inhibited by pretreatment of HMVEC-L with BEL or pretreatment of PMN with CV3988, a PAF receptor specific antagonist. Collectively, these data support our hypothesis that iPLA2 activity is responsible for membrane phospholipid hydrolysis in response to tryptase or thrombin stimulation in HMVEC-L. Therefore selective inhibition of iPLA2 may be a pharmacological target to inhibit the early inflammation in pulmonary vasculature that occurs as a consequence of mast cell degranulation or acute lung injury. PMID:19059366

Rastogi, Prerna; McHowat, Jane

2009-02-28

115

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. PMID:22022533

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

116

Once Phosphorylated, Tyrosines in Carboxyl Terminus of Protein-tyrosine Kinase Syk Interact with Signaling Proteins, Including TULA-2, a Negative Regulator of Mast Cell Degranulation*  

PubMed Central

Activation of the high affinity IgE-binding receptor (Fc?RI) results in the tyrosine phosphorylation of two conserved tyrosines located close to the COOH terminus of the protein-tyrosine kinase Syk. Synthetic peptides representing the last 10 amino acids of the tail of Syk with these two tyrosines either nonphosphorylated or phosphorylated were used to precipitate proteins from mast cell lysates. Proteins specifically precipitated by the phosphorylated peptide were identified by mass spectrometry. These included the adaptor proteins SLP-76, Nck-1, Grb2, and Grb2-related adaptor downstream of Shc (GADS) and the protein phosphatases SHIP-1 and TULA-2 (also known as UBASH3B or STS-1). The presence of these in the precipitates was further confirmed by immunoblotting. Using the peptides as probes in far Western blots showed direct binding of the phosphorylated peptide to Nck-1 and SHIP-1. Immunoprecipitations suggested that there were complexes of these proteins associated with Syk especially after receptor activation; in these complexes are Nck, SHIP-1, SLP-76, Grb2, and TULA-2 (UBASH3B or STS-1). The decreased expression of TULA-2 by treatment of mast cells with siRNA increased the Fc?RI-induced tyrosine phosphorylation of the activation loop tyrosines of Syk and the phosphorylation of phospholipase C-?2. There was parallel enhancement of the receptor-induced degranulation and activation of nuclear factor for T cells or nuclear factor ?B, indicating that TULA-2, like SHIP-1, functions as a negative regulator of Fc?RI signaling in mast cells. Therefore, once phosphorylated, the terminal tyrosines of Syk bind complexes of proteins that are positive and negative regulators of signaling in mast cells. PMID:22267732

de Castro, Rodrigo Orlandini; Zhang, Juan; Groves, Jacqueline R.; Barbu, Emilia Alina; Siraganian, Reuben P.

2012-01-01

117

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

118

Balance between activating NKG2D, DNAM-1, NKp44 and NKp46 and inhibitory CD94/NKG2A receptors determine natural killer degranulation towards rheumatoid arthritis synovial fibroblasts.  

PubMed

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and synovial hyperplasia leading to progressive joint destruction. Fibroblast-like synoviocytes (FLS) are central components of the aggressive, tumour-like synovial structure termed pannus, which invades the joint space and cartilage. A distinct natural killer (NK) cell subset expressing the inhibitory CD94/NKG2A receptor is present in RA synovial fluid. Little is known about possible cellular interactions between RA-FLS and NK cells. We used cultured RA-FLS and the human NK cell line Nishi, of which the latter expresses an NK receptor repertoire similar to that of NK cells in RA synovial fluid, as an in vitro model system of RA-FLS/NK cell cross-talk. We show that RA-FLS express numerous ligands for both activating and inhibitory NK cell receptors, and stimulate degranulation of Nishi cells. We found that NKG2D, DNAM-1, NKp46 and NKp44 are the key activating receptors involved in Nishi cell degranulation towards RA-FLS. Moreover, blockade of the interaction between CD94/NKG2A and its ligand HLA-E expressed on RA-FLS further enhanced Nishi cell degranulation in co-culture with RA-FLS. Using cultured RA-FLS and the human NK cell line Nishi as an in vitro model system of RA-FLS/NK cell cross-talk, our results suggest that cell-mediated cytotoxicity of RA-FLS may be one mechanism by which NK cells influence local joint inflammation in RA. PMID:24673109

Nielsen, Natasja; Pascal, Veronique; Fasth, Andreas E R; Sundström, Yvonne; Galsgaard, Elisabeth D; Ahern, David; Andersen, Martin; Baslund, Bo; Bartels, Else M; Bliddal, Henning; Feldmann, Marc; Malmström, Vivianne; Berg, Louise; Spee, Pieter; Söderström, Kalle

2014-08-01

119

Hydroxylated fullerenes inhibit neutrophil function in fathead minnow (Pimephales promelas Rafinesque, 1820).  

PubMed

Hydroxylated fullerenes act as potent inhibitors of cytochrome P450-dependent monooxygenases, and are reported to be very strong antioxidants quenching reactive oxygen species (ROS) production. Effects of nanosized hydroxylated fullerenes on fish neutrophil function and immune gene transcription was investigated using fathead minnow (Pimephales promelas). Neutrophil function assays were used to determine the effects of fullerene exposure in vitro and in vivo on oxidative burst, degranulation and extracellular trap (NETs) release, and the innate immune gene transcription was determined with quantitative PCR (qPCR). Application of fullerenes (0.2-200 microgmL(-1)in vitro) caused concentration dependent inhibition of oxidative burst and suppressed the release of NETs and degranulation of primary granules (up to 70, 40, and 50% reduction in activity compared to non-treated control, respectively). Transcription of interleukin 11 and myeloperoxidase genes was significantly increased and transcription of elastase 2 gene was significantly decreased in fish exposed to hydroxylated fullerenes for 48h in vivo (12 and 3 fold increase, and 5 fold decrease, respectively). Observed changes in gene transcription and neutrophil function indicate potential for hydroxylated fullerenes to interfere with the evolutionary conserved innate immune system responses and encourages the use of fish models in studies of nanoparticle immunotoxicity. PMID:21122929

Jovanovi?, Boris; Anastasova, Lora; Rowe, Eric W; Pali?, Dušan

2011-01-25

120

Cheonggukjang ethanol extracts inhibit a murine allergic asthma via suppression of mast cell-dependent anaphylactic reactions.  

PubMed

Cheonggukjang (CGJ), a traditional Korean fermented soybean food, exerts immunomodulatory effects. Asthma is the most common chronic allergic disease to be associated with immune response to environmental allergens. In the pathogenesis of asthma, histamine is one of the important inflammatory mediators released from granules of mast cells. In this study, we evaluated the therapeutic effect of CGJ on a mouse model of ovalbumin (OVA)-induced asthma via the suppression of histamine release. C57BL/6 mice were sensitized by intraperitoneal injection of OVA or a phosphate-buffered saline (PBS) control and then challenged with OVA inhalation. Mice were treated intraperitoneally with either 70% ethanol-extracted CGJ (CGJE) (100 mg/kg/day) or equivalent PBS. Asthma-related inflammation was assessed by bronchoalveolar lavage fluid cell counts and histopathological and immunohistochemical analysis of lung tissues. To elucidate the mechanisms of asthma inhibition by CGJE treatment, we also examined degranulation and histamine release of compound 48/80-induced rat peritoneal mast cells (RPMCs). Treatment with CGJE downregulated the number of eosinophils and monocytes in the lungs of mice challenged with OVA and suppressed histopathological changes, such as eosinophil infiltration, mucus accumulation, goblet cell hyperplasia, and collagen fiber deposits. Moreover, CGJE alleviated compound 48/80-induced mast cell degranulation and histamine release from RPMCs through inhibition of calcium (Ca˛?) uptake as well as ear swelling by infiltration of inflammatory cells. These findings demonstrated that CGJE can be used as an antiasthmatic dietary supplements candidate for histamine-mediated asthma. PMID:24456365

Bae, Min-Jung; Shin, Hee Soon; See, Hye-Jeong; Chai, Ok Hee; Shon, Dong-Hwa

2014-01-01

121

Mechanism of photobiological effects of psoralens: the involvement of photo-oxidized psoralens as reactive intermediate species in induction of photosensitized hemolysis and skin erythema  

NASA Astrophysics Data System (ADS)

Psoralens combined with UVA irradiation are used for the treatment of skin and autoimmune diseases. In the present paper the involvement of psoralen photooxidation products (POP) into induction of PUVA-erythema was studied. Under low fluence rate (LFR) UVA-irradiation and/or at low psoralen concentrations POP-products were predominantly formed, which were detected by spin trp method and possessed immunosuppressive activity. Under high fluence rate (HFR) UVA-irradiation and/or at high psoralen concentrations POP2-products were predominantly formed, which could be detected by Fe(II)-induced chemiluminescence and possessed hemolytic activity. Both PUVA- and POP-induced hemolysis of erythrocytes as well as PUVA-erythema were strongly activated with the increase in UVA-fluence rate. Both LFR and HFR PUVA-hemolysis as well as POP-hemolysis were strongly activated by Fe(II)-ions, bivalent cation chelators produced different effects on these processes depending on UVA fluence rate. Ethylenediaminetetraacetate (EDTA), and o- fenanthroline were found to inhibit LFT PUVA-erythema and enhanced HFR PUVA-erythema. Similar regulatory effects of EDTA were found for PUVA- and POP-induced hemolysis. EDTA inhibited LFT PUVA-hemolysis and activated HFR PUVA- and POP-hemolysis that suggests a participation of POP1- products in induction of LFR PUVA-hemolysis and LFT PUVA- erythema and POP2-products in induction of HFR PUVA- hemolysis and HFR PUVA-erythema.

Lysenko, Eugene P.; Kyagova, Alla A.; Potapenko, Alexander Y.

2002-07-01

122

Inhibitory effects of whisky congeners on IgE-mediated degranulation in rat basophilic leukemia RBL-2H3 cells and passive cutaneous anaphylaxis reaction in mice.  

PubMed

Whisky is matured in oak casks. Many nonvolatile substances (whisky congeners, WC) seep from the oak cask during the maturing process. In this study, three antiallergic agents (syringaldehyde, SA; lyoniresinol, Lyo; and ellagic acid, EA) were isolated from WC. Treatment with SA, Lyo, and EA reduced the elevation of intracellular free Ca(2+) concentration ([Ca(2+)]i) and intracellular ROS production caused by FcepsilonRI activation. The inhibitions of the elevation of [Ca(2+)]i and intracellular ROS production by SA and Lyo were mainly due to the suppression of the NADPH oxidase activity and scavenging of the produced radical, respectively. On the other hand, EA inactivated spleen tyrosine kinase and led to the inhibition of the elevation of [Ca(2+)]i and intracellular ROS production. Furthermore, it was found that WC strongly inhibited IgE binding to the FcepsilonRIalpha chain, whereas SA, Lyo, and EA did not indicate this inhibitory effect. These results suggest that WC inhibits allergic reactions through multiple mechanisms. To disclose the in vivo effects of WC, SA, Lyo, and EA, these compounds were administered to type I allergic model mice, and the passive cutaneous anaphylaxis (PCA) reaction was measured. These compounds remarkably suppressed the PCA reaction. Taken together, these findings suggest that WC seemed to be beneficial to ameliorate allergic reactions. PMID:20507065

Itoh, Tomohiro; Tsukane, Mariko; Koike, Minako; Nakamura, Chizu; Ohguchi, Kenji; Ito, Masafumi; Akao, Yukihiro; Koshimizu, Seiichi; Nozawa, Yoshinori; Wakimoto, Toshiyuki; Nukaya, Haruo; Suwa, Yoshihide

2010-06-23

123

Inhibiting PTEN.  

PubMed

PTEN (phosphatase and tensin homologue deleted on chromosome 10) is well known as a tumour suppressor. In dephosphorylating the 3-position of the inositol ring of phosphoinositides such as PtdIns(3,4,5)P(3), PTEN's lipid phosphatase activity is an important counteracting mechanism in PI3K (phosphoinositide 3-kinase) signalling. This is essential for cell motility and migration due to the achievement of a PtdIns(3,4,5)P(3)/PtdIns(4,5)P(2) gradient that is also involved in metastasis. Furthermore, PTEN's tumour suppressor role is linked to the control of cell-cycle progression and cell proliferation by counteracting Akt (also called protein kinase B) signalling which is PtdIns(3,4,5)P(3)-dependent. Akt is upstream of several kinases involved in proliferation and apoptotic signalling which are often found to be deregulated or mutated in tumours. However, Akt is also the key enzyme in insulin signalling regulating glucose uptake and cell growth. Therefore PTEN has recently moved into the spotlight as a drug target in diabetes. This review summarizes studies undertaken on PTEN's role in glucose uptake, insulin resistance, diabetes and its controversial role in GLUT (glucose transporter)-mediated glucose uptake. Currently available techniques for inhibiting PTEN and the suitability of PTEN as a drug target will be discussed. PMID:17371253

Rosivatz, E

2007-04-01

124

Tumor necrosis factor-induced degranulation in adherent human neutrophils is dependent on CD11b/CD18-integrin-triggered oscillations of cytosolic free Ca2+.  

PubMed Central

We have recently been able to correlate closely the "spontaneous" oscillatory activity of cytosolic free Ca2+ in adherent human neutrophils with the ability of tumor necrosis factor (TNF) to induce secretion of granule proteins from these cells. In the present work we show with a single-cell technique that preincubation of human neutrophils with antibodies to CD18, the common beta chain of leukocyte adhesion proteins, inhibits TNF-induced secretion of lactoferrin in a time- and concentration-dependent manner. Similar effects of CD18 antibodies were found on chemotactic factor (fMet-Leu-Phe)- but not on phorbol 12-myristate 13-acetate-induced secretion, suggesting that cell-surface-receptor-mediated secretion is dependent on integrin-associated signals. Similarly, antibodies to CD11b (alpha chain of macrophage 1) also inhibited TNF- and fMet-Leu-Phe- but not phorbol 12-myristate 13-acetate-stimulated release of lactoferrin. Antibodies to CD11a (alpha chain of lymphocyte function-associated antigen 1) or CD11c (alpha chain of p150,95) had only a minimal effect on agonist-induced secretion. Data obtained in several laboratories, including our own, made us suspect that integrin interaction with the surface is responsible for the oscillatory activity of cytosolic free Ca2+ in adherent cells. Indeed, preincubation with antibodies to either CD18 or CD11b, but not to CD11c, inhibited the oscillations of cytosolic free Ca2+ in adherent neutrophils. This inhibitory effect was evident both as a reduction of the number of responding cells and as a reduction of the oscillatory activity in the cells. In conclusion, the oscillatory activity of cytosolic free Ca2+ in adherent neutrophils is mediated through the CD18/CD11b integrins. The generation of this Ca2+ signal may explain how adherence, by way of the integrins, changes the functional properties of the cell and enables TNF to induce secretion. PMID:1979172

Richter, J; Ng-Sikorski, J; Olsson, I; Andersson, T

1990-01-01

125

Programmed death (PD)-1:PD-ligand 1/PD-ligand 2 pathway inhibits T cell effector functions during human tuberculosis.  

PubMed

Protective immunity against Mycobacterium tuberculosis requires the generation of cell-mediated immunity. We investigated the expression and role of programmed death 1 (PD-1) and its ligands, molecules known to modulate T cell activation, in the regulation of IFN-gamma production and lytic degranulation during human tuberculosis. We demonstrated that specific Ag-stimulation increased CD3+PD-1+ lymphocytes in peripheral blood and pleural fluid from tuberculosis patients in direct correlation with IFN-gamma production from these individuals. Moreover, M. tuberculosis-induced IFN-gamma participated in the up-regulation of PD-1 expression. Blockage of PD-1 or PD-1 and its ligands (PD-Ls: PD-L1, PD-L2) enhanced the specific degranulation of CD8+ T cells and the percentage of specific IFN-gamma-producing lymphocytes against the pathogen, demonstrating that the PD-1:PD-Ls pathway inhibits T cell effector functions during active M. tuberculosis infection. Furthermore, the simultaneous blockage of the inhibitory receptor PD-1 together with the activation of the costimulatory protein signaling lymphocytic activation molecule led to the promotion of protective IFN-gamma responses to M. tuberculosis, even in patients with weak cell-mediated immunity against the bacteria. Together, we demonstrated that PD-1 interferes with T cell effector functions against M. tuberculosis, suggesting that PD-1 has a key regulatory role during the immune response of the host to the pathogen. PMID:18566376

Jurado, Javier O; Alvarez, Ivana B; Pasquinelli, Virginia; Martínez, Gustavo J; Quiroga, María F; Abbate, Eduardo; Musella, Rosa M; Chuluyan, H Eduardo; García, Verónica E

2008-07-01

126

Exocytosis acts as a modulator of the ILT4-mediated inhibition of neutrophil functions  

PubMed Central

Neutrophils play a major role in inflammatory responses and immune defense against pathogens. Even though expression of inhibitory receptors has been reported on neutrophils, their role remains poorly defined. Here we show that primary human neutrophils expressed immunoglobulin-like transcript 4 (ILT4) inhibitory receptor and that this expression was induced during differentiation of the myelomonoblast PLB-985 cell line into “neutrophil-like” cells. Functional assays indicated that human leukocyte antigen G, the preferred ligand of ILT4, inhibited the phagocytic function of neutrophils. ILT4 engagement also impaired reactive oxygen species production induced through CD32a and both receptors were found colocalized into neutrophil lipid rafts. Moreover, neutrophil degranulation induced through inflammatory stimuli increased ILT4 expression as a result of the rapid translocation of an intracellular pool to the cell surface. Consequently to this ILT4 up-regulation, the human leukocyte antigen G-mediated inhibition of neutrophil phagocytic function was enhanced. Finally, we found that ILT4 up-regulation induced on healthy donor neutrophils following stimulation was impaired in presence of plasma from patients with sepsis. Similarly, ILT4 up-regulation was inhibited in neutrophils from septic patients. Altogether, our results reveal a unique mechanism of regulation of neutrophil functions through ILT4 and its exocytosis that may have implications in inflammatory disorders. PMID:24133137

Baudhuin, Jeremy; Migraine, Julie; Faivre, Valerie; Loumagne, Laure; Lukaszewicz, Anne-Claire; Payen, Didier; Favier, Benoit

2013-01-01

127

Piperine inhibits type II phosphatidylinositol 4-kinases: a key component in phosphoinositides turnover.  

PubMed

Piperine has been shown to have anti-inflammatory properties. The molecular mechanisms by which it mediates anti-inflammatory activities remain elusive. Type II phosphatidylinositol 4-kinase(s) are key components in Fc?RI receptor-mediated signaling leading to inflammatory mediators release in RBL-2H3 cells. The effects of piperine on IgE-mediated signaling and mast cell degranulation were investigated. Pretreatment of RBL-2H3 cells with piperine inhibited IgE-induced activation of type II PtdIns 4-kinase(s). In vitro lipid kinase assays showed piperine-inhibited type II PtdIns 4-kinase activity in a dose-dependent fashion with no effect on PtdIns 3-kinase activity. Concomitantly, pretreatment of RBL-2H3 cells with piperine also inhibited IgE-induced ?-hexosaminidase release in RBL-2H3 cells. These results suggest that type II PtdIns 4-kinases are part of piperine-mediated anti-inflammatory signaling mechanisms. PMID:24671493

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

2014-08-01

128

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

PubMed Central

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

129

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

130

Methods of Inhibiting Inflammation.  

National Technical Information Service (NTIS)

The invention provides a method of inhibiting inflammation in a mammal, by administering to the mammal composition containing a compound which inhibits the expression or activity of a microsomal triglyceride transfer protein.

R. S. Blumberg

2004-01-01

131

Methods of Inhibiting Inflammation.  

National Technical Information Service (NTIS)

The invention provides a method of inhibiting inflammation in a mammal, by administering to the mammal composition containing a compound which inhibits the expression or activity of a microsomal triglyceride transfer protein.

R. S. Blumberg

2005-01-01

132

Targeting the KIT Activating Switch Control Pocket: A Novel Mechanism to Inhibit Neoplastic Mast Cell Proliferation and Mast Cell Activation  

PubMed Central

Activating mutations in the receptor tyrosine kinase KIT, most notably KIT D816V, are commonly observed in patients with systemic mastocytosis. Thus, inhibition of KIT has been a major focus for treatment of this disorder. Here we investigated a novel approach to such inhibition. Utilizing rational drug design, we targeted the switch pocket (SP) of KIT which regulates its catalytic conformation. Two SP inhibitors thus identified, DP-2976 and DP-4851, were examined for effects on neoplastic mast cell proliferation and mast cell activation. Autophosphorylation of both wild type (WT) and, where also examined, KIT D816V was blocked by these compounds in transfected 293T cells, HMC 1.1 and 1.2 human mast cell lines; and in CD34+-derived human mast cells activated by stem cell factor (SCF). Both inhibitors induced apoptosis in the neoplastic mast cell lines and reduced survival of primary bone marrow mast cells from patients with mastocytosis. Moreover, the SP inhibitors more selectively blocked SCF potentiation of Fc?RI-mediated degranulation. Overall, SP inhibitors represent an innovative mechanism of KIT inhibition whose dual suppression of KIT D816V neoplastic mast cell proliferation and SCF enhanced mast cell activation may provide significant therapeutic benefits. PMID:22907049

Bai, Yun; Bandara, Geethani; Chan, Eunice Ching; Maric, Irina; Simakova, Olga; Bandara, Sachini N.; Lu, Wei-Ping; Wise, Scott C.; Flynn, Daniel L.; Metcalfe, Dean D.; Gilfillan, Alasdair M.; Wilson, Todd M.

2012-01-01

133

Inhibiting eukaryotic transcription  

PubMed Central

This review first discusses ways in which we can evaluate transcription inhibition, describe changes in nuclear structure due to transcription inhibition, and report on genes that are paradoxically stimulated by transcription inhibition. Next, it summarizes the characteristics and mechanisms of commonly used inhibitors: ?-amanitin is highly selective for RNAP II and RNAP III but its action is slow, actinomycin D is fast but its selectivity is poor, CDK9 inhibitors such as DRB and flavopiridol are fast and reversible but many genes escape transcription inhibition. New compounds, such as triptolide, are fast and selective and able to completely arrest transcription by triggering rapid degradation of RNAP II. PMID:21922053

2011-01-01

134

Histamine H4-receptors inhibit mast cell renin release in ischemia/reperfusion via protein kinase C ?-dependent aldehyde dehydrogenase type-2 activation.  

PubMed

Renin released by ischemia/reperfusion (I/R) from cardiac mast cells (MCs) activates a local renin-angiotensin system (RAS) causing arrhythmic dysfunction. Ischemic preconditioning (IPC) inhibits MC renin release and consequent activation of this local RAS. We postulated that MC histamine H4-receptors (H4Rs), being G?i/o-coupled, might activate a protein kinase C isotype-? (PKC?)-aldehyde dehydrogenase type-2 (ALDH2) cascade, ultimately eliminating MC-degranulating and renin-releasing effects of aldehydes formed in I/R and associated arrhythmias. We tested this hypothesis in ex vivo hearts, human mastocytoma cells, and bone marrow-derived MCs from wild-type and H4R knockout mice. We found that activation of MC H4Rs mimics the cardioprotective anti-RAS effects of IPC and that protection depends on the sequential activation of PKC? and ALDH2 in MCs, reducing aldehyde-induced MC degranulation and renin release and alleviating reperfusion arrhythmias. These cardioprotective effects are mimicked by selective H4R agonists and disappear when H4Rs are pharmacologically blocked or genetically deleted. Our results uncover a novel cardioprotective pathway in I/R, whereby activation of H4Rs on the MC membrane, possibly by MC-derived histamine, leads sequentially to PKC? and ALDH2 activation, reduction of toxic aldehyde-induced MC renin release, prevention of RAS activation, reduction of norepinephrine release, and ultimately to alleviation of reperfusion arrhythmias. This newly discovered protective pathway suggests that MC H4Rs may represent a new pharmacologic and therapeutic target for the direct alleviation of RAS-induced cardiac dysfunctions, including ischemic heart disease and congestive heart failure. PMID:24696042

Aldi, Silvia; Takano, Ken-ichi; Tomita, Kengo; Koda, Kenichiro; Chan, Noel Y-K; Marino, Alice; Salazar-Rodriguez, Mariselis; Thurmond, Robin L; Levi, Roberto

2014-06-01

135

Contact inhibition and malignancy  

Microsoft Academic Search

The role of contact inhibition in influencing the behaviour of malignant cells is discussed in a review. Although tissue culture cannot simulate the immense complexity of the conditions in vivo, some of the distinctive features of malignant invasion can be conveniently observed with this technique. The evidence derived from this technique indicates that defective contact inhibition of movement of malignant

M. Abercrombie

1979-01-01

136

Saccadic Inhibition in Reading  

Microsoft Academic Search

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 saliency of the visual

Eyal M. Reingold; Dave M. Stampe

2004-01-01

137

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

138

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

139

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

140

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

141

Uptake of donor lymphocytes treated with 8-methoxypsoralen and ultraviolet A light by recipient dendritic cells induces CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T cells and down-regulates cardiac allograft rejection  

SciTech Connect

Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy and has been demonstrated to be beneficial for graft-vs-host disease and solid-organ allograft rejection. ECP involves reinfusion of a patient's autologous peripheral blood leukocytes treated ex vivo with 8-methoxypsoralen and UVA light radiation (PUVA). Previous studies focused only on ECP treatment of recipient immune cells. Our study is the first to extend the target of ECP treatment to donor immune cells. The results of in vitro co-culture experiments demonstrate uptake of donor PUVA-treated splenic lymphocytes (PUVA-SPs) by recipient immature dendritic cells (DCs). Phagocytosis of donor PUVA-SPs does not stimulate phenotype maturation of recipient DCs. In the same co-culture system, donor PUVA-SPs enhanced production of interleukin-10 and interferon-{gamma} by recipient DCs and impaired the subsequent capability of recipient DCs to stimulate recipient naive T cells. Phagocytosis of donor PUVA-SP (PUVA-SP DCs) by recipient DCs shifted T-cell responses in favor of T helper 2 cells. Infusion of PUVA-SP DCs inhibited cardiac allograft rejection in an antigen-specific manner and induced CD4{sup +}CD25{sup high}Foxp3{sup +} regulatory T cells. In conclusion, PUVA-SP DCs simultaneously deliver the donor antigen and the regulatory signal to the transplant recipient, and thus can be used to develop a novel DC vaccine for negative immune regulation and immune tolerance induction.

Zheng, De-Hua [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China)] [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China); Dou, Li-Ping [Department of Hematology, Chinese PLA General Hospital, No. 28 Fu-Xing Road, Beijing 100853 (China)] [Department of Hematology, Chinese PLA General Hospital, No. 28 Fu-Xing Road, Beijing 100853 (China); Wei, Yu-Xiang; Du, Guo-Sheng; Zou, Yi-Ping; Song, Ji-Yong; Zhu, Zhi-Dong; Cai, Ming; Qian, Ye-Yong [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China)] [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China); Shi, Bing-Yi, E-mail: shibingyi@medmail.com.cn [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China)] [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China)

2010-05-14

142

Inhibition of Autoxidation.  

National Technical Information Service (NTIS)

Methods for inhibiting the autoxidation of organic substrates are reviewed. Antioxidants can be divided into two broad groups according to whether they reduce the rate of chain initiation (preventive antioxidants) or interfere with the normal propagation ...

K. U. Ingold

1967-01-01

143

AOP description: Acetylcholinesterase inhibition  

EPA Science Inventory

This adverse outcome pathway (AOP) leverages existing knowledge in the open literature to describe the linkage between inhibition of acetylcholinesterase (AChE) and the subsequent mortality resulting from impacts at cholinergic receptors. The AOP takes a chemical category approa...

144

Psychotherapy by reciprocal inhibition  

Microsoft Academic Search

Reciprocal inhibition is a process of relearning whereby in the presence of a stimulus a non-anxiety-producing response is\\u000a continually repeated until it extinguishes the old, undesirable response. A variety of the techniques based on reciprocal\\u000a inhibition, such as systematic desensitization, avoidance conditioning, and the use of assertion, are described in detail.\\u000a Behavior therapy techniques evaluated on the basis of their

Joseph Wolpe

1968-01-01

145

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. PMID:21437195

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

2011-01-01

146

Antigen-specific inhibition of high-avidity T cell target lysis by low-avidity T cells via trogocytosis.  

PubMed

Current vaccine conditions predominantly elicit low-avidity cytotoxic T lymphocytes (CTLs), which are non-tumor-cytolytic but indistinguishable by tetramer staining or enzyme-linked immunospot from high-avidity CTLs. Using CTL clones of high or low avidity for melanoma antigens, we show that low-avidity CTLs can inhibit tumor lysis by high-avidity CTLs in an antigen-specific manner. This phenomenon operates in vivo: high-avidity CTLs control tumor growth in animals but not in combination with low-avidity CTLs specific for the same antigen. The mechanism involves stripping of specific peptide-major histocompatibility complexes (pMHCs) via trogocytosis by low-avidity melanoma-specific CTLs without degranulation, leading to insufficient levels of specific pMHC on target cell surface to trigger lysis by high-avidity CTLs. As such, peptide repertoire on the cell surface is dynamic and continually shaped by interactions with T cells. These results describe immune regulation by low-avidity T cells and have implications for vaccine design. PMID:25088413

Chung, Brile; Stuge, Tor B; Murad, John P; Beilhack, Georg; Andersen, Emily; Armstrong, Brian D; Weber, Jeffrey S; Lee, Peter P

2014-08-01

147

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

148

Gas hydrate inhibition  

Microsoft Academic Search

This patent describes a process for inhibiting gas hydrate formation in the production fluid of a well, connected facilities and pipelines of the well comprising injecting into the well inhibitor comprising a carrier and a polycyclicpolyetherpolyol. This patent also describes a process for shutting-in a well having a fluid therein which is susceptible to the formation of gas hydrates. It

A. H. Hale; A. K. R. Dewan; G. C. Blytas

1991-01-01

149

Latent inhibition in schizophrenia  

Microsoft Academic Search

Latent inhibition (LI) refers to the retarded acquisition of a conditioned response that occurs if the subject being tested is first preexposed to the to-be-conditioned stimulus (CS) without the paired unconditioned stimulus (UCS). Because the ‘irrelevance’ of the to-be-conditioned stimulus is established during non-contingent preexposure, the slowed acquisition of the CS-UCS association is thought to reflect the process of overcoming

Neal R. Swerdlow; David L. Braff; Heidi Hartston; William Perry; Mark A. Geyer

1996-01-01

150

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

151

Arginine inhibits serpins.  

PubMed

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 antithrombin, antiplasmin, or anti-C1-esterase activity was determined: A total of 20 microL of pooled normal plasma or 7% human albumin was added to 100 microL of 0-2.67 M arginine, pH 8.6, 10 microL of 26 mIU/mL thrombin in 7% human albumin, and 30 microL of 1.7 mM CHG-Ala-Arg-pNA (37 degrees C). DeltaA at 405 nm was determined, by using a microtiter plate reader. Thrombin was substituted by plasmin or C1-esterase, and the chromogenic peptide substrates inhibited similarly by arginine: the IC(50) for arginine against the amidolytic activity of these proteases is about 400 mM. Arginine at very high concentrations inhibits serpins. This is important, if stabilization of a biological fluid is a prerequisite for valid activities of serine proteases. In addition, these high concentrations of arginine might be a new gentle principle to inhibit pathogens that need serpins for their pathophysiology. PMID:17456633

Stief, Thomas W

2007-04-01

152

Substance P inhibits natural killer cell cytotoxicity through the neurokinin-1 receptor  

PubMed Central

SP is a potent neuroimmunomodulator that functions through ligating members of the neurokinin receptor family, one of which, NK1R, is widely expressed in immune cells. As in humans, circulating SP levels are increased in pathologic states associated with impairment of NK cell functions, such as depression and HIV infection, we hypothesized that SP has a direct, inhibitory effect upon NK cells. We have studied a clonal human NK cell line (YTS) as well as ex vivo human NK cells and have determined that truncated and full-length NK1R isoforms are expressed in and SP bound by ex vivo NK cells and the YTS NK cell line. Incubation of YTS cells with 10?6 M SP and ex vivo NK cells with 10?5 M SP inhibited cytotoxic ability by ?20% and reduced degranulation. This inhibitory effect upon cytotoxicity was partially prevented by the NK1R antagonist CP96,345. The treatment of YTS or ex vivo NK cells with SP neither down-modulated NCR expression nor affected triggering receptor-induced NF-?B activation. Preincubation of YTS cells with SP, however, did abbreviate the typically prolonged intracellular calcium increase induced by target cell engagement and reduced triggering receptor-induced pERK. Thus, SP has the potential to regulate NK cell functions and acts downstream from neurokinin receptors to modulate NK cell activation signaling. This mechanism may contribute to impairment of NK cell function in certain disease states associated with increased circulating SP. Antagonism of this system may present an opportunity to augment NK cell function therapeutically in selected human diseases. PMID:20940324

Monaco-Shawver, Linda; Schwartz, Lynnae; Tuluc, Florin; Guo, Chang-Jiang; Lai, Jian Ping; Gunnam, Satya M.; Kilpatrick, Laurie E.; Banerjee, Pinaki P.; Douglas, Steven D.; Orange, Jordan S.

2011-01-01

153

Immunization with Hypoallergens of Shrimp Allergen Tropomyosin Inhibits Shrimp Tropomyosin Specific IgE Reactivity  

PubMed Central

Designer proteins deprived of its IgE-binding reactivity are being sought as a regimen for allergen-specific immunotherapy. Although shrimp tropomyosin (Met e 1) has long been identified as the major shellfish allergen, no immunotherapy is currently available. In this study, we aim at identifying the Met e 1 IgE epitopes for construction of hypoallergens and to determine the IgE inhibitory capacity of the hypoallergens. IgE-binding epitopes were defined by three online computational models, ELISA and dot-blot using sera from shrimp allergy patients. Based on the epitope data, two hypoallergenic derivatives were constructed by site-directed mutagenesis (MEM49) and epitope deletion (MED171). Nine regions on Met e 1 were defined as the major IgE-binding epitopes. Both hypoallergens MEM49 and MED171 showed marked reduction in their in vitro reactivity towards IgE from shrimp allergy patients and Met e 1-sensitized mice, as well as considerable decrease in induction of mast cell degranulation as demonstrated in passive cutaneous anaphylaxis assay. Both hypoallergens were able to induce Met e 1-recognizing IgG antibodies in mice, specifically IgG2a antibodies, that strongly inhibited IgE from shrimp allergy subjects and Met e 1-sensitized mice from binding to Met e 1. These results indicate that the two designer hypoallergenic molecules MEM49 and MED171 exhibit desirable preclinical characteristics, including marked reduction in IgE reactivity and allergenicity, as well as ability to induce blocking IgG antibodies. This approach therefore offers promises for development of immunotherapeutic regimen for shrimp tropomyosin allergy. PMID:25365343

Wai, Christine Y. Y.; Leung, Nicki Y. H.; Ho, Marco H. K.; Gershwin, Laurel J.; Shu, Shang An; Leung, Patrick S. C.; Chu, Ka Hou

2014-01-01

154

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

155

Innovative Therapy of CTCL: Beyond PUVA and Nitrogen Mustard  

PubMed Central

Synopsis Cutaneous T Cell Lymphoma is a malignancy of skin homing T cells. This unique population of lymphocytes requires alternative therapies than those used in nodal lymphomas. Although phototherapy and nitrogen mustard have been standard treatments for decades, newer therapies have been arriving with increased frequency. Moreover some therapies, currently used to treat other disease, have been used in CTCL with good effect. These innovative therapies in CTCL are discussed, with review of current data and examples of how these therapies may be utilized today. PMID:20510760

Heald, Peter

2010-01-01

156

Changes in cell ultrastructure and inhibition of JAK1/STAT3 signaling pathway in CBRH-7919 cells with astaxanthin.  

PubMed

Astaxanthin (AST), a xanthophylls carotenoid, possesses significant anticancer effects. However, to date, the molecular mechanism of anticancer remains unclear. In the present research, we studied the anticancer mechanism of AST, including the changes in cell ultrastructure, such as the mitochondrion, rough endoplasmic reticulum (RER), Golgi complex, and cytoskeleton, the inhibition of Janus kinase 1(JAK1)/transduction and the activators of the transcription-3 (STAT3) signaling pathway using rat hepatocellular carcinoma CBRH-7919 cells. Cell apoptosis was evaluated and the expressions of JAK1, STAT3, non-metastasis23-1 (nm23-1), and apoptotic gene like B-cell lymphoma/leukemia-2 (bcl-2), B-cell lymphoma-extra large (bcl-xl), proto-oncogene proteins c myc (c-myc) and bcl-2- associated X (bax) were also examined. The results showed that AST could induce cancer cell apoptosis. Under transmission electron microscope, the ultrastructure of treated cells were not clearly distinguishable, the membranes of the mitochondrion, RER, Golgi complex were broken or loosened, and the endoplasmic reticulum (ER) was degranulated. Cytoskeleton depolymerization of the microtubule system led to the collapse of extended vimentin intermediate filament bundles into short agglomerations with disordered distributions. AST inhibited the expression of STAT3, its upstream activator JAK1, and the STAT3 target antiapoptotic genes bcl-2, bcl-xl, and c-myc. Conversely, AST enhanced the expressions of nm23-1 and bax. Overall, our findings demonstrate that AST could induce the apoptosis of CBRH-7919 cells, which are involved in cell ultrastructure and the JAK1/STAT3 signaling pathway. PMID:22889354

Song, Xiaodong; Wang, Meirong; Zhang, Lixia; Zhang, Jinjin; Wang, Xiuwen; Liu, Wenbo; Gu, Xinbin; Lv, Changjun

2012-11-01

157

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

SciTech Connect

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

Park, Kui Lea [Center for Drug Development Assistance, National Institute of Food Drug Safety Evaluation (NIFDS), KFDA, Cheongwon-gun (Korea, Republic of)] [Center for Drug Development Assistance, National Institute of Food Drug Safety Evaluation (NIFDS), KFDA, Cheongwon-gun (Korea, Republic of); Ko, Na Young; Lee, Jun Ho; Kim, Do Kyun; Kim, Hyuk Soon; Kim, A-Ram; Her, Erk; Kim, Bokyung [Department of Immunology and physiology, College of Medicine, Konkuk University, Chungju (Korea, Republic of)] [Department of Immunology and physiology, College of Medicine, Konkuk University, Chungju (Korea, Republic of); Kim, Hyung Sik [College of Pharmacy, Pusan National University, Busan (Korea, Republic of)] [College of Pharmacy, Pusan National University, Busan (Korea, Republic of); Moon, Eun-Yi [Department of Bioscience and Biotechnology, College of Biological Science, Sejong University, Seoul (Korea, Republic of)] [Department of Bioscience and Biotechnology, College of Biological Science, Sejong University, Seoul (Korea, Republic of); Kim, Young Mi [College of Pharmacy, Duksung Women's University, Seoul (Korea, Republic of)] [College of Pharmacy, Duksung Women's University, Seoul (Korea, Republic of); Kim, Hang-Rae, E-mail: hangrae2@snu.ac.kr [Department of Anatomy, Seoul National University College of Medicine, Seoul (Korea, Republic of)] [Department of Anatomy, Seoul National University College of Medicine, Seoul (Korea, Republic of); Choi, Wahn Soo, E-mail: wahnchoi@kku.ac.kr [Department of Immunology and physiology, College of Medicine, Konkuk University, Chungju (Korea, Republic of)

2011-12-15

158

Gas hydrate inhibition  

SciTech Connect

This patent describes a process for inhibiting gas hydrate formation in the production fluid of a well, connected facilities and pipelines of the well comprising injecting into the well inhibitor comprising a carrier and a polycyclicpolyetherpolyol. This patent also describes a process for shutting-in a well having a fluid therein which is susceptible to the formation of gas hydrates. It comprises preparing a gas hydrate inhibitor by admixing an alcohol with a carrier, the carrier and the alcohol and the quantities thereof being selected to be compatible with the well and effective to prevent the formation of gas hydrates in the well fluid; selecting an appropriate location, depending upon the type of well being shut-in, and injecting the gas hydrate inhibitor into the well at the location; and shutting-in the well.

Hale, A.H.; Dewan, A.K.R.; Blytas, G.C.

1991-12-31

159

[Penicillium-inhibiting yeasts].  

PubMed

The objective of this work was to establish the in vitro and in vivo inhibition of post-harvest pathogenic moulds by yeasts in order to make a biocontrol product. Post-harvest pathogenic moulds Penicillium digitatum, P. italicum, P. ulaiense, Phyllosticta sp., Galactomyces geotrichum and yeasts belonging to genera Brettanomyces, Candida, Cryptococcus, Kloeckera, Pichia, Rhodotorula were isolated from citrus fruits. Some yeasts strains were also isolated from other sources. The yeasts were identified by their macro and micro-morphology and physiological tests. The in vitro and in vivo activities against P. digitatum or P. ulaiense were different. Candida cantarellii and one strain of Pichia subpelliculosa produced a significant reduction of the lesion area caused by the pathogenic moulds P. digitatum and P. ulaiense, and could be used in a biocontrol product formulation. PMID:15786872

Benítez Ahrendts, M R; Carrillo, L

2004-01-01

160

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

161

Chemical limits to flame inhibition  

Microsoft Academic Search

This paper deals with the ultimate limits of chemical contributions to flame inhibition. Particular attention is focussed on the inhibition cycles which regenerate the inhibitor. This leads to the definition of an idealized “perfect” inhibition cycle. It is demonstrated that for such an inhibitor in a stoichiometric methane\\/air flame, additive levels in the 0.001–0.01 mole percent range will lead to

V. Babushok; W. Tsang; G. T. Linteris; D. Reinelt

1998-01-01

162

Inhibition of Erythrocyte Invasion and Plasmodium falciparum Merozoite Surface Protein 1 Processing by Human Immunoglobulin G1 (IgG1) and IgG3 Antibodies ?  

PubMed Central

Antigen-specific antibodies (Abs) to the 19-kDa carboxy-terminal region of Plasmodium falciparum merozoite surface protein 1 (MSP119) play an important role in protective immunity to malaria. Mouse monoclonal Abs (MAbs) 12.10 and 12.8 recognizing MSP119 can inhibit red cell invasion by interfering with MSP1 processing on the merozoite surface. We show here that this ability is dependent on the intact Ab since Fab and F(ab?)2 fragments derived from MAb 12.10, although capable of binding MSP1 with high affinity and competing with the intact antibody for binding to MSP1, were unable to inhibit erythrocyte invasion or MSP1 processing. The DNA sequences of the variable (V) regions of both MAbs 12.8 and 12.10 were obtained, and partial amino acid sequences of the same regions were confirmed by mass spectrometry. Human chimeric Abs constructed by using these sequences, which combine the original mouse V regions with human ?1 and ?3 constant regions, retain the ability to bind to both parasites and recombinant MSP119, and both chimeric human immunoglobulin G1s (IgG1s) were at least as good at inhibiting erythrocyte invasion as the parental murine MAbs 12.8 and 12.10. Furthermore, the human chimeric Abs of the IgG1 class (but not the corresponding human IgG3), induced significant NADPH-mediated oxidative bursts and degranulation from human neutrophils. These chimeric human Abs will enable investigators to examine the role of human Fc? receptors in immunity to malaria using a transgenic parasite and mouse model and may prove useful in humans for neutralizing parasites as an adjunct to antimalarial drug therapy. PMID:19805526

Lazarou, Maria; Patińo, José A. Guevara; Jennings, Richard M.; McIntosh, Richard S.; Shi, Jianguo; Howell, Steven; Cullen, Eilish; Jones, Tarran; Adame-Gallegos, Jaime R.; Chappel, Jonathan A.; McBride, Jana S.; Blackman, Michael J.; Holder, Anthony A.; Pleass, Richard J.

2009-01-01

163

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. PMID:23029308

Zhu, Keqing

2012-01-01

164

Inhibition of glucagon secretion.  

PubMed

This chapter describes a physiological and profound effect of amylin to inhibit meal-related glucagon secretion. Glucagon is processed from a large precursor, proglucagon, in a tissue-specific manner in pancreatic alpha-cells. In addition to amino acid nutrient stimuli, glucagon is also secreted in response to stressful stimuli, such as hypoglycemia and hypovolemia. Glucagon primarily acts on liver to initiate glycogenolysis and gluconeogenesis, resulting in a rapid increase in endogenous production of glucose. With longer stimulation, glucagon action at the liver results in a glucose-sparing activation of free fatty acid oxidation and production of ketones. During hypoglycemia, glucagon secretion is clearly a protective feed-back, defending the organism against damaging effects of low glucose in brain and nerves (neuroglycopenia). Amino acid-stimulated glucagon secretion during meals has a different purpose: amino acids stimulate insulin secretion, which mobilizes amino acid transporters and effects their storage in peripheral tissues. At the same time, insulin obligatorily recruits GLUT4 glucose transporters in muscle and fat. The hypoglycemic potential of such GLUT4 mobilization is averted only by the simultaneous liberation of endogenous glucose in response to feedforward (anticipatory) glucagon secretion. The effect of amylin and its agonists to inhibit amino acid-stimulated glucagon secretion is both potent (EC50 = 18 pM) and profound (approximately 70% inhibition). This glucagonostatic action appears to be extrinsic to the pancreatic islet, occurring in intact animals and in patients, but not in isolated islets or isolated perfused pancreas preparations. On the other hand, the effect of hypoglycemia to stimulate glucagon secretion, which is intrinsic to the islet and occurs in isolated preparations, is not affected by amylin or its agonists. The physiological interpretation of these actions fits with the general concept, illustrated in Fig. 1, that amylin and insulin secreted in response to meals shut down endogenous production as a source of glucose, in favor of that derived from the meal. Amylin and insulin secreted in response to nutrients already absorbed act as a feedback switch for glucose sourcing. The insulinotropic (incretin) gut peptides, GLP-1 and GIP, secreted in response to yet-to-be-absorbed intraluminal nutrients, amplify beta-cell secretion and thereby activate the glucose sourcing switch in a feedforward manner. Hypoglycemia-stimulated glucagon secretion and nutrient (amino acid)-stimulated glucagon secretion are two clearly different processes, differently affected by amylin. The balance of glucose fluxes is disturbed in diabetic states, partly as a result of inappropriate glucagon secretion. Although glucose production due to glucagon secreted in response to hypoglycemia is normal or even reduced in diabetic patients, the secretion of glucagon (and production of endogenous glucose) in response to protein meals is typically exaggerated. Absence of appropriate beta-cell suppression of alpha-cell secretion has been invoked as a mechanism that explains exaggerated glucagon responses, especially prevalent in patients with deficient beta-cell secretion (type 1 diabetes and insulinopenic type 2 diabetes). A proposed benefit of insulin replacement therapy is the reduction of absolute or relative hyperglucagonemia. High glucagon is said to be necessary for ketosis in severe forms of diabetes. A further benefit of reversing hyperglucagonemia is reduction of the excessive endogenous glucose production that contributes to fasting and postprandial hyperglycemia in diabetes. The idea that amylin is a part of the beta-cell drive that normally limits glucagon secretion after meals fits with the observation that glucagon secretion is exaggerated in amylin-deficient states (diabetes characterized by beta-cell failure). This proposal is further supported by the observation that postprandial glucagon suppression is restored following amylin replacement therapy in such states. These observations argue for a therapeu

Young, Andrew

2005-01-01

165

Research Article Inhibition Versus Switching  

E-print Network

information. We used a task-switching paradigm that can distinguish between these two processes. Two rumination are associated with difficulties in switching to a new task set, but not with inhibitionResearch Article Inhibition Versus Switching Deficits in Different Forms of Rumination Anson J

Banich, Marie T.

166

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

167

Propolis inhibits osteoclast maturation.  

PubMed

Propolis, a natural product produced by the honey bee, has been successfully used in medicine as an anti-inflammatory and antimicrobial agent. Traumatic injuries to the teeth, especially avulsion injuries, present a challenging situation for the clinician because of post-treatment complications, such as inflammatory and/or replacement resorption. Agents that reduce osteoclast numbers and activity may be useful in the treatment of traumatic injuries to the teeth. In this study, we evaluated propolis as an anti-resorptive agent. Calcitriol-stimulated mouse marrow cultures, which contain both osteoclasts and osteoblasts, were exposed to the ethanol extracts of propolis or vehicle control and stained for tartrate-resistant acid phosphatase (TRAP)-activity to identify osteoclasts. A significant, dose-dependent reduction in multinuclear TRAP+ cells was demonstrated, although the propolis treatment accommodated cell growth and survival (P < 0.05). Propolis also reduced the formation of actin rings in pure cultures of RAW 264.7 osteoclast-like cells, suggesting that it exerts direct actions on osteoclast maturation. In summary, our data suggest that propolis inhibits late stages of osteoclast maturation including fusion of osteoclasts precursors to form giant cells and formation of actin rings. This supports the hypothesis that it may prove useful as a medicament to reduce resorption associated with traumatic injuries to the teeth. PMID:19843135

Pileggi, Roberta; Antony, Kathryn; Johnson, Kristie; Zuo, Jian; Shannon Holliday, L

2009-12-01

168

Contact inhibition in tissue culture  

Microsoft Academic Search

Conclusions  Contact inhibition of movement is here defined simply as the stopping of the continued locomotion of a cell in the direction\\u000a which has produced a collision with another cell; so that one cell does not use another as a substratum. Amongst fibroblasts\\u000a and epithelial cells this inhibition seems to be brought about by a mechanism which it is suggested consists

M. Abercrombie

1970-01-01

169

Inhibition of MMPs by alcohols  

PubMed Central

Objectives While screening the activity of potential inhibitors of matrix metalloproteinases (MMPs), due to the limited water solubility of some of the compounds, they had to be solubilized in ethanol. When ethanol solvent controls were run, they were found to partially inhibit MMPs. Thus, the purpose of this study was to compare the MMP-inhibitory activity of a series of alcohols. Methods The possible inhibitory activity of a series of alcohols was measured against soluble rhMMP-9 and insoluble matrix-bound endogenous MMPs of dentin in completely demineralized dentin. Increasing concentrations (0.17, 0.86, 1.71 and 4.28 moles/L) of a homologous series of alcohols (i.e. methanol, ethanol, propanols, butanols, pentanols, hexanols, the ethanol ester of methacrylic acid, heptanols and octanol) were compared to ethanediol, and propanediol by regression analysis to calculate the molar concentration required to inhibit MMPs by 50% (i.e. the IC50). Results Using two different MMP models, alcohols were shown to inhibit rhMMP-9 and the endogenous proteases of dentin matrix in a dose-dependent manner. The degree of MMP inhibition by alcohols increased with chain length up to 4 methylene groups. Based on the molar concentration required to inhibit rhMMP-9 fifty percent, 2-hydroxyethylmethacrylate (HEMA), 3-hexanol, 3-heptanol and 1-octanol gave the strongest inhibition. Significance The results indicate that alcohols with 4 methylene groups inhibit MMPs more effectively than methanol or ethanol. MMP inhibition was inversely related to the Hoy's solubility parameter for hydrogen bonding forces of the alcohols (i.e. to their hydrophilicity). PMID:21676453

Tezvergil-Mutluay, Arzu; Agee, Kelli A.; Hoshika, Tomohiro; Uchiyama, Toshikazu; Tjaderhane, Leo; Breschi, Lorenzo; Mazzoni, Annalisa; Thompson, Jeremy M.; McCracken, Courtney E.; Looney, Stephen W.; Tay, Franklin R.; Pashley, David H.

2011-01-01

170

1,25(OH)2 vitamin D3-dependent inhibition of platelet Ca2+ signaling and thrombus formation in klotho-deficient mice.  

PubMed

Platelets are activated by increased cytosolic Ca(2+) concentration ([Ca(2+)]i) following store-operated calcium entry (SOCE) accomplished by calcium-release-activated calcium (CRAC) channel moiety Orai1 and its regulator STIM1. In other cells, Ca(2+) transport is regulated by 1,25(OH)2 vitamin D3 [1,25(OH)2D3]. 1,25(OH)2D3 formation is inhibited by klotho and excessive in klotho-deficient mice (kl/kl). The present study explored the effect of klotho deficiency on platelet Ca(2+) signaling and activation. Platelets and megakaryocytes isolated from WT and kl/kl-mice were analyzed by RT-PCR, Western blotting, confocal microscopy, Fura-2-fluorescence, patch clamp, flow cytometry, aggregometry, and flow chamber. STIM1/Orai1 transcript and protein levels, SOCE, agonist-induced [Ca(2+)]i increase, activation-dependent degranulation, integrin ?IIb?3 activation and aggregation, and thrombus formation were significantly blunted in kl/kl platelets (by 27-90%). STIM1/Orai1 transcript and protein levels, as well as CRAC currents, were significantly reduced in kl/kl megakaryocytes (by 38-73%) and 1,25(OH)2D3-treated WT megakaryocytes. Nuclear NF-?B subunit p50/p65 abundance was significantly reduced in kl/kl-megakaryocytes (by 51-76%). Transfection with p50/p65 significantly increased STIM1/Orai1 transcript and protein levels in megakaryocytic MEG-01 cells (by 46-97%). Low-vitamin D diet (LVD) of kl/kl mice normalized plasma 1,25(OH)2D3 concentration and function of platelets and megakaryocytes. Klotho deficiency inhibits platelet Ca(2+) signaling and activation, an effect at least partially due to 1,25(OH)2D3-dependent down-regulation of NF-?B activity and STIM1/Orai1 expression in megakaryocytes. PMID:24522202

Borst, Oliver; Münzer, Patrick; Schmid, Evi; Schmidt, Eva-Maria; Russo, Antonella; Walker, Britta; Yang, Wenting; Leibrock, Christina; Szteyn, Kalina; Schmidt, Sebastian; Elvers, Margitta; Faggio, Caterina; Shumilina, Ekaterina; Kuro-o, Makoto; Gawaz, Meinrad; Lang, Florian

2014-05-01

171

Analytical aspects of enzyme reversible inhibition.  

PubMed

A simple graphical method for the determination of reversible inhibition type, inhibition constant (Ki) and estimation of fifty percent of inhibition I?? of an enzyme reaction is described. The method consists of plotting experimental data as "degree of inhibition" versus the inhibitor concentration at two or more concentrations of substrate. Diagnosis of inhibition type is based on determination of and the observation of the shift of the inhibition curves. Relationship between I50 and inhibition constant Ki was discussed. A simplified hyperbolae equation of degree of inhibition showing kinetic orders of 1 and zero at low and high concentrations of inhibitors respectively is proposed. The relative error of inhibitor concentration increased drastically when degree of inhibition reached values of 90%. Examples of published inhibition reports as well as an experimental example of amperometric biosensor based on tyrosinase inhibition by benzoic acid were in agreement with the proposed theoretical approach. PMID:24274310

Amine, Aziz; El Harrad, Loubna; Arduini, Fabiana; Moscone, Danila; Palleschi, Giuseppe

2014-01-01

172

Reduction of stuttering: the dual inhibition hypothesis.  

PubMed

Treatment for stuttering attempts to reduce or eliminate the observable core markers of the disorder, specifically repetitions and prolongation. In this hypothesis, it is proposed that stuttering may be inhibited by two distinct yet related procedures: active inhibition and passive inhibition. Active inhibition is brought about when the person who stutters makes volitional changes to his or her speaking pattern, such as when employing behavioral modification techniques. Passive inhibition automatically inhibits the involuntary stuttering block and can be induced from an external source, such as altered auditory feedback, or by the use of sufficient active inhibition. It is suggested that passively inhibiting stuttering results in speech that is more automatic, natural sounding, and truly fluent speech than the speech that is derived primarily from active inhibition. Evidence of passive inhibition resulting from active inhibition can be seen when people who stutter exhibit uncontrolled fluency following behavioral therapy. PMID:11863400

Saltuklaroglu, T; Dayalu, V N; Kalinowski, J

2002-01-01

173

Behavioral inhibition and childhood stuttering  

PubMed Central

Purpose The purpose of this study was to assess the relation of behavioral inhibition to stuttering and speech/language output in preschool-age children who do (CWS) and do not stutter (CWNS). Method Participants were preschool-age (ages 36 to 68 months), including 26 CWS (22 males) and 28 CWNS (13 males). Participants’ behavioral inhibition (BI) was assessed by measuring the latency to their sixth spontaneous comment during conversation with an unfamiliar experimenter, using methodology developed by Kagan, Reznick, and Gibbons (1989). In addition to these measures of BI, each participant’s stuttered and non-stuttered disfluencies and mean length of utterance (in morphemes) were assessed. Results Among the more salient findings, it was found that (1) there was no significant difference in BI between preschool-age CWS and CWNS as a group, (2) when extremely high versus low inhibited children were selected, there were more CWS with higher BI and fewer CWS with lower BI when compared to their CWNS peers, and (3) more behaviorally inhibited CWS, when compared to less behaviorally inhibited CWS, exhibited more stuttering. Conclusions Findings are taken to suggest that one aspect of temperament (i.e., behavioral inhibition) is exhibited by some preschool-age CWS and that these children stutter more than CWS with lower behavioral inhibition. The present results seem to support continued study of the association between young children’s temperamental characteristics and stuttering, the diagnostic entity (i.e., CWS versus CWNS), as well as stuttering, the behavior (e.g., frequency of stuttered disfluencies). PMID:23773669

Choi, Dahye; Conture, Edward G.; Walden, Tedra A.; Lambert, Warren E.; Tumanova, Victoria

2013-01-01

174

Bacterial Inhibition by Electrical Stimulation  

PubMed Central

Significance: Much evidence shows that electrical stimulation (ES) promotes the wound healing process. The inhibitory effect of ES on bacterial growth has been proposed as a mechanism to explain the useful effects of ES on wound healing. Bacterial burden has been associated with chronic wounds. The extensive use of antibiotics can lead to the spread of multiple drug resistant bacteria. Whether biophysical energies, such as ES, can be used as a treatment modality against pathogenic microorganisms remains an open question. Recent Advances: The research literature provides evidence for useful effects of ES in terms of inhibition of bacterial growth. The type of ES, its polarity, and the intensity of the current play a major role in establishment of antibacterial effects. Both direct current (DC) and high voltage pulse current are more effective at inhibiting bacterial growth than are other types of ES. The exact mechanism underlying the antibacterial effects of ES is not clear. Critical Issues: Available evidence indicates that microampere DC (?ADC) is better than other ES types for inhibition of bacterial growth. The results of most studies also support the application of cathodal current for bacterial growth inhibition. The current intensity of ES would appear to be tolerable by humans if used clinically for treatment of infected wounds. Future Directions: The cathodal ?ADC appears to be more effective for inhibition of microorganism growth. Further research, especially in vivo, is necessary to clarify the inhibitory effects of ES on wound bacterial infections. PMID:24761349

Asadi, Mohammad Reza; Torkaman, Giti

2014-01-01

175

Remote inhibition of polymer degradation.  

SciTech Connect

Polymer degradation has been explored on the basis of synergistic infectious and inhibitive interaction between separate materials. A dual stage chemiluminescence detection system with individually controlled hot stages was applied to probe for interaction effects during polymer degradation in an oxidizing environment. Experimental confirmation was obtained that volatile antioxidants can be transferred over a relatively large distance. The thermal degradation of a polypropylene (PP) sample receiving traces of inhibitive antioxidants from a remote source is delayed. Similarly, volatiles from two stabilized elastomers were also capable of retarding a degradation process remotely. This observation demonstrates inhibitive cross-talk as a novel interactive phenomenon between different polymers and is consequential for understanding general polymer interactions, fundamental degradation processes and long-term aging effects of multiple materials in a single environment.

Clough, Roger Lee; Celina, Mathias Christopher

2005-08-01

176

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

177

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. PMID:24146907

Xin, Ziqiang; Liu, Guofang

2013-01-01

178

SPECIFIC INHIBITION OF CHLOROPLAST REPLICATION  

E-print Network

In Euglena gracilis the synthesis of the chloroplast from its precursor, the proplastid, is separated in time from the division or replication of the organelle which occurs just prior to cell division (10, 12). The proplastids are only found in darkgrown cells and rapidly form chloroplasts when such cells are exposed to light. The proplastids divide during dark growth. Ultraviolet irradiation inhibits proplastid division or replication but does not interfere with the proplastid's ability to synthesize chloroplasts (12). Chloroplast replication is also inhibited by ultraviolet irradiation (8). Euglena, then, is an excellent organism for the study of chloroplast synthesis and replication. Nalidixic acid (-ethyl 1-4 dihydro-7-methyl-

In Euglena; Nalidixic Acid

179

Action spectra for photosynthetic inhibition  

NASA Technical Reports Server (NTRS)

The ultraviolet action spectrum for photosynthesis inhibition was determined to fall between that of the general DNA action spectrum and the generalized plant action spectrum. The characteristics of this action spectrum suggest that a combination of pronounced increase in effectiveness with decreasing wavelength, substantial specificity for the UV-B waveband, and very diminished response in the UV-A waveband result in large radiation amplification factors when the action spectra are used as weighting functions. Attempted determination of dose/response relationships for leaf disc inhibition provided inconclusive data from which to deconvolute an action spectrum.

Caldwell, M. M.; Flint, S.; Camp, L. B.

1981-01-01

180

[Ulcer therapy without acid inhibition].  

PubMed

The mechanism of action of ulcer drugs without acid inhibition appears to involve improvement of defensive factors of the gastroduodenal mucosa. The concept of ulcer healing without acid inhibition is attractive for theoretical reasons, because doubts have arisen about the safety of elevation of intragastric pH, especially in long-term treatment of peptic ulcer disease. Ulcer drugs that do not affect gastric acidity may therefore be preferred, provided they compare favorably to the best acid inhibitors available in terms of efficacy, adverse effects and other requirements. Among these drugs, sucralfate fulfills these criteria to a large extent. PMID:6547542

Koelz, H R

1984-05-19

181

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

182

Infant Predictors of Behavioural Inhibition  

ERIC Educational Resources Information Center

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…

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

2008-01-01

183

Subliminal priming of intentional inhibition.  

PubMed

Intentional choice is an important process underlying human behaviour. Intentional inhibition refers to the capacity to endogenously cancel an about-to-be-executed action at the last moment. Previous research suggested that such intentional inhibitory control requires conscious effort and awareness. Here we show that intentional decisions to inhibit are nevertheless influenced by unconscious processing. In a novel version of the Go/No-Go task, participants made speeded keypress actions to a Go target, or withheld responses to a No-Go target, or made free, spontaneous choices whether to execute or inhibit a keypress when presented with a free-choice target. Prior to each target, subliminal masked prime arrows were presented. Primes could be congruent with the Go or No-Go arrows, or neutral. Response times and proportion of action choices were measured. Primes were presented at latencies that would give either positive or negative compatibility effects (PCE, Experiment 1, and NCE, Experiment 2, respectively), based on previous literature. Go-primes at positive-compatibility latencies facilitated speeded response times as expected, but did not influence number of choices to act on free-choice trials. However, when Go primes were presented at negative-compatibility latencies, "free" decisions to inhibit were significantly increased. Decisions to act or not can be unconsciously manipulated, at least by inhibitory mechanisms. The cognitive mechanisms for intentionally withholding an action can be influenced by unconscious processing. We discuss possible moral and legal implications of these findings. PMID:24334316

Parkinson, Jim; Haggard, Patrick

2014-02-01

184

Human cytomegalovirus inhibits erythropoietin production.  

PubMed

Anemia is a feature of CKD and a complication of renal transplantation, often caused by impaired production of erythropoietin. The kidney is a target organ for human cytomegalovirus (hCMV) in such patients, but it is not known whether hCMV effects erythropoietin production. We found that kidneys from patients with CKD were positive for hCMV protein and that blood levels of hCMV IgG inversely correlated with red blood cell count. In mice, systemic murine cytomegalovirus infection decreased serum erythropoietin levels. In human erythropoietin-producing cells, hCMV inhibited hypoxia-induced expression of erythropoietin mRNA and protein. hCMV early gene expression was responsible, as ultraviolet-inactivated virus had no effect and valganciclovir treatment showed that late gene expression was nonessential. Hypoxia-induced gene transcription is controlled by the transcription factors hypoxia-inducible transcription factor (HIF)-1? and HIF2?, which are constitutively produced but stable only under low oxygen conditions. We found that hCMV inhibited constitutive production of HIF2? mRNA. HIF2? is thought to be the master regulator of erythropoietin transcription. Single-cell analysis revealed that nuclear accumulation of HIF2? was inhibited in hCMV-infected cells, and the extent of inhibition correlated with hCMV protein expression. Our findings suggest that renal hCMV infection could induce or exacerbate anemia in patients. PMID:24722450

Butler, Lynn M; Dzabic, Mensur; Bakker, Frank; Davoudi, Belghis; Jeffery, Hannah; Religa, Piotr; Bojakowski, Krzysztof; Yaiw, Koon-Chu; Rahbar, Afsar; Söderberg-Naucler, Cecilia

2014-08-01

185

Autoionization inhibited by internal interferences  

Microsoft Academic Search

Measurements of autoionizing Rydberg states of barium are presented, with principal quantum numbers ranging between 14 and 100. The results indicate that the interelectron Coulomb interaction can be adjusted to inhibit autoionization by variation of the principal quantum number in a doubly excited Rydberg series. In this manner, three-orders-of-magnitude change has been observed in the autoionization rate for states whose

J. Neukammer; H. Rinneberg; G. Joensson; W. E. Cooke; H. Hieronymus; A. König; K. Vietzke; H. Spinger-Bolk

1985-01-01

186

Behavioral Inhibition to the Unfamiliar.  

ERIC Educational Resources Information Center

A group of 43 children classified as either behaviorally inhibited or uninhibited at 21 months were observed at four years of age in situations designed to evaluate behavior with an unfamiliar peer, heart rate and heart rate variability to cognitively challenging tasks, reluctance to answer difficult questions, and differential fixation of an…

Kagan, Jerome; And Others

1984-01-01

187

Tagetitoxin inhibits chloroplast RNA synthesis  

SciTech Connect

Tagetitoxin is a non-host specific phytotoxin which inhibits chloroplast development. Chloroplast encoded gene products as well as their transcripts are conspicuously depleted in toxin-treated tissue. Intact chloroplasts from 8-9 day old peas were incubated for 60 min. in the presence of tagetitoxin. This treatment reduced RNA synthesis but did not affect protein synthesis as measured by the incorporation of radiolabeled uridine or methionine, respectively. Tagetitoxin also inhibited chloroplast RNA synthesis in vitro. Total UTP incorporation was reduced 50% by 0.5..mu..M tagetitoxin in transcriptionally active chloroplast extracts containing 5mg/ml protein. In vitro transcription with purified E. coli RNA polymerase was also inhibited by tagetitoxin, yet wheat germ RNA polymerase II and several bacteriophage RNA polymerase enzymes were unaffected. Recent evidence suggests that RNA polymerase from chloroplasts and prokaryotes may share extensive homology. In light of this evidence and the authors own data, they propose that tagetitoxin directly inhibits chloroplast RNA polymerase.

Mathews, D.E.; Durbin, R.D.

1987-04-01

188

Inhibition and facilitation in schizotypy  

Microsoft Academic Search

Participants scoring high and low on a schizotypy scale (n?=?18 in each group) switched between naming words and naming colors in a Stroop task in congruent, neutral, and incongruent conditions. The findings were that, while being slower and less accurate overall than low schizotypes, the high schizotypy group did not display disproportionately greater Stroop inhibition or facilitation, suggesting intact selective

Michelle Cimino; Marina Haywood

2008-01-01

189

Selective serotonin reuptake inhibition modulates response inhibition in Parkinson's disease  

PubMed Central

Impulsivity is common in Parkinson’s disease even in the absence of impulse control disorders. It is likely to be multifactorial, including a dopaminergic ‘overdose’ and structural changes in the frontostriatal circuits for motor control. In addition, we proposed that changes in serotonergic projections to the forebrain also contribute to response inhibition in Parkinson’s disease, based on preclinical animal and human studies. We therefore examined whether the selective serotonin reuptake inhibitor citalopram improves response inhibition, in terms of both behaviour and the efficiency of underlying neural mechanisms. This multimodal magnetic resonance imaging study used a double-blind randomized placebo-controlled crossover design with an integrated Stop-Signal and NoGo paradigm. Twenty-one patients with idiopathic Parkinson’s disease (46–76 years old, 11 male, Hoehn and Yahr stage 1.5–3) received 30 mg citalopram or placebo in addition to their usual dopaminergic medication in two separate sessions. Twenty matched healthy control subjects (54–74 years old, 12 male) were tested without medication. The effects of disease and drug on behavioural performance and regional brain activity were analysed using general linear models. In addition, anatomical connectivity was examined using diffusion tensor imaging and tract-based spatial statistics. We confirmed that Parkinson’s disease caused impairment in response inhibition, with longer Stop-Signal Reaction Time and more NoGo errors under placebo compared with controls, without affecting Go reaction times. This was associated with less stop-specific activation in the right inferior frontal cortex, but no significant difference in NoGo-related activation. Although there was no beneficial main effect of citalopram, it reduced Stop-Signal Reaction Time and NoGo errors, and enhanced inferior frontal activation, in patients with relatively more severe disease (higher Unified Parkinson’s Disease Rating Scale motor score). The behavioural effect correlated with the citalopram-induced enhancement of prefrontal activation and the strength of preserved structural connectivity between the frontal and striatal regions. In conclusion, the behavioural effect of citalopram on response inhibition depends on individual differences in prefrontal cortical activation and frontostriatal connectivity. The correlation between disease severity and the effect of citalopram on response inhibition may be due to the progressive loss of forebrain serotonergic projections. These results contribute to a broader understanding of the critical roles of serotonin in regulating cognitive and behavioural control, as well as new strategies for patient stratification in clinical trials of serotonergic treatments in Parkinson’s disease. PMID:24578545

Ye, Zheng; Altena, Ellemarije; Nombela, Cristina; Housden, Charlotte R.; Maxwell, Helen; Rittman, Timothy; Huddleston, Chelan; Rae, Charlotte L.; Regenthal, Ralf; Sahakian, Barbara J.; Barker, Roger A.; Robbins, Trevor W.

2014-01-01

190

Inhibition by phase transfer catalysts  

Microsoft Academic Search

While phase transfer catalysts have generally a positive effect on substitution of halides by rhodanide ion in two-phase reaction systems changing the structure of alkyl halide from primary to tert.-alkyl groups, catalysis reverses into inhibition. The assumption that this is due to the change in reaction mechanism from SN2 to SN1 was proved on hydrolysis of triphenylmethyl chloride in a

J. Šilhánek; J. Bartl; R. Mat?ju; M. Zbirovský

1982-01-01

191

Methanogenic Inhibition by Arsenic Compounds  

Microsoft Academic Search

The acute acetoclastic methanogenic inhibition of several inorganic and organic arsenicals was assayed. Trivalent species, i.e., methylarsonous acid and arsenite, were highly inhibitory, with 50% inhibitory concen- trations of 9.1 and 15.0 M, respectively, whereas pentavalent species were generally nontoxic. The nitrophe- nylarsonate derivate, roxarsone, displayed moderate toxicity. Arsenic is a high-priority pollutant that is widely distributed in the environment.

Reyes Sierra-Alvarez; Irail Cortinas; Umur Yenal; Jim A. Field

2004-01-01

192

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

193

Inhibition of Macroautophagy Triggers Apoptosis†  

PubMed Central

Mammalian cells were observed to die under conditions in which nutrients were depleted and, simultaneously, macroautophagy was inhibited either genetically (by a small interfering RNA targeting Atg5, Atg6/Beclin 1-1, Atg10, or Atg12) or pharmacologically (by 3-methyladenine, hydroxychloroquine, bafilomycin A1, or monensin). Cell death occurred through apoptosis (type 1 cell death), since it was reduced by stabilization of mitochondrial membranes (with Bcl-2 or vMIA, a cytomegalovirus-derived gene) or by caspase inhibition. Under conditions in which the fusion between lysosomes and autophagosomes was inhibited, the formation of autophagic vacuoles was enhanced at a preapoptotic stage, as indicated by accumulation of LC3-II protein, ultrastructural studies, and an increase in the acidic vacuolar compartment. Cells exhibiting a morphology reminiscent of (autophagic) type 2 cell death, however, recovered, and only cells with a disrupted mitochondrial transmembrane potential were beyond the point of no return and inexorably died even under optimal culture conditions. All together, these data indicate that autophagy may be cytoprotective, at least under conditions of nutrient depletion, and point to an important cross talk between type 1 and type 2 cell death pathways. PMID:15657430

Boya, Patricia; Gonzalez-Polo, Rosa-Ana; Casares, Noelia; Perfettini, Jean-Luc; Dessen, Philippe; Larochette, Nathanael; Metivier, Didier; Meley, Daniel; Souquere, Sylvie; Yoshimori, Tamotsu; Pierron, Gerard; Codogno, Patrice; Kroemer, Guido

2005-01-01

194

Inhibition of Hsp90 in Streptomyces coelicolor  

E-print Network

Inhibition of the chaperone protein Hsp90 in plants and insects has been found to result in drastic changes in phenotype. We investigated the effect of Hsp90 inhibition on the bacteria Streptomyces coelicolor. These changes ...

Wu, Katherine A. (Katherine Ann)

2005-01-01

195

IGF-1 receptor antagonism inhibits autophagy  

E-print Network

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...

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

196

8, 87438771, 2008 Inhibition of ice  

E-print Network

ACPD 8, 8743­8771, 2008 Inhibition of ice crystallisation B. J. Murray Title Page Abstract Chemistry and Physics Discussions Inhibition of ice crystallisation in highly viscous aqueous organic acid­8771, 2008 Inhibition of ice crystallisation B. J. Murray Title Page Abstract Introduction Conclusions

Paris-Sud XI, Université de

197

Honokiol Inhibits Lung Tumorigenesis through Inhibition of Mitochondrial Function.  

PubMed

Honokiol is an important bioactive compound found in the bark of Magnolia tree. It is a nonadipogenic PPAR? agonist and capable of inhibiting the growth of a variety of tumor types both in vitro and in xenograft models. However, to fully appreciate the potential chemopreventive activity of honokiol, a less artificial model system is required. To that end, this study examined the chemopreventive efficacy of honokiol in an initiation model of lung squamous cell carcinoma (SCC). This model system uses the carcinogen N-nitroso-trischloroethylurea (NTCU), which is applied topically, reliably triggering the development of SCC within 24 to 26 weeks. Administration of honokiol significantly reduced the percentage of bronchial that exhibit abnormal lung SCC histology from 24.4% bronchial in control to 11.0% bronchial in honokiol-treated group (P = 0.01) while protecting normal bronchial histology (present in 20.5% of bronchial in control group and 38.5% of bronchial in honokiol-treated group. P = 0.004). P63 staining at the SCC site confirmed the lung SCCs phenotype. In vitro studies revealed that honokiol inhibited lung SCC cells proliferation, arrested cells at the G1-S cell-cycle checkpoint, while also leading to increased apoptosis. Our study showed that interfering with mitochondrial respiration is a novel mechanism by which honokiol changed redox status in the mitochondria, triggered apoptosis, and finally leads to the inhibition of lung SCC. This novel mechanism of targeting mitochondrial suggests honokiol as a potential lung SCC chemopreventive agent. Cancer Prev Res; 7(11); 1149-59. ©2014 AACR. PMID:25245764

Pan, Jing; Zhang, Qi; Liu, Qian; Komas, Steven M; Kalyanaraman, Balaraman; Lubet, Ronald A; Wang, Yian; You, Ming

2014-11-01

198

Action inhibition in Tourette syndrome.  

PubMed

Tourette syndrome is a neuropsychiatric disorder characterized by tics. Tic generation is often linked to dysfunction of inhibitory brain networks. Some previous behavioral studies found deficiencies in inhibitory motor control in Tourette syndrome, but others suggested normal or even better-than-normal performance. Furthermore, neural correlates of action inhibition in these patients are poorly understood. We performed event-related functional magnetic resonance imaging during a stop-signal reaction-time task in 14 uncomplicated adult Tourette patients and 15 healthy controls. In patients, we correlated activations in stop-signal reaction-time task with their individual motor tic frequency. Task performance was similar in both groups. Activation of dorsal premotor cortex was stronger in the StopSuccess than in the Go condition in healthy controls. This pattern was reversed in Tourette patients. A significant positive correlation was present between motor tic frequency and activations in the supplementary motor area during StopSuccess versus Go in patients. Inhibitory brain networks differ between healthy controls and Tourette patients. In the latter the supplementary motor area is probably a key relay of inhibitory processes mediating both suppression of tics and inhibition of voluntary action. © 2014 International Parkinson and Movement Disorder Society. PMID:24995958

Ganos, Christos; Kühn, Simone; Kahl, Ursula; Schunke, Odette; Feldheim, Jan; Gerloff, Christian; Roessner, Veit; Bäumer, Tobias; Thomalla, Götz; Haggard, Patrick; Münchau, Alexander

2014-10-01

199

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. PMID:17124493

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

200

The History of Acid Inhibition  

E-print Network

I review here the history of inhibition of gastric acid. References are limited to books and reviews in which detailed citations can be found. ANTACIDS In ancient times, acids were not understood in the modem chemical sense but merely as bitter sour liquids [1]. Some foods were thought acidic, and if the stomach had an ulcer, everything acrid was to be avoided and soothing remedies such as starch and milk used. Antacids neutralize, rather than inhibit, acid secretion but could not be rationally prescribed until acids were understood in the modern chemical sense. Hydrochloric acid has been known since the early fifteenth century, thought to be in the stomach by Paracelsus in the sixteenth and by Van Helmont in the seventeenth century, but it was not until 1823 that Prout definitively identified free hydrochloric acid in the gastric juice of man and animals and made quantitative measurements of its concentration. Antacids became widely used only this century, especially in association with Sippytype diets for ulcers [2]. As recently as the 1960s, orthodox gastroenterologists believed that gastric acidity was reduced by minimizing the amount of acid-stimulating foods such

J. H. Barona

1994-01-01

201

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

2012-02-28

202

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

203

Progesterone Inhibits Endometrial Cancer Invasiveness by Inhibiting the TGF? Pathway.  

PubMed

Increased expression of TGF? isoforms in human endometrial cancer correlates with decreased survival and poor prognosis. Progesterone has been shown to exert a chemoprotective effect against endometrial cancer, and previous animal models have suggested that these effects are accompanied by changes in TGF?. The goal of this study was to characterize the effect of progesterone on TGF? signaling pathway components and on TGF?-induced protumorigenic activities in endometrial cancer cell lines. Progesterone significantly decreased expression of three TGF? isoforms at 72 hours after treatment except for TGF?2 in HEC-1B and TGF?3 in Ishikawa cells. Progesterone treatment for 120 hours attenuated expression of the three isoforms in all cell lines. Progesterone exposure for 72 hours reduced expression of TGF? receptors in HEC-1B cells and all but TGF?R1 in Ishikawa cells. Progesterone reduced TGF?R3 expression in RL-95 cells at 72 hours, but TGF?R1 and ?R2 expression levels were not affected by progesterone at any time point. SMAD2/3 and pSMAD2/3 were substantially reduced at 72 hours in all cell lines. SMAD4 expression was reduced in RL-95 cells at 24 hours and in HEC-1B and Ishikawa cells at 72 hours following progesterone treatment. Furthermore, progesterone effectively inhibited basal and TGF?1-induced cancer cell viability and invasion, which was accompanied by increased E-cadherin and decreased vimentin expression. An inhibitor of TGF?RI blocked TGF?1-induced effects on cell viability and invasion and attenuated antitumor effects of progesterone. These results suggest that downregulation of TGF? signaling is a key mechanism underlying progesterone inhibition of endometrial cancer growth. Cancer Prev Res; 7(10); 1045-55. ©2014 AACR. PMID:25070663

Bokhari, Amber A; Lee, Laura R; Raboteau, Dewayne; Hamilton, Chad A; Maxwell, George L; Rodriguez, Gustavo C; Syed, Viqar

2014-10-01

204

Magnetic Catalysis vs Magnetic Inhibition  

E-print Network

We discuss the fate of chiral symmetry in an extremely strong magnetic field B. We investigate not only quark fluctuations but also neutral meson effects. The former would enhance the chiral-symmetry breaking at finite B according to the Magnetic Catalysis, while the latter would suppress the chiral condensate once B exceeds the scale of the hadron structure. Using a chiral model we demonstrate how neutral mesons are subject to the dimensional reduction and the low dimensionality favors the chiral-symmetric phase. We point out that this effect, the Magnetic Inhibition, can be a feasible explanation for recent lattice-QCD data indicating the decreasing behavior of the chiral-restoration temperature with increasing B.

Kenji Fukushima; Yoshimasa Hidaka

2012-09-06

205

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

206

A Fusion-Inhibiting Peptide against Rift Valley Fever Virus Inhibits Multiple, Diverse Viruses  

E-print Network

virus), Class II (Andes virus), or Class III (vesicular stomatitis virus) fusion proteins using, we show that infectivity can be inhibited for diverse, unrelated RNA viruses that have Class I (EbolaA Fusion-Inhibiting Peptide against Rift Valley Fever Virus Inhibits Multiple, Diverse Viruses

207

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

208

RNA III Inhibiting Peptide Inhibits In Vivo Biofilm Formation by Drug-Resistant Staphylococcus aureus  

Microsoft Academic Search

Staphylococcus aureus is a prevalent cause of bacterial infections associated with indwelling medical devices. RNA III inhibiting peptide (RIP) is known to inhibit S. aureus pathogenesis by disrupting quorum-sensing mechanisms. RIP was tested in the present study for its ability to inhibit S. aureus biofilm formation in a rat Dacron graft model. The activity of RIP was synergistic with those

Andrea Giacometti; Oscar Cirioni; Yael Gov; Roberto Ghiselli; Maria Simona Del Prete; Federico Mocchegiani; Vittorio Saba; Fiorenza Orlando; Giorgio Scalise; Naomi Balaban; Giorgio Dell' Acqua

2003-01-01

209

Inhibition and the right inferior frontal cortex  

Microsoft Academic Search

It is controversial whether different cognitive functions can be mapped to discrete regions of the prefrontal cortex (PFC). The localisationist tradition has associated one cognitive function – inhibition – by turns with dorsolateral prefrontal cortex (DLPFC), inferior frontal cortex (IFC), or orbital frontal cortex (OFC). Inhibition is postulated to be a mechanism by which PFC exerts its effects on subcortical

Adam R. Aron; Trevor W. Robbins; Russell A. Poldrack

2004-01-01

210

Preparing for Selective Inhibition within Frontostriatal Loops  

PubMed Central

Action inhibition can globally prevent all motor output or selectively cancel specific actions during concurrent motor output. Here we examine the behavioral and neural basis of selective inhibition focusing on the role of preparation. In 18 healthy human participants we manipulated the extent to which they could prepare for selective inhibition by providing or withholding information on what actions might need to be stopped. We show that, on average, information improves both speed and selectivity of inhibition. Functional magnetic resonance imaging data show that preparation for selective inhibition engages the inferior frontal gyrus, supplementary motor area, and striatum. Examining interindividual differences, we find the benefit of proactive control to speed and selectivity of inhibition trade off against each other, such that an improvement in stopping speed leads to a deterioration of selectivity of inhibition, and vice versa. This trade-off is implemented through engagement of the dorsolateral prefrontal cortex and putamen. Our results suggest proactive selective inhibition is implemented within frontostriatal structures, and we provide evidence that a speed-selectivity trade-off might underlie a range of findings reported previously. PMID:24227719

Guitart-Masip, Marc; Lutti, Antoine; Dolan, Raymond J.

2013-01-01

211

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

212

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

213

Inhibition of medulloblastoma cell invasion by Slit  

Microsoft Academic Search

Invasion of brain tumor cells has made primary malignant brain neoplasms among the most recalcitrant to therapeutic strategies. We tested whether the secreted protein Slit2, which guides the projection of axons and developing neurons, could modulate brain tumor cell invasion. Slit2 inhibited the invasion of medulloblastoma cells in a variety of in vitro models. The effect of Slit2 was inhibited

T E Werbowetski-Ogilvie; M Seyed Sadr; N Jabado; A Angers-Loustau; N Y R Agar; J Wu; R Bjerkvig; J P Antel; D Faury; Y Rao; R F Del Maestro

2006-01-01

214

Ethanol inhibition of Saccharomyces and Candida enzymes  

Microsoft Academic Search

Ethanol inhibition of several hydrolases (sucrase, maltase, trehalase, melezitase and cellobiase) has been measured in both highly ethanol-tolerant Saccharomyces strains (R) and in Candida strains less tolerant to ethanol (S). Cells were either grown in the presence of ethanol and the activities of the enzymes measured without preincubation in this alcohol (“in situ” inhibition assay), or the culture was grown

Encarnación Martín-Rendón; Juan Jiménez; Tahía Benítez

1989-01-01

215

Reduced surround inhibition in musicians.  

PubMed

To investigate whether surround inhibition (SI) in the motor system is altered in professional musicians, we performed a transcranial magnetic stimulation (TMS) study in 10 professional musicians and 15 age-matched healthy non-musicians. TMS was set to be triggered by self-initiated flexion of the index finger at different intervals ranging from 3 to 1,000 ms. Average motor evoked potential (MEP) amplitudes obtained from self-triggered TMS were normalized to average MEPs of the control TMS at rest and expressed as a percentage. Normalized MEP amplitudes of the abductor digiti minimi (ADM) muscles were compared between the musicians and non-musicians with the primary analysis being the intervals between 3 and 80 ms (during the movement). A mixed-design ANOVA revealed a significant difference in normalized ADM MEPs during the index finger flexion between groups, with less SI in the musicians. This study demonstrated that the functional operation of SI is less strong in musicians than non-musicians, perhaps due to practice of movement synergies involving both muscles. Reduced SI, however, could lead susceptible musicians to be prone to develop task-specific dystonia. PMID:22543743

Shin, Hae-Won; Kang, Suk Y; Hallett, Mark; Sohn, Young H

2012-06-01

216

Shed syndecan-2 inhibits angiogenesis  

PubMed Central

ABSTRACT Angiogenesis is essential for the development of a normal vasculature, tissue repair and reproduction, and also has roles in the progression of diseases such as cancer and rheumatoid arthritis. The heparan sulphate proteoglycan syndecan-2 is expressed on mesenchymal cells in the vasculature and, like the other members of its family, can be shed from the cell surface resulting in the release of its extracellular core protein. The purpose of this study was to establish whether shed syndecan-2 affects angiogenesis. We demonstrate that shed syndecan-2 regulates angiogenesis by inhibiting endothelial cell migration in human and rodent models and, as a result, reduces tumour growth. Furthermore, our findings show that these effects are mediated by the protein tyrosine phosphatase receptor CD148 (also known as PTPRJ) and this interaction corresponds with a decrease in active ?1 integrin. Collectively, these data demonstrate an unexplored pathway for the regulation of new blood vessel formation and identify syndecan-2 as a therapeutic target in pathologies characterised by angiogenesis. PMID:25179601

De Rossi, Giulia; Evans, Alun R.; Kay, Emma; Woodfin, Abigail; McKay, Tristan R.; Nourshargh, Sussan; Whiteford, James R.

2014-01-01

217

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. PMID:16666393

Leslie, Charles A.; Romani, Roger J.

1988-01-01

218

Photo-Activated Psoralen Binds the ErbB2 Catalytic Kinase Domain, Blocking ErbB2 Signaling and Triggering Tumor Cell Apoptosis  

PubMed Central

Photo-activation of psoralen with UVA irradiation, referred to as PUVA, is used in the treatment of proliferative skin disorders. The anti-proliferative effects of PUVA have been largely attributed to psoralen intercalation of DNA, which upon UV treatment, triggers the formation of interstrand DNA crosslinks (ICL) that inhibit transcription and DNA replication. Here, we show that PUVA exerts antitumor effects in models of human breast cancer that overexpress the ErbB2 receptor tyrosine kinase oncogene, through a new mechanism. Independent of ICL formation, the antitumor effects of PUVA in ErbB2+ breast cancer models can instead be mediated through inhibition of ErbB2 activation and signaling. Using a mass spectroscopy-based approach, we show for the first time that photo-activated 8MOP (8-methoxypsoralen) interacts with the ErbB2 catalytic autokinase domain. Furthermore, PUVA can reverse therapeutic resistance to lapatinib and other ErbB2 targeted therapies, including resistance mediated via expression of a phosphorylated, truncated form of ErbB2 (p85ErbB2) that is preferentially expressed in tumor cell nuclei. Current ErbB2 targeted therapies, small molecule kinase inhibitors or antibodies, do not block the phosphorylated, activated state of p85ErbB2. Here we show that PUVA reduced p85ErbB2 phosphorylation leading to tumor cell apoptosis. Thus, in addition to its effects on DNA and the formation of ICL, PUVA represents a novel ErbB2 targeted therapy for the treatment of ErbB2+ breast cancers, including those that have developed resistance to other ErbB2 targeted therapies. PMID:24551203

Xia, Wenle; Gooden, David; Liu, Leihua; Zhao, Sumin; Soderblom, Erik J.; Toone, Eric J.; Beyer, Wayne F.; Walder, Harold; Spector, Neil L.

2014-01-01

219

Inhibition of Growth of Tetrahymena piriformis by Certain Steroids  

Microsoft Academic Search

SUMMARY: The growth of Tetrahyrnena piriformis W is inhibited by several steroids of mammalian origin. The degree of inhibition is related to the molecular configuration. All of the effective growth inhibitors were of the carbon-21 or pregnane series. Hydroxyl substitution at carbon-1 1 enhanced inhibition, while hydroxyl sub- stitution at carbon-17 lowered the potency of inhibition. The inhibition of growth

R. L. CONNER

1959-01-01

220

Corrosion inhibition in oil and gas production  

SciTech Connect

This paper discusses practical aspects of the design and implementation of a corrosion inhibition program for oil and gas production, including choice of system, inhibitor testing and selection, performance monitoring, and inhibition problems. Corrosion inhibition is used to ensure safe operations and to improve profits. This paper focuses on the economic aspects of inhibition. The type of failures discussed here involve loss of production or assets, but not catastrophic failures (eg, well blow-out) where safety or environmental factors predominate. Corrosion failures must be economically significant to justify the implementation of a downhole corrosion inhibition program. Inhibition is one of several alternative methods for controlling corrosion. The choice of method is driven by both economical and technical considerations. The criteria include: technical competence, feasibility of implementation, compatibility with the rest of the production system, and initial and maintenance costs. The design of a corrosion inhibition program involves several steps from inhibitor selection to performance monitoring. Each step of the process must be carefully addressed to ensure the success of the program.

Kapusta, S.D. [Shell Western E and P Inc., Houston, TX (United States); Place, M.C. [Project Associates, Metairie, LA (United States)

1994-12-31

221

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. PMID:23575830

Cafaro, Jon; Rieke, Fred

2013-01-01

222

Homeostatic Competition between Phasic and Tonic Inhibition*  

PubMed Central

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

2013-01-01

223

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

224

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. PMID:12232405

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

1994-01-01

225

Spontaneously reactivation of acetylcholinesterase inhibited by diisopropylfluorophosphate.  

PubMed

When electric eel acetylcholinesterase is inhibited by diisopropylfluorophosphate at 0 degree C most of the enzyme is irreversibly inactivated. However, 0.13--0.18% of the initial activity returns spontaneously after the unbound inhibitor is removed or when the inhibited enzyme is diluted into a large excess of competing substrate. A subsequent inhibition-reactivation cycle results in an essentially complete return of activity with minimal aging. The extent of aging increases substantially when inhibition and reactivation are performed at temperatures above 0 degree C. The free energy of activation for spontaneous reactivation was determined to be 20.1 kcal . mol-1. This large free energy of activation indicates that the reactivation process is a typical dephosphorylation reaction. The computer program used in determining the rate constants and the final extent of reactivation may be widely applicable in similar kinetic studies. PMID:7272315

Lanks, K W; Seleznick, M J

1981-07-24

226

Inhibition of urinary calculi -- a spectroscopic study  

NASA Astrophysics Data System (ADS)

Although a considerable number of investigations have already been undertaken and many causes such as life habits, metabolic disorders, and genetic factors have been noted as sources that accelerate calculi depositions and aggregations, there are still plenty of unanswered questions regarding efficient inhibition and treatment mechanisms. Thus, in an attempt to acquire more insights, we propose here a detailed scientific study of kidney stone formation and growth inhibition based on a traditional medicine approach with Rotula Aquatica Lour (RAL) herbal extracts. A simplified single diffusion gel growth technique was used for synthesizing the samples for the present study. The unexpected Zn presence in the sample with RAL inhibitor, as revealed by XPS measurements, explains the inhibition process and the dramatic reflectance of the incident light observed in the infrared transmission studies. Raman data demonstrate potential binding of the inhibitor with the oxygen of the kidney stone. Photoluminescence results corroborate to provide additional evidence of Zn-related inhibition.

Manciu, Felicia; Govani, Jayesh; Durrer, William; Reza, Layra; Pinales, Luis

2008-10-01

227

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...

228

Anthracycline-induced phospholipase A2 inhibition  

PubMed Central

The purpose of this essay is to overview our findings that membrane-associated calcium-independent phospholipase A2 is markedly inhibited by low, clinically relevant concentrations of anthracyclines. Our studies suggest that due to the essential role of this enzyme in membrane homeostasis, its inhibition can be one of the early culprits leading to anthracycline-induced cardiac dysfunction. The clinical importance and potential pharmaceutical use of this new phenomenon await further studies. PMID:17652810

Swift, Luther; McHowat, Jane; Sarvazyan, Narine

2011-01-01

229

Current Understanding of Mullerian-Inhibiting Substance  

Microsoft Academic Search

\\u000a In the ovary, Mullerian-Inhibiting Substance (MIS) is produced by the granulosa cells of early developing follicles and inhibits\\u000a the transition from the primordial to the primary follicular stage. MIS levels can be measured in serum and have been shown\\u000a to be proportional to the number of small antral follicles. In women, serum MIS levels decrease with age and are undetectable

Antonio La Marca; Giovanna Sighinolfi; Annibale Volpe

230

Anthracycline-induced phospholipase A 2 inhibition  

Microsoft Academic Search

The purpose of this essay is to overview our findings that membrane-associated calcium-independent phospholipase A2 is markedly inhibited by low, clinically relevant concentrations of anthracyclines. Our studies suggest that due to the essential\\u000a role of this enzyme in membrane homeostasis, its inhibition can be one of the early culprits leading to anthracycline-induced\\u000a cardiac dysfunction. The clinical importance and potential pharmaceutical

Luther Swift; Jane McHowat; Narine Sarvazyan

2007-01-01

231

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

232

Inhibited solid propellant composition containing beryllium hydride  

NASA Technical Reports Server (NTRS)

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-terminated polybutadiene. It was found that a small amount of lecithin inhibits the reaction of beryllium hydride with the acid groups in carboxy terminated polybutadiene.

Thompson, W. W. (inventor)

1978-01-01

233

Low dose proteasome inhibition affects alternative splicing.  

PubMed

Protein degradation by the ubiquitin proteasome system ensures controlled degradation of structural proteins, signaling mediators, and transcription factors. Inhibition of proteasome function by specific proteasome inhibitors results in dose-dependent cellular effects ranging from induction of apoptosis to protective stress responses. The present study seeks to identify nuclear regulators mediating the protective stress response to low dose proteasome inhibition. Primary human endothelial cells were treated with low doses of the proteasome inhibitor MG132 for 2 h, and proteomic analysis of nuclear extracts was performed. Using a 2-D differential in gel electrophoresis (DIGE) approach, we identified more than 24 splice factors to be differentially regulated by low dose proteasome inhibition. In particular, several isoforms of hnRNPA1 were shown to be increased, pointing toward altered posttranslational modification of hnRNPA1 upon proteasome inhibition. Elevated levels of splice factors were associated with a different alternative splicing pattern in response to proteasome inhibition as determined by Affymetrix exon array profiling. Of note, we observed alternative RNA processing for stress associated genes such as caspases and heat shock proteins. Our study provides first evidence that low dose proteasome inhibition affects posttranscriptional regulation of splice factors and early alternative splicing events. PMID:22702956

Bieler, Sven; Hammer, Elke; Gesell-Salazar, Manuela; Völker, Uwe; Stangl, Karl; Meiners, Silke

2012-08-01

234

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. PMID:22852071

Vanachayangkul, Pattaraporn; Tolleson, William H.

2012-01-01

235

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

2012-01-01

236

Activin inhibits telomerase activity in cancer  

SciTech Connect

Activin is a pleiotropic cytokine with broad tissue distributions. Recent studies demonstrate that activin-A inhibits cancer cell proliferation with unknown mechanisms. In this report, we demonstrate that recombinant activin-A induces telomerase inhibition in cancer cells. In breast and cervical cancer cells, activin-A resulted in telomerase activity in a concentration-dependent manner. Significant inhibition was observed at 10 ng/ml of activin-A, with a near complete inhibition at 80 ng/ml. Consistently, activin-A induced repression of the telomerase reverse transcriptase (hTERT) gene, with the hTERT gene to be suppressed by 60-80% within 24 h. In addition, activin-A induced a concomitant increase in Smad3 signaling and decrease of the hTERT gene promoter activity in a concentration-dependent fashion. These data suggest that activin-A triggered telomerase inhibition by down-regulating hTERT gene expression is involved in activin-A-induced inhibition of cancer cell proliferation.

Katik, Indzi; Mackenzie-Kludas, Charley; Nicholls, Craig [Department of Immunology, Monash University, Melbourne (Australia)] [Department of Immunology, Monash University, Melbourne (Australia); Jiang, Fang-Xu [Centre for Diabetes Research, Western Australian Institute for Medical Research and The University of Western Australia, Perth (Australia)] [Centre for Diabetes Research, Western Australian Institute for Medical Research and The University of Western Australia, Perth (Australia); Zhou, Shufeng [School of Health Sciences, RMIT University, Melbourne (Australia)] [School of Health Sciences, RMIT University, Melbourne (Australia); Li, He [Department of Immunology, Monash University, Melbourne (Australia)] [Department of Immunology, Monash University, Melbourne (Australia); Liu, Jun-Ping, E-mail: jun-ping.liu@med.monash.edu.au [Department of Immunology, Monash University, Melbourne (Australia)] [Department of Immunology, Monash University, Melbourne (Australia)

2009-11-27

237

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

238

Inhibition of osteoblast apoptosis by thrombin.  

PubMed

The multifunctional serine protease thrombin has been shown to be a specific agonist for a variety of functional responses of cells including osteoblasts. The current study was conducted to determine if thrombin was capable of inhibiting apoptosis in osteoblasts, and if so, to examine the mechanism by which this occurred. Thrombin (20-100 nM) significantly inhibited apoptosis in serum-starved cultures of the human osteoblast-like Saos-2 cell line and cultures of primary osteoblasts isolated from mouse calvariae, as well as dexamethasone-treated primary mouse osteoblasts. Inhibition of serum deprivation-induced apoptosis was shown to require thrombin's specific proteolytic activity. Primary mouse osteoblasts were found to express two functional thrombin receptors, PAR-1 and PAR-4. Thrombin inhibited serum deprivation-induced apoptosis in osteoblasts isolated from PAR-1 null mice to the same degree as in osteoblasts isolated from wild-type mice. Treatment of serum-deprived osteoblasts, isolated from either PAR-1 null or wild-type mice, with a PAR-4-activating peptide failed to significantly inhibit apoptosis compared to the relevant control. Medium conditioned by thrombin-treated osteoblasts, in which thrombin had been inactivated, was able to inhibit serum deprivation-induced osteoblast apoptosis almost as well as thrombin itself. Blocking protein synthesis, by cycloheximide pretreatment of the conditioning cells, prevented this action. The ability of known osteoblast survival factors, such as transforming growth factor beta1, fibroblast growth factor-2, insulin-like growth factor-II, and interleukin-6, to inhibit serum deprivation-induced osteoblast apoptosis was also tested. None of these factors was able to inhibit serum deprivation-induced osteoblast apoptosis to the same extent as thrombin. The results presented here demonstrate that thrombin treatment of osteoblasts inhibits apoptosis induced either by dexamethasone or by serum deprivation. Furthermore, it does so independently of the known thrombin receptors by bringing about the synthesis and/or secretion of an unknown survival factor or factors, which then act in an autocrine fashion to inhibit apoptosis. PMID:14555279

Pagel, Charles N; de Niese, Michael R; Abraham, Linda A; Chinni, Carla; Song, Shu Jun; Pike, Robert N; Mackie, Eleanor J

2003-10-01

239

Triaryl Pyrazoline Compound Inhibits Flavivirus RNA Replication  

PubMed Central

Triaryl pyrazoline {[5-(4-chloro-phenyl)-3-thiophen-2-yl-4,5-dihydro-pyrazol-1-yl]-phenyl-methanone} inhibits flavivirus infection in cell culture. The inhibitor was identified through high-throughput screening of a compound library using a luciferase-expressing West Nile (WN) virus infection assay. The compound inhibited an epidemic strain of WN virus without detectable cytotoxicity (a 50% effective concentration of 28 ?M and a compound concentration of ?300 ?M required to reduce 50% cell viability). Besides WN virus, the compound also inhibited other flaviviruses (dengue, yellow fever, and St. Louis encephalitis viruses), an alphavirus (Western equine encephalitis virus), a coronavirus (mouse hepatitis virus), and a rhabdovirus (vesicular stomatitis virus). However, the compound did not suppress an orthomyxovirus (influenza virus) or a retrovirus (human immunodeficiency virus type 1). Mode-of-action analyses in WN virus showed that the compound did not inhibit viral entry or virion assembly but specifically suppressed viral RNA synthesis. To examine the mechanism of inhibition of dengue virus, we developed two replicon systems for dengue type 1 virus: (i) a stable cell line that harbored replicons containing a luciferase reporter and a neomycin phosphotransferase selection marker and (ii) a luciferase-expressing replicon that could differentiate between viral translation and RNA replication. Analyses of the compound in the dengue type 1 virus replicon systems showed that it weakly suppressed viral translation but significantly inhibited viral RNA synthesis. Overall, the results demonstrate that triaryl pyrazoline exerts a broad spectrum of antiflavivirus activity through potent inhibition of viral RNA replication. This novel inhibitor could be developed for potential treatment of flavivirus infection. PMID:16569847

Puig-Basagoiti, Francesc; Tilgner, Mark; Forshey, Brett M.; Philpott, Sean M.; Espina, Noel G.; Wentworth, David E.; Goebel, Scott J.; Masters, Paul S.; Falgout, Barry; Ren, Ping; Ferguson, David M.; Shi, Pei-Yong

2006-01-01

240

IGF-1 receptor antagonism inhibits autophagy  

PubMed Central

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.

2013-01-01

241

Thrombin inhibits migration of human hepatic myofibroblasts.  

PubMed

Several lines of data recently pointed out a role of the serine proteinase thrombin in liver fibrogenesis, but its mechanism of action is unknown. The aim of this study was to evaluate the effect of thrombin on the migration of human liver myofibroblasts. We show here that thrombin inhibits both basal migration and platelet-derived growth factor (PDGF)-BB-induced migration of myofibroblasts. By using a thrombin antagonist, a protease-activated receptor (PAR)-1 mimetic peptide, and a PAR-1 antibody, we show that this effect is dependent on the catalytic activity of thrombin and on PAR-1 activation. Thrombin's effect on basal migration was dependent on cyclooxygenase 2 (COX-2) activation because it was blocked by the COX-2 inhibitors NS-398 and nimesulide, and pharmacological studies showed that it was relayed through prostaglandin E(2) and its EP(2) receptor. On the other hand, thrombin-induced inhibition of PDGF-BB-induced migration was not dependent on COX-2. We show that thrombin inhibits PDGF-induced Akt-1 phosphorylation. This effect was consecutive to inhibition of PDGF-beta receptor activation through active dephosphorylation. Thus thrombin, through two distinct mechanisms, inhibits both basal- and PDGF-BB-induced migration of human hepatic liver myofibroblasts. The fine tuning of myofibroblast migration may be one of the mechanisms used by thrombin to regulate liver fibrogenesis. PMID:17379757

Gillibert-Duplantier, Jennifer; Neaud, Véronique; Blanc, Jean-Frédéric; Bioulac-Sage, Paulette; Rosenbaum, Jean

2007-07-01

242

Dendroarchitecture and lateral inhibition in thalamic barreloids.  

PubMed

Thalamic cells that relay vibrissa information to barrel cortex are clustered within whisker-related modules termed barreloids. Each barreloid receives input from one principal whisker and inhibitory inputs from reticular thalamic neurons with receptive fields that correspond to that same whisker. Although the proximal dendrites of relay cells are confined to their home barreloid, distal dendrites often extend into surrounding barreloids representing adjacent whiskers on the mystacial pad. It was proposed that this arrangement provides a substrate for a mechanism of lateral inhibition that operates remotely on extrabarreloid dendrites. In the present study, we identified adjacent whiskers that suppressed activity below background levels in barreloid cells, and we used a double-labeling protocol to relate the efficacy of inhibition to the dendroarchitecture of the cells. Significant suppression of background discharges was produced by 92% of adjacent whiskers within rows, by 48% of adjacent whiskers within arcs, but was never observed after deflection of nonadjacent whiskers. The magnitude of lateral inhibition increases linearly as the cumulated length of dendrites increases in the barreloid representing an adjacent whisker (R2 = 0.86; p < 0.0001). As distance between cell bodies and the border of an adjacent barreloid increases, dendritic length in that adjacent barreloid diminishes and so does inhibition. Considering time differences between the arrival of principal and adjacent whisker inputs in barreloids, our data suggest that inhibition operating distally on dendrites acts as a spatial filter that primarily suppresses adjacent whisker inputs and so contributes to enhance edge detection. PMID:15240801

Lavallée, Philippe; Deschęnes, Martin

2004-07-01

243

Anticancer Alkaloid Lamellarins Inhibit Protein Kinases  

PubMed Central

Lamellarins, a family of hexacyclic pyrrole alkaloids originally isolated from marine invertebrates, display promising anti-tumor activity. They induce apoptotic cell death through multi-target mechanisms, including inhibition of topoisomerase I, interaction with DNA and direct effects on mitochondria. We here report that lamellarins inhibit several protein kinases relevant to cancer such as cyclin-dependent kinases, dual-specificity tyrosine phosphorylation activated kinase 1A, casein kinase 1, glycogen synthase kinase-3 and PIM-1. A good correlation is observed between the effects of lamellarins on protein kinases and their action on cell death, suggesting that inhibition of specific kinases may contribute to the cytotoxicity of lamellarins. Structure/activity relationship suggests several paths for the optimization of lamellarins as kinase inhibitors. PMID:19172192

Baunbaek, Dianne; Trinkler, Nolwenn; Ferandin, Yoan; Lozach, Olivier; Ploypradith, Poonsakdi; Rucirawat, Somsak; Ishibashi, Fumito; Iwao, Masatomo; Meijer, Laurent

2008-01-01

244

Neural inhibition enables selection during language processing  

PubMed Central

Whether grocery shopping or choosing words to express a thought, selecting between options can be challenging, especially for people with anxiety. We investigate the neural mechanisms supporting selection during language processing and its breakdown in anxiety. Our neural network simulations demonstrate a critical role for competitive, inhibitory dynamics supported by GABAergic interneurons. As predicted by our model, we find that anxiety (associated with reduced neural inhibition) impairs selection among options and associated prefrontal cortical activity, even in a simple, nonaffective verb-generation task, and the GABA agonist midazolam (which increases neural inhibition) improves selection, whereas retrieval from semantic memory is unaffected when selection demands are low. Neural inhibition is key to choosing our words. PMID:20813959

Snyder, Hannah R.; Hutchison, Natalie; Nyhus, Erika; Curran, Tim; Banich, Marie T.; O'Reilly, Randall C.; Munakata, Yuko

2010-01-01

245

Suppression without inhibition in visual cortex.  

PubMed

Neurons in primary visual cortex (V1) are thought to receive inhibition from other V1 neurons selective for a variety of orientations. Evidence for this inhibition is commonly found in cross-orientation suppression: responses of a V1 neuron to optimally oriented bars are suppressed by superimposed mask bars of different orientation. We show, however, that suppression is unlikely to result from intracortical inhibition. First, suppression can be obtained with masks drifting too rapidly to elicit much of a response in cortex. Second, suppression is immune to hyperpolarization (through visual adaptation) of cortical neurons responding to the mask. Signals mediating suppression might originate in thalamus, rather than in cortex. Thalamic neurons exhibit some suppression; additional suppression might arise from depression at thalamocortical synapses. The mechanisms of suppression are subcortical and possibly include the very first synapse into cortex. PMID:12194874

Freeman, Tobe C B; Durand, Séverine; Kiper, Daniel C; Carandini, Matteo

2002-08-15

246

Quantifying hydrate formation and kinetic inhibition  

SciTech Connect

In the Prausnitz tradition, molecular and macroscopic evidence of hydrate formation and kinetic inhibition is presented. On the microscopic level, the first Raman spectra are presented for the formation of both uninhibited and inhibited methane hydrates with time. This method has the potential to provide a microscopic-based kinetics model. Three macroscopic aspects of natural gas hydrate kinetic inhibition are also reported: (1) The effect of hydrate dissociation residual structures was measured, which has application in decreasing the time required for subsequent formation. (2) The performance of a kinetic inhibitor (poly(N-vinylcaprolactam) or PVCap) was measured and correlated as a function of PVCap molecular weight and concentrations of PVCap, methanol, and salt in the aqueous phase. (3) Long-duration test results indicated that the use of PVCap can prevent pipeline blockage for a time exceeding the aqueous phase residence time in some gas pipelines.

Sloan, E.D.; Subramanian, S.; Matthews, P.N.; Lederhos, J.P.; Khokhar, A.A. [Colorado School of Mines, Golden, CO (United States). Center for Hydrate Research] [Colorado School of Mines, Golden, CO (United States). Center for Hydrate Research

1998-08-01

247

Selective Inhibition of Carotenoid Cleavage Dioxygenases  

PubMed Central

Members of the carotenoid cleavage dioxygenase family catalyze the oxidative cleavage of carotenoids at various chain positions, leading to the formation of a wide range of apocarotenoid signaling molecules. To explore the functions of this diverse enzyme family, we have used a chemical genetic approach to design selective inhibitors for different classes of carotenoid cleavage dioxygenase. A set of 18 arylalkyl-hydroxamic acids was synthesized in which the distance between an iron-chelating hydroxamic acid and an aromatic ring was varied; these compounds were screened as inhibitors of four different enzyme classes, either in vitro or in vivo. Potent inhibitors were found that selectively inhibited enzymes that cleave carotenoids at the 9,10 position; 50% inhibition was achieved at submicromolar concentrations. Application of certain inhibitors at 100 ?m to Arabidopsis node explants or whole plants led to increased shoot branching, consistent with inhibition of 9,10-cleavage. PMID:19098002

Sergeant, Martin J.; Li, Jian-Jun; Fox, Christine; Brookbank, Nicola; Rea, Dean; Bugg, Timothy D. H.; Thompson, Andrew J.

2009-01-01

248

Inhibition of melanogenesis by Xanthium strumarium L.  

PubMed

Xanthium strumarium L. (Asteraceae) is traditionally used in Korea to treat skin diseases. In this study, we investigated the effects of a X. strumarium stem extract on melanin synthesis. It inhibited melanin synthesis in a concentration-dependent manner, but it did not directly inhibit tyrosinase, the rate-limiting melanogenic enzyme, and instead downregulated microphthalmia-associated transcription factor (MITF) and tyrosinase expression. MITF, the master regulator of pigmentation, is a target of the Wnt signaling pathway, which includes glycogen synthase kinase 3? (GSK3?) and ?-catenin. Hence, the influence of X. strumarium stem extract on GSK3? and ?-catenin was further investigated. X. strumarium induced GSK3? phosphorylation (inactivation), but the level of ?-catenin did not change. Moreover, a specific GSK3? inhibitor restored X. strumarium-induced melanin reduction. Hence, we suggest that X. strumarium inhibits melanin synthesis through downregulation of tyrosinase via GSK3? phosphorylation. PMID:22484949

Li, Hailan; Min, Young Sil; Park, Kyoung-Chan; Kim, Dong-Seok

2012-01-01

249

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, Sřren N; Sřrensen, Trine H; Anderson, Lars; Borch, Kim; Westh, Peter

2013-03-01

250

Inhibition of myeloperoxidase by salicylhydroxamic acid.  

PubMed Central

Salicylhydroxamic acid inhibited the luminol-dependent chemiluminescence of human neutrophils stimulated by phorbol 12-myristate 13-acetate or the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe). This compound had no inhibitory effect on the kinetics of O2.- generation or O2 uptake during the respiratory burst, but inhibited both the peroxidative activity of purified myeloperoxidase and the chemiluminescence generated by a cell-free myeloperoxidase/H2O2 system. The concentration of salicylhydroxamic acid necessary for complete inhibition of myeloperoxidase activity was 30-50 microM (I50 values of 3-5 microM) compared with the non-specific inhibitor NaN3, which exhibited maximal inhibition at 100-200 microM (I50 values of 30-50 microM). Whereas taurine inhibited the luminol chemiluminescence of an H2O2/HOC1 system by HOC1 scavenging, this compound had little effect on myeloperoxidase/H2O2-dependent luminol chemiluminescence; in contrast, 10 microM-salicylhydroxamic acid did not quench HOC1 significantly but greatly diminished myeloperoxidase/H2O2-dependent luminol chemiluminescence, indicating that its effects on myeloperoxidase chemiluminescence were largely due to peroxidase inhibition rather than non-specific HOC1 scavenging. Salicylhydroxamic acid prevented the formation of myeloperoxidase Compound II, but only at low H2O2 concentrations, suggesting that it may compete for the H2O2-binding site on the enzyme. These data suggest that salicylhydroxamic acid may be used as a potent inhibitor to delineate the function of myeloperoxidase in neutrophil-mediated inflammatory events. PMID:2543361

Davies, B; Edwards, S W

1989-01-01

251

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. PMID:14660371

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

252

Rust inhibiting additive compositions for oils  

SciTech Connect

Compositions which include mixtures of a calcium hydroxide overbased oil-soluble calcium sulfonate, hexylene glycol and a surfactant consisting of an ethoxylated aliphatic amine, particularly, diethoxylated cocoamine or diethoxylated soyamine, are useful as rust inhibiting additives for oils and the like. By incorporating these compositions in petroleum based oils such as petroleum based oils of lubricating oil quality which come into contact with metal surfaces under conditions such that the metal surfaces tend to rust or otherwise be subject to deterioration it is possible to inhibit rust formation on such metal surfaces.

Haugen, H.

1980-09-23

253

Composition and method for corrosion inhibition  

SciTech Connect

A composition is provided which, when applied to a metal surface, forms a corrosion-inhibiting film thereon. The composition comprises an epoxy resin, an effective amount of a curing agent for the epoxy resin, an alcohol, and a hydrocarbon diluent. The composition is applied by contacting the metal surface with the composition as one solution or as a hydrocarbon solution of the epoxy resin and a solution comprising the alcohol and the curing agent. The composition is particularly useful in the treatment of down-well metal surfaces in oil and gas wells to inhibit the corrosion of the metal.

Wu, Y.

1985-07-02

254

Bacterial contact-dependent growth inhibition (CDI)  

PubMed Central

Bacteria cooperate to form multicellular communities and compete against one another for environmental resources. Here, we review recent advances in our understanding of bacterial competition mediated by contact-dependent growth inhibition (CDI) systems. Different CDI+ bacteria deploy a variety of toxins to inhibit neighboring cells and protect themselves from autoinhibition by producing specific immunity proteins. The genes encoding CDI toxin–immunity pairs appear to be exchanged between cdi loci and are often associated with other toxin-delivery systems in diverse bacteria. CDI also appears to facilitate cooperative behavior between kin, suggesting that these systems may have other roles beyond competition. PMID:23473845

Ruhe, Zachary C.; Low, David A.; Hayes, Christopher S.

2013-01-01

255

Enhanced neuronal response induced by fast inhibition  

NASA Astrophysics Data System (ADS)

We report a facilitatory role of inhibitory synaptic input that can enhance a neuron’s firing rate, in contrast to the conventional belief that inhibition suppresses firing. We study this phenomenon using the Hodgkin-Huxley model of spike generation with random Poisson trains of subthreshold excitatory and inhibitory inputs. Enhancement occurs when, by chance, brief inhibition leads excitation with a favorable timing and counterintuitively induces a reduction of the spike threshold. The basic mechanism is also illustrated with the phaseplane analysis of a two variable model.

Dodla, Ramana; Rinzel, John

2006-01-01

256

Tehranolide inhibits cell proliferation via calmodulin inhibition, PDE, and PKA activation.  

PubMed

Tehranolide, natural sesquiterpene lactone with an endoperoxide group, has been shown to inhibit cell growth in cancer cells. Tehranolide was purified from Artemisia diffusa. To detect cell viability and proliferation, MTT assay was performed. In order to determine the role of tehranolide on calmodulin (CaM) structure and activity, its effects were evaluated with fluorescence emission spectra and CaM-mediated activation of phosphodiesterase (PDE1), in comparison with artemisinin. In fact, PDE1 inhibition, cAMP accumulation, and cAMP-dependent protein kinase A (PKA) activation were examined. The inhibitory effect of tehranolide on CaM structure is more than artemisinin. The kinetic analysis of tehranolide-CaM interaction has shown that this agent competitively inhibited the activation of PDE1 without affecting Vmax. Tehranolide increased Km value in higher amounts compared with artemisinin. Moreover, tehranolide had a cytotoxic effect on K562 cell line but not on normal human lymphocytes. Additionally, PDE inhibition and consequent cAMP accumulation and PKA activity were required for inhibiting cancer cell growth by tehranolide. Our results show that tehranolide significantly reduces cell proliferation in a time and dose-dependent manner in K562 cells via CaM inhibition, following PDE inhibition, cAMP accumulation, and consequent PKA activity. PMID:24222327

Noori, Shokoofe; Hassan, Zuhair M

2014-01-01

257

Inhibitory spillover: Intentional motor inhibition produces incidental limbic inhibition via right inferior frontal cortex  

PubMed Central

Neurocognitive studies have observed rIFC involvement in motor, cognitive, and affective inhibition, suggesting that rIFC is a common inhibitory mechanism across psychological domains. If true, intentional inhibition in one domain may have unintended inhibitory effects (‘spillover’) in other domains. The present study used an emotional go/no-go task that produces responses in both motor and affective domains, but induces intentional inhibition in only the motor domain. Data support the hypothesis that intentional inhibition in the motor domain, via rIFC, produces inhibitory spillover in the affective domain. Specifically, we observed increased rIFC along with reduced amygdala activity when participants intentionally inhibited motor responses during the presentation of negatively-valenced stimuli, and greater inverse connectivity between these regions during motor inhibition in a PPI analysis. Given the absence of intentional affect regulation, these results suggest that intentional inhibition of a motor response dampens the amygdala activation coincident with affective stimuli to the extent that rIFC activation is higher. PMID:19426813

Berkman, Elliot T.; Burklund, Lisa; Lieberman, Matthew D.

2009-01-01

258

Inhibition of photosynthesis by heavy metals  

Microsoft Academic Search

Inhibition of photosynthesis by heavy metals is well documented. In this review the results are compared between in vitro experiments on isolated systems (chloroplasts, enzymes ­.), experiments on excised leaves and intact plants and algae in vivo. In vitro experiments suggest potential sites of heavy metal interaction with photosynthesis at several levels of organisation, which are not necessarily confirmed in

H. Clijsters; F. Assche

1985-01-01

259

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

260

Product Inhibition in Native-State Proteolysis  

PubMed Central

The proteolysis kinetics of intact proteins by nonspecific proteases provides valuable information on transient partial unfolding of proteins under native conditions. Native-state proteolysis is an approach to utilize the proteolysis kinetics to assess the energetics of partial unfolding in a quantitative manner. In native-state proteolysis, folded proteins are incubated with nonspecific proteases, and the rate of proteolysis is determined from the disappearance of the intact protein. We report here that proteolysis of intact proteins by nonspecific proteases, thermolysin and subtilisin deviates from first-order kinetics. First-order kinetics has been assumed for the analysis of native-state proteolysis. By analyzing the kinetics of proteolysis with varying concentrations of substrate proteins and also with cleavage products, we found that the deviation from first-order kinetics results from product inhibition. A kinetic model including competitive product inhibition agrees well with the proteolysis time course and allows us to determine the uninhibited rate constant for proteolysis as well as the apparent inhibition constant. Our finding suggests that the likelihood of product inhibition must be considered for quantitative assessment of proteolysis kinetics. PMID:25360755

Kasper, Joseph R.; Andrews, Elizabeth C.; Park, Chiwook

2014-01-01

261

Salinomycin, a polyether ionophoric antibiotic, inhibits adipogenesis  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer Salinomycin inhibits preadipocyte differentiation into adipocytes. Black-Right-Pointing-Pointer Salinomycin inhibits transcriptional regulation of adipogenesis. Black-Right-Pointing-Pointer Pharmacological effects of salinomycin suggest toxicity in cancer therapy. -- Abstract: The polyether ionophoric antibiotics including monensin, salinomycin, and narasin, are widely used in veterinary medicine and as food additives and growth promoters in animal husbandry including poultry farming. Their effects on human health, however, are not fully understood. Recent studies showed that salinomycin is a cancer stem cell inhibitor. Since poultry consumption has risen sharply in the last three decades, we asked whether the consumption of meat tainted with growth promoting antibiotics might have effects on adipose cells. We showed in this report that the ionophoric antibiotics inhibit the differentiation of preadipocytes into adipocytes. The block of differentiation is not due to the induction of apoptosis nor the inhibition of cell proliferation. In addition, salinomycin also suppresses the transcriptional activity of the CCAAT/enhancer binding proteins and the peroxisome proliferator-activated receptor {gamma}. These results suggest that the ionophoric antibiotics can be exploited as novel anti-obesity therapeutics and as pharmacological probes for the study of adipose biology. Further, the pharmacological effects of salinomycin could be a harbinger of its toxicity on the adipose tissue and other susceptible target cells in cancer therapy.

Szkudlarek-Mikho, Maria; Saunders, Rudel A. [Department of Medicine, Biochemistry and Cancer Biology, Center for Diabetes and Endocrine Research, College of Medicine, University of Toledo, Toledo, OH 43614 (United States)] [Department of Medicine, Biochemistry and Cancer Biology, Center for Diabetes and Endocrine Research, College of Medicine, University of Toledo, Toledo, OH 43614 (United States); Yap, Sook Fan [Faculty of Medicine and Health Sciences, Department of Pre-Clinical Sciences, University of Tunku Abdul Rahman (Malaysia)] [Faculty of Medicine and Health Sciences, Department of Pre-Clinical Sciences, University of Tunku Abdul Rahman (Malaysia); Ngeow, Yun Fong [Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603 (Malaysia)] [Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603 (Malaysia); Chin, Khew-Voon, E-mail: khew-voon.chin@utoledo.edu [Department of Medicine, Biochemistry and Cancer Biology, Center for Diabetes and Endocrine Research, College of Medicine, University of Toledo, Toledo, OH 43614 (United States)] [Department of Medicine, Biochemistry and Cancer Biology, Center for Diabetes and Endocrine Research, College of Medicine, University of Toledo, Toledo, OH 43614 (United States)

2012-11-30

262

Notch Receptor Activation Inhibits Oligodendrocyte Differentiation  

Microsoft Academic Search

In this study, we show that oligodendrocyte differentiation is powerfully inhibited by activation of the Notch pathway. Oligodendrocytes and their precursors in the developing rat optic nerve express Notch1 receptors and, at the same time, retinal ganglion cells express Jagged1, a ligand of the Notch1 receptor, along their axons. Jagged1 expression is developmentally regulated, decreasing with a time course that

Songli Wang; Andrei D Sdrulla; Guy diSibio; Gay Bush; Donna Nofziger; Carol Hicks; Gerry Weinmaster; Ben A Barres

1998-01-01

263

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

264

Original article ?-endorphin inhibition of progesterone secretion  

E-print Network

Original article ?-endorphin inhibition of progesterone secretion by porcine granulosa cells, Cracow, Poland (Received 24 April 1997; accepted 11May 1998) Abstract - Exogenous ¡3-endorphin to elucidate the role of (3-endorphin in follicu- lar steroidogenesis. ¡3-endorphin decreased basal

Paris-Sud XI, Université de

265

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

266

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

267

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

268

Temporal Preparation, Response Inhibition and Impulsivity  

ERIC Educational Resources Information Center

Temporal preparation and impulsivity involve overlapping neural structures (prefrontal cortex) and cognitive functions (response inhibition and time perception), however, their interrelations had not been investigated. We studied such interrelations by comparing the performance of groups with low vs. high non-clinical trait impulsivity during a…

Correa, Angel; Trivino, Monica; Perez-Duenas, Carolina; Acosta, Alberto; Lupianez, Juan

2010-01-01

269

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

270

Aqueous rust-inhibiting and lubricating compositions  

SciTech Connect

Rust-inhibiting compounds, especially for aqueous systems such as tool-lubricating emulsions for machine tools and which consist of amine salts of a number of monoaminoalkylene dicarboxylic acids are disclosed. These rust-inhibitors are used in combination with water and an alkanolamine. Examples and test results are given.

Brandolese, E.

1983-06-14

271

Rust inhibiting additive compositions for oils  

Microsoft Academic Search

Compositions which include mixtures of a calcium hydroxide overbased oil-soluble calcium sulfonate, hexylene glycol and a surfactant consisting of an ethoxylated aliphatic amine, particularly, diethoxylated cocoamine or diethoxylated soyamine, are useful as rust inhibiting additives for oils and the like. By incorporating these compositions in petroleum based oils such as petroleum based oils of lubricating oil quality which come into

1980-01-01

272

Temperament and the Development of Inhibited Approach.  

ERIC Educational Resources Information Center

Studied the early development of inhibited approach through the observation of 48 infants. Subjects (aged 6.5, 10, and 13.5 months) were observed longitudinally as they reached for toys under high- and low-novelty/intensity conditions. Predictions that temperament would affect reaching behavior (with happy children reaching more quickly and…

Rothbart, Mary Klevjord

1988-01-01

273

Brief article Central inhibition ability modulates  

E-print Network

for this effect is the presence of motion distractors prior to the motion target, and we proposed. To investigate this, we compared the extent of the attention- induced motion blindness effect with performance on central inhibition tasks: Stroop colour naming and negative priming. A negative correlation between Stroop

Aberdeen, University of

274

Dexamethasone Inhibits Interleukin-1?-Induced Corneal Neovascularization  

PubMed Central

Dexamethasone, a synthetic corticosteroid, is widely used as a potent anti-inflammatory drug in various diseases including corneal angiogenesis. However, dexamethasone’s impact on interleukin (IL)-1?-dependent inflammatory angiogenesis is unknown. Here, we show that dexamethasone inhibits IL-1?-induced neovascularization and the expression of the angiogenesis-related factors, vascular endothelial growth factor-A, KC, and prostaglandin E2 in the mouse cornea 2 days after IL-1? implantation. IL-1? caused I?B-? phosphorylation in corneal stromal cells but not in infiltrated CD11b+ cells 2 days after IL-1? implantation. In contrast, both cell types were positive for phosphorylated I?B-? 4 days after IL-1? implantation. Dexamethasone significantly inhibited I?B-? phosphorylation 2 and 4 days after IL-1? implantation. Furthermore, dexamethasone inhibited IL-1?-induced expression of vascular endothelial growth factor-A, KC, and prostaglandin E2, and signaling of nuclear factor (NF)-?B in corneal fibroblasts in vitro. A selective NF-?B inhibitor attenuated IL-1?-induced corneal angiogenesis. These findings suggest that NF-?B activation in the corneal stromal cells is an important early event during IL-1?-induced corneal angiogenesis and that dexamethasone inhibits IL-1?-induced angiogenesis partially via blocking NF-?B signaling. PMID:17690185

Nakao, Shintaro; Hata, Yasuaki; Miura, Muneki; Noda, Kousuke; Kimura, Yusuke N.; Kawahara, Shuhei; Kita, Takeshi; Hisatomi, Toshio; Nakazawa, Toru; Jin, Yiping; Dana, M. Reza; Kuwano, Michihiko; Ono, Mayumi; Ishibashi, Tatsuro; Hafezi-Moghadam, Ali

2007-01-01

275

Theobromine inhibits sensory nerve activation and cough  

Microsoft Academic Search

Cough is a common and protective reflex, but persistent coughing is debilitating and impairs quality of life. Antitussive treatment using opioids is limited by unacceptable side effects, and there is a great need for more effective remedies. The present study demonstrates that theobromine, a methylxanthine derivative present in cocoa, effectively inhibits citric acid- induced cough in guinea-pigs in vivo. Furthermore,

Omar S. Usmani; Maria G. Belvisi; Hema J. Patel; Natascia Crispino; Mark A. Birrell; Márta Korbonits; Peter J. Barnes

2004-01-01

276

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

277

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.

278

Cell Reports Inhibition of ATPIF1 Ameliorates  

E-print Network

death by allowing for the maintenance of mitochondrial membrane potential. ATPIF1 loss pro- tectsCell Reports Report Inhibition of ATPIF1 Ameliorates Severe Mitochondrial Respiratory Chain Mitochondrial respiratory chain disorders are char- acterized by loss of electron transport chain (ETC) activity

Sabatini, David M.

279

Neural inhibition enables selection during language processing  

E-print Network

to express a thought (4�6). People with anxiety disorders find coping with too many options particularlyNeural inhibition enables selection during language processing Hannah R. Snyder, Natalie Hutchison grocery shopping or choosing words to express a thought, selecting between options can be challenging

Banich, Marie T.

280

Neural inhibition enables selection during language processing  

E-print Network

to express a thought (4­6). People with anxiety disorders nd coping with too many options particularly difNeural inhibition enables selection during language processing Hannah R. Snyder, Natalie Hutchison grocery shopping or choosing words to express a thought, selecting between options can be challenging

O'Reilly, Randall C.

281

Inhibition of cellulase by fermentation products  

SciTech Connect

Cellulosic materials are important resources for the production of fuels and chemicals. One of the processes designed to utilize cellulosic materials is enzymatic hydrolysis followed by fermentation to final products. It was shown that simultaneous saccharification and fermentation (SSF) is effective in the production of ethanol from cellulose. The acceleration of the rate of cellulose degradation in SSF was caused by less inhibition of cellulase by ethanol than by glucose and/or cellobiose. In order to apply the SSF method effectively to the production of substances derived from glucose by fermentation, several conditions should be satisfied. One of them is the coincidence of conditions of enzymatic hydrolysis and fermentation of hydrolyzate, such as pH and temperature. The second condition is that the inhibition of cellulase by the final product is less than that by glucose and/or cellobiose. There has been a comprehensive review and some reports on inhibition of cellulase by saccharides such as glucose, cellobiose, xylose, lactose, maltose, metals, and some chemicals such as dyes, detergents, halogenated compounds, and phenolic compounds. In this communication, the inhibition of cellulase by several substances derived by fermentation of glucose is reported. 7 references.

Takagi, M.

1984-12-01

282

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

283

Subsea valve apparatus having hydrate inhibiting injection  

Microsoft Academic Search

In accordance with an illustrative embodiment of the present invention, a valve placed in a subsea blowout preventer stack during a production test of a well producing gas comprises a valve body containing two valve elements in series and a releasable control unit. A fluid to inhibit the formation of natural-gas hydrates can be injected into the valve body by

J. Franc; P. H. Goldschild

1981-01-01

284

Hydrate Inhibition Design for Deepwater Completions  

Microsoft Academic Search

This paper will review the design considerations for gas hydrate prevention in deepwater well completions. The influence of seafloor temperature, wellbore pressure, water production rate and composition of gas on hydrate inhibition system design will be discussed. The impact of various inhibitors will be discussed in relationship to the design of the system and potential handling problems. Examples will review

Janardhan Davalath; J. W. Barker

1995-01-01

285

Inhibition of Gas Hydrates in Deepwater Drilling  

Microsoft Academic Search

With the movement of offshore rigs into deep water, the problem of gas hydrates has become an important issue in drilling. If a kick is taken, gas hydrates can form in the blowout preventer (BOP) or chokelines while the kick is circulated out. The water-based pill presented here significantly improves gas-hydrate inhibition. This pill, which can be spotted in the

Arthur Hale; Ashok Dewan

1990-01-01

286

Kinetics of ethanol inhibition in alcohol fermentation  

Microsoft Academic Search

The inhibitory effect of ethanol on yeast growth and fermentation has been studied for the strain Saccharo-myces cerevisiae ATCC No. 4126 under anaerobic batch conditions. The results obtained reveal that there is no striking difference between the response of growth and ethanol fermentation. Two kinetic models are also proposed to describe the kinetic pattern of ethanol inhibition on the specific

J. H. T. Luong; J. H. T

1985-01-01

287

The Mechanism Underlying Inhibition of Saccadic Return  

ERIC Educational Resources Information Center

Human observers take longer to re-direct gaze to a previously fixated location. Although there has been some exploration of the characteristics of inhibition of saccadic return (ISR), the exact mechanisms by which ISR operates are currently unknown. In the framework of accumulation models of response times, in which evidence is integrated over…

Ludwig, Casimir J. H.; Farrell, Simon; Ellis, Lucy A.; Gilchrist, Iain D.

2009-01-01

288

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

289

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...

290

Inhibition of activation of dsRNA-dependent protein kinase and tumour growth inhibition  

Microsoft Academic Search

Inhibition of dsRNA-activated protein kinase (PKR), not only attenuates muscle atrophy in a murine model of cancer cachexia\\u000a (MAC16), but it also inhibits tumour growth. In vitro the PKR inhibitor maximally inhibited growth of MAC16 tumour cells at\\u000a a concentration of 200 nM, which was also maximally effective in attenuating phosphorylation of PKR and of eukaryotic initiation\\u000a factor (eIF)2 on the ?-subunit.

Helen L. Eley; Pria S. McDonald; Steven T. Russell; Michael J. Tisdale

2009-01-01

291

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...

292

Serine\\/threonine protein phosphatase inhibition enhances the effect of thymidylate synthase inhibition  

Microsoft Academic Search

Purpose The serine\\/threonine protein phosphatases 1 (PP1) and 2A (PP2A) are key enzymes in regulating entry into the cell cycle, mitosis and apoptosis. Inhibition of PP1 and PP2A is associated with enhanced S-phase entry culminating in G 2\\/M arrest and apoptotic cell death. Thymidylate synthase (TS) is a key regulatory enzyme in DNA synthesis, inhibition of which is often a

Jennette A. Sakoff; Ian J. Howitt; Stephen P. Ackland; Adam McCluskey

2004-01-01

293

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

2012-08-01

294

Inhibiting platelet-stimulated blood coagulation by inhibition of mitochondrial respiration  

PubMed Central

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.

2012-01-01

295

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

296

Structural analysis of kasugamycin inhibition of translation.  

PubMed

The prokaryotic ribosome is an important target of antibiotic action. We determined the X-ray structure of the aminoglycoside kasugamycin (Ksg) in complex with the Escherichia coli 70S ribosome at 3.5-A resolution. The structure reveals that the drug binds within the messenger RNA channel of the 30S subunit between the universally conserved G926 and A794 nucleotides in 16S ribosomal RNA, which are sites of Ksg resistance. To our surprise, Ksg resistance mutations do not inhibit binding of the drug to the ribosome. The present structural and biochemical results indicate that inhibition by Ksg and Ksg resistance are closely linked to the structure of the mRNA at the junction of the peptidyl-tRNA and exit-tRNA sites (P and E sites). PMID:16998486

Schuwirth, Barbara S; Day, J Michael; Hau, Cathy W; Janssen, Gary R; Dahlberg, Albert E; Cate, Jamie H Doudna; Vila-Sanjurjo, Antón

2006-10-01

297

Blocking of potentiation of latent inhibition.  

PubMed

We present a theory of latent inhibition based on the Pearce-Hall (Pearce & Hall, 1980) model for classical conditioning. Its central features are (1) that the associability of a stimulus declines as it comes to predict its consequences and (2) that nonreinforced exposure to a stimulus engages an associative learning process that makes the stimulus an accurate predictor of its consequences (in this case, the occurrence of no event). A formalization of this theory is shown to accommodate the finding that preexposure in compound with another cue can potentiate latent inhibition to the target cue. It further predicts that preexposure to the added cue will eliminate the potentiation effect. An experiment using rats and the flavor-aversion procedure confirmed this prediction. PMID:20822295

Hall, Geoffrey; Rodriguez, Gabriel

2011-01-01

298

Breaking of seed dormancy by catalase inhibition.  

PubMed Central

Germination of some dormant seeds is promoted by solutions of thiourea, sodium nitrite, and hydroxylamine salts. The promotions are accompanied by irreversible inhibition of catalase (EC 1.11.1.6) in extracts from the seeds. The seeds are also promoted in germination by catechol and pyrogallol solutions. These effects are recorded for lettuce (Lactuca sativa L. cv. Grand Rapids) and pigweed (Amaranthus albus L.) seeds. The results indicae that metabolically derived hydrogen peroxide, spared from decomposition by catalase inhibition, oxidizes reduced NADPH required as the oxidant in the pentose pathway of glucose use. The metabolic system for such use of H2O2 involves the enzymes, peroxidase (EC 1.11.1.7) and pyridine nucleotide quinone oxidoreductase (EC 1.6.99.2), which are present in the dormant seed prior to imbibition of water. PMID:235126

Hendricks, S B; Taylorson, R B

1975-01-01

299

Preventing MIC through microbial adhesion inhibition  

SciTech Connect

The key to the alteration of conditions at a metal surface before the initiation of microbially induced corrosion (MIC) is the formation of a biofilm. Thus, prevention of bacterial adhesion processes on metal surfaces would be one of the potential weapons to avoid MIC. Serum globulin and by-products were used to prevent bacterial adhesion on different corrosion resistant metal surfaces generally used as implantable biomaterials. In this paper an immunoglobulin combination (IgA, IgG and IgM) has been used to prevent the formation of Pseudomonas fluorescens (P.fluorescens) biofilms on carbon steel and two different types of stainless steel (SS). A marked inhibition of bacterial adhesion was found under different experimental conditions. Several microscopic techniques were used for assessing adhesion inhibition while the electrochemical behavior of the steels was evaluated by means of different electrochemical techniques applied in the presence and in the absence of the immunoglobulins.

Videla, H.A. [Univ. of La Plata (Argentina). Dept. of Chemistry; Guiamet, P.S.; Gomez de Saravia, S.G. [INIFTA, La Plata (Argentina). Bioelectrochemistry Section

1998-12-31

300

Inhibition of IL-12 production by thalidomide.  

PubMed

The immunomodulatory properties of thalidomide are currently being exploited therapeutically in conditions as diverse as erythema nodosum leprosum, chronic graft-vs-host disease, rheumatoid arthritis, and sarcoidosis. The relevant mechanism of action of thalidomide in these diseases remains unclear. The important role recently ascribed to IL-12, a cytokine critical to the development of cellular immune responses, in the pathogenesis of several of these conditions led us to examine whether thalidomide affects the production of IL-12. Thalidomide potently suppressed the production of IL-12 from human PBMC and primary human monocytes in a concentration-dependent manner. Thalidomide-induced inhibition of IL-12 production was additive to that induced by suboptimal inhibiting doses of dexamethasone, and occurred by a mechanism independent of known endogenous inhibitors of IL-12 production. These results suggest that thalidomide may have therapeutic utility in a wide range of immunologic disorders that are characterized by inappropriate cellular immune responses. PMID:9366446

Moller, D R; Wysocka, M; Greenlee, B M; Ma, X; Wahl, L; Flockhart, D A; Trinchieri, G; Karp, C L

1997-11-15

301

Hydrate inhibition design for deepwater completions  

SciTech Connect

This paper will review the design considerations for gas hydrate prevention in deepwater well completions. The influence of seafloor temperature, wellbore pressure, water production rate and composition of gas on hydrate inhibition system design will be discussed. The impact of various inhibitors will be discussed in relationship to the design of the system and potential handling problems. Examples will review design considerations for sizing of subsea inhibitor lines, selection of injection depth below the seafloor and hardware requirements. Case histories of inhibitor injection systems used in deepwater completions and during testing of deepwater exploration wells will be reviewed. The benefits of insulated tubing to enhance inhibition design will be discussed. Also, a method will be introduced that can be used to estimate the maximum inhibitor injection rate to avoid salt precipitation from completion fluid or produced water.

Davalath, J.; Barker, J.W. [Exxon Co. International, Houston, TX (United States)

1995-06-01

302

Methamphetamine Inhibits Antigen Processing, Presentation, and Phagocytosis  

PubMed Central

Methamphetamine (Meth) is abused by over 35 million people worldwide. Chronic Meth abuse may be particularly devastating in individuals who engage in unprotected sex with multiple partners because it is associated with a 2-fold higher risk for obtaining HIV and associated secondary infections. We report the first specific evidence that Meth at pharmacological concentrations exerts a direct immunosuppressive effect on dendritic cells and macrophages. As a weak base, Meth collapses the pH gradient across acidic organelles, including lysosomes and associated autophagic organelles. This in turn inhibits receptor-mediated phagocytosis of antibody-coated particles, MHC class II antigen processing by the endosomal–lysosomal pathway, and antigen presentation to splenic T cells by dendritic cells. More importantly Meth facilitates intracellular replication and inhibits intracellular killing of Candida albicans and Cryptococcus neoformans, two major AIDS-related pathogens. Meth exerts previously unreported direct immunosuppressive effects that contribute to increased risk of infection and exacerbate AIDS pathology. PMID:18282092

Joset, Danielle; Ray, Yonaton; Gacser, Attila; Toussi, Sima; Mizushima, Noboru; Nosanchuk, Josh; Goldstein, Harris; Loike, John; Sulzer, David; Santambrogio, Laura

2008-01-01

303

Immunoregulatory functions of mTOR inhibition  

Microsoft Academic Search

The potent immunosuppressive action of rapamycin is commonly ascribed to inhibition of growth factor-induced T cell proliferation. However, it is now evident that the serine\\/threonine protein kinase mammalian target of rapamycin (mTOR) has an important role in the modulation of both innate and adaptive immune responses. mTOR regulates diverse functions of professional antigen-presenting cells, such as dendritic cells (DCs), and

H?th R. Turnquist; Giorgio Raimondi; Angus W. Thomson

2009-01-01

304

Inhibition of metal corrosion by bacteria  

Microsoft Academic Search

Corrosion inhibition of steel (ASTM A619) by two marine isolates, Pseudomonas sp.S9 and Serratia marces?cens EF190, was investigated by weight loss measurements of metal coupons placed in static batch cultures. Artificial seawater with (VNSS) and without (NSS) nutrients was used. The effects of bulk? and surface localised cells were compared. Adhesion of cells to the metal surface was quantified microscopically.Corrosion

Amelie Pedersen; Malte Hermansson

1991-01-01

305

Hydrochlorothiazide inhibits osteoclastic bone resorption In vitro  

Microsoft Academic Search

Long-term thiazide diuretic use is associated with higher bone mineral density and reduced hip fracture rates, which are attributed to increased serum calcium levels and decreased parathyroid activity that lead to decreased bone resorption. The present study shows that 1–100 µM hydro-chlorothiazide (HCTZ) dose dependently inhibits bone resorption by isolated rat osteoclasts in the bone slice assay with an IC50

T. J. Hall; M. Schaueblin

1994-01-01

306

Inhibition of Gammaherpesvirus Replication by RNA Interference  

Microsoft Academic Search

RNA interference (RNAi) is a conserved mechanism in which double-stranded, small interfering RNAs (siRNAs) trigger a sequence-specific gene-silencing process. Here we describe the inhibition of murine her- pesvirus 68 replication by siRNAs targeted to sequences encoding Rta, an immediate-early protein known as an initiator of the lytic viral gene expression program, and open reading frame 45 (ORF 45), a conserved

Qingmei Jia; Ren Sun

2003-01-01

307

Inhibition of mammalian cathepsins by Plesiomonas shigelloides  

Microsoft Academic Search

To study molecular mechanisms underlying self-defense of the bacterial pathogenPlesiomonas shigelloides against host inflammatory and immune responses, we evaluated its interactions with mammalian papain-like cathepsins that\\u000a are essential for host immunity. When grown under anaerobic, but not aerobic, conditions,P. shigelloides was shown to bind and inhibit papain, a model representative of the papain family of cysteine proteinases. This points to

A. Pavlova; K. K?ová?ek; I. ?ižnár; C. Gonzalez-Rey

2006-01-01

308

Caffeine inhibits acetylcholinesterase, but not butyrylcholinesterase.  

PubMed

Caffeine is an alkaloid with a stimulant effect in the body. It can interfere in transmissions based on acetylcholine, epinephrine, norepinephrine, serotonin, dopamine and glutamate. Clinical studies indicate that it can be involved in the slowing of Alzheimer disease pathology and some other effects. The effects are not well understood. In the present work, we focused on the question whether caffeine can inhibit acetylcholinesterase (AChE) and/or, butyrylcholinesterase (BChE), the two enzymes participating in cholinergic neurotransmission. A standard Ellman test with human AChE and BChE was done for altering concentrations of caffeine. The test was supported by an in silico examination as well. Donepezil and tacrine were used as standards. In compliance with Dixon's plot, caffeine was proved to be a non-competitive inhibitor of AChE and BChE. However, inhibition of BChE was quite weak, as the inhibition constant, Ki, was 13.9 ± 7.4 mol/L. Inhibition of AChE was more relevant, as Ki was found to be 175 ± 9 µmol/L. The predicted free energy of binding was -6.7 kcal/mol. The proposed binding orientation of caffeine can interact with Trp86, and it can be stabilize by Tyr337 in comparison to the smaller Ala328 in the case of human BChE; thus, it can explain the lower binding affinity of caffeine for BChE with reference to AChE. The biological relevance of the findings is discussed. PMID:23698772

Pohanka, Miroslav; Dobes, Petr

2013-01-01

309

Henri Laborit and the inhibition of action.  

PubMed

Henri Laborit was one of the founders of modern neuropsychopharmacology, having discovered, or participated in, the discovery of chlorpromazine, gamma-OH, clomethiazole, and minaprine. He also put forward a theory regarding the necessity of counteracting the negative consequences of defense mechanisms during anesthesia or behavioral inhibition. The scope of his work covers neurophysiology, pharmacology, psychiatry, and psychosomatics. His independence of spirit meant that most of his research was not done within university settings. PMID:24733976

Kunz, Edward

2014-03-01

310

When inhibition not excitation synchronizes neural firing  

Microsoft Academic Search

Excitatory and inhibitory synaptic coupling can have counter-intuitive effects on the synchronization of neuronal firing. While it might appear that excitatory coupling would lead to synchronization, we show that frequently inhibition rather than excitation synchronizes firing. We study two identical neurons described by integrate-and-fire models, general phase-coupled models or the Hodgkin-Huxley model with mutual, non-instantaneous excitatory or inhibitory synapses between

CARL VAN VREESWIJK; L. F. Abbott; G. Bard Ermentrout

1994-01-01

311

Prostaglandins inhibit renal ammoniagenesis in the rat.  

PubMed Central

We describe the inhibitory effect of prostaglandins (PGs) on in vivo rat renal ammonia synthesis. The influence of systemic pH upon urinary PG excretion and ammoniagenesis was also investigated. Finally, PG production by incubated rat renal cortical slices was suppressed to investigate the PG-ammonia interplay in the absence of changes in renal blood flow, glomerular filtration rate, ambient electrolyte concentrations or extrarenal hormonal factors. In vivo ammonia synthesis doubled and PG excretion fell by 44% in normal rats, after intravenous administration of 1 mg/kg of meclofenamate. Higher doses of meclofenamate further augmented ammonia production and further reduced PG excretion. PG depletion was also associated with an increase in fractional excretion of ammonia (FENH3) that was independent of changes in urine flow rate or pH. Acute metabolic acidosis (AMA) increased total ammonia synthesis but also stimulated PG production. Administration of meclofenamate to rats with mild AMA markedly reduced urinary PG excretion, further augmented ammonia synthesis, and significantly increased the FENH3. Inhibition of stimulated PG synthesis during severe AMA did not increase ammoniagenesis or FENH3. Acute metabolic alkalosis did not alter production of PGs or ammonia, but reduced the FENH3 by 42%. Meclofenamate nearly normalized the FENH3 but stimulated synthesis to a lesser degree than was seen in nonalkalotic rats that received meclofenamate. Inhibition of PG synthesis in incubated rat renal cortical slices also stimulated ammoniagenesis. Conversely, stimulation of PG synthesis decreased ammonia production and acidification of the incubation medium increased prostaglandin F2 alpha production. Thus, in vitro findings support the in vivo results. We conclude that PGs inhibit ammonia synthesis in normal rats and in those undergoing mild AMA. Severe acidosis overrides this inhibitory effect of PGs, whereas metabolic alkalosis suppresses the stimulatory effect of PG synthesis inhibition. Images PMID:6470150

Jones, E R; Beck, T R; Kapoor, S; Shay, R; Narins, R G

1984-01-01

312

A mechanistic study of corrosion inhibiting admixtures  

Microsoft Academic Search

Purpose – This research aims to unravel the role of salt contamination and corrosion inhibiting admixtures in the processes of cement hydration and rebar corrosion. Design\\/methodology\\/approach – Mortar samples were prepared with NaCl and one of three corrosion inhibitors, sodium nitrite, disodium ?-glycerophosphate, or N,N?-dimethylethanolamine, admixed. After 28 days curing, all steel-mortar samples were ponded with 3 percent NaCl solution

Tuan Anh Nguyen; Xianming Shi

2009-01-01

313

Inhibition of gas hydrates by methanol  

Microsoft Academic Search

A molecular-thermodynamic correlation has been developed for calculating the inhibition effect of methanol on the formation of hydrates in moist gas mixtures. Six phases are potentially present in these mixtures: gas, aqueous liquid, hydrocarbon liquid, ice, and hydrate structures I and II. For a given temperature and system composition, the molecular-thermodynamic method described allows computation of the hydrate-point pressure as

F. E. Anderson; J. M. Prausnitz

1986-01-01

314

Inhibition of SN38 glucuronidation by ketoconazole  

Microsoft Academic Search

Background\\/Aims: Ketoconazole has been shown to inhibit the glucuronidation of the UGT2B7 substrates AZT and lorazepam. Its effect on UGT1A substrates is unknown. A recent study (Kehrer et al, JClin Oncol, 2002) found that co-administration of irinotecan and ketoconazole led to a significant increase in the formation of SN-38. This study investigates whether ketoconazole contributes to the increase in SN-38

W. Yong; J. Ramirez; F. Innocenti; M. J. Ratain

2005-01-01

315

Inhibition of HIV1 Entry into Cells  

Microsoft Academic Search

Treatments for HIV-1 include drugs which act to inhibit specific steps in the virus life cycle such as reverse transcription and viral maturation. In 1995 breakthroughs were made in our understanding of the entry of HIV-1 into cells. HIV-1 was shown to use, in addition to the CD4 receptor, chemokine co-receptors, primarily CCR5 and CXCR4, for entry into CD4+ T

Karen F. T. Copeland

2006-01-01

316

Structural Basis for Sirtuin Activity and Inhibition*  

PubMed Central

Sir2 proteins, or sirtuins, are a family of enzymes that catalyze NAD+-dependent deacetylation reactions and can also process ribosyltransferase, demalonylase, and desuccinylase activities. More than 40 crystal structures of sirtuins have been determined, alone or in various liganded forms. These high-resolution architectural details lay the foundation for understanding the molecular mechanisms of catalysis, regulation, substrate specificity, and inhibition of sirtuins. In this minireview, we summarize these structural features and discuss their implications for understanding sirtuin function. PMID:23086949

Yuan, Hua; Marmorstein, Ronen

2012-01-01

317

Chondroitin sulphate inhibits connective tissue mast cells  

PubMed Central

Mast cells derive from the bone marrow and are responsible for the development of allergic and possibly inflammatory reactions. Mast cells are stimulated by immunoglobulin E (IgE) and specific antigen, but also by a number of neuropeptides such as neurotensin (NT), somatostatin or substance P (SP), to secrete numerous pro-inflammatory molecules that include histamine, cytokines and proteolytic enzymes.Chondroitin sulphate, a major constituent of connective tissues and of mast cell secretory granules, had a dose-dependent inhibitory effect on rat peritoneal mast cell release of histamine induced by the mast cell secretagogue compound 48/80 (48/80). This inhibition was stronger than that of the clinically available mast cell ‘stabilizer' disodium cromoglycate (cromolyn). Inhibition by chondroitin sulphate increased with the length of preincubation and persisted after the drug was washed off, while the effect of cromolyn was limited by rapid tachyphylaxis.Immunologic stimulation of histamine secretion from rat connective tissue mast cells (CTMC) was also inhibited, but this effect was weaker in umbilical cord-derived human mast cells and was absent in rat basophilic leukemia (RBL) cells which are considered homologous to mucosal mast cells (MMC). Oligo- and monosaccharides were not as effective as the polysaccharides.Inhibition, documented by light and electron microscopy, involved a decrease of intracellular calcium ion levels shown by confocal microscopy and image analysis. Autoradiography at the ultrastructural level showed that chondroitin sulphate was mostly associated with plasma and perigranular membranes.Chondroitin sulphate appears to be a potent mast cell inhibitor of allergic and nonimmune stimulation with potential clinical implications. PMID:11082109

Theoharides, T C; Patra, P; Boucher, W; Letourneau, R; Kempuraj, D; Chiang, G; Jeudy, S; Hesse, Leah; Athanasiou, A

2000-01-01

318

Mechanisms of proteoglycan inhibition of hydroxyapatite growth  

Microsoft Academic Search

Summary  Purified bovine nasal cartilage proteoglycans (aggregate and subunit containing fractions) and to a lesser degree, chondroitin\\u000a 4-sulfate of physiological size, retard seeded hydroxyapatite (HA) growthin vitro. The large hydrodynamic size and high charge density of these macromolecules are believed to be associated with the ability\\u000a of proteoglycans to inhibit HA formation and growth. We now demonstrate the involvement of the

Chun-Chang Chen; Adele L. Boskey

1985-01-01

319

Henri Laborit and the inhibition of action  

PubMed Central

Henri Laborit was one of the founders of modern neuropsychopharmacology, having discovered, or participated in, the discovery of chlorpromazine, gamma-OH, clomethiazole, and minaprine. He also put forward a theory regarding the necessity of counteracting the negative consequences of defense mechanisms during anesthesia or behavioral inhibition. The scope of his work covers neurophysiology, pharmacology, psychiatry, and psychosomatics. His independence of spirit meant that most of his research was not done within university settings. PMID:24733976

Kunz, Edward

2014-01-01

320

Motivational influences on response inhibition measures  

PubMed Central

Psychological research has placed great emphasis on inhibitory control due to its integral role in normal cognition and clinical disorders. The stop-signal task, in conjunction with the stop-signal reaction time (SSRT) measure, provides a well-established paradigm for measuring motor response inhibition. However, the influence of motivation and strategic decision-making on stop-signal performance and SSRT has not been examined. In the present study, we conceptualize the stop-signal paradigm as a decision-making task involving the tradeoff between fast responding and accurate inhibition. In four experiments, we demonstrate that this performance tradeoff is influenced by inherent motivational biases as well as explicit strategic control, resulting in systematic differences in conventional measures of inhibitory ability, such as SSRT. Within subjects, we found that SSRT was lower when participants favored correct stopping over fast responding, and was higher when participants favored fast responding over correct stopping. We present a novel variant of the stop-signal task that uses a monetary incentive structure to manipulate motivated speed-accuracy tradeoffs. By sampling performance at multiple tradeoff settings, we obtain a measure of inhibitory ability that is not confounded with motivational or strategic bias, and thus, more easily interpretable when comparing across participants. We present a working theoretical model to explain the effects of motivational context on response inhibition. PMID:20364928

Leotti, Lauren A.; Wager, Tor D.

2014-01-01

321

Inhibition of enveloped viruses infectivity by curcumin.  

PubMed

Curcumin, a natural compound and ingredient in curry, has antiinflammatory, antioxidant, and anticarcinogenic properties. Previously, we reported that curcumin abrogated influenza virus infectivity by inhibiting hemagglutination (HA) activity. This study demonstrates a novel mechanism by which curcumin inhibits the infectivity of enveloped viruses. In all analyzed enveloped viruses, including the influenza virus, curcumin inhibited plaque formation. In contrast, the nonenveloped enterovirus 71 remained unaffected by curcumin treatment. We evaluated the effects of curcumin on the membrane structure using fluorescent dye (sulforhodamine B; SRB)-containing liposomes that mimic the viral envelope. Curcumin treatment induced the leakage of SRB from these liposomes and the addition of the influenza virus reduced the leakage, indicating that curcumin disrupts the integrity of the membranes of viral envelopes and of liposomes. When testing liposomes of various diameters, we detected higher levels of SRB leakage from the smaller-sized liposomes than from the larger liposomes. Interestingly, the curcumin concentration required to reduce plaque formation was lower for the influenza virus (approximately 100 nm in diameter) than for the pseudorabies virus (approximately 180 nm) and the vaccinia virus (roughly 335 × 200 × 200 nm). These data provide insights on the molecular antiviral mechanisms of curcumin and its potential use as an antiviral agent for enveloped viruses. PMID:23658730

Chen, Tzu-Yen; Chen, Da-Yuan; Wen, Hsiao-Wei; Ou, Jun-Lin; Chiou, Shyan-Song; Chen, Jo-Mei; Wong, Min-Liang; Hsu, Wei-Li

2013-01-01

322

Inhibition of Enveloped Viruses Infectivity by Curcumin  

PubMed Central

Curcumin, a natural compound and ingredient in curry, has antiinflammatory, antioxidant, and anticarcinogenic properties. Previously, we reported that curcumin abrogated influenza virus infectivity by inhibiting hemagglutination (HA) activity. This study demonstrates a novel mechanism by which curcumin inhibits the infectivity of enveloped viruses. In all analyzed enveloped viruses, including the influenza virus, curcumin inhibited plaque formation. In contrast, the nonenveloped enterovirus 71 remained unaffected by curcumin treatment. We evaluated the effects of curcumin on the membrane structure using fluorescent dye (sulforhodamine B; SRB)-containing liposomes that mimic the viral envelope. Curcumin treatment induced the leakage of SRB from these liposomes and the addition of the influenza virus reduced the leakage, indicating that curcumin disrupts the integrity of the membranes of viral envelopes and of liposomes. When testing liposomes of various diameters, we detected higher levels of SRB leakage from the smaller-sized liposomes than from the larger liposomes. Interestingly, the curcumin concentration required to reduce plaque formation was lower for the influenza virus (approximately 100 nm in diameter) than for the pseudorabies virus (approximately 180 nm) and the vaccinia virus (roughly 335 × 200 × 200 nm). These data provide insights on the molecular antiviral mechanisms of curcumin and its potential use as an antiviral agent for enveloped viruses. PMID:23658730

Wen, Hsiao-Wei; Ou, Jun-Lin; Chiou, Shyan-Song; Chen, Jo-Mei; Wong, Min-Liang; Hsu, Wei-Li

2013-01-01

323

Apoptosis induced by inhibition of intercellular contact  

PubMed Central

The LIM 1863 colon carcinoma cell line grows as structural organoids of goblet and columnar cells around a central lumen and provides a model for the development of stem cells in the normal colon. The organoid structure can be disrupted by removal of calcium from the medium, resulting in a suspension of single cells. Upon readdition of calcium, the cells reform the organoid structure over a period of 24 h, and ultrastructural examination of the reforming cells reveals that this involves a complex process that we have termed clutching. To determine the adhesion molecules involved in organoid formation we attempted to block this process by single cell suspensions of LIM 1863 reseeded in the presence of monoclonal antibodies. An anti-integrin antibody directed against a conformational epitope on the alpha v subunit totally inhibited organoid reformation. As a consequence of this inhibition of cell contact the colon carcinoma cells rapidly underwent apoptosis. Investigations of the apoptotic pathway involved suggested an induction mechanism since the onset of apoptosis in the contact- inhibited cells showed specific increased synthesis of 68- and 72-kD proteins. In addition, immunoblotting of cytosolic and nuclear extracts of the cells revealed the rapid translocation of the tumor suppressor gene product, p53 to the cell nucleus upon induction of apoptosis. These results suggest that cell-cell adhesion may be a vital regulator of colon development overcome in tumor cells by loss of adhesion molecules or of functional p53 protein. PMID:8163556

1994-01-01

324

Anandamide inhibits breast tumor-induced angiogenesis  

PubMed Central

Breast cancer is one of the most frequently diagnosed malignancies and a leading cause of cancer death in women. Great advances in the treatment of primary tumors have led to a significant increment in the overall survival rates, however recurrence and metastatic disease, the underlying cause of death, are still a medical challenge. Breast cancer is highly dependent on neovascularization to progress. In the last years several anti-angiogenic drugs have been developed and administered to patients in combination with chemotherapeutic drugs. Collected preclinical evidence has proposed the endocannabinoid system as a potential target in cancer. The endocannabinoid anandamide has been reported to affect breast cancer growth at multiple levels, by inhibiting proliferation, migration and invasiveness in vitro and in vivo and by directly inhibiting angiogenesis. Aim of the present work is to investigate if anandamide is able to affect the proangiogenic phenotype of the highly invasive and metastatic breast cancer cells MDA-MB-231. We found that following anandamide treatment, MDAMB-231 cells lose their ability to stimulate endothelial cells proliferation in vitro, due to a significant inhibition of all the pro-angiogenic factors produced by these cells. This finding adds another piece of evidence to the anti-tumor efficacy of anandamide in breast cancer. PMID:25147760

Picardi, P; Ciaglia, E; Proto, MC; Pisanti, S

2014-01-01

325

LRRK2 inhibition attenuates microglial inflammatory responses.  

PubMed

Missense mutations in leucine-rich repeat kinase 2 (LRRK2) cause late-onset Parkinson's disease (PD), and common genetic variation in LRRK2 modifies susceptibility to Crohn's disease and leprosy. High levels of LRRK2 expression in peripheral monocytes and macrophages suggest a role for LRRK2 in these cells, yet little is known about LRRK2 expression and function in immune cells of the brain. Here, we demonstrate a role for LRRK2 in mediating microglial proinflammatory responses and morphology. In a murine model of neuroinflammation, we observe robust induction of LRRK2 in microglia. Experiments with toll-like receptor 4 (TLR4)-stimulated rat primary microglia show that inflammation increases LRRK2 activity and expression, while inhibition of LRRK2 kinase activity or knockdown of protein attenuates TNF? secretion and nitric oxide synthase (iNOS) induction. LRRK2 inhibition blocks TLR4 stimulated microglial process outgrowth and impairs ADP stimulated microglial chemotaxis. However, actin inhibitors that phenocopy inhibition of process outgrowth and chemotaxis fail to modify TLR4 stimulation of TNF? secretion and inducible iNOS induction, suggesting that LRRK2 acts upstream of cytoskeleton control as a stress-responsive kinase. These data demonstrate LRRK2 in regulating responses in immune cells of the brain and further implicate microglial involvement in late-onset PD. PMID:22302802

Moehle, Mark S; Webber, Philip J; Tse, Tonia; Sukar, Nour; Standaert, David G; DeSilva, Tara M; Cowell, Rita M; West, Andrew B

2012-02-01

326

Structural basis for transcription inhibition by tagetitoxin  

PubMed Central

Tagetitoxin (Tgt) inhibits plastid-encoded, bacterial and some eukaryotic RNA polymerases (RNAPs) by an unknown mechanism. A 2.4?-resolution structure of the Thermus thermophilus RNAP/Tgt complex revealed that Tgt-binding site within the RNAP secondary channel overlaps with that of the stringent control effector ppGpp, which partially protects RNAP from Tgt inhibition. Tgt binding is mediated exclusively through polar interactions with the ? and ?? residues whose substitutions confer resistance to Tgt in vitro. Importantly, a Tgt phosphate, together with two active site acidic residues, coordinates the third Mg2+ ion distinct from the two catalytic metal ions. We show that Tgt inhibits all RNAP catalytic reactions and propose a mechanism in which the Tgt-bound Mg2+ ion plays a key role in stabilization of an inactive transcription intermediate. This and other recent studies suggest that Mg-mediated remodeling of the active site could be a common theme in the regulation of catalysis by nucleic acid enzymes. PMID:16273103

Vassylyev, Dmitry G.; Svetlov, Vladimir; Vassylyeva, Marina N.; Perederina, Anna; Igarashi, Noriyuki; Matsugaki, Naohiro; Wakatsuki, Soichi; Artsimovitch, Irina

2005-01-01

327

Activated microglia inhibit axonal growth through RGMa.  

PubMed

By causing damage to neural networks, spinal cord injuries (SCI) often result in severe motor and sensory dysfunction. Functional recovery requires axonal regrowth and regeneration of neural network, processes that are quite limited in the adult central nervous system (CNS). Previous work has shown that SCI lesions contain an accumulation of activated microglia, which can have multiple pathophysiological influences. Here, we show that activated microglia inhibit axonal growth via repulsive guidance molecule a (RGMa). We found that microglia activated by lipopolysaccharide (LPS) inhibited neurite outgrowth and induced growth cone collapse of cortical neurons in vitro--a pattern that was only observed when there was direct contact between microglia and neurons. After microglia were activated by LPS, they increased expression of RGMa; however, treatment with RGMa-neutralizing antibodies or transfection of RGMa siRNA attenuated the inhibitory effects of microglia on axonal outgrowth. Furthermore, minocycline, an inhibitor of microglial activation, attenuated the effects of microglia and RGMa expression. Finally, we examined whether these in vitro patterns could also be observed in vivo. Indeed, in a mouse SCI model, minocycline treatment reduced the accumulation of microglia and decreased RGMa expression after SCI, leading to reduced dieback in injured corticospinal tracts. These results suggest that activated microglia play a major role in inhibiting axon regeneration via RGMa in the injured CNS. PMID:21957482

Kitayama, Mari; Ueno, Masaki; Itakura, Toru; Yamashita, Toshihide

2011-01-01

328

Enhanced and Inhibited Gravity Wave Spectra.  

NASA Astrophysics Data System (ADS)

Balloon measurements were used to investigate gravity waves in the upper troposphere and lower stratosphere above the Canadian high Arctic. The amount of gravity wave activity in the stratosphere was found to be related to particular meteorological conditions that influence the generation and propagation of mountain waves. Enhanced wave activity was observed to occur when there was a small change in wind direction in the troposphere and high wind speed at the ground. These conditions correspond to strong wave generation by flow over the ground of upward-propagating waves that do not encounter critical level filtering. Inhibited wave activity was observed when the wind direction changed by more than 180° in the troposphere or when the wind speed was relatively weak at the ground. These conditions correspond to critical level filtering and weak generation of upward-propagating waves. The vertical wavenumber spectrum of perturbation potential energy was enhanced at all resolved scales when the conditions were favorable for upward wave propagation. The average enhanced spectral magnitude increased in proportion to the increase in N2 (buoyancy frequency squared) between the troposphere and stratosphere. When the background atmospheric conditions inhibited upward wave propagation the spectral magnitude did not change between the troposphere and stratosphere, despite a factor of 4 increase in N2. The enhanced spectra are consistent with the current gravity wave paradigm but the inhibited spectra are not so readily explained.

Whiteway, James A.

1999-05-01

329

Phytic Acid Inhibits Lipid Peroxidation In Vitro  

PubMed Central

Phytic acid (PA) has been recognized as a potent antioxidant and inhibitor of iron-catalyzed hydroxyl radical formation under in vitro and in vivo conditions. Therefore, the aim of the present study was to investigate, with the use of HPLC/MS/MS, whether PA is capable of inhibiting linoleic acid autoxidation and Fe(II)/ascorbate-induced peroxidation, as well as Fe(II)/ascorbate-induced lipid peroxidation in human colonic epithelial cells. PA at 100??M and 500??M effectively inhibited the decay of linoleic acid, both in the absence and presence of Fe(II)/ascorbate. The observed inhibitory effect of PA on Fe(II)/ascorbate-induced lipid peroxidation was lower (10–20%) compared to that of autoxidation. PA did not change linoleic acid hydroperoxides concentration levels after 24 hours of Fe(II)/ascorbate-induced peroxidation. In the absence of Fe(II)/ascorbate, PA at 100??M and 500??M significantly suppressed decomposition of linoleic acid hydroperoxides. Moreover, PA at the tested nontoxic concentrations (100??M and 500??M) significantly decreased 4-hydroxyalkenal levels in Caco-2 cells which structurally and functionally resemble the small intestinal epithelium. It is concluded that PA inhibits linoleic acid oxidation and reduces the formation of 4-hydroxyalkenals. Acting as an antioxidant it may help to prevent intestinal diseases induced by oxygen radicals and lipid peroxidation products. PMID:24260736

Weglarz, Ludmila; Dzierzewicz, Zofia

2013-01-01

330

Silver-Palladium Surfaces Inhibit Biofilm Formation?  

PubMed Central

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 used as model organisms, and batch and flow chamber setups were used as model systems. In the case of the silver-sensitive strain, the silver-palladium surfaces killed the bacteria and prevented biofilm formation under conditions of low or high bacterial load. In the case of the silver-resistant strain, the silver-palladium surfaces killed surface-associated bacteria and prevented biofilm formation under conditions of low bacterial load, whereas under conditions of high bacterial load, biofilm formation occurred upon a layer of surface-associated dead bacteria. PMID:19151185

Chiang, Wen-Chi; Schroll, Casper; Hilbert, Lisbeth Rischel; M?ller, Per; Tolker-Nielsen, Tim

2009-01-01

331

Somatomedins inhibit protein degradation in muscle cell  

SciTech Connect

Protein degradation has been measured in cultures of L6 myotubes as the rate of release of trichloroacetic acid-soluble radioactivity after prelabeling cell protein with (/sup 3/H) leucine. Insulin-like growth factor-I (IGF-1), ovine somatomedin (oSM) and insulin (I), at concentrations from 10/sup -11/M to 10/sup -7/M (5 x 10/sup -7/M-oSM) were added at the beginning of a 4-hour degradation period to determine the effects of these hormones on inducible proteolysis occurring in serum-free media. In addition the effects of fetal bovine serum, at concentrations from 1% to 30%, on protein degradation were determined in parallel experiments to relate serum inhibition of proteolysis to somatomedin actions. Results from this study indicate the apparent half maximal inhibition of proteolysis (18%, 15%, 11%) occurred at .4nM-IGF-1, .6nM-oSM and 4nM-I, respectively. Thus protein degradation was approximately 10 times more sensitive to somatomedins than insulin. The half maximal inhibition of proteolysis (15%) observed with serum occurred at 7.7%. The magnitude of the response between IFG-I and serum (37% vs. 31%) was similar. These results are consistent with the hypothesis that somatomedins are important factors in regulating growth and development of muscle.

Roeder, R.A.; Blann, D.L.; Bauer, C.A.; Hossner, K.L.

1986-03-01

332

46 CFR 154.1818 - Certification of inhibition.  

Code of Federal Regulations, 2010 CFR

...2010-10-01 2010-10-01 false Certification of inhibition. 154.1818 Section 154.1818 Shipping COAST GUARD...LIQUEFIED GASES Operations § 154.1818 Certification of inhibition. (a) Except as provided in §...

2010-10-01

333

Inhibition of the activity of mushroom tyrosinase by alkylbenzoic acids  

Microsoft Academic Search

The inhibition kinetics of alkylbenzoic acids on the diphenolase activity of mushroom tyrosinase have been investigated. The results show that the alkylbenzoic acids assayed can lead to reversible inhibition of the enzyme; furthermore, o-toluic acid and m-toluic acid are mixed-type inhibitors and p-alkylbenzoic acids are uncompetitive inhibitors. The inhibition constants have been determined. For these p-alkylbenzoic acids, the inhibition strength

Xiao-Hong Huang; Qing-Xi Chen; Qin Wang; Kang-Kang Song; Jun Wang; Li Sha; Xiong Guan

2006-01-01

334

Effective neuroleptic medication removes prepulse inhibition deficits in schizophrenia patients  

Microsoft Academic Search

Background: The magnitude of the startle eyeblink response is reduced if the startle eliciting stimulus is shortly preceded by another stimulus. There is evidence that schizophrenia patients exhibit impairments in this so-called prepulse inhibition. Our study investigated whether prepulse inhibition is affected by neuroleptic drug treatment as is suggested by animal research.Methods: Prepulse inhibition was tested in five unmedicated and

Almut I. Weike; Ulrike Bauer; Alfons O. Hamm

2000-01-01

335

Inhibition of chlorophyll synthesis by high concentrations of carbon dioxide  

Microsoft Academic Search

High concentrations of carbon dioxide inhibit the greening of etiolated plants. In the presence of 20% oxygen, concentrations of carbon dioxide of 10% and above inhibited the production of chlorophyll in etiolated leaves of barley, wheat, and dwarf French bean. On return to air, recovery from this inhibition took place rapidly. High concentrations of carbon dioxide were also inhibitory when

B. T. Steer; D. A. Walker

1964-01-01

336

Lactate Acid Inhibition of Salmonella Typhimurium in Yogurt  

Microsoft Academic Search

We determined how lactic acid inhibits growth of Salmonella typhimurium in yogurt. This inhibition was demonstrated by microscopic examination not to be due to bacteriolysis. Neither growth nor meta- bolic activity could be initiated after cells were washed in phosphate buffer and exposed to 1.5% lactic acid for 1 h at 3 7°C, indicating that lactic acid inhibition is irreversible.

Howard E. Rubin; Thomas Nerad; Frizell Vaughan

1982-01-01

337

Mechanism of nitrite inhibition of cellular respiration in Pseudomonas aeruginosa  

Microsoft Academic Search

One of the principal mechanisms of nitrite inhibition of cellular respiration has been considered to be the interference with the action of iron-containing enzymes. In procaryotic systems, the effect of nitrite on cellular metabolism remains unclear. This study provides evidence which shows a direct inhibition by a low concentration of nitrite on a highly purified oxidase inPseudomonas aeruginosa. The inhibition

Tsanyen Yang

1985-01-01

338

Possible mechanisms for the inhibition of photosynthesis by ozone  

Microsoft Academic Search

Tropospheric ozone produced by industrial civilization is widespread. Although the levels are not clearly life threatening, they do have the potential to inhibit normal plant productivity, thought to be by an inhibition of photosynthesis. While the mechanism for this inhibition is not yet clear, there are several hypotheses for its cause. It is unlikely that ozone can penetrate the cell

Robert L. Heath

1994-01-01

339

A fusion-inhibiting peptide against Rift Valley fever virus inhibits multiple, diverse viruses.  

PubMed

For enveloped viruses, fusion of the viral envelope with a cellular membrane is critical for a productive infection to occur. This fusion process is mediated by at least three classes of fusion proteins (Class I, II, and III) based on the protein sequence and structure. For Rift Valley fever virus (RVFV), the glycoprotein Gc (Class II fusion protein) mediates this fusion event following entry into the endocytic pathway, allowing the viral genome access to the cell cytoplasm. Here, we show that peptides analogous to the RVFV Gc stem region inhibited RVFV infectivity in cell culture by inhibiting the fusion process. Further, we show that infectivity can be inhibited for diverse, unrelated RNA viruses that have Class I (Ebola virus), Class II (Andes virus), or Class III (vesicular stomatitis virus) fusion proteins using this single peptide. Our findings are consistent with an inhibition mechanism similar to that proposed for stem peptide fusion inhibitors of dengue virus in which the RVFV inhibitory peptide first binds to both the virion and cell membranes, allowing it to traffic with the virus into the endocytic pathway. Upon acidification and rearrangement of Gc, the peptide is then able to specifically bind to Gc and prevent fusion of the viral and endocytic membranes, thus inhibiting viral infection. These results could provide novel insights into conserved features among the three classes of viral fusion proteins and offer direction for the future development of broadly active fusion inhibitors. PMID:24069485

Koehler, Jeffrey W; Smith, Jeffrey M; Ripoll, Daniel R; Spik, Kristin W; Taylor, Shannon L; Badger, Catherine V; Grant, Rebecca J; Ogg, Monica M; Wallqvist, Anders; Guttieri, Mary C; Garry, Robert F; Schmaljohn, Connie S

2013-01-01

340

Inhibition of return arises from inhibition of response processes: an analysis of oscillatory beta activity.  

PubMed

Abstract In the orienting of attention paradigm, inhibition of return (IOR) refers to slowed responses to targets presented at the same location as a preceding stimulus. No consensus has yet been reached regarding the stages of information processing underlying the inhibition. We report the results of an electro-encephalogram experiment designed to examine the involvement of response inhibition in IOR. Using a cue-target design and a target-target design, we addressed the role of response inhibition in a location discrimination task. Event-related changes in beta power were measured because oscillatory beta activity has been shown to be related to motor activity. Bilaterally located sources in the primary motor cortex showed event-related beta desynchronization (ERD) both at cue and target presentation and a rebound to event-related beta synchronization (ERS) after movement execution. In both designs, IOR arose from an enhancement of beta synchrony. IOR was related to an increase of beta ERS in the target-target design and to a decrease of beta ERD in the cue-target design. These results suggest an important role of response inhibition in IOR. PMID:17919085

Pastötter, Bernhard; Hanslmayr, Simon; Bäuml, Karl-Heinz

2008-01-01

341

Potent inhibition of CYP2D6 by haloperidol metabolites: stereoselective inhibition by reduced haloperidol  

PubMed Central

Aims We evaluated the inhibitory effect of haloperidol and its metabolites on CYP2D6 activity in order to better understand the potential role of these metabolites in drug interactions involving haloperidol. Methods The inhibitory effects of haloperidol and five of its metabolites on dextrorphan formation from dextromethorphan, a marker probe of CYP2D6 activity, were measured in human liver microsomal preparations. Apparent kinetic parameters for enzyme inhibition were determined by nonlinear regression analysis of the data. Results Racemic reduced haloperidol and its metabolite, RHPTP competitively inhibited dextromethorphan O-demethylation with estimated Ki values (0.24 µm and 0.09 µm, respectively) that were substantially lower than that of haloperidol (0.89 µm). The inhibitory effect of S(–)-reduced haloperidol was more potent than the R(+)-enantiomer, with estimated Ki values of 0.11 µm and 1.1 µm, respectively. The pyridinium metabolite of haloperidol, HPP+ inhibited the enzyme activity noncompetitively with a Ki value of 0.79 µm. The N-dealkylated metabolites of haloperidol (FBPA and CPHP) had a diminished inhibitory potency. While FBPA showed no notable inhibitory effect on dextrorphan formation, CPHP showed moderate competitive inhibition with a Ki value of 20.9 µm. Conclusions The principal metabolites of haloperidol inhibit CYP2D6, suggesting that they might contribute to the inhibitory effects of the drug. Reduced haloperidol seems to inhibit CYP2D6 activity in an enantioselective manner with the physiologically occurring S(–) enantiomer being more potent. PMID:11167668

Shin, Jae-Gook; Kane, Khadidjatou; Flockhart, David A

2001-01-01

342

Polychlorobiphenyls inhibit skeletal muscle differentiation in culture.  

PubMed

Polychlorinated biphenyls (PCBs) are ubiquitous and persistent pollutants whose role in developmental toxicity is of great concern. The observation that the offspring of PCB-exposed mothers (both in humans and rodents) display reduced body mass prompted us to investigate the effects of commercial mixtures of PCB congeners (Aroclor 1232, 1254, and 1262) on differentiation of both a myogenic cell line and primary myogenic cell cultures. The fusion of L6 myoblasts into multinucleated myotubes and the increase of creatine kinase (CK) activity were dose-dependently inhibited by Aroclor 1254 at concentrations (0.1-4 microg/ml) that caused no effect on cell density. Ultrastructural analysis demonstrated that Aroclor 1254 also prevented the accumulation of contractile filaments while inducing hypertrophy of the smooth endoplasmic reticulum and appearance of membrane-filled autophagosomes. Half-maximal inhibition (IC50) of CK activity accumulation occurred at 0.01 microg/ml for Aroclor 1262, 2 microg/ml for Aroclor 1254, and 8 microg/ml for Aroclor 1232. Aroclor-dependent inhibition of myogenic differentiation was also shown by the reduced expression and nuclear accumulation of beta-galactosidase in primary cultures of fetal myoblasts from transgenic mice expressing this reporter gene under the control of the myosin light chain promoter. These data show that skeletal muscle differentiation is specifically impaired by PCBs and may explain the reported depression of body mass growth in PCB-exposed offspring at birth. Furthermore, myogenic cell cultures are highly sensitive to PCBs and allow the detection of biological effects of environmental levels of these pollutants. PMID:11559021

Coletti, D; Palleschi, S; Silvestroni, L; Cannavň, A; Vivarelli, E; Tomei, F; Molinaro, M; Adamo, S

2001-09-15

343

Ozone inhibition of photosynthesis in Chlorella sorokiniana  

SciTech Connect

Exposure of Chlorella sorokiniana (07-11-05) to ozone inhibits photosynthesis. In this study, the effects of ozone on O/sub 2/ evolution and fluorescence yields are used to characterize this inhibition. At an ozone dose of about 3 micromoles delivered to 2 x 10/sup 9/ cells, the photosynthetic rate of the cells is inhibited 50%, as indicated by a decrease in bicarbonate-stimulated O/sub 2/ evolution (control rate, 1.4 +- 0.3 x 10/sup -15/ moles per cell per minute). Normal patterns of chlorophyll fluorescence are also altered. Upon continuous exposure to ozone (3.5 x 10/sup -7/ moles O/sub 3/ per minute), three stages of change in relative fluorescence yields are observed: (a) a rise in variable yield with no corresponding change in nonvariable yield (after 1-2 minutes), which was interpreted to be a shift in the energy flow pathway; (b) a decline in variable yield with a slight rise in nonvariable yield (requiring 3-5 minutes), interpreted to be a blockage in the CO/sub 2/ fixation pathways; and (c) complete blockage of variable yield with a concurrent decline in nonvariable yield (8-10 minutes), interpreted to be a destruction of the pigment system. The timing of each stage depended upon the ozone concentration and its delivery rate to the cell suspension. These results are compared with ozone-induced decline in photosynthesis and leaf water potential changes reported for other plant systems. Evidence is also presented to suggest that ozone effects on the photosynthetic processes are attributable to ionic imbalances brought about by ozone interaction with the plasmalemma rather than a direct effect on the chloroplast. 25 references, 6 figures, 2 tables.

Heath, R.L.; Frederick, P.E.; Chimiklis, P.E.

1982-01-01

344

Inhibition, Executive Function, and Freezing of Gait  

PubMed Central

Background Studies suggest that freezing of gait (FoG) in people with Parkinson’s disease (PD) is associated with declines in executive function (EF). However, EF is multi-faceted, including three dissociable components: inhibiting prepotent responses, switching between task sets, and updating working memory. Objective This study investigated which aspect of EF is most strongly associated with FoG in PD. Method Three groups were studied: adults with PD (with and without FoG) and age-matched, healthy adults. All participants completed a battery of cognitive tasks previously shown to discriminate among the three EF components. Participants also completed a turning-in-place task that was scored for FoG by neurologists blind to subjects’ self-reported FoG. Results Compared to both other groups, participants with FoG showed significant performance deficits in tasks associated with inhibitory control, even after accounting for differences in disease severity, but no significant deficits in task-switching or updating working memory. Surprisingly, the strongest effect was an intermittent tendency of participants with FoG to hesitate, and thus miss the response window, on go trials in the Go-Nogo task. The FoG group also made slower responses in the conflict condition of the Stroop task. Physician-rated FoG scores were correlated both with failures to respond on go trials and with failures to inhibit responses on nogo trials in the Go-Nogo task. Conclusion These results suggest that FoG is associated with a specific inability to appropriately engage and release inhibition, rather than with a general executive deficit. PMID:24496099

Cohen, Rajal G.; Klein, Krystal A.; Nomura, Mariko; Fleming, Michael; Mancini, Martina; Giladi, Nir; Nutt, John G.; Horak, Fay B.

2014-01-01

345

Mirk kinase inhibition targets ovarian cancer ascites  

PubMed Central

The Mirk/dyrk1B gene is commonly amplified or upregulated in ovarian cancers, and Mirk is an active kinase in these cancers. Mirk mediates cancer cell survival by decreasing toxic ROS levels through maintaining expression of a series of antioxidant genes, possibly through its transcriptional activator functions. Mirk has the unusual property of being most active in quiescent cancer cells because of marked transcriptional downregulation by Akt/mTOR signaling and by MEK/erk signaling in cycling cells. Metastatic ovarian cancer cells form ascites, non-adherent multicellular aggregates floating within the peritoneal fluid. Most ascites cancer cells are in a reversible quiescent, dormant state, suggesting that Mirk might be expressed in these quiescent cells and thus a therapeutic target. The current studies show that ovarian cancer cell line spheroids that mimic ascites cancer spheroids were largely quiescent in G0/G1, and enriched in Mirk and the quiescence proteins, p130/Rb2 and the CDKI p27. Mirk kinase inhibition in spheroids made from established cell lines and in patient-derived ascites cancer cell spheroids reduced spheroid volume, disrupted spheroid structure to single cells, increased apoptosis, and decreased cell numbers. Earlier studies had shown that the mTOR inhibitor RAD001 increased transcription of the Mirk/dyrk1B gene, so treatments combined RAD001 with the most active Mirk kinase inhibitor. The number of ascites cells from 9 patients was reduced a similar amount by cisplatin, Mirk kinase inhibition or RAD001, but reduced substantially more, about 90%, by concurrent treatment with both the Mirk kinase inhibitor EHT5372 and RAD001. Addition of RAD001 increased the amount of toxic ROS induced by Mirk kinase inhibition. Two ascites samples taken one month apart gave similar drug responses, showing reproducibility of the techniques. Thus Mirk/dyrk1B kinase may be a therapeutic target in ovarian cancer ascites. PMID:25061503

Deng, Xiaobing; Hu, Jing; Cunningham, Mary J.; Friedman, Eileen

2014-01-01

346

Triaryl Pyrazoline Compound Inhibits Flavivirus RNA Replication  

Microsoft Academic Search

Triaryl pyrazoline {(5-(4-chloro-phenyl)-3-thiophen-2-yl-4,5-dihydro-pyrazol-1-yl)-phenyl-methanone} in- hibits flavivirus infection in cell culture. The inhibitor was identified through high-throughput screening of a compound library using a luciferase-expressing West Nile (WN) virus infection assay. The compound inhibited an epidemic strain of WN virus without detectable cytotoxicity (a 50% effective concentration of 28 M and a compound concentration of >300 M required to reduce 50%

Francesc Puig-Basagoiti; Mark Tilgner; Brett M. Forshey; Sean M. Philpott; Noel G. Espina; David E. Wentworth; Scott J. Goebel; Paul S. Masters; Barry Falgout; Ping Ren; David M. Ferguson; Pei-Yong Shi

2006-01-01

347

Inhibition of ?-galactosidases with mono- and disaccharides  

NASA Astrophysics Data System (ADS)

It was demonstrated that, in reactions of the hydrolysis of model substrate 2-nitrophenyl-?-D-galactopyranoside (2-NPGP) monosaccharides D-fructose and D-xylose with hydroxyl substituents oppositely directed at the neighboring carbon atoms in the furan ring, as in D-glucose, act as noncompetitive inhibitors of ?-galactosidase from E. coli; for mushroom, ?-galactosidases from P. canescens and A. oryzae D-galactose is a stronger inhibitor. It was also found that the inhibition constant is the highest in the case of the most active enzyme ( E. coli) and is the lowest for the least active one ( P. canescens).

Pilipenko, O. S.; Atyaksheva, L. F.; Chukhrai, E. S.

2010-01-01

348

Triptolide Directly Inhibits dCTP Pyrophosphatase  

PubMed Central

Triptolide is a potent natural product, with documented antiproliferative, immunosuppressive, anti-inflammatory, antifertility, and anti-polycystic kidney disease effects. Despite a wealth of knowledge about the biology of this compound, direct intracellular target proteins have remained elusive. We synthesized a biotinylated photoaffinity derivative of triptolide, and used it to identify dCTP pyrophosphatase 1 (DCTPP1) as a triptolide-interacting protein. Free triptolide interacts directly with recombinant DCTPP1, and inhibits the enzymatic activity of this protein. Triptolide is thus the first dCTP pyrophosphatase inhibitor identified, and DCTPP1 is a biophysically validated target of triptolide. PMID:21671327

Corson, Timothy W.; Cavga, Huseyin; Aberle, Nicholas; Crews, Craig M.

2012-01-01

349

GALVANOTROPISM AND "REVERSAL OF INHIBITION" BY STRYCHNINE  

PubMed Central

The cathodically galvanotropic orientation of nemerteans, Lineus, and the anodic orientation of the gephyrean Echiurus, are reversed by the action of strychnine under conditions such that the typical "reversal of inhibition" induced by this substance is apparent. Nicotine does not give this result. Since it is necessary to assume that the strychnine effect is due to action upon the central ganglia, and since the galvanotropic effect depends upon action of the current on nerve cell bodies of the central ganglia, it must be assumed that the locus of reversal by strychnine is not perikaryal, but presumably synaptic. PMID:19872331

Crozier, W. J.

1927-01-01

350

Inhibition of gas hydrates by methanol  

SciTech Connect

A molecular-thermodynamic correlation has been developed for calculating the inhibition effect of methanol on the formation of hydrates in moist gas mixtures. Six phases are potentially present in these mixtures: gas, aqueous liquid, hydrocarbon liquid, ice, and hydrate structures I and II. For a given temperature and system composition, the molecular-thermodynamic method described allows computation of the hydrate-point pressure as well as relative amounts and compositions of all coexisting phases. Good agreement is obtained when calculated results are compared with diverse experimental data reported in the literature. The correlation given here may be useful for computer-aided design for gas processing and transportation.

Anderson, F.E.; Prausnitz, J.M.

1986-08-01

351

Na+/K+-ATPase: Activity and inhibition  

NASA Astrophysics Data System (ADS)

The aim of the study was to give an overview of the mechanism of inhibition of Na+/K+-ATPase activity induced by some specific and non specific inhibitors. For this purpose, the effects of some ouabain like compounds (digoxin, gitoxin), noble metals complexes ([PtCl2DMSO2], [AuCl4]-, [PdCl4]2-, [PdCl(dien)]+, [PdCl(Me4dien)]+), transition metal ions (Cu2+, Zn2+, Fe2+, Co2+), and heavy metal ions (Hg2+, Pb2+, Cd2+) on the activity of Na+/K+-ATPase from rat synaptic plasma membranes (SPM), porcine cerebral cortex and human erythrocytes were discussed.

?olovi?, M.; Krsti?, D.; Krinulovi?, K.; Momi?, T.; Savi?, J.; Vuja?i?, A.; Vasi?, V.

2009-09-01

352

Emergence of clustering: Role of inhibition  

NASA Astrophysics Data System (ADS)

Though biological and artificial complex systems having inhibitory connections exhibit a high degree of clustering in their interaction pattern, the evolutionary origin of clustering in such systems remains a challenging problem. Using genetic algorithm we demonstrate that inhibition is required in the evolution of clique structure from primary random architecture, in which the fitness function is assigned based on the largest eigenvalue. Further, the distribution of triads over nodes of the network evolved from mixed connections reveals a negative correlation with its degree providing insight into origin of this trend observed in real networks.

Dwivedi, Sanjiv K.; Jalan, Sarika

2014-09-01

353

Formation and inhibition of photochemical smog  

SciTech Connect

Photochemical smog is caused by a free-radical chain mechanism which converts NO to NO/sub 2/. The NO/sub 2/ further reacts to produce ozone, nitric acid, and peracylnitrates. This chain mechanism can be inhibited by suitable free-radical scavengers. The chemistry and toxicology of one such free-radical scavenger, diethylhydroxylamine, has been studied in depth. It has been shown to be effective, safe, and practical for use in urban atmospheres to prevent photochemical smog formation. 42 references.

Heicklen, J.

1987-01-01

354

Differential effects of cognitive inhibition and intelligence on creativity  

PubMed Central

There are different conceptions about how cognitive inhibition is related to creativity. Creativity has either been associated with effective inhibition, or with disinhibition, or with an adaptive engagement of inhibition. In this study, we examined the relationship of cognitive inhibition, assessed by means of the random motor generation task, with different measures of creativity. We also analyzed whether this relation is mediated by intelligence. We generally found a positive correlation of inhibition and creativity measures. Moreover, latent variable analyses indicate that inhibition may primarily promote the fluency of ideas, whereas intelligence specifically promotes the originality of ideas. These findings support the notion that creative thought involves executive processes and may help to better understand the differential role of inhibition and intelligence in creativity. PMID:22945970

Benedek, Mathias; Franz, Fabiola; Heene, Moritz; Neubauer, Aljoscha C.

2012-01-01

355

Inhibition of ?-1,4-Glucan Biosynthesis by Deoxyglucose 1  

PubMed Central

GDP- and UDP-deoxyglucose inhibit the incorporation of glucose from UDP-glucose into dolichyl phosphate glucose and dolichyl pyrophosphate oligosaccharides. GDP-deoxyglucose inhibits by competing with the physiological nucleotide sugars for dolichyl phosphate, and dolichyl phosphate deoxyglucose is formed. This inhibition is reversed by excess of dolichyl phosphate. UDP-deoxyglucose does not give rise to a lipid-linked derivative, and inhibition by this analog is not reversed by dolichyl phosphate. The UDP- and GDP-derivatives of deoxyglucose inhibit the incorporation of glucose into glucose-containing glycoproteins. This effect seems to be the result of the inhibition of lipid intermediates glucosylation and is comparable to the effect produced by coumarin. Cellulose synthetase activity is not affected by UDP- or GDP-deoxyglucose. On the other hand, deoxyglucose inhibits the formation of ?-1,4-glucans in vivo. PMID:16662803

Datema, Roelf; Schwarz, Ralph T.; Rivas, Liliana A.; Lezica, Rafael Pont

1983-01-01

356

Differential effects of cognitive inhibition and intelligence on creativity.  

PubMed

There are different conceptions about how cognitive inhibition is related to creativity. Creativity has either been associated with effective inhibition, or with disinhibition, or with an adaptive engagement of inhibition. In this study, we examined the relationship of cognitive inhibition, assessed by means of the random motor generation task, with different measures of creativity. We also analyzed whether this relation is mediated by intelligence. We generally found a positive correlation of inhibition and creativity measures. Moreover, latent variable analyses indicate that inhibition may primarily promote the fluency of ideas, whereas intelligence specifically promotes the originality of ideas. These findings support the notion that creative thought involves executive processes and may help to better understand the differential role of inhibition and intelligence in creativity. PMID:22945970

Benedek, Mathias; Franz, Fabiola; Heene, Moritz; Neubauer, Aljoscha C

2012-09-01

357

Inhibition of DNA replication by ultraviolet light.  

PubMed Central

DNA replication in ultraviolet-irradiated HeLa cells was studied by two different techniques: measurements of the kinetics of semiconservative DNA synthesis, and DNA fiber autoradiography. In examining the kinetics of semiconservative DNA synthesis, density label was used to avoid measuring the incorporation due to repair replication. The extent of inhibition varied with time. After doses of less than 10J/m2 the rate was initially depressed but later showed some recovery. After higher doses, a constant, low rate of synthesis was seen for at least the initial 6 h. An analysis of these data indicated that the inhibition of DNA synthesis could be explained by replication forks halting at pyrimidine dimers. DNA fiber autoradiography was used to further characterize replication after ultraviolet irradiation. The average length of labeled segments in irradiated cells increased in the time immediately after irradiation, and then leveled off. This is the predicted pattern if DNA synthesis in each replicon continued at its previous rate until a lesion is reached, and then halted. The frequency of lesions that block synthesis is approximately the same as the frequency of pyrimidine dimers. PMID:938725

Edenberg, H J

1976-01-01

358

Salinomycin, A Polyether Ionophoric Antibiotic, Inhibits Adipogenesis  

PubMed Central

The polyether ionophoric antibiotics including monensin, salinomycin, and narasin, are widely used in veterinary medicine and as food additives and growth promoters in animal husbandry including poultry farming. Their effects on human health, however, are not fully understood. Recent studies showed that salinomycin is a cancer stem cell inhibitor. Since poultry consumption has risen sharply in the last three decades, we asked whether the consumption of meat tainted with growth promoting antibiotics might have effects on adipose cells. We showed in this report that the ionophoric antibiotics inhibit the differentiation of preadipocytes into adipocytes. The block of differentiation is not due to the induction of apoptosis nor the inhibition of cell proliferation. In addition, salinomycin also suppresses the transcriptional activity of the CCAAT/enhancer binding proteins and the peroxisome proliferator-activated receptor ?. These results suggest that the ionophoric antibiotics can be exploited as novel anti-obesity therapeutics and as pharmacological probes for the study of adipose biology. Further, the pharmacological effects of salinomycin could be a harbinger of its toxicity on the adipose tissue and other susceptible target cells in cancer therapy. PMID:23123626

Szkudlarek-Mikho, Maria; Saunders, Rudel A.; Yap, Sook Fan; Ngeow, Yun Fong; Chin, Khew-Voon

2012-01-01

359

Sodium orthovanadate inhibits p53-mediated apoptosis.  

PubMed

Sodium orthovanadate (vanadate) inhibits the DNA-binding activity of p53, but its precise effects on p53 function have not been examined. Here, we show that vanadate exerts a potent antiapoptotic activity through both transcription-dependent and transcription-independent mechanisms relative to other p53 inhibitors, including pifithrin (PFT) alpha. We compared the effects of vanadate to PFTalpha and PFTmicro, an inhibitor of transcription-independent apoptosis by p53. Vanadate suppressed p53-associated apoptotic events at the mitochondria, including the loss of mitochondrial membrane potential, the conformational change of Bax and Bak, the mitochondrial translocation of p53, and the interaction of p53 with Bcl-2. Similarly, vanadate suppressed the apoptosis-inducing activity of a mitochondrially targeted temperature-sensitive p53 in stable transfectants of SaOS-2 cells. In radioprotection assays, which rely on p53, vanadate completely protected mice from a sublethal dose of 8 Gy and partially from a lethal dose of 12 Gy. Together, our findings indicated that vanadate effectively suppresses p53-mediated apoptosis by both transcription-dependent and transcription-independent pathways, and suggested that both pathways must be inhibited to completely block p53-mediated apoptosis. PMID:20048077

Morita, Akinori; Yamamoto, Shinichi; Wang, Bing; Tanaka, Kaoru; Suzuki, Norio; Aoki, Shin; Ito, Azusa; Nanao, Tomohisa; Ohya, Soichiro; Yoshino, Minako; Zhu, Jin; Enomoto, Atsushi; Matsumoto, Yoshihisa; Funatsu, Osamu; Hosoi, Yoshio; Ikekita, Masahiko

2010-01-01

360

Structural basis of kynurenine 3-monooxygenase inhibition.  

PubMed

Inhibition of kynurenine 3-monooxygenase (KMO), an enzyme in the eukaryotic tryptophan catabolic pathway (that is, kynurenine pathway), leads to amelioration of Huntington's-disease-relevant phenotypes in yeast, fruitfly and mouse models, as well as in a mouse model of Alzheimer's disease. KMO is a flavin adenine dinucleotide (FAD)-dependent monooxygenase and is located in the outer mitochondrial membrane where it converts l-kynurenine to 3-hydroxykynurenine. Perturbations in the levels of kynurenine pathway metabolites have been linked to the pathogenesis of a spectrum of brain disorders, as well as cancer and several peripheral inflammatory conditions. Despite the importance of KMO as a target for neurodegenerative disease, the molecular basis of KMO inhibition by available lead compounds has remained unknown. Here we report the first crystal structure of Saccharomyces cerevisiae KMO, in the free form and in complex with the tight-binding inhibitor UPF 648. UPF 648 binds close to the FAD cofactor and perturbs the local active-site structure, preventing productive binding of the substrate l-kynurenine. Functional assays and targeted mutagenesis reveal that the active-site architecture and UPF 648 binding are essentially identical in human KMO, validating the yeast KMO-UPF 648 structure as a template for structure-based drug design. This will inform the search for new KMO inhibitors that are able to cross the blood-brain barrier in targeted therapies against neurodegenerative diseases such as Huntington's, Alzheimer's and Parkinson's diseases. PMID:23575632

Amaral, Marta; Levy, Colin; Heyes, Derren J; Lafite, Pierre; Outeiro, Tiago F; Giorgini, Flaviano; Leys, David; Scrutton, Nigel S

2013-04-18

361

Inhibition of Aflatoxin Production by Surfactants  

PubMed Central

The effect of 12 surfactants on aflatoxin production, growth, and conidial germination by the fungus Aspergillus flavus is reported. Five nonionic surfactants, Triton X-100, Tergitol NP-7, Tergitol NP-10, polyoxyethylene (POE) 10 lauryl ether, and Latron AG-98, reduced aflatoxin production by 96 to 99% at 1% (wt/vol). Colony growth was restricted by the five nonionic surfactants at this concentration. Aflatoxin production was inhibited 31 to 53% by lower concentrations of Triton X-100 (0.001 to 0.0001%) at which colony growth was not affected. Triton X-301, a POE-derived anionic surfactant, had an effect on colony growth and aflatoxin production similar to that of the five POE-derived nonionic surfactants. Sodium dodecyl sulfate (SDS), an anionic surfactant, and dodecyltrimethylammonium bromide, a cationic surfactant, suppressed conidial germination at 1% (wt/vol). SDS had no effect on aflatoxin production or colony growth at 0.001%. The degree of aflatoxin inhibition by a surfactant appears to be a function of the length of the hydrophobic and hydrophilic chains of POE-derived surfactants. Images PMID:16349144

Rodriguez, Susan B.; Mahoney, Noreen E.

1994-01-01

362

A Wee1 checkpoint inhibits anaphase onset  

PubMed Central

Cdk1 drives both mitotic entry and the metaphase-to-anaphase transition. Past work has shown that Wee1 inhibition of Cdk1 blocks mitotic entry. Here we show that the budding yeast Wee1 kinase, Swe1, also restrains the metaphase-to-anaphase transition by preventing Cdk1 phosphorylation and activation of the mitotic form of the anaphase-promoting complex/cyclosome (APCCdc20). Deletion of SWE1 or its opposing phosphatase MIH1 (the budding yeast cdc25+) altered the timing of anaphase onset, and activation of the Swe1-dependent morphogenesis checkpoint or overexpression of Swe1 blocked cells in metaphase with reduced APC activity in vivo and in vitro. The morphogenesis checkpoint also depended on Cdc55, a regulatory subunit of protein phosphatase 2A (PP2A). cdc55? checkpoint defects were rescued by mutating 12 Cdk1 phosphorylation sites on the APC, demonstrating that the APC is a target of this checkpoint. These data suggest a model in which stepwise activation of Cdk1 and inhibition of PP2ACdc55 triggers anaphase onset. PMID:23751495

Lianga, Noel; Williams, Elizabeth C.; Kennedy, Erin K.; Dore, Carole; Pilon, Sophie; Girard, Stephanie L.; Deneault, Jean-Sebastien

2013-01-01

363

Inhibition Of Washed Sludge With Sodium Nitrite  

SciTech Connect

This report describes the results of electrochemical tests used to determine the relationship between the concentration of the aggressive anions in washed sludge and the minimum effective inhibitor concentration. Sodium nitrate was added as the inhibitor because of its compatibility with the DWPF process. A minimum of 0.05M nitrite is required to inhibit the washed sludge simulant solution used in this study. When the worst case compositions and safety margins are considered, it is expected that a minimum operating limit of nearly 0.1M nitrite will be specified. The validity of this limit is dependent on the accuracy of the concentrations and solubility splits previously reported. Sodium nitrite additions to obtain 0.1M nitrite concentrations in washed sludge will necessitate the additional washing of washed precipitate in order to decrease its sodium nitrite inhibitor requirements sufficiently to remain below the sodium limits in the feed to the DWPF. Nitrite will be the controlling anion in "fresh" washed sludge unless the soluble chloride concentration is about ten times higher than predicted by the solubility splits. Inhibition of "aged" washed sludge will not be a problem unless significant chloride dissolution occurs during storage. It will be very important tomonitor the composition of washed sludge during processing and storage.

Congdon, J. W.; Lozier, J. S.

2012-09-25

364

BART inhibits pancreatic cancer cell invasion by inhibiting ARL2-mediated RhoA inactivation.  

PubMed

We report that BART plays a role in inhibiting cell invasion by regulating the activity of the Rho GTPase protein RhoA in pancreatic cancer cells. BART was originally identified as a binding partner of ARL2, a small G-protein implicated as a regulator of microtubule dynamics and folding. We show that BART interacts with GTP-bound ARL2 and is required for the binding of GTP-bound ARL2 with active forms of RhoA at leading edges in migrating cancer cells. GTP-bound ARL2 inactivates RhoA and BART prevents ARL2 from regulating RhoA activity. Thus, BART binds to and functions as an inhibitor of ARL2 at leading edges of migrating cells, thereby increasing the amount of active RhoA. Treatment with the Rho inhibitor C3 exoenzyme induces cell invasion by pancreatic cancer cells to the same level as that of cells in which BART is stably knocked down by RNA interference. GTP-bound ARL2 acts as a RhoA inhibitor by a mechanism that involves the induction of actin-cytoskeleton rearrangements. We show that BART decreases actin-cytoskeleton rearrangements by inhi-biting ARL2 function and by increasing the amount of active RhoA in pancreatic cancer cells. Our results imply that BART increases active RhoA by inhibiting ARL2 function, which in turn inhibits invasiveness of cancer cells. PMID:21833473

Taniuchi, Keisuke; Iwasaki, Shinji; Saibara, Toshiji

2011-11-01

365

Rethinking Inhibition Theory: On the Problematic Status of the Inhibition Theory for Forgetting  

ERIC Educational Resources Information Center

The standard textbook account of interference and forgetting is based on the assumption that retrieval of a memory trace is affected by competition by other memory traces. In recent years, a number of researchers have questioned this view and have proposed an alternative account of forgetting based on a mechanism of suppression. In this inhibition

Raaijmakers, Jeroen G. W.; Jakab, Emoke

2013-01-01

366

Visualization-Based Analysis for a Mixed-Inhibition Binary PBPK Model: Determination of Inhibition Mechanism  

Microsoft Academic Search

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 sensitivity and identifiability analyses of the model were performed to determine the conditions under which four inhibitory parameters describing inhibitor binding could be estimated. The sensitivity methods were

Kristin K. Isaacs; Marina V. Evans; Thomas R. Harris

2004-01-01

367

Propofol Stimulates Noradrenalin-Inhibited Neurons in the Ventrolateral Preoptic Nucleus by Reducing GABAergic Inhibition  

PubMed Central

Background The cellular mechanisms underlying the sedative effect of general anesthetics are not completely understood. Accumulating evidence indicates that the ventrolateral preoptic area (VLPO) of the hypothalamus plays a critical role. The VLPO contains two major types of neurons, the noradrenalin-inhibited GABAergic projecting neurons (NA(?) neurons), and the noradrenalin-excited interneurons (NA(+) neurons) which are probably also gamma-aminobutyric acid (GABA)-containing neurons. Our previous work suggests that NA(?) neurons are normally under the inhibitory control of NA(+) neurons. Previous studies also show that GABAergic agents including propofol activate GABAergic projecting neurons in the VLPO, which is believed to lead to the inhibition of the arousal-producing nuclei in the tuberomammillary nucleus and sedation. However, how propofol activates VLPO neurons remains unclear. We explored the possibility that propofol activates NA(?) neurons indirectly, by inhibiting GABAergic transmission including those from VLPO NA(+) neurons. Methods Electrophysiological activities were recorded from VLPO cells in acute brain slices of rats. Results Propofol facilitates the discharges of NA(?) neurons and reduces the frequency, but not the amplitude of spontaneous GABAergic inhibitory postsynaptic currents in NA(?) neurons. Conversely, propofol suppressed the discharges of NA(+) neurons. Conclusion Propofol excites VLPO NA(?) neurons by reducing GABAergic transmission, at least in part by inhibiting VLPO NA(+) neurons. This may be a critical mechanism contributing to propofol-induced sedation. PMID:23780420

Liu, Yu-Wei; Zuo, Wanhong; Ye, Jiang-Hong

2013-01-01

368

Progress of biosensors based on cholinesterase inhibition.  

PubMed

Biosensors are available and applicable for detection and characterization of specific inhibitors of many enzymes. In this review, biosensors based on fixed acetylcholinesterase (AChE) or butyrylcholinesterase (BChE) are presented. Inhibition of selected enzymes by various compounds, such as organophosphorus and carbamate pesticides, nerve agents (e.g. sarin or VX), and other natural toxins (e.g. aflatoxins), was employed to develop specific assays using biosensors only. Biosensor technology brings potential miniaturization and portability, when it is compared to standard methods. Construction of biosensors based on cholinesterases became a more important issue within the last decades. Novel approach with recombinant proteins, microelectrodes and immobilization protocol related to nanotechnologies opened new insight to the cholinesterase based biosensor construction and its perspective via routine assays. This review is focused on novel trends within such biosensors as a result of the known platform. PMID:19442145

Pohanka, Miroslav; Musilek, Kamil; Kuca, Kamil

2009-01-01

369

Normal interhemispheric inhibition in persistent developmental stuttering.  

PubMed

Imaging studies suggest a right hemispheric (pre)motor overactivity in patients with persistent developmental stuttering (PDS). The interhemispheric inhibition (IHI) studied with transcranial magnetic stimulation is an established measure of the interplay between right and left motor areas. We assessed IHI in 15 young male adults with PDS and 15 age-matched fluent-speaking subjects. We additionally studied the ipsilateral silent period (iSP) duration. We found no significant between-group difference for IHI or for iSP duration. We conclude that the interplay between the primary motor cortices is normal in patients with PDS. The abnormal right motor and premotor activity observed in functional imaging studies on PDS are not likely to reflect altered primary motor cortex excitability, but are likely to have a different origin. PMID:19224611

Sommer, Martin; Knappmeyer, Kathrin; Hunter, Evke Jane; Gudenberg, Alexander Wolffvon; Neef, Nicole; Paulus, Walter

2009-04-15

370

RIG-I activation inhibits ebolavirus replication.  

PubMed

Hemorrhagic fever viruses are associated with rapidly progressing severe disease with high case fatality, making them of public health and biothreat importance. Effective antivirals are not available for most of the members of this diverse group of viruses. A broad spectrum strategy for antiviral development would be very advantageous. Perhaps the most challenging target would be the highly immunosuppressive filoviruses, ebolavirus and marburgvirus, associated with aerosol infectivity and case fatalities in the 80-90% range. Here we report that activation of evolutionarily conserved cytosolic viral nucleic acid sensor, RIG-I can cause severe inhibition of ebolavirus replication. These findings indicate that RIG-I-based therapies may provide an attractive approach for antivirals against Ebola hemorrhagic fever, and possibly other HF viruses. PMID:19628240

Spiropoulou, Christina F; Ranjan, Priya; Pearce, Melissa B; Sealy, Tara K; Albarińo, César G; Gangappa, Shivaprakash; Fujita, Takashi; Rollin, Pierre E; Nichol, Stuart T; Ksiazek, Thomas G; Sambhara, Suryaprakash

2009-09-15

371

Triple helix formation inhibits DNA gyrase activity.  

PubMed

The goal of this work was to examine the effect of triple helix-forming oligonucleotides on a gyrase target region and on the activity of the enzyme. Using melting temperature measurements and gel mobility shift analysis, it was found that modified oligonucleotides can form a triple helix along the 29-nucleotide region of a 32-bp duplex representing part of the gyrase DNA-target sequence of the 162-bp fragment from pBR322. Triplex formation with this target region has been achieved at pH 7.5 by using a synthetic oligonucleotide in which cytosine was replaced by the C-nucleoside of 2-aminopyridine. The results of the enzymic experiments in vitro with the 162-bp fragment demonstrated that the cleavage reaction mediated by gyrase can be efficiently inhibited by the triplex-forming oligonucleotide modified with 2-aminopyridine. A possible inhibitory mechanism is discussed. PMID:10645778

Simon, H; Förtsch, I; Burckhardt, G; Gabrielyan, A; Birch-Hirschfeld, E; Stelzner, A; Prévot-Halter, I; Leumann, C; Zimmer, C

1999-12-01

372

Monoamine modulation of tonic GABAA inhibition.  

PubMed

In recent years, it has become evident that many neurotransmitters and endogenous ligands differentially modulate synaptic ?-aminobutyric acid type A receptors (sGABAARs) and extrasynaptic GABAAR (eGABAARs). In this mini-review, we will summarize the available evidence on the ability of the monoamines serotonin (5-HT), noradrenaline (NA), and, in particular, dopamine (DA) to alter the functional response of eGABAARs, thus either increasing or decreasing tonic GABAA inhibition. Although this field of research is still in its infancy, it has already been demonstrated that eGABAARs show a nucleus-selective and neuronal-type-selective regulation by monoamines in a way that differs from that of sGABAARs. Further work will undoubtedly advance our knowledge of the intricate talk between monoamines and eGABAAR and may ultimately provide new leads for the treatment of neurological and neuropsychiatric disorders, where alteration in GABAAR function is one of the underlying causes. PMID:24468610

Crunelli, Vincenzo; Di Giovanni, Giuseppe

2014-01-01

373

Inhibition of gas hydrates in deepwater drilling  

SciTech Connect

With the movement of offshore rigs into deep water, the problem of gas hydrates has become an important issue in drilling. If a kick is taken, gas hydrates can form in the blowout preventer (BOP) or chokelines while the kick is circulated out. The water-based pill presented here significantly improves gas-hydrate inhibition. This pill, which can be spotted in the BOP and weighted up, is environmentally safe and easily adaptable to offshore operations. Compatible with commonly used drilling fluids, the pill can be mixed directly into the mud system without any adverse effects after the danger of hydrate formation diminishes. This technology is an important safety consideration for deepwater drilling well control and hydrate-free operations above the mudline.

Hale, A.H.; Dewan, A.K.R. (Shell Development Co., Houston, TX (USA))

1990-06-01

374

The mode of retinal presynaptic inhibition switches with light intensity  

PubMed Central

Summary Excitatory amino acid transporters (EAATs) terminate signaling in the CNS by clearing released glutamate. Glutamate also evokes an EAAT-mediated Cl? current, but its role in CNS signaling is poorly understood. We show in mouse retina that EAAT-mediated Cl? currents that were evoked by light inhibit rod pathway signaling. EAATs reside on rod bipolar cell (RBC) axon terminals where GABA and glycine receptors also mediate light-evoked inhibition. We found that the mode of inhibition depended on light intensity. Dim light evoked GABAergic and glycinergic inhibition with rapid kinetics and a large spatial extent. Bright light evoked predominantly EAAT-mediated inhibition with slow kinetics and a small spatial extent. The switch to EAAT-mediated signaling in bright light supplements receptor-mediated signaling to expand the dynamic range of inhibition and contributes to the transition from rod to cone signaling by suppressing rod pathway signaling in bright light conditions. PMID:22457487

Ichinose, Tomomi; Lukasiewicz, Peter D.

2012-01-01

375

Molecular mechanisms of DNA repair inhibition by caffeine  

SciTech Connect

Caffeine potentiates the mutagenic and lethal effects of genotoxic agents. It is thought that this is due, at least in some organisms, to inhibition of DNA repair. However, direct evidence for inhibition of repair enzymes has been lacking. Using purified Escherichia coli DNA photolyase and (A)BC excinuclease, we show that the drug inhibits photoreactivation and nucleotide excision repair by two different mechanisms. Caffeine inhibits photoreactivation by interfering with the specific binding of photolyase to damaged DNA, and it inhibits nucleotide excision repair by promoting nonspecific binding of the damage-recognition subunit, UvrA, of (A)BC excinuclease. A number of other intercalators, including acriflavin and ethidium bromide, appear to inhibit the excinuclease by a similar mechanism--that is, by trapping the UvrA subunit in nonproductive complexes on undamaged DNA.

Selby, C.P.; Sancar, A. (Univ. of North Carolina School of Medicine, Chapel Hill (USA))

1990-05-01

376

Enoxacin Directly Inhibits Osteoclastogenesis without Inducing Apoptosis*  

PubMed Central

Enoxacin has been identified as a small molecule inhibitor of binding between the B2-subunit of vacuolar H+-ATPase (V-ATPase) and microfilaments. It inhibits bone resorption by calcitriol-stimulated mouse marrow cultures. We hypothesized that enoxacin acts directly and specifically on osteoclasts by disrupting the interaction between plasma membrane-directed V-ATPases, which contain the osteoclast-selective a3-subunit of V-ATPase, and microfilaments. Consistent with this hypothesis, enoxacin dose-dependently reduced the number of multinuclear cells expressing tartrate-resistant acid phosphatase (TRAP) activity produced by RANK-L-stimulated osteoclast precursors. Enoxacin (50 ?m) did not induce apoptosis as measured by TUNEL and caspase-3 assays. V-ATPases containing the a3-subunit, but not the “housekeeping” a1-subunit, were isolated bound to actin. Treatment with enoxacin reduced the association of V-ATPase subunits with the detergent-insoluble cytoskeleton. Quantitative PCR revealed that enoxacin triggered significant reductions in several osteoclast-selective mRNAs, but levels of various osteoclast proteins were not reduced, as determined by quantitative immunoblots, even when their mRNA levels were reduced. Immunoblots demonstrated that proteolytic processing of TRAP5b and the cytoskeletal protein l-plastin was altered in cells treated with 50 ?m enoxacin. Flow cytometry revealed that enoxacin treatment favored the expression of high levels of DC-STAMP on the surface of osteoclasts. Our data show that enoxacin directly inhibits osteoclast formation without affecting cell viability by a novel mechanism that involves changes in posttranslational processing and trafficking of several proteins with known roles in osteoclast function. We propose that these effects are downstream to blocking the binding interaction between a3-containing V-ATPases and microfilaments. PMID:22474295

Toro, Edgardo J.; Zuo, Jian; Ostrov, David A.; Catalfamo, Dana; Bradaschia-Correa, Vivian; Arana-Chavez, Victor; Caridad, Aliana R.; Neubert, John K.; Wronski, Thomas J.; Wallet, Shannon M.; Holliday, L. Shannon

2012-01-01

377

Enoxacin directly inhibits osteoclastogenesis without inducing apoptosis.  

PubMed

Enoxacin has been identified as a small molecule inhibitor of binding between the B2-subunit of vacuolar H+-ATPase (V-ATPase) and microfilaments. It inhibits bone resorption by calcitriol-stimulated mouse marrow cultures. We hypothesized that enoxacin acts directly and specifically on osteoclasts by disrupting the interaction between plasma membrane-directed V-ATPases, which contain the osteoclast-selective a3-subunit of V-ATPase, and microfilaments. Consistent with this hypothesis, enoxacin dose-dependently reduced the number of multinuclear cells expressing tartrate-resistant acid phosphatase (TRAP) activity produced by RANK-L-stimulated osteoclast precursors. Enoxacin (50 ?M) did not induce apoptosis as measured by TUNEL and caspase-3 assays. V-ATPases containing the a3-subunit, but not the "housekeeping" a1-subunit, were isolated bound to actin. Treatment with enoxacin reduced the association of V-ATPase subunits with the detergent-insoluble cytoskeleton. Quantitative PCR revealed that enoxacin triggered significant reductions in several osteoclast-selective mRNAs, but levels of various osteoclast proteins were not reduced, as determined by quantitative immunoblots, even when their mRNA levels were reduced. Immunoblots demonstrated that proteolytic processing of TRAP5b and the cytoskeletal protein L-plastin was altered in cells treated with 50 ?M enoxacin. Flow cytometry revealed that enoxacin treatment favored the expression of high levels of DC-STAMP on the surface of osteoclasts. Our data show that enoxacin directly inhibits osteoclast formation without affecting cell viability by a novel mechanism that involves changes in posttranslational processing and trafficking of several proteins with known roles in osteoclast function. We propose that these effects are downstream to blocking the binding interaction between a3-containing V-ATPases and microfilaments. PMID:22474295

Toro, Edgardo J; Zuo, Jian; Ostrov, David A; Catalfamo, Dana; Bradaschia-Correa, Vivian; Arana-Chavez, Victor; Caridad, Aliana R; Neubert, John K; Wronski, Thomas J; Wallet, Shannon M; Holliday, L Shannon

2012-05-18

378

Risperidone inhibits voltage-gated sodium channels.  

PubMed

In contrast to several other antipsychotic drugs, the effects of the atypical antipsychotic risperidone on voltage-gated sodium channels have not been characterized yet, despite its wide clinical use. Here we performed whole-cell voltage-clamp recordings to analyze the effects of risperidone on voltage-dependent sodium currents of N1E-115 mouse neuroblastoma cells carried by either endogenous sodium channels or transfected NaV1.6 channels. Risperidone inhibited both endogenous and NaV1.6-mediated sodium currents at concentrations that are expected around active synaptic release sites owing to its strong accumulation in synaptic vesicles. When determined for pharmacologically isolated NaV1.6, risperidone inhibited peak inward currents with an IC50 of 49 µM. Channel block occurred in a state-dependent fashion with risperidone displaying a fourfold higher affinity for the inactivated state than for the resting state. As a consequence of the low state dependence, risperidone produced only a small, but significant leftward shift of the steady-state inactivation curve and it required concentrations ? 30 µM to significantly slow the time course of recovery from inactivation. Risperidone (10 µM) gave rise to a pronounced use-dependent block when sodium currents were elicited by trains of brief voltage pulses at higher frequencies. Our data suggest that, compared to other antipsychotic drugs as well as to local anesthetics and sodium channel-targeting anticonvulsants, risperidone displays an unusual blocking profile where a rather low degree of state dependence is associated with a prominent use-dependent block. PMID:24508524

Brauner, Jan M; Hessler, Sabine; Groemer, Teja W; Alzheimer, Christian; Huth, Tobias

2014-04-01

379

Graphene oxide strongly inhibits amyloid beta fibrillation  

NASA Astrophysics Data System (ADS)

Since amyloid beta fibrillation (A?F) plays an important role in the development of neurodegenerative diseases, we investigated the effect of graphene oxide (GO) and their protein-coated surfaces on the kinetics of A? fibrillation in the aqueous solution. We showed that GO and their protein-covered surfaces delay the A?F process via adsorption of amyloid monomers. Also, the large available surface of GO sheets can delay the A?F process by adsorption of amyloid monomers. The inhibitory effect of the GO sheet was increased when we increase the concentration from 10% (in vitro; stimulated media) to 100% (in vivo; stimulated media). Conclusion: our results revealed that GO and their surface proteins inhibit A?F by decreasing the kinetic reaction.Since amyloid beta fibrillation (A?F) plays an important role in the development of neurodegenerative diseases, we investigated the effect of graphene oxide (GO) and their protein-coated surfaces on the kinetics of A? fibrillation in the aqueous solution. We showed that GO and their protein-covered surfaces delay the A?F process via adsorption of amyloid monomers. Also, the large available surface of GO sheets can delay the A?F process by adsorption of amyloid monomers. The inhibitory effect of the GO sheet was increased when we increase the concentration from 10% (in vitro; stimulated media) to 100% (in vivo; stimulated media). Conclusion: our results revealed that GO and their surface proteins inhibit A?F by decreasing the kinetic reaction. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr31657a

Mahmoudi, Morteza; Akhavan, Omid; Ghavami, Mahdi; Rezaee, Farhad; Ghiasi, Seyyed Mohammad Amin

2012-11-01

380

Inhibition studies on Vibrio cholerae neuraminidase.  

PubMed

A series of viral neuraminidase inhibitors showing no structural analogy to neuraminic acids have been tested to find whether they are effective inhibitors of V. cholerae neuraminidase, too. Here we report the results obtained with the N-phenyloxamic acid derivatives 2 to 6 (R-NH-CO-COOR'; R = -C6H5NO2, -C6H5OH, -C6H5NH2; R' = -H, -C2H5; see Table 1) and with simple aromatic compounds structurally related to R, i.e. 4-nitroaniline (7), N-acetyl-4-nitroaniline (8), 4-nitrophenol (9), 2,4-dinitrophenol (10), and 4-aminophenol (11) (see Table 2). The inhibitory effects of 2 to 11 were studied according to the method of Dixon[19] in 0.1m sodium acetate buffer, pH 5.5, 2mM CaCl2, at 37 degrees C using the benzyl-alpha-ketoside of N-acetyl-D-neuraminic acid (1) as a substrate. The compounds 2 to 11 are shown to be competitive inhibitors of the enzymatic hydrolysis of the alpha-ketoside 1. The competitive inhibition kinetics are supported by the method of Lineweaver and Burk[20]. The inhibition constants (Ki) are found to be in the range of 0.03 to 5.7 mM. The simple aromatic compounds 7 to 11 show higher inhibitory activities than the phenyloxamic acid derivatives 2 to 6. In addition, significant differences in the Ki values were observed within the two series of inhibitors, whereby those containing a nitro group were most effective. PMID:856712

Brossmer, R; Keilich, G; Ziegler, D

1977-03-01

381

Inhibition of the ablation rate of graphite by gaseous chlorine.  

NASA Technical Reports Server (NTRS)

Investigation of the inhibiting effect of gaseous chlorine on the ablation rate of graphite. It is shown that small amounts of chlorine gas, when present in a supersonic high-temperature air environment, can inhibit the ablation rate of graphite and depress its surface temperature below that measured in pure air. The ablation inhibition performance of chlorine is presented in graphs in terms of mass loss rate and surface temperature depression as a function of chlorine concentration.

Maahs, H. G.

1972-01-01

382

The role of inhibition in task switching: A review  

Microsoft Academic Search

The concept of inhibition plays a major role in cognitive psychology. In the present article, we review the evidence for the\\u000a inhibition of task sets. In the first part, we critically discuss empirical findings of task inhibition from studies that\\u000a applied variants of the task-switching methodology and argue that most of these findings— such as switch cost asymmetries—are\\u000a ambiguous. In

Iring Koch; Miriam Gade; Stefanie Schuch; Andrea M. Philipp

2010-01-01

383

Tyrosinase inhibition by isophthalic acid: Kinetics and computational simulation  

Microsoft Academic Search

Using inhibition kinetics and computational simulation, we studied the reversible inhibition of tyrosinase by isophthalic acid (IPA). IPA inhibited tyrosinase in a complex manner with Ki=17.8±1.8mM. Measurements of intrinsic and ANS-binding fluorescence showed that IPA induced no changes in tertiary protein structure. For further insight, we predicted the 3D structure of tyrosinase and used a docking algorithm to simulate binding

Yue-Xiu Si; Shang-Jun Yin; Hae Young Chung; Li Yan; Zhi-Rong Lü; Hai-Meng Zhou; Jun-Mo Yang; Guo-Ying Qian; Yong-Doo Park

2011-01-01

384

Adenosine and adenosine analogs inhibit phosphodiesterase activity in the heart  

Microsoft Academic Search

Adenosine and its analogs (-)-N6-phenylisopropyladenosine and 5'-N-ethylcarboxamideadenosine inhibit cAMP and cGMP phosphodiesterase activity in guinea-pig atrial and ventricular preparations at concentrations of 100 µmol l-1 and higher. These effects are probably unrelated to the inotropic effects of these substances. However, inhibition of cAMP breakdown may compensate for the adenosine-induced inhibition of adenylate cyclase and may thus at least partially explain

Wilfried Meyer; Monika Nose; Wilhelm Schmitz; Hasso Scholz

1984-01-01

385

Geranylgeranyl diphosphate depletion inhibits breast cancer cell migration  

Microsoft Academic Search

Summary  The objective of this study was to determine whether geranylgeranyl diphosphate synthase inhibition, and therefore geranylgeranyl\\u000a diphosphate depletion, interferes with breast cancer cell migration. Digeranyl bisphosphonate is a specific geranylgeranyl\\u000a diphosphate synthase inhibitor. We demonstrate that digeranyl bisphosphonate depleted geranylgeranyl diphosphate and inhibited\\u000a protein geranylgeranylation in MDA-MB-231 cells. Similar to GGTI-286, a GGTase I inhibitor, digeranyl bisphosphate significantly\\u000a inhibited migration

Amel Dudakovic; Huaxiang Tong; Raymond J. Hohl

386

In Vitro Measurement of Pollen Tube Growth Inhibition  

PubMed Central

A method for estimating inhibition of pollen tube growth was developed. Pollen is placed in straight lines on an agar surface where it responds uniformly and predictably to aqueous solutions of germination-inhibiting substances located in wells at the ends of the lines. A scale of ratings, roughly corresponding to serial, doubled concentrations of inhibiting substances, was devised. Water-soluble organic solvents are relatively noninhibitory, salts are variable, and metabolic inhibitors have strong inhibitory effects. Pollens differ in their susceptibility to inhibition and in their response to particular substances. PMID:16658085

Martin, Franklin W.

1972-01-01

387

Timing of growth inhibition following shoot inversion in Pharbitis nil  

NASA Technical Reports Server (NTRS)

Shoot inversion in Pharbitis nil results in the enhancement of ethylene production and in the inhibition of elongation in the growth zone of the inverted shoot. The initial increase in ethylene production previously was detected within 2 to 2.75 hours after inversion. In the present study, the initial inhibition of shoot elongation was detected within 1.5 to 4 hours with a weighted mean of 2.4 hours. Ethylene treatment of upright shoots inhibited elongation in 1.5 hours. A cause and effect relationship between shoot inversion-enhanced ethylene production and inhibition of elongation cannot be excluded.

Abdel-Rahman, A. M.; Cline, M. G.

1989-01-01

388

Inhibition of Mild Steel Corrosion under Hydrodynamic Conditions  

SciTech Connect

The inhibition of mild steel corrosion by 4-amino-5-phenyl-4H-1, 2, 4-trizole-3-thiol (APTT) in 2.5 M H{sub 2}SO{sub 4} solution and the effect of hydrodynamic condition on inhibition process were studied. The hydrodynamic condition experiments are simulated by rotating cylinder electrode (RCE). Change of open circuit potential (OCP) with immersion time and potentiodynamic polarization were used to study the effect of hydrodynamic conditions on the inhibition process. Results obtained from changes of open circuit potential (OCP) with immersion time, and potentiodynamic polarization are in good agreement and indicated that the inhibition process was flow velocity dependence.

Musa, Ahmed Y.; Kadhum, Abdul Amir H.; Mohamad, Abu Bakar; Takriff, Mohd Sobri; Kamarudin, Siti Kartom [Department of Chemical and Process Engineering, Universiti Kebangsaan Malaysia, Bangi, 43600, Selangor (Malaysia); Daud, Abdul Razak [School of Applied Physics, Universiti Kebangsaan Malaysia, Bangi, 43600, Selangor (Malaysia)

2010-07-07

389

Myopotential inhibition of unipolar AV sequential (DVI) pacemaker.  

PubMed

Whereas myopotential inhibition of QRS-inhibited (VVI) pacemakers is well known, its occurrence in patients with AV sequential (DVI) pacemakers has not been reported. The present communication deals with spontaneous and induced myopotential inhibition of a multiprogrammable Intermedics unipolar AV sequential (DVI) pacemaker. The bedside maneuvers that were performed in the patient exposed the problem, therefore serving to establish the diagnosis. Although external adjustment of the sensitivity was the simple, non-invasive solution in this case, more studies are required to determine the success rate of this approach as well as the incidence and clinical significance of myopotential inhibition of unipolar DVI pacemakers. PMID:6181468

Echeverria, H J; Luceri, R M; Thurer, R J; Castellanos, A

1982-01-01

390

Novel Functional Aspect of Antihistamines: The Impact of Bepotastine Besilate on Substance P-Induced Events  

PubMed Central

Besides histamine, substance P (SP) has been demonstrated to play a crucial role in pruritic skin diseases. Although antihistamines are frequently used for pruritic skin diseases, little is known concerning the effect on an SP-induced event such as mast cell degranulation and the upregulation of adhesion molecules or the nitric oxide (NO) synthesis in endothelial cells. Our aim was to study the effect of bepotastine besilate on SP-induced degranulation of rat basophillic leukemia (RBL-2H3) cells and expression of adhesion molecules and NO synthesis in human dermal microvascular endothelial cells (HMVECs). Bepotastine besilate significantly inhibited SP-induced degranulation of RBL-2H3 cells and NO synthesis in HMVECs. Bepotastine besilate significantly inhibited expression of adhesion molecules in HMVESs, while it failed to suppress SP-induced upregulation of the adhesion molecules in HMVECs. Therefore, bepotastine besilate is assumed to act favorably on SP-induced basophil degranulation and NO synthesis in HMVECs. PMID:20975801

Kitaba, Shun; Murota, Hiroyuki; Yahata, Yoko; Azukizawa, Hiroaki; Katayama, Ichiro

2009-01-01

391

Mycobacterium tuberculosis inhibits IFN-gamma transcriptional responses without inhibiting activation of STAT1.  

PubMed

IFN-gamma activates macrophages to kill diverse intracellular pathogens, but does not activate human macrophages to kill virulent Mycobacterium tuberculosis. We tested the hypothesis that this is due to inhibition of IFN-gamma signaling by M. tuberculosis and found that M. tuberculosis infection of human macrophages blocks several responses to IFN-gamma, including killing of Toxoplasma gondii and induction of FcgammaRI. The inhibitory effect of M. tuberculosis is directed at transcription of IFN-gamma-responsive genes, but does not affect proximal steps in the Janus kinase-STAT pathway, as STAT1alpha tyrosine and serine phosphorylation, dimerization, nuclear translocation, and DNA binding are intact in M. tuberculosis-infected cells. In contrast, there is a marked decrease in IFN-gamma-induced association of STAT1 with the transcriptional coactivators CREB binding protein and p300 in M. tuberculosis-infected macrophages, indicating that M. tuberculosis directly or indirectly disrupts this protein-protein interaction that is essential for transcriptional responses to IFN-gamma. Gamma-irradiated M. tuberculosis and isolated cell walls reproduce the effects of live bacteria, indicating that the bacterial component(s) that initiates inhibition of IFN-gamma responses is constitutively expressed. Although lipoarabinomannan has been found to exert effects on macrophages, it does not account for the inhibitory effects of cell walls. These results indicate that one mechanism for M. tuberculosis to evade the human immune response is to inhibit the IFN-gamma signaling pathway, and that the mechanism of inhibition is distinct from that reported for Leishmania donovani or CMV, in that it targets the interaction of STAT1 with the basal transcriptional apparatus. PMID:10490990

Ting, L M; Kim, A C; Cattamanchi, A; Ernst, J D

1999-10-01

392

Receptor inhibition by immunoglobulins: Specific inhibition by autistic children, their relatives, and control subjects  

Microsoft Academic Search

Forty-two parents of children with autistic disorder, 15 children with autistic disorder, 17 siblings of children with autistic disorder, and 12 unrelated normal adult controls were studied to determine if immunoglobulins isolated from their plasma would inhibit binding of the 5HT1A agonist, [3H]-8-hydroxy-N,N-dipropyl-2-aminotetralin (DPAT) to 5HT1A receptors in human hippocampal membranes. There were no significant differences among the means of

Edwin H. Cook; Bruce D. Perry; Glyn Dawson; Mark S. Wainwright; Bennett L. Leventhal

1993-01-01

393

Ischemia/reperfusion injury: effect of simultaneous inhibition of plasma cascade systems versus specific complement inhibition.  

PubMed

Ischemia/reperfusion injury (IRI) may occur from ischemia due to thrombotic occlusion, trauma or surgical interventions, including transplantation, with subsequent reestablishment of circulation. Time-dependent molecular and structural changes result from the deprivation of blood and oxygen in the affected tissue during ischemia. Upon restoration of blood flow a multifaceted network of plasma cascades is activated, including the complement-, coagulation-, kinin-, and fibrinolytic system, which plays a major role in the reperfusion-triggered inflammatory process. The plasma cascade systems are therefore promising therapeutic targets for attenuation of IRI. Earlier studies showed beneficial effects through inhibition of the complement system using specific complement inhibitors. However, pivotal roles in IRI are also attributed to other cascades. This raises the question, whether drugs, such as C1 esterase inhibitor, which regulate more than one cascade at a time, have a higher therapeutic potential. The present review discusses different therapeutic approaches ranging from specific complement inhibition to simultaneous inhibition of plasma cascade systems for reduction of IRI, gives an overview of the plasma cascade systems in IRI as well as highlights recent findings in this field. PMID:24384116

Duehrkop, Claudia; Rieben, Robert

2014-03-01

394

Tumor suppressor XAF1 induces apoptosis, inhibits angiogenesis and inhibits tumor growth in hepatocellular carcinoma  

PubMed Central

X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1), a XIAP-binding protein, is a tumor suppressor gene. XAF1 was silent or expressed lowly in most human malignant tumors. However, the role of XAF1 in hepatocellular carcinoma (HCC) remains unknown. In this study, we investigated the effect of XAF1 on tumor growth and angiogenesis in hepatocellular cancer cells. Our results showed that XAF1 expression was lower in HCC cell lines SMMC-7721, Hep G2 and BEL-7404 and liver cancer tissues than that in paired non-cancer liver tissues. Adenovirus-mediated XAF1 expression (Ad5/F35-XAF1) significantly inhibited cell proliferation and induced apoptosis in HCC cells in dose- and time- dependent manners. Infection of Ad5/F35-XAF1 induced cleavage of caspase -3, -8, -9 and PARP in HCC cells. Furthermore, Ad5/F35-XAF1 treatment significantly suppressed tumor growth in a xenograft model of liver cancer cells. Western Blot and immunohistochemistry staining showed that Ad5/F35-XAF1 treatment suppressed expression of vascular endothelial growth factor (VEGF), which is associated with tumor angiogenesis, in cancer cells and xenograft tumor tissues. Moreover, Ad5/F35-XAF1 treatment prolonged the survival of tumor-bearing mice. Our results demonstrate that XAF1 inhibits tumor growth by inducing apoptosis and inhibiting tumor angiogenesis. XAF1 may be a promising target for liver cancer treatment. PMID:24980821

Zhu, Li Ming; Shi, Dong Mei; Dai, Qiang; Cheng, Xiao Jiao; Yao, Wei Yan; Sun, Ping Hu; Ding, Yan Fei; Qiao, Min Min; Wu, Yun Lin; Jiang, Shi Hu; Tu, Shui Ping

2014-01-01

395

Inhibiting the HSP90 chaperone destabilizes macrophage migration inhibitory factor and thereby inhibits breast tumor progression  

PubMed Central

Intracellular macrophage migration inhibitory factor (MIF) often becomes stabilized in human cancer cells. MIF can promote tumor cell survival, and elevated MIF protein correlates with tumor aggressiveness and poor prognosis. However, the molecular mechanism facilitating MIF stabilization in tumors is not understood. We show that the tumor-activated HSP90 chaperone complex protects MIF from degradation. Pharmacological inhibition of HSP90 activity, or siRNA-mediated knockdown of HSP90 or HDAC6, destabilizes MIF in a variety of human cancer cells. The HSP90-associated E3 ubiquitin ligase CHIP mediates the ensuing proteasome-dependent MIF degradation. Cancer cells contain constitutive endogenous MIF–HSP90 complexes. siRNA-mediated MIF knockdown inhibits proliferation and triggers apoptosis of cultured human cancer cells, whereas HSP90 inhibitor-induced apoptosis is overridden by ectopic MIF expression. In the ErbB2 transgenic model of human HER2-positive breast cancer, genetic ablation of MIF delays tumor progression and prolongs overall survival of mice. Systemic treatment with the HSP90 inhibitor 17AAG reduces MIF expression and blocks growth of MIF-expressing, but not MIF-deficient, tumors. Together, these findings identify MIF as a novel HSP90 client and suggest that HSP90 inhibitors inhibit ErbB2-driven breast tumor growth at least in part by destabilizing MIF. PMID:22271573

Schulz, Ramona; Marchenko, Natalia D.; Holembowski, Lena; Fingerle-Rowson, Gunter; Pesic, Marina; Zender, Lars; Dobbelstein, Matthias

2012-01-01

396

Cerebellar inhibition of inferior olivary transmission in the decerebrate ferret.  

PubMed

Stimulation around the superior cerebellar peduncle or within the deep cerebellar nuclei is known to inhibit the inferior olive with a very long latency. It has been suggested that this inhibition is mediated by the GABA-ergic nucleo-olivary pathway, but alternative explanations such as activation of an indirect excitatory pathway or a pathway via the red nucleus are possible. A long-latency inhibition via the nucleo-olivary pathway would have profound implications for cerebellar function and the present study was performed to test alternative explanations and to characterize the nucleo-olivary inhibition. Climbing fibre responses (CFRs), evoked by periorbital stimulation and recorded from the cerebellar cortex, could be inhibited by stimulation of two distinct mesencephalic areas. One was located within the superior cerebellar peduncle and the other about 1 mm further ventrally. Inhibition evoked from either area occurred in the inferior olive and was independent of a red nucleus relay. Single Purkinje cell recordings revealed that inhibition from the ventral area was not secondary to olivary activation. It is concluded that stimulation of the ventral area activated nucleo-olivary fibres. The inhibition elicited by stimulation within the peduncle probably resulted from indirect activation on the nucleo-olivary fibres via antidromic activation of the interpositus nucleus. The time courses of the inhibition from the two areas were indistinguishable. The duration of the strongest inhibition was short and had a sharp peak at about 30 ms. It is suggested that the time course of the inhibition is important for temporal regulation of learned responses. PMID:16132968

Svensson, P; Bengtsson, F; Hesslow, G

2006-01-01

397

Inhibition of photosynthesis by a fluoroquinolone antibiotic.  

PubMed

Recent microcosm studies have revealed that fluoroquinolone (FQ) antibiotics can have ecotoxicological impacts on photosynthetic organisms, but little is known about the mechanisms of toxicity. We employed a combination of modeling and experimental techniques to explore how FQs may have these unintended secondary toxic effects. Structure-activity analysis revealed that the quinolone ring and secondary amino group typically present in FQ antibiotics may mediate their action as quinone site inhibitors in photosystem II (PS-II), a key enzyme in photosynthetic electron transport. Follow-up molecular simulations involving nalidixic acid (Naldx), a nonfluorinated quinolone with a demonstrated adverse impact on photosynthesis, and ciprofloxacin (Cipro), the most commonly used FQ antibiotic, showed that both may interfere stereochemically with the catalytic activity of reaction center II (RC-II), the pheophytin-quinone-type center present in PS-II. Naldx can occupy the same binding site as the secondary quinone acceptor (Q(B)) in RC-II and interact with amino acid residues required for the enzymatic reduction of Q(B). Cipro binds in a somewhat different manner, suggesting a different mechanism of interference. Fluorescence induction kinetics, a common method of screening for PS-II inhibition, recorded for photoexcited thylakoid membranes isolated from Cipro-exposed spinach chloroplasts, indicated that Cipro interferes with the transfer of energy from excited antenna chlorophyll molecules to the reaction center in RC-II ([Cipro] >or= 5 microM in vitro and >or=10 microM in vivo) and thus delays the kinetics of photoreduction of the primary quinone acceptor (Q(A); [Cipro] >or= 0.6 microM in vitro). Spinach plants exposed to Cipro exhibited severe growth inhibition characterized by a decrease in both the synthesis of leaves and growth of the roots ([Cipro] >or= 0.5 microM in vivo). Our results thus demonstrate that Cipro and related FQ antibiotics may interfere with photosynthetic pathways, in addition to causing morphological deformities in higher plants. PMID:20070075

Aristilde, Ludmilla; Melis, Anastasios; Sposito, Garrison

2010-02-15

398

SYNAPTIC INHIBITION IN AN ISOLATED NERVE CELL  

PubMed Central

Following the preceding studies on the mechanisms of excitation in stretch receptor cells of crayfish, this investigation analyzes inhibitory activity in the synapses formed by two neurons. The cell body of the receptor neuron is located in the periphery and sends dendrites into a fine muscle strand. The dendrites receive innervation through an accessory nerve fiber which has now been established to be inhibitory. There exists a direct peripheral inhibitory control mechanism which can modulate the activity of the stretch receptor. The receptor cell which can be studied in isolation was stimulated by stretch deformation of its dendrites or by antidromic excitation and the effect of inhibitory impulses on its activity was analyzed. Recording was done mainly with intracellular leads inserted into the cell body. 1. Stimulation of the relatively slowly conducting inhibitory nerve fiber either decreases the afferent discharge rate or stops impulses altogether in stretched receptor cells. The inhibitory action is confined to the dendrites and acts on the generator mechanism which is set up by stretch deformation. By restricting depolarization of the dendrites above a certain level, inhibition prevents the generator potential from attaining the "firing level" of the cell. 2. The same inhibitory impulse may set up a postsynaptic polarization or a depolarization, depending on the resting potential level of the cell. The membrane potential at which the inhibitory synaptic potential reverses its polarity, the equilibrium level, may vary in different preparations. The inhibitory potentials increase as the resting potential is displaced in any direction from the inhibitory equilibrium. 3. The inhibitory potentials usually rise to a peak in about 2 msec. and decay in about 30 msec. After repetitive inhibitory stimulation a delayed secondary polarization phase has frequently been seen, prolonging the inhibitory action. Repetitive inhibitory excitation may also be followed by a period of facilitation. Some examples of "direct" excitation by the depolarizing action of inhibitory impulses are described. 4. The interaction between antidromic and inhibitory impulses was studied. The results support previous conclusions (a) that during stretch the dendrites provide a persisting "drive" for the more central portions of the receptor cell, and (b) that antidromic all-or-none impulses do not penetrate into the distal portions of stretch-depolarized dendrites. The "after-potentials" of antidromic impulses are modified by inhibition. 5. Evidence is presented that inhibitory synaptic activity increases the conductance of the dendrites. This effect may occur in the absence of inhibitory potential changes. PMID:13252239

Kuffler, Stephen W.; Eyzaguirre, Carlos

1955-01-01

399

Inhibition of CaMKK2 Stimulates Osteoblast Formation and Inhibits Osteoclast Differentiation  

PubMed Central

Bone remodeling, a physiological process characterized by bone formation by osteoblasts (OB) and resorption of pre-existing bone matrix by osteoclasts (OC), is vital for the maintenance of healthy bone tissue in adult humans. Imbalances in this vital process result in pathological conditions including osteoporosis. Owing to its initial asymptomatic nature, osteoporosis is often detected only after the patient has sustained significant bone loss or a fracture. Hence, anabolic therapeutics that stimulates bone accrual is in high clinical demand. Here we identify Ca2+/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) as a potential target for such therapeutics, as its inhibition enhances OB differentiation and bone growth and suppresses OC differentiation. Mice null for CaMKK2 possess higher trabecular bone mass in their long bones, along with significantly more OBs and fewer multinuclear OCs. Whereas Camkk2?/? MSCs yield significantly higher numbers of OBs, bone marrow cells from Camkk2?/? mice produce fewer multinuclear OCs, in vitro. Acute inhibition of CaMKK2 by its selective, cell-permeable pharmacological inhibitor STO-609 also results in increased OB and diminished OC formation. Further, we find phospho-protein kinase A (PKA) and Ser133 phosphorylated form of cyclic adenosine monophosphate (cAMP) response element binding protein (pCREB) to be markedly elevated in OB progenitors deficient in CaMKK2. On the other hand, genetic ablation of CaMKK2 or its pharmacological inhibition in OC progenitors results in reduced pCREB as well as significantly reduced levels of its transcriptional target, nuclear factor of activated T cells c1 (NFATc1). Moreover, in vivo administration of STO-609 results in increased OBs and diminished OCs, conferring significant protection from ovariectomy (OVX)-induced osteoporosis in adult mice. Overall, our findings reveal a novel function for CaMKK2 in bone remodeling and highlight the potential for its therapeutic inhibition as a valuable bone anabolic strategy that also inhibits OC differentiation in the treatment of osteoporosis. PMID:23408651

Cary, Rachel L.; Waddell, Seid; Racioppi, Luigi; Long, Fanxin; Novack, Deborah V.; Voor, Michael J.; Sankar, Uma

2013-01-01

400

Oxime-induced reactivation of carboxylesterase inhibited by organophosphorus compounds  

SciTech Connect

A structure-activity analysis of the ability of oximes to reactivate rat plasma carboxylesterase (CaE) that was inhibited by organophosphorus (OP) compounds revealed that uncharged oximes, such as diacetylmonoxime or monoisonitrosoacetone, were better reactivators than cationic oximes. Cationic oximes that are excellent reactivators of OP-inhibited acetylcholinesteraser such as pyridinium-2-aldoxime or the bis-pyridinium oximes, HI-6 and TMB-4, produced poor reactivation of OP-inhibited CaE. The best uncharged reactivator was diacetylmonoxime which produced complete reactivation at 0.3 mM in 2 hr of CaE that was inhibited by organophosphinates, alkoxy-containing phosphates, and alkoxy-containing phosphonates. Complete reactivation of CaE could be achieved even after inhibition by phosphonates with highly branched alkoxy groups, such as sarin and soman, that undergo rapid aging with acetylcholinesterase. CaE that was inhibited by phosphonates or phosphates that contained aryloxy groups were reactivated to a lower extent. The cause of this decreased reactivation appears to be an oxime-induced aging reaction that competes with the reactivation reaction. This oxime-induced aging reaction is accelerated by electron-withdrawing substituents on the aryloxy groups of phosphonates and by the presence of multiple aryloxy groups on phosphates. Thus, reactivation and aging of OP-inhibited CaE differ from the same processes for OP-inhibited acetylcholinesterase in both their oxime specificity and inhibitor specificity and, presumably, in their underlying mechanisms.

Maxwell, D.M.; Lieske, C.N.; Brecht, K.M.

1993-05-13

401

Cognitive Inhibition in Students with and without Dyslexia and Dyscalculia  

ERIC Educational Resources Information Center

The present study presents a comparison of the cognitive inhibition abilities of dyslexic, dyscalculic, and control students. The participants were 45 dyslexic students, 45 dyscalculic students, and 45 age-, gender-, and IQ-matched control students. The major evaluation tools included six cognitive inhibition tasks which were restructured during…

Wang, Li-Chih; Tasi, Hung-Ju; Yang, Hsien-Ming

2012-01-01

402

Action spectra for the inhibition of growth in radish hypocotyls  

Microsoft Academic Search

In etiolated seedlings of Raphanus sativus L. the inhibition of hypocotyl elongation by continuous light showed a major bimodal peak of action in the red and far-red, and two minor peaks in the blue regions of the spectrum. It is argued that, under conditions of prolonged irradiation, phytochrome is the pigment controlling the inhibition of hypocotyl elongation by red and

Ann M. Jose; Daphne Vince-Prue

1977-01-01

403

Secondary School Students' Views of Inhibiting Factors in Seeking Counselling  

ERIC Educational Resources Information Center

This study examines secondary school students' perceptions of inhibiting factors in seeking counselling. Responses to a questionnaire completed by 1346 secondary school students were analysed using quantitative and qualitative methods. Exploratory factor analysis highlighted that within 21 pre-defined inhibiting factors, items loaded strongly on…

Chan, Stephanie; Quinn, Philip

2012-01-01

404

Contribution of human uropontin to inhibition of calcium oxalate crystallization  

Microsoft Academic Search

Contribution of human uropontin to inhibition of calcium oxalate crystallization. Uropontin (UP) is known to inhibit the growth and nucleation of calcium oxalate monohydrate (COM) crystals, and it also impedes attachment of calcium oxalate crystals to cultured renal epithelial cells. However, its role in normal defense against renal crystallization, and in pathogenesis of nephrolithiasis is unclear. In this study we

John R Asplin; Denise Arsenault; Joan H Parks; Fredric L Coe; John R Hoyer

1998-01-01

405

Mouse brain gangliosides. Their property of inhibiting EEE virus hemagglutination  

Microsoft Academic Search

Summary Gangliosides isolated from the brain of ten-day-old Swiss albino mice were purified by thin layer chromatography, and the resulting purified gangliosides were tested for their ability to inhibit hemagglutination by Eastern Equine Encephalitis virus. The trisialoganglioside and the more rapidly migrating of the two disialogangliosides were found to inhibit hemagglutination. It is postulated that the neuraminic acid moiety of

Marta T. Zapata; S. Paglini

1973-01-01

406

Inhibition of Return: Support for Generality of the Phenomenon  

Microsoft Academic Search

Inhibition of return (IOR), first described in 1984, was considered to be a general phenomenon for ensuring that attention would be allocated to successive stimuli in the environment. In the present research, IOR was expressed in forced-choice identification tasks with either reaction time or accuracy as the dependent measure. Thus, the generality of IOR was supported, because response inhibition cannot

Marylou Cheal; Garvin Chastain

1999-01-01

407

Distractor Inhibition: Principles of Operation during Selective Attention  

ERIC Educational Resources Information Center

Research suggests that although target amplification acts as the main determinant of the efficacy of selective attention, distractor inhibition contributes under some circumstances. Here we aimed to gain insight into the operating principles that regulate the use of distractor inhibition during selective attention. The results suggest that, in…

Wyatt, Natalie; Machado, Liana

2013-01-01

408

46 CFR 153.912 - Certificate of inhibition or stabilization.  

Code of Federal Regulations, 2010 CFR

... 2010-10-01 2010-10-01 false Certificate of inhibition or stabilization. 153.912 Section 153.912 Shipping...Documents and Cargo Information § 153.912 Certificate of inhibition or stabilization. (a) When a cargo in Table 1...

2010-10-01

409

Simulating cholinesterase inhibition in birds caused by dietary insecticide exposure  

USGS Publications Warehouse

We describe a stochastic simulation model that simulates avian foraging in an agricultural landscape to evaluate factors affecting dietary insecticide exposure and to predict post-exposure cholinesterase (ChE) inhibition. To evaluate the model, we simulated published field studies and found that model predictions of insecticide decay and ChE inhibition reasonably approximated most observed results. Sensitivity analysis suggested that foraging location usually influenced ChE inhibition more than diet preferences or daily intake rate. Although organophosphorus insecticides usually caused greater inhibition than carbamate insecticides, insecticide toxicity appeared only moderately important. When we simulated impact of heavy insecticide applications during breeding seasons of 15 wild bird species, mean maximum ChE inhibition in most species exceeded 20% at some point. At this level of inhibition, birds may experience nausea and/or may exhibit minor behavioral changes. Simulated risk peaked in April-May and August-September and was lowest in July. ChE inhibition increased with proportion of vegetation in the diet. This model, and ones like it, may help predict insecticide exposure of and sublethal ChE inhibition in grassland animals, thereby reducing dependence of ecological risk assessments on field studies alone.

Corson, M. S.; Mora, M. A.; Grant, W. E.

1998-01-01

410

Inhibition of aerobic respiration and dissimilatory perchlorate reduction using cyanide  

Microsoft Academic Search

The effect of low concentrations of cyanide on dissimilatory perchlorate and chlorate reduction and aerobic respiration was examined using pure cultures of Azospira sp. KJ. Cyanide at a concentration of 38 ?M inhibited cell growth on perchlorate, chlorate and molecular oxygen, but it did not inhibit the activity of chlorite dismutase. When oxygen accumulation was prevented by adding an oxygen

Yanguang Song; Bruce E. Logan

2004-01-01

411

The Affective Consequences of Cognitive Inhibition: Devaluation or Neutralization?  

ERIC Educational Resources Information Center

Affective evaluations of previously ignored visual stimuli are more negative than those of novel items or prior targets of attention or response. This has been taken as evidence that inhibition has negative affective consequences. But inhibition could act instead to attenuate or "neutralize" preexisting affective salience, predicting opposite…

Frischen, Alexandra; Ferrey, Anne E.; Burt, Dustin H. R.; Pistchik, Meghan; Fenske, Mark J.

2012-01-01

412

Left inferior frontal gyrus is critical for response inhibition  

Microsoft Academic Search

BACKGROUND: Lesion studies in human and non-human primates have linked several different regions of prefrontal cortex (PFC) with the ability to inhibit inappropriate motor responses. However, recent functional neuroimaging studies have specifically implicated right inferior PFC in response inhibition. Right frontal dominance for inhibitory motor control has become a commonly accepted view, although support for this position has not been

Diane Swick; Victoria Ashley; And U. Turken

2008-01-01

413

Pyrazine derivatives in cigarette smoke inhibit hamster oviductal functioning  

Microsoft Academic Search

BACKGROUND: Our past studies have shown that cigarette smoke inhibits oviductal functioning in vivo and in vitro. The goals in this study were to identify pyrazine derivatives in cigarette smoke solutions that inhibit ciliary beat frequency, oocyte pickup rate, and infundibular smooth muscle contraction in the hamster oviduct and to determine their lowest observable adverse effect levels (LOAELs) using in

Karen Riveles; Ryan Roza; Janet Arey; Prue Talbot

2004-01-01

414

Converting enzyme inhibition and progressive glomerulosclerosis in the rat  

Microsoft Academic Search

Converting enzyme inhibition and progressive glomerulosclerosis in the rat. The effect of converting enzyme inhibition (CEI) by captopril (CAP, 500 mg\\/liter drinking water) on the development and progression of glomerulosclerosis (GS) was studied in six groups of male unine-phrectomized (UN) Wistar rats. In group A, treated with CAP for four to five weeks after UN, a reduction in systolic blood

Joke J B Beukers; Annemieke van der Wal; Philip J Hoedemaeker; Jan J Weening

1987-01-01

415

Belief Inhibition in Children's Reasoning: Memory-Based Evidence  

ERIC Educational Resources Information Center

Adult reasoning has been shown as mediated by the inhibition of intuitive beliefs that are in conflict with logic. The current study introduces a classic procedure from the memory field to investigate belief inhibition in 12- to 17-year-old reasoners. A lexical decision task was used to probe the memory accessibility of beliefs that were cued…

Steegen, Sara; Neys, Wim De

2012-01-01

416

ORIGINAL ARTICLE Inhibition of Maternal Behaviour by Central Infusion of  

E-print Network

@ucr.edu). Stress can inhibit maternal behaviour and increase rates of child abuse in humans and other animals, Madison, WI, USA. Stress can inhibit maternal behaviour and increase the risk of off- spring abuse to impaired maternal behaviour and increased abusive behaviour (1­3). Similarly, chronic psychosocial

Saltzman, Wendy

417

Extracts of ginkgo biloba leaves inhibit monoamine oxidase  

Microsoft Academic Search

Extracts of Ginkgo biloba leaves produce reversible inhibition of rat brain monoamine oxidase (MAO). Both MAO-A and -B types were inhibited to a similar extent. The MAO inhibitory compound(s) were present in dried or fresh Ginkgo biloba leaves as well as in commercially available capsules of Ginkgo biloba and appear to be heat stable with relatively low molecular weight. MAO

Helen L. White; Philip W. Scates; Barrett R. Cooper

1996-01-01

418

Modelling Myc inhibition as a cancer therapy Laura Soucek1  

E-print Network

LETTERS Modelling Myc inhibition as a cancer therapy Laura Soucek1 , Jonathan Whitfield1 , Carla P-specific cancer therapy. Myc is deregulated and overexpressed in most cancer cells, where it hijacks the diverse be systemically and reversibly inhibited in tissues of adult animals through inducible expression of the dominant

Cai, Long

419

Original article Inhibition of Escherichia coli O157:H7  

E-print Network

Original article Inhibition of Escherichia coli O157:H7 in commercial and traditional fermented and indigenous lactic acid bacteria (LAB) and the survival of Escherichia coli O157:H7 in fermented goat's milk to growth and acid production. However, E. coli O157:H7 was inhibited in the LP-activated milk

Paris-Sud XI, Université de

420

Ligand accumulation counteracts therapeutic inhibition of receptor systems  

E-print Network

systems by competitive inhibition is the objective of various protein drugs in development and on the market. A variety of receptor systems also constitute a degradation mechanism for ligand and drug via interplay between ligand kinetics, drug pharmacokinetics, and the drug effect arising from the inhibition

Duffy, Ken